Pauline Anderson

A new type of laser therapy is safe and effective for children with drug-resistant epilepsy, new research suggests. In a study of nearly 150 children, more than half of those who received MRI-guided laser interstitial thermal therapy (MRgLITT) were seizure free at 1 year.

Results show that this “is a new and promising therapy” for children for whom drug therapy has failed, said study investigator Elysa Widjaja, MD, a pediatric neuroradiologist at the Hospital for Sick Children and professor in the department of medical imaging, University of Toronto.

In addition, the procedure is less invasive and requires a shorter hospital stay than does open epilepsy surgery, Dr. Widjaja said.

The findings were presented at the annual meeting of the American Epilepsy Society, which was held online this year because of the COVID-19 pandemic.
 

Registry study

To date, most published studies on the laser procedure have had a small number of participants from only a few centers, Dr. Widjaja noted. “The aim of our registry is to collect data from multiple centers in both Canada and the U.S. to try to get a better understanding of the outcomes following laser therapy and the complications associated with this treatment,” she said.

In the procedure, a surgeon drills a tiny hole through the skull and, guided by MRI, inserts a very thin laser fiber into the center of the lesion. Heat then ablates the affected brain region.

From the dedicated registry, researchers recruited 182 children who were treated with MRgLITT at seven pediatric centers in the United States and two centers in Canada. The youngest patient was aged 14 months, and the oldest was aged 21 years (mean age, 11.2 years). Some pediatric hospitals treat patients up to age 21, Dr. Widjaja noted.

All of the study participants had focal epilepsy, “so the seizures are coming from a defined area of the brain,” she added. In addition, study participants’ conditions were drug-resistant, defined as conditions in which two antiseizure medications had previously failed.

The mean age at seizure onset was 5.4 years, and the mean number of antiepileptic drugs that were taken was 2.3.

Before receiving the therapy, children typically undergo extensive analyses, including MRI and video electroencephalography, to pinpoint where in the brain the seizures originate. Dr. Widjaja noted that the specific area of the brain that is affected varies widely from child to child.

The investigators collected baseline clinical characteristic and procedural data, including ablation site, type of lesion, length of stay, complications, number of MRgLITT procedures, and seizure outcome. To gather this information, they used a secure electronic platform designed to collect and store research data.
 

Seizure freedom

Among 137 patients for whom 1-year seizure outcomes were available, seizure freedom was reported for 74 patients (54%). In a recent meta-analysis conducted by the investigators, the rate of seizure-free outcomes following epilepsy surgery was about 65%. Although this rate is higher than with the laser therapy, Dr. Widjaja pointed out that the laser intervention is less invasive and the hospital stay of a mean of 3.3 days is shorter than the week or so needed after surgery. This, she said, makes the procedure cost-effective.

Unlike surgery, laser therapy is also “particularly good” at reaching lesions deep in the brain without damaging surrounding tissue, Dr. Widjaja said.

Although the researchers have not evaluated seizure outcomes with respect to age, Dr. Widjaja believes age is not a major factor in outcomes. “I suspect it’s the type of lesion and how big the lesion is that mainly influences the outcome, rather than actual age,” she said.

Complications related to the laser therapy, including infections and bleeding, occurred in 15% of patients. Neurologic deficits affected about 8% of patients; however, these tended to be transient, Dr. Widjaja noted. There were two cases (1%) of permanent neurologic deficits, both of which involved weakness of arms or legs. This, said Dr. Widjaja, is less than the 5% rate of permanent neurologic deficits that occur following surgery, as reported in the literature.

There were no cases of major intracranial hemorrhage among the participants. At 30 days, there was one reported death.

Laser therapy is limited to relatively small lesions of no more than about 2 cm on average, Dr. Widjaja said. “We normally can’t treat huge lesions using laser therapy; they would need surgery.” However, it is possible to treat the same area twice. In the current study, 20 patients (11%) underwent laser therapy on one region on two occasions. Of these participants, 12 (60%) achieved freedom from seizures.

Dr. Widjaja noted that two additional epilepsy centers will soon be providing laser therapy and will expand the registry. In addition, the investigators are building a surgery registry that will enable them to compare outcomes of laser treatment with surgery.

Currently, laser therapy is available only at specialized epilepsy centers that perform surgery.
 

‘Very important’ research

Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, Boston, called this is “a very important study.”

Laser therapy “offers the opportunity for very rapid recovery from a minimally invasive, targeted technique while simultaneously offering promising outcomes,” said Dr. Goldenholz, who was not involved with the research.

He noted the importance of the investigators’ choosing freedom from seizures as the outcome of interest. In addition, the 54% seizure-freedom rate in the study is “substantially better” than rates from other interventions, he said.

“To put the results into perspective, other work has found that these same patients would have a less than 10% chance of seizure freedom if many different drug combinations were tried,” said Dr. Goldenholz.

He noted that the 1-year outcomes “are a good first time point” but that it is very important to assess longer-term outcomes. “Often, postsurgical outcomes are worse when looking at 2 or 5 years postoperatively,” he added. These longer-term data will be important “to fully inform our patients about long-term prognosis,” Dr. Goldenholz said.

Still, given the overall favorable results so far, “I think more centers will be likely to explore this newer technology,” he said.

The study was funded by the Pediatric Epilepsy Research Foundation. The study authors and Dr. Goldenholz report no relevant financial relationships.

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

A new type of laser therapy is safe and effective for children with drug-resistant epilepsy, new research suggests. In a study of nearly 150 children, more than half of those who received MRI-guided laser interstitial thermal therapy (MRgLITT) were seizure free at 1 year.

Results show that this “is a new and promising therapy” for children for whom drug therapy has failed, said study investigator Elysa Widjaja, MD, a pediatric neuroradiologist at the Hospital for Sick Children and professor in the department of medical imaging, University of Toronto.

In addition, the procedure is less invasive and requires a shorter hospital stay than does open epilepsy surgery, Dr. Widjaja said.

The findings were presented at the annual meeting of the American Epilepsy Society, which was held online this year because of the COVID-19 pandemic.
 

Registry study

To date, most published studies on the laser procedure have had a small number of participants from only a few centers, Dr. Widjaja noted. “The aim of our registry is to collect data from multiple centers in both Canada and the U.S. to try to get a better understanding of the outcomes following laser therapy and the complications associated with this treatment,” she said.

In the procedure, a surgeon drills a tiny hole through the skull and, guided by MRI, inserts a very thin laser fiber into the center of the lesion. Heat then ablates the affected brain region.

From the dedicated registry, researchers recruited 182 children who were treated with MRgLITT at seven pediatric centers in the United States and two centers in Canada. The youngest patient was aged 14 months, and the oldest was aged 21 years (mean age, 11.2 years). Some pediatric hospitals treat patients up to age 21, Dr. Widjaja noted.

All of the study participants had focal epilepsy, “so the seizures are coming from a defined area of the brain,” she added. In addition, study participants’ conditions were drug-resistant, defined as conditions in which two antiseizure medications had previously failed.

The mean age at seizure onset was 5.4 years, and the mean number of antiepileptic drugs that were taken was 2.3.

Before receiving the therapy, children typically undergo extensive analyses, including MRI and video electroencephalography, to pinpoint where in the brain the seizures originate. Dr. Widjaja noted that the specific area of the brain that is affected varies widely from child to child.

The investigators collected baseline clinical characteristic and procedural data, including ablation site, type of lesion, length of stay, complications, number of MRgLITT procedures, and seizure outcome. To gather this information, they used a secure electronic platform designed to collect and store research data.
 

Seizure freedom

Among 137 patients for whom 1-year seizure outcomes were available, seizure freedom was reported for 74 patients (54%). In a recent meta-analysis conducted by the investigators, the rate of seizure-free outcomes following epilepsy surgery was about 65%. Although this rate is higher than with the laser therapy, Dr. Widjaja pointed out that the laser intervention is less invasive and the hospital stay of a mean of 3.3 days is shorter than the week or so needed after surgery. This, she said, makes the procedure cost-effective.

Unlike surgery, laser therapy is also “particularly good” at reaching lesions deep in the brain without damaging surrounding tissue, Dr. Widjaja said.

Although the researchers have not evaluated seizure outcomes with respect to age, Dr. Widjaja believes age is not a major factor in outcomes. “I suspect it’s the type of lesion and how big the lesion is that mainly influences the outcome, rather than actual age,” she said.

Complications related to the laser therapy, including infections and bleeding, occurred in 15% of patients. Neurologic deficits affected about 8% of patients; however, these tended to be transient, Dr. Widjaja noted. There were two cases (1%) of permanent neurologic deficits, both of which involved weakness of arms or legs. This, said Dr. Widjaja, is less than the 5% rate of permanent neurologic deficits that occur following surgery, as reported in the literature.

There were no cases of major intracranial hemorrhage among the participants. At 30 days, there was one reported death.

Laser therapy is limited to relatively small lesions of no more than about 2 cm on average, Dr. Widjaja said. “We normally can’t treat huge lesions using laser therapy; they would need surgery.” However, it is possible to treat the same area twice. In the current study, 20 patients (11%) underwent laser therapy on one region on two occasions. Of these participants, 12 (60%) achieved freedom from seizures.

Dr. Widjaja noted that two additional epilepsy centers will soon be providing laser therapy and will expand the registry. In addition, the investigators are building a surgery registry that will enable them to compare outcomes of laser treatment with surgery.

Currently, laser therapy is available only at specialized epilepsy centers that perform surgery.
 

‘Very important’ research

Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, Boston, called this is “a very important study.”

Laser therapy “offers the opportunity for very rapid recovery from a minimally invasive, targeted technique while simultaneously offering promising outcomes,” said Dr. Goldenholz, who was not involved with the research.

He noted the importance of the investigators’ choosing freedom from seizures as the outcome of interest. In addition, the 54% seizure-freedom rate in the study is “substantially better” than rates from other interventions, he said.

“To put the results into perspective, other work has found that these same patients would have a less than 10% chance of seizure freedom if many different drug combinations were tried,” said Dr. Goldenholz.

He noted that the 1-year outcomes “are a good first time point” but that it is very important to assess longer-term outcomes. “Often, postsurgical outcomes are worse when looking at 2 or 5 years postoperatively,” he added. These longer-term data will be important “to fully inform our patients about long-term prognosis,” Dr. Goldenholz said.

Still, given the overall favorable results so far, “I think more centers will be likely to explore this newer technology,” he said.

The study was funded by the Pediatric Epilepsy Research Foundation. The study authors and Dr. Goldenholz report no relevant financial relationships.

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

A new type of laser therapy is safe and effective for children with drug-resistant epilepsy, new research suggests. In a study of nearly 150 children, more than half of those who received MRI-guided laser interstitial thermal therapy (MRgLITT) were seizure free at 1 year.

Results show that this “is a new and promising therapy” for children for whom drug therapy has failed, said study investigator Elysa Widjaja, MD, a pediatric neuroradiologist at the Hospital for Sick Children and professor in the department of medical imaging, University of Toronto.

In addition, the procedure is less invasive and requires a shorter hospital stay than does open epilepsy surgery, Dr. Widjaja said.

The findings were presented at the annual meeting of the American Epilepsy Society, which was held online this year because of the COVID-19 pandemic.
 

Registry study

To date, most published studies on the laser procedure have had a small number of participants from only a few centers, Dr. Widjaja noted. “The aim of our registry is to collect data from multiple centers in both Canada and the U.S. to try to get a better understanding of the outcomes following laser therapy and the complications associated with this treatment,” she said.

In the procedure, a surgeon drills a tiny hole through the skull and, guided by MRI, inserts a very thin laser fiber into the center of the lesion. Heat then ablates the affected brain region.

From the dedicated registry, researchers recruited 182 children who were treated with MRgLITT at seven pediatric centers in the United States and two centers in Canada. The youngest patient was aged 14 months, and the oldest was aged 21 years (mean age, 11.2 years). Some pediatric hospitals treat patients up to age 21, Dr. Widjaja noted.

All of the study participants had focal epilepsy, “so the seizures are coming from a defined area of the brain,” she added. In addition, study participants’ conditions were drug-resistant, defined as conditions in which two antiseizure medications had previously failed.

The mean age at seizure onset was 5.4 years, and the mean number of antiepileptic drugs that were taken was 2.3.

Before receiving the therapy, children typically undergo extensive analyses, including MRI and video electroencephalography, to pinpoint where in the brain the seizures originate. Dr. Widjaja noted that the specific area of the brain that is affected varies widely from child to child.

The investigators collected baseline clinical characteristic and procedural data, including ablation site, type of lesion, length of stay, complications, number of MRgLITT procedures, and seizure outcome. To gather this information, they used a secure electronic platform designed to collect and store research data.
 

Seizure freedom

Among 137 patients for whom 1-year seizure outcomes were available, seizure freedom was reported for 74 patients (54%). In a recent meta-analysis conducted by the investigators, the rate of seizure-free outcomes following epilepsy surgery was about 65%. Although this rate is higher than with the laser therapy, Dr. Widjaja pointed out that the laser intervention is less invasive and the hospital stay of a mean of 3.3 days is shorter than the week or so needed after surgery. This, she said, makes the procedure cost-effective.

Unlike surgery, laser therapy is also “particularly good” at reaching lesions deep in the brain without damaging surrounding tissue, Dr. Widjaja said.

Although the researchers have not evaluated seizure outcomes with respect to age, Dr. Widjaja believes age is not a major factor in outcomes. “I suspect it’s the type of lesion and how big the lesion is that mainly influences the outcome, rather than actual age,” she said.

Complications related to the laser therapy, including infections and bleeding, occurred in 15% of patients. Neurologic deficits affected about 8% of patients; however, these tended to be transient, Dr. Widjaja noted. There were two cases (1%) of permanent neurologic deficits, both of which involved weakness of arms or legs. This, said Dr. Widjaja, is less than the 5% rate of permanent neurologic deficits that occur following surgery, as reported in the literature.

There were no cases of major intracranial hemorrhage among the participants. At 30 days, there was one reported death.

Laser therapy is limited to relatively small lesions of no more than about 2 cm on average, Dr. Widjaja said. “We normally can’t treat huge lesions using laser therapy; they would need surgery.” However, it is possible to treat the same area twice. In the current study, 20 patients (11%) underwent laser therapy on one region on two occasions. Of these participants, 12 (60%) achieved freedom from seizures.

Dr. Widjaja noted that two additional epilepsy centers will soon be providing laser therapy and will expand the registry. In addition, the investigators are building a surgery registry that will enable them to compare outcomes of laser treatment with surgery.

Currently, laser therapy is available only at specialized epilepsy centers that perform surgery.
 

‘Very important’ research

Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, Boston, called this is “a very important study.”

Laser therapy “offers the opportunity for very rapid recovery from a minimally invasive, targeted technique while simultaneously offering promising outcomes,” said Dr. Goldenholz, who was not involved with the research.

He noted the importance of the investigators’ choosing freedom from seizures as the outcome of interest. In addition, the 54% seizure-freedom rate in the study is “substantially better” than rates from other interventions, he said.

“To put the results into perspective, other work has found that these same patients would have a less than 10% chance of seizure freedom if many different drug combinations were tried,” said Dr. Goldenholz.

He noted that the 1-year outcomes “are a good first time point” but that it is very important to assess longer-term outcomes. “Often, postsurgical outcomes are worse when looking at 2 or 5 years postoperatively,” he added. These longer-term data will be important “to fully inform our patients about long-term prognosis,” Dr. Goldenholz said.

Still, given the overall favorable results so far, “I think more centers will be likely to explore this newer technology,” he said.

The study was funded by the Pediatric Epilepsy Research Foundation. The study authors and Dr. Goldenholz report no relevant financial relationships.

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

Sudden unexpected death in epilepsy (SUDEP) may explain 3% of all sudden deaths in children – a prevalence rate that is at least three times greater than previously reported estimates – new research shows.

Just a few years ago, the message regarding SUDEP was that “it’s very rare in children so you don’t need to worry about it,” said study investigator Vicky Whittemore, PhD, program director at the National Institute of Neurological Disorders and Stroke.

These new study results should refocus the message that “the condition is rare, but not as rare as we thought it was,” she said.

The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

Population-based study

Most of the research examining the pediatric SUDEP rate in the United States is based on convenience samples, with few population-based studies.

The investigators used data from the National Institutes of Health/Centers for Disease Control and Prevention Sudden Death in the Young Case Registry. The CDC set up the registry several years ago to record cases of sudden infant death syndrome and sudden deaths in children resulting from violence, trauma, and abuse. Its mandate has since expanded, and the registry now includes data on sudden cardiac death and SUDEP in children.

The current study included children with SUDEP or cardiac/SUDEP who were aged 0-17 years from several states or jurisdictions from 2015 to 2017. Cases were deemed to be SUDEP if the patient had a history of epilepsy, with or without evidence of seizure at the time of death, but excluding status epilepticus.

Criteria for cardiac/SUDEP cases included having a family history of a heritable cardiac condition or sudden death before age 50 years, a personal history of cardiac disease, or a clinical history suggestive of a cardiac disorder, such as death during exertion.

This second category, said Dr. Whittemore, might capture children with Dravet syndrome, a type of epilepsy caused by a genetic mutation that affects both the heart and the brain. “In these cases, it’s sometimes difficult to tell if the child died due to a heart complication or due to epilepsy,” she said.

The analysis included 1,776 cases. Of these, 3% were categorized as SUDEP, and 1% were categorized as cardiac/SUDEP.

The relatively high prevalence of SUDEP was somewhat unexpected, inasmuch as previous reports estimated the rate to be 0.5%-1%, said Dr. Whittemore.

She noted that the current study is population based and included all cases of child death, whereas past reports relied on death certificates. “That probably missed a lot of deaths because they weren’t recorded accurately on the death certificate or weren’t reported in a way that anyone could ascertain that it was a death in someone that had epilepsy.”
 

Racial differences

Autopsy rates were lower for SUDEP (70%), compared with other categories of death in the registry (81%-100%).

In most jurisdictions, parents must give consent for an autopsy to be performed for a child, and many parents who have suffered such a sudden loss don’t want further investigation, said Dr. Whittemore. “If you know your child had epilepsy, doing an autopsy really isn’t going to tell you very much. You already know they had epilepsy; you may not know the cause of the epilepsy, but an autopsy isn’t going to reveal as much as it would in children with sudden cardiac death.”

SUDEP was equally common in boys and girls. However, the SUDEP mortality rate was higher in Black children (0.32/100,000) than in White children (0.22/100,000). It’s unclear from this study why this is so, but another study that examined SUDEP rates by ZIP code suggested that the higher rate may be caused by socioeconomic factors, said Dr. Whittemore. “Black children from a lower-income family who don’t have access to care may not be getting as good treatment and so have more uncontrolled seizures, which may lead to higher incidence of SUDEP.”

SUDEP occurred at all ages, but mortality rates were highest among patients aged 0-1 year (0.53/100,000) and in those aged 14-17 years (0.31/100,000). Dr. Whittemore speculated that SUDEP rates were higher among the youngest patients because their seizures have just started, and it may be more difficult to bring them under control. In the past, some of these cases may have been classified as sudden infant death syndrome but are now recognized as SUDEP.

As for the older group, research shows that puberty can result in poorer seizure control, which may put teens at elevated risk for SUDEP, said Dr. Whittemore. She added that, as teens continue to age, SUDEP risk may continue to increase. Dr. Whittemore suggested that young adults who head off to college may stop taking their antiseizure medications or consume alcohol while taking these drugs.
 

Failure of arousal

The study results revealed that most SUDEP cases occurred during sleep without a witness. Dr. Whittemore believes that sleeping with one’s face in a pillow may prevent the reflex required to turn the head to breathe. “It’s sort of a failure of arousal that is potentially the underlying mechanism.”

In some cases, there are signs children had a seizure just prior to death, said Dr. Whittemore.

The researchers have now collected information for 2018 and 2019 and plan to add these data to the current 3-year results. “We will now expand our analysis to include these new numbers to make sure the trends we saw in those 3 years are continuing,” said Dr. Whittemore. The new results should help raise awareness that SUDEP is not as rare as previously believed.

Parents of children with epilepsy can take steps to help reduce the risk for SUDEP, she added. For example, they can use night monitors, and for the children at highest risk (e.g., those with Dravet syndrome), they can use an “alarm blanket” that alerts them when the child moves.
 

Much is still unknown

Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, New York, who has participated in SUDEP research, said it “raises important questions about SUDEP in children and about racial disparities in SUDEP.”

The understanding of SUDEP so far “leaves much to be desired,” said Dr. Goldenholz. “We don’t yet know why it happens, and we don’t yet know how to prevent it.” The current study “brings a couple of new data points to the table which need further validation, confirmation, and explanation.”

The Sudden Death in Young Case Registry is supported by the National Heart, Lung, and Blood Institute; the National Institute of Neurological Disorders and Stroke; and the CDC. The investigators and Dr. Goldenholz disclosed no relevant financial relationships.

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

Sudden unexpected death in epilepsy (SUDEP) may explain 3% of all sudden deaths in children – a prevalence rate that is at least three times greater than previously reported estimates – new research shows.

Just a few years ago, the message regarding SUDEP was that “it’s very rare in children so you don’t need to worry about it,” said study investigator Vicky Whittemore, PhD, program director at the National Institute of Neurological Disorders and Stroke.

These new study results should refocus the message that “the condition is rare, but not as rare as we thought it was,” she said.

The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

Population-based study

Most of the research examining the pediatric SUDEP rate in the United States is based on convenience samples, with few population-based studies.

The investigators used data from the National Institutes of Health/Centers for Disease Control and Prevention Sudden Death in the Young Case Registry. The CDC set up the registry several years ago to record cases of sudden infant death syndrome and sudden deaths in children resulting from violence, trauma, and abuse. Its mandate has since expanded, and the registry now includes data on sudden cardiac death and SUDEP in children.

The current study included children with SUDEP or cardiac/SUDEP who were aged 0-17 years from several states or jurisdictions from 2015 to 2017. Cases were deemed to be SUDEP if the patient had a history of epilepsy, with or without evidence of seizure at the time of death, but excluding status epilepticus.

Criteria for cardiac/SUDEP cases included having a family history of a heritable cardiac condition or sudden death before age 50 years, a personal history of cardiac disease, or a clinical history suggestive of a cardiac disorder, such as death during exertion.

This second category, said Dr. Whittemore, might capture children with Dravet syndrome, a type of epilepsy caused by a genetic mutation that affects both the heart and the brain. “In these cases, it’s sometimes difficult to tell if the child died due to a heart complication or due to epilepsy,” she said.

The analysis included 1,776 cases. Of these, 3% were categorized as SUDEP, and 1% were categorized as cardiac/SUDEP.

The relatively high prevalence of SUDEP was somewhat unexpected, inasmuch as previous reports estimated the rate to be 0.5%-1%, said Dr. Whittemore.

She noted that the current study is population based and included all cases of child death, whereas past reports relied on death certificates. “That probably missed a lot of deaths because they weren’t recorded accurately on the death certificate or weren’t reported in a way that anyone could ascertain that it was a death in someone that had epilepsy.”
 

Racial differences

Autopsy rates were lower for SUDEP (70%), compared with other categories of death in the registry (81%-100%).

In most jurisdictions, parents must give consent for an autopsy to be performed for a child, and many parents who have suffered such a sudden loss don’t want further investigation, said Dr. Whittemore. “If you know your child had epilepsy, doing an autopsy really isn’t going to tell you very much. You already know they had epilepsy; you may not know the cause of the epilepsy, but an autopsy isn’t going to reveal as much as it would in children with sudden cardiac death.”

SUDEP was equally common in boys and girls. However, the SUDEP mortality rate was higher in Black children (0.32/100,000) than in White children (0.22/100,000). It’s unclear from this study why this is so, but another study that examined SUDEP rates by ZIP code suggested that the higher rate may be caused by socioeconomic factors, said Dr. Whittemore. “Black children from a lower-income family who don’t have access to care may not be getting as good treatment and so have more uncontrolled seizures, which may lead to higher incidence of SUDEP.”

SUDEP occurred at all ages, but mortality rates were highest among patients aged 0-1 year (0.53/100,000) and in those aged 14-17 years (0.31/100,000). Dr. Whittemore speculated that SUDEP rates were higher among the youngest patients because their seizures have just started, and it may be more difficult to bring them under control. In the past, some of these cases may have been classified as sudden infant death syndrome but are now recognized as SUDEP.

As for the older group, research shows that puberty can result in poorer seizure control, which may put teens at elevated risk for SUDEP, said Dr. Whittemore. She added that, as teens continue to age, SUDEP risk may continue to increase. Dr. Whittemore suggested that young adults who head off to college may stop taking their antiseizure medications or consume alcohol while taking these drugs.
 

Failure of arousal

The study results revealed that most SUDEP cases occurred during sleep without a witness. Dr. Whittemore believes that sleeping with one’s face in a pillow may prevent the reflex required to turn the head to breathe. “It’s sort of a failure of arousal that is potentially the underlying mechanism.”

In some cases, there are signs children had a seizure just prior to death, said Dr. Whittemore.

The researchers have now collected information for 2018 and 2019 and plan to add these data to the current 3-year results. “We will now expand our analysis to include these new numbers to make sure the trends we saw in those 3 years are continuing,” said Dr. Whittemore. The new results should help raise awareness that SUDEP is not as rare as previously believed.

Parents of children with epilepsy can take steps to help reduce the risk for SUDEP, she added. For example, they can use night monitors, and for the children at highest risk (e.g., those with Dravet syndrome), they can use an “alarm blanket” that alerts them when the child moves.
 

Much is still unknown

Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, New York, who has participated in SUDEP research, said it “raises important questions about SUDEP in children and about racial disparities in SUDEP.”

The understanding of SUDEP so far “leaves much to be desired,” said Dr. Goldenholz. “We don’t yet know why it happens, and we don’t yet know how to prevent it.” The current study “brings a couple of new data points to the table which need further validation, confirmation, and explanation.”

The Sudden Death in Young Case Registry is supported by the National Heart, Lung, and Blood Institute; the National Institute of Neurological Disorders and Stroke; and the CDC. The investigators and Dr. Goldenholz disclosed no relevant financial relationships.

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

Sudden unexpected death in epilepsy (SUDEP) may explain 3% of all sudden deaths in children – a prevalence rate that is at least three times greater than previously reported estimates – new research shows.

Just a few years ago, the message regarding SUDEP was that “it’s very rare in children so you don’t need to worry about it,” said study investigator Vicky Whittemore, PhD, program director at the National Institute of Neurological Disorders and Stroke.

These new study results should refocus the message that “the condition is rare, but not as rare as we thought it was,” she said.

The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

Population-based study

Most of the research examining the pediatric SUDEP rate in the United States is based on convenience samples, with few population-based studies.

The investigators used data from the National Institutes of Health/Centers for Disease Control and Prevention Sudden Death in the Young Case Registry. The CDC set up the registry several years ago to record cases of sudden infant death syndrome and sudden deaths in children resulting from violence, trauma, and abuse. Its mandate has since expanded, and the registry now includes data on sudden cardiac death and SUDEP in children.

The current study included children with SUDEP or cardiac/SUDEP who were aged 0-17 years from several states or jurisdictions from 2015 to 2017. Cases were deemed to be SUDEP if the patient had a history of epilepsy, with or without evidence of seizure at the time of death, but excluding status epilepticus.

Criteria for cardiac/SUDEP cases included having a family history of a heritable cardiac condition or sudden death before age 50 years, a personal history of cardiac disease, or a clinical history suggestive of a cardiac disorder, such as death during exertion.

This second category, said Dr. Whittemore, might capture children with Dravet syndrome, a type of epilepsy caused by a genetic mutation that affects both the heart and the brain. “In these cases, it’s sometimes difficult to tell if the child died due to a heart complication or due to epilepsy,” she said.

The analysis included 1,776 cases. Of these, 3% were categorized as SUDEP, and 1% were categorized as cardiac/SUDEP.

The relatively high prevalence of SUDEP was somewhat unexpected, inasmuch as previous reports estimated the rate to be 0.5%-1%, said Dr. Whittemore.

She noted that the current study is population based and included all cases of child death, whereas past reports relied on death certificates. “That probably missed a lot of deaths because they weren’t recorded accurately on the death certificate or weren’t reported in a way that anyone could ascertain that it was a death in someone that had epilepsy.”
 

Racial differences

Autopsy rates were lower for SUDEP (70%), compared with other categories of death in the registry (81%-100%).

In most jurisdictions, parents must give consent for an autopsy to be performed for a child, and many parents who have suffered such a sudden loss don’t want further investigation, said Dr. Whittemore. “If you know your child had epilepsy, doing an autopsy really isn’t going to tell you very much. You already know they had epilepsy; you may not know the cause of the epilepsy, but an autopsy isn’t going to reveal as much as it would in children with sudden cardiac death.”

SUDEP was equally common in boys and girls. However, the SUDEP mortality rate was higher in Black children (0.32/100,000) than in White children (0.22/100,000). It’s unclear from this study why this is so, but another study that examined SUDEP rates by ZIP code suggested that the higher rate may be caused by socioeconomic factors, said Dr. Whittemore. “Black children from a lower-income family who don’t have access to care may not be getting as good treatment and so have more uncontrolled seizures, which may lead to higher incidence of SUDEP.”

SUDEP occurred at all ages, but mortality rates were highest among patients aged 0-1 year (0.53/100,000) and in those aged 14-17 years (0.31/100,000). Dr. Whittemore speculated that SUDEP rates were higher among the youngest patients because their seizures have just started, and it may be more difficult to bring them under control. In the past, some of these cases may have been classified as sudden infant death syndrome but are now recognized as SUDEP.

As for the older group, research shows that puberty can result in poorer seizure control, which may put teens at elevated risk for SUDEP, said Dr. Whittemore. She added that, as teens continue to age, SUDEP risk may continue to increase. Dr. Whittemore suggested that young adults who head off to college may stop taking their antiseizure medications or consume alcohol while taking these drugs.
 

Failure of arousal

The study results revealed that most SUDEP cases occurred during sleep without a witness. Dr. Whittemore believes that sleeping with one’s face in a pillow may prevent the reflex required to turn the head to breathe. “It’s sort of a failure of arousal that is potentially the underlying mechanism.”

In some cases, there are signs children had a seizure just prior to death, said Dr. Whittemore.

The researchers have now collected information for 2018 and 2019 and plan to add these data to the current 3-year results. “We will now expand our analysis to include these new numbers to make sure the trends we saw in those 3 years are continuing,” said Dr. Whittemore. The new results should help raise awareness that SUDEP is not as rare as previously believed.

Parents of children with epilepsy can take steps to help reduce the risk for SUDEP, she added. For example, they can use night monitors, and for the children at highest risk (e.g., those with Dravet syndrome), they can use an “alarm blanket” that alerts them when the child moves.
 

Much is still unknown

Commenting on the study, Daniel Goldenholz, MD, PhD, division of epilepsy, department of neurology, Beth Israel Deaconess Medical Center, New York, who has participated in SUDEP research, said it “raises important questions about SUDEP in children and about racial disparities in SUDEP.”

The understanding of SUDEP so far “leaves much to be desired,” said Dr. Goldenholz. “We don’t yet know why it happens, and we don’t yet know how to prevent it.” The current study “brings a couple of new data points to the table which need further validation, confirmation, and explanation.”

The Sudden Death in Young Case Registry is supported by the National Heart, Lung, and Blood Institute; the National Institute of Neurological Disorders and Stroke; and the CDC. The investigators and Dr. Goldenholz disclosed no relevant financial relationships.

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

Children with epilepsy with no previous psychiatric diagnosis have alarmingly high rates of suicidal thoughts and behaviors, new research suggests. In a study of more than 100 youth with the disorder, more than 40% had depression, 30% had anxiety, and about 1 in 10 exhibited signs of suicidal thoughts and behaviors.

These rates “are really worrisome” and highlight the need to screen all children and young adults with epilepsy for psychiatric disorders, said study author Tatiana Falcone, MD, assistant professor of neurology and child and adolescent psychiatry at the Cleveland Clinic.

“It’s very important to screen for suicidality and for depression and anxiety, even when patients aren’t reporting symptoms,” said Dr. Falcone.

Previous research shows children with epilepsy will attend the emergency room with symptoms such as headache or stomachache “when the main reason for the visit was the kid was suicidal,” Dr. Falcone said. “Unless you ask the specific question: ‘Are you having thoughts about hurting yourself?’ this will go unreported,” she added.

The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

Red flag

Not much is known about suicidality in children and youth with epilepsy except that depression and anxiety – the most common psychiatric comorbidities in this population – appear to contribute to suicidal thoughts.

Dr. Falcone said that she and her colleagues often see children and adolescents with epilepsy in their clinic who have attempted suicide. In recent years, the clinicians have increased efforts to try to identify them before they carry out a successful suicide attempt, said lead investigator Anjali Dagar, MD, clinical research psychiatry fellow at Cleveland Clinic.

The study included 119 patients aged 10-24 years (mean age, 15.8 years; 54.6% female). All attended an epilepsy clinic or underwent testing in the pediatric epilepsy monitoring unit at the Cleveland Clinic and did not have a psychiatric diagnosis.

Epilepsy severity ranged among study participants. About half were drug resistant and were at the center for surgical evaluation and the others were newly diagnosed.

Participants filled out questionnaires to self-report psychiatric conditions. The validated screening tools included the Center for Epidemiological Studies Depression Scale for Children (CES-DC), the Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Ask Suicide–Screening Questions (ASQ).

A score of 15 or higher on the CES-DC indicates a risk for depression. On the SCARED test, a score higher than 32 indicates anxiety. Recent research has shown that anxiety is a main risk factor “in moving people from contemplating suicide to actually carrying it out,” Dr. Falcone said.

The ASQ includes four questions about suicidal thoughts and whether respondents have tried to hurt themselves. Dr. Dagar noted that a positive response to any of these questions should raise a red flag.
 

Very high rates

Results showed that almost one-third (30.2%) of the participants scored positive for anxiety on SCARED and 41.2% scored positive for depression on the CSE-DC. These are “very high” rates, Dr. Falcone said. For comparison, the rate of reported anxiety is less than 10% in school surveys.

In addition, the Centers for Disease Control and Prevention reports about 3% of 2- to 17-year-olds in the general population have depression. Even compared with other chronic illnesses (including diabetes, heart disease, and cancer), children with epilepsy have a higher rate of depression, said Dr. Falcone.

More than 1 in 10 (10.9%) participants in the study exhibited signs of suicidality, as shown by having at least one positive response on the ASQ. “That’s a lot,” and much higher than the estimated rate in the general teen population, Dr. Falcone noted.

She noted that “these are just general kids with epilepsy” who had not been previously diagnosed with a psychiatric disorder.

“Depression, anxiety, and suicidality are very frequent comorbidities in patients with epilepsy; and even if a patient is not reporting any symptoms, we should be asking these questions to help them,” she said.

Study participants who had at least one positive response on the ASQ had a mean score of 32.1 on the SCARED, compared with a mean score of 18.3 for those who did not have a positive response on the ASQ (P = .003).

“We wanted to see if there was a direct association in our sample between anxiety and suicidal thoughts, and we found [that] yes there was,” Dr. Falcone said. There was also an association with depression. More than 26% of participants who scored 16 or higher on the CES-DC indicated at least one positive response on the ASQ. This is significantly higher than those who scored 15 or below on the CES-DC (P < .0001).
 

Bidirectional relationship

The findings suggest that either depression or anxiety may contribute to suicidal thoughts or behaviors, Dr. Dagar said. “It’s like two hands. It could be anxiety leading to suicidality, or it could be depression, or it could be both.”

Dr. Falcone noted that children with epilepsy who aren’t sure when they’ll get their next seizure, or who are bullied at school for being different, may be especially prone to anxiety or depression.

There’s a bit of a “chicken-and-egg” relationship between depression and epilepsy, a disorder affecting electrical signals in the brain, she said. Previous research has shown that a “bidirectional relationship” is involved.

“Even in patients with depression who are not diagnosed with epilepsy, the incidence of epilepsy is 3% higher just because you have depression,” Dr. Falcone said.

Suicidal youth tend to attempt suicide more than once. Dr. Falcone and colleagues are trying to intervene “at different levels,” be that in the hospital or as an outpatient, to prevent this from happening. “We want to find out what different things we can do to engage them and improve the probability they don’t reattempt,” she said.

All children and youth with epilepsy should be screened for anxiety, depression, and suicidal thoughts and behaviors. From age 10 years, children with epilepsy should be screened at least once a year, but those with a psychiatric disorder should be screened more often, Dr. Falcone added. The investigators note their findings need to be confirmed in larger, more diverse studies.
 

Importance of screening

Michael Privitera, MD, director of the Epilepsy Center and professor of neurology at the University of Cincinnati Gardner Neuroscience Institute, said the findings reinforce that, as with adults, depression and anxiety are common in children with epilepsy.

“Neurologists should take advantage of the many psychiatric screening tools available to identify these problems in their pediatric and adult patients,” Dr. Privitera said. Even more importantly, screening may help identify those who may be at highest risk of suicide.

The study was funded by the Health Resources Services Administration. The investigators and Dr. Privitera have disclosed no relevant financial relationships.

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

Children with epilepsy with no previous psychiatric diagnosis have alarmingly high rates of suicidal thoughts and behaviors, new research suggests. In a study of more than 100 youth with the disorder, more than 40% had depression, 30% had anxiety, and about 1 in 10 exhibited signs of suicidal thoughts and behaviors.

These rates “are really worrisome” and highlight the need to screen all children and young adults with epilepsy for psychiatric disorders, said study author Tatiana Falcone, MD, assistant professor of neurology and child and adolescent psychiatry at the Cleveland Clinic.

“It’s very important to screen for suicidality and for depression and anxiety, even when patients aren’t reporting symptoms,” said Dr. Falcone.

Previous research shows children with epilepsy will attend the emergency room with symptoms such as headache or stomachache “when the main reason for the visit was the kid was suicidal,” Dr. Falcone said. “Unless you ask the specific question: ‘Are you having thoughts about hurting yourself?’ this will go unreported,” she added.

The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

Red flag

Not much is known about suicidality in children and youth with epilepsy except that depression and anxiety – the most common psychiatric comorbidities in this population – appear to contribute to suicidal thoughts.

Dr. Falcone said that she and her colleagues often see children and adolescents with epilepsy in their clinic who have attempted suicide. In recent years, the clinicians have increased efforts to try to identify them before they carry out a successful suicide attempt, said lead investigator Anjali Dagar, MD, clinical research psychiatry fellow at Cleveland Clinic.

The study included 119 patients aged 10-24 years (mean age, 15.8 years; 54.6% female). All attended an epilepsy clinic or underwent testing in the pediatric epilepsy monitoring unit at the Cleveland Clinic and did not have a psychiatric diagnosis.

Epilepsy severity ranged among study participants. About half were drug resistant and were at the center for surgical evaluation and the others were newly diagnosed.

Participants filled out questionnaires to self-report psychiatric conditions. The validated screening tools included the Center for Epidemiological Studies Depression Scale for Children (CES-DC), the Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Ask Suicide–Screening Questions (ASQ).

A score of 15 or higher on the CES-DC indicates a risk for depression. On the SCARED test, a score higher than 32 indicates anxiety. Recent research has shown that anxiety is a main risk factor “in moving people from contemplating suicide to actually carrying it out,” Dr. Falcone said.

The ASQ includes four questions about suicidal thoughts and whether respondents have tried to hurt themselves. Dr. Dagar noted that a positive response to any of these questions should raise a red flag.
 

Very high rates

Results showed that almost one-third (30.2%) of the participants scored positive for anxiety on SCARED and 41.2% scored positive for depression on the CSE-DC. These are “very high” rates, Dr. Falcone said. For comparison, the rate of reported anxiety is less than 10% in school surveys.

In addition, the Centers for Disease Control and Prevention reports about 3% of 2- to 17-year-olds in the general population have depression. Even compared with other chronic illnesses (including diabetes, heart disease, and cancer), children with epilepsy have a higher rate of depression, said Dr. Falcone.

More than 1 in 10 (10.9%) participants in the study exhibited signs of suicidality, as shown by having at least one positive response on the ASQ. “That’s a lot,” and much higher than the estimated rate in the general teen population, Dr. Falcone noted.

She noted that “these are just general kids with epilepsy” who had not been previously diagnosed with a psychiatric disorder.

“Depression, anxiety, and suicidality are very frequent comorbidities in patients with epilepsy; and even if a patient is not reporting any symptoms, we should be asking these questions to help them,” she said.

Study participants who had at least one positive response on the ASQ had a mean score of 32.1 on the SCARED, compared with a mean score of 18.3 for those who did not have a positive response on the ASQ (P = .003).

“We wanted to see if there was a direct association in our sample between anxiety and suicidal thoughts, and we found [that] yes there was,” Dr. Falcone said. There was also an association with depression. More than 26% of participants who scored 16 or higher on the CES-DC indicated at least one positive response on the ASQ. This is significantly higher than those who scored 15 or below on the CES-DC (P < .0001).
 

Bidirectional relationship

The findings suggest that either depression or anxiety may contribute to suicidal thoughts or behaviors, Dr. Dagar said. “It’s like two hands. It could be anxiety leading to suicidality, or it could be depression, or it could be both.”

Dr. Falcone noted that children with epilepsy who aren’t sure when they’ll get their next seizure, or who are bullied at school for being different, may be especially prone to anxiety or depression.

There’s a bit of a “chicken-and-egg” relationship between depression and epilepsy, a disorder affecting electrical signals in the brain, she said. Previous research has shown that a “bidirectional relationship” is involved.

“Even in patients with depression who are not diagnosed with epilepsy, the incidence of epilepsy is 3% higher just because you have depression,” Dr. Falcone said.

Suicidal youth tend to attempt suicide more than once. Dr. Falcone and colleagues are trying to intervene “at different levels,” be that in the hospital or as an outpatient, to prevent this from happening. “We want to find out what different things we can do to engage them and improve the probability they don’t reattempt,” she said.

All children and youth with epilepsy should be screened for anxiety, depression, and suicidal thoughts and behaviors. From age 10 years, children with epilepsy should be screened at least once a year, but those with a psychiatric disorder should be screened more often, Dr. Falcone added. The investigators note their findings need to be confirmed in larger, more diverse studies.
 

Importance of screening

Michael Privitera, MD, director of the Epilepsy Center and professor of neurology at the University of Cincinnati Gardner Neuroscience Institute, said the findings reinforce that, as with adults, depression and anxiety are common in children with epilepsy.

“Neurologists should take advantage of the many psychiatric screening tools available to identify these problems in their pediatric and adult patients,” Dr. Privitera said. Even more importantly, screening may help identify those who may be at highest risk of suicide.

The study was funded by the Health Resources Services Administration. The investigators and Dr. Privitera have disclosed no relevant financial relationships.

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

Children with epilepsy with no previous psychiatric diagnosis have alarmingly high rates of suicidal thoughts and behaviors, new research suggests. In a study of more than 100 youth with the disorder, more than 40% had depression, 30% had anxiety, and about 1 in 10 exhibited signs of suicidal thoughts and behaviors.

These rates “are really worrisome” and highlight the need to screen all children and young adults with epilepsy for psychiatric disorders, said study author Tatiana Falcone, MD, assistant professor of neurology and child and adolescent psychiatry at the Cleveland Clinic.

“It’s very important to screen for suicidality and for depression and anxiety, even when patients aren’t reporting symptoms,” said Dr. Falcone.

Previous research shows children with epilepsy will attend the emergency room with symptoms such as headache or stomachache “when the main reason for the visit was the kid was suicidal,” Dr. Falcone said. “Unless you ask the specific question: ‘Are you having thoughts about hurting yourself?’ this will go unreported,” she added.

The findings were presented at the American Epilepsy Society’s 74th Annual Meeting, which was held online this year because of the COVID-19 pandemic.
 

Red flag

Not much is known about suicidality in children and youth with epilepsy except that depression and anxiety – the most common psychiatric comorbidities in this population – appear to contribute to suicidal thoughts.

Dr. Falcone said that she and her colleagues often see children and adolescents with epilepsy in their clinic who have attempted suicide. In recent years, the clinicians have increased efforts to try to identify them before they carry out a successful suicide attempt, said lead investigator Anjali Dagar, MD, clinical research psychiatry fellow at Cleveland Clinic.

The study included 119 patients aged 10-24 years (mean age, 15.8 years; 54.6% female). All attended an epilepsy clinic or underwent testing in the pediatric epilepsy monitoring unit at the Cleveland Clinic and did not have a psychiatric diagnosis.

Epilepsy severity ranged among study participants. About half were drug resistant and were at the center for surgical evaluation and the others were newly diagnosed.

Participants filled out questionnaires to self-report psychiatric conditions. The validated screening tools included the Center for Epidemiological Studies Depression Scale for Children (CES-DC), the Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Ask Suicide–Screening Questions (ASQ).

A score of 15 or higher on the CES-DC indicates a risk for depression. On the SCARED test, a score higher than 32 indicates anxiety. Recent research has shown that anxiety is a main risk factor “in moving people from contemplating suicide to actually carrying it out,” Dr. Falcone said.

The ASQ includes four questions about suicidal thoughts and whether respondents have tried to hurt themselves. Dr. Dagar noted that a positive response to any of these questions should raise a red flag.
 

Very high rates

Results showed that almost one-third (30.2%) of the participants scored positive for anxiety on SCARED and 41.2% scored positive for depression on the CSE-DC. These are “very high” rates, Dr. Falcone said. For comparison, the rate of reported anxiety is less than 10% in school surveys.

In addition, the Centers for Disease Control and Prevention reports about 3% of 2- to 17-year-olds in the general population have depression. Even compared with other chronic illnesses (including diabetes, heart disease, and cancer), children with epilepsy have a higher rate of depression, said Dr. Falcone.

More than 1 in 10 (10.9%) participants in the study exhibited signs of suicidality, as shown by having at least one positive response on the ASQ. “That’s a lot,” and much higher than the estimated rate in the general teen population, Dr. Falcone noted.

She noted that “these are just general kids with epilepsy” who had not been previously diagnosed with a psychiatric disorder.

“Depression, anxiety, and suicidality are very frequent comorbidities in patients with epilepsy; and even if a patient is not reporting any symptoms, we should be asking these questions to help them,” she said.

Study participants who had at least one positive response on the ASQ had a mean score of 32.1 on the SCARED, compared with a mean score of 18.3 for those who did not have a positive response on the ASQ (P = .003).

“We wanted to see if there was a direct association in our sample between anxiety and suicidal thoughts, and we found [that] yes there was,” Dr. Falcone said. There was also an association with depression. More than 26% of participants who scored 16 or higher on the CES-DC indicated at least one positive response on the ASQ. This is significantly higher than those who scored 15 or below on the CES-DC (P < .0001).
 

Bidirectional relationship

The findings suggest that either depression or anxiety may contribute to suicidal thoughts or behaviors, Dr. Dagar said. “It’s like two hands. It could be anxiety leading to suicidality, or it could be depression, or it could be both.”

Dr. Falcone noted that children with epilepsy who aren’t sure when they’ll get their next seizure, or who are bullied at school for being different, may be especially prone to anxiety or depression.

There’s a bit of a “chicken-and-egg” relationship between depression and epilepsy, a disorder affecting electrical signals in the brain, she said. Previous research has shown that a “bidirectional relationship” is involved.

“Even in patients with depression who are not diagnosed with epilepsy, the incidence of epilepsy is 3% higher just because you have depression,” Dr. Falcone said.

Suicidal youth tend to attempt suicide more than once. Dr. Falcone and colleagues are trying to intervene “at different levels,” be that in the hospital or as an outpatient, to prevent this from happening. “We want to find out what different things we can do to engage them and improve the probability they don’t reattempt,” she said.

All children and youth with epilepsy should be screened for anxiety, depression, and suicidal thoughts and behaviors. From age 10 years, children with epilepsy should be screened at least once a year, but those with a psychiatric disorder should be screened more often, Dr. Falcone added. The investigators note their findings need to be confirmed in larger, more diverse studies.
 

Importance of screening

Michael Privitera, MD, director of the Epilepsy Center and professor of neurology at the University of Cincinnati Gardner Neuroscience Institute, said the findings reinforce that, as with adults, depression and anxiety are common in children with epilepsy.

“Neurologists should take advantage of the many psychiatric screening tools available to identify these problems in their pediatric and adult patients,” Dr. Privitera said. Even more importantly, screening may help identify those who may be at highest risk of suicide.

The study was funded by the Health Resources Services Administration. The investigators and Dr. Privitera have disclosed no relevant financial relationships.

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

Adjunctive oral prednisone appears to significantly reduce cluster headache attacks, new research shows. Results of the multicenter, randomized, double-blind trial show that patients who received the steroid had 25% fewer attacks in the first week of therapy, compared with their counterparts who received placebo.

In addition, more than a third of patients in the prednisone group were pain free, and for almost half, headache frequency was reduced by at least 50% at day 7 of treatment.

These findings provide clear evidence that prednisone, in conjunction with the use of verapamil, is effective in cluster headache, said lead author Mark Obermann, MD, director, Center for Neurology, Asklepios Hospitals Seesen (Germany), and associate professor, University of Duisburg-Essen (Germany).

The key message, he added, is that all patients with cluster headache should receive prednisone at the start of an episode.

The study was published online Nov. 24 in the Lancet Neurology.
 

‘Suicide headaches’

Cluster headaches are intense unilateral attacks of facial and head pain. They last 15-180 minutes and predominantly affect men. They are accompanied by trigeminal autonomic symptoms and are extremely painful. “They’re referred to as ‘suicide headaches’ because the pain is so severe that patients often report they think about killing themselves to get rid of the pain,” said Dr. Obermann.

The cause is unclear, although there is some evidence that the hypothalamus is involved. The headaches sometimes follow a “strict circadian pattern,” said Dr. Obermann. He noted that the attacks might occur over a few weeks or months and then not return for months or even years.

An estimated 1 in 1,000 people experience cluster headache, but the condition is underrecognized, and research is scarce and poorly funded. Previous research does show that the calcium channel blocker verapamil, which is used to treat high blood pressure, is effective in cluster headache. However, it takes about 14 days to work and has to be slowly titrated because of cardiac side effects, said Dr. Obermann. For these reasons, international guidelines recommend initiating short-term preventive treatment with corticosteroids to suppress, or at least lessen, cluster headache attacks until long-term prevention is effective.

Although some clinicians treat cluster headaches with corticosteroids, others don’t because of a lack of evidence that shows they are effective. “There’s no evidence whatsoever on what the correct dose is or whether it helps at all. This is the gap we wanted to close,” said Dr. Obermann.

The study included 116 adult patients with cluster headache from 10 centers who were experiencing a cluster headache episode and were not taking prophylactic medication.

The trial only included patients who had an attack within 30 days of their current episode. The investigators included this restriction to reduce the possibility of spontaneous remission, which is “a big problem” in cluster headache trials, he said. To confirm that episodes were cluster headache attacks, patients were also required to have moderate to severe pain, indicated by a score of at least 5 on a numerical rating scale in which 0 indicates no pain and 10 indicates the worse imaginable pain.

Participants were allowed to use treatments for acute attack, but these therapies were limited to triptans, high-flow oxygen, intranasal lidocaine, ergotamine, and oral analgesics.
 

Debilitating pain

Patients were randomly assigned to receive oral prednisone (n = 53) or placebo (n = 56). The study groups were matched with respect to demographic and clinical characteristics. Prednisone was initiated at 100 mg/d for 5 days and was then tapered by 20 mg every 3 days in the active-treatment group. All patients also received oral verapamil at a starting dose of 40 mg three times per day. The dose was increased every 3 days by 40 mg to a maximum of 360 mg/d.

All participants received pantoprazole 20 mg to prevent the gastric side effects of prednisone. An attack was defined as a unilateral headache of moderate to severe intensity. The study lasted 28 days.

The study’s primary outcome was the mean number of cluster headache attacks during the first week of treatment with prednisone versus placebo.

The mean number of attacks during the first week of treatment was 7.1 in the prednisone group and 9.5 in the placebo group, for a difference of –2.4 attacks (95% confidence interval, –4.8 to –0.03; P = .002). “This might not sound like much,” but reducing the number of daily attacks from, say, eight to six “really makes a difference because the attacks are so painful,” said Dr. Obermann.

The prednisone group also came out on top for a number secondary outcomes. After the first 7 days, attacks ceased in 35% of the prednisone group versus 7% in the placebo group.
 

‘Clear evidence’ of efficacy

About 49% of patients who took prednisone reported a reduction of at least 50% in attack frequency at day 7. By comparison, 15% of patients who received placebo reported such a reduction. The number of cluster attacks at day 28 was less in the prednisone group than in the patients who received placebo.

With respect to treatment effect, the difference between prednisone and placebo gradually lessened over time “in parallel to the verapamil dose reaching its therapeutic effect,” the investigators noted. “Therefore, attack frequency reduction slowly converged between groups,” they added.

The study results provide “clear evidence” and should reassure clinicians that short-term prednisone early in a cluster headache attack is effective, said Dr. Obermann.

Adverse events, which included headache, palpitations, dizziness, and nausea, were as expected and were similar in the two groups. There were only two severe adverse events, both of which occurred in participants in the placebo group.

Dr. Obermann said the investigators were surprised that so many patients in the study were taking analgesics. “Analgesics don’t work in cluster headache; they just don’t work in this kind of pain.”

He noted that prednisone exposure of study patients spanned only 19 days and amounted to only 1,100 mg, which he believes is safe.

The prednisone dose used in the study is “what most clinicians use in clinical practice,” although there have been reports of success using 500 mg of IV prednisone over 5 days, said Dr. Obermann. He added that it would be “interesting to see if 50 mg would be just as good” as a starting dose.

Potential limitations of the study include the fact that the majority of participants were White, so the findings may not be generalizable to other populations.
 

Long-awaited results

In an accompanying editorial, Anne Ducros, MD, PhD, professor of neurology and director of the Headache Center, Montpellier (France) University Hospital, said the study provides “strong and long-awaited evidence supporting the use of oral steroids as a transitional treatment option.”

The trial “raises many topics for future research,” one of which is the long-term safety of prednisone for patients with cluster headache, said Dr. Ducros. She noted that use of high-dose steroids once or twice a year for 15 years or more “has the potential for severe systemic toxic effects,” such as corticosteroid-induced osteonecrosis of the femoral head.

Other questions about corticosteroid use for patients with cluster headache remain. These include understanding whether these agents provide better efficacy than occipital nerve injections and determining the optimal verapamil regimen, she noted.

In addition, the risk for oral steroid misuse needs to be studied, she said. She noted that drug misuse is common among patients with cluster headache.

Despite these questions, the results of this new study “provide an important step forward for patients with cluster headache, for whom safe and effective transitional therapies are much needed,” Dr. Ducros wrote.


Dr. Obermann has received fees from Sanofi, Biogen, Novartis, Teva Pharmaceuticals, and Eli Lilly and grants from Allergan and Heel Pharmaceuticals outside of this work. Dr. Ducros has received fees from Amgen, Novartis, Teva, and Eli Lilly; grants from the Programme Hospitalier de Recherche Clinique and from the Appel d’Offre Interne of Montpellier University Hospital; and nonfinancial support from SOS Oxygene.

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

Adjunctive oral prednisone appears to significantly reduce cluster headache attacks, new research shows. Results of the multicenter, randomized, double-blind trial show that patients who received the steroid had 25% fewer attacks in the first week of therapy, compared with their counterparts who received placebo.

In addition, more than a third of patients in the prednisone group were pain free, and for almost half, headache frequency was reduced by at least 50% at day 7 of treatment.

These findings provide clear evidence that prednisone, in conjunction with the use of verapamil, is effective in cluster headache, said lead author Mark Obermann, MD, director, Center for Neurology, Asklepios Hospitals Seesen (Germany), and associate professor, University of Duisburg-Essen (Germany).

The key message, he added, is that all patients with cluster headache should receive prednisone at the start of an episode.

The study was published online Nov. 24 in the Lancet Neurology.
 

‘Suicide headaches’

Cluster headaches are intense unilateral attacks of facial and head pain. They last 15-180 minutes and predominantly affect men. They are accompanied by trigeminal autonomic symptoms and are extremely painful. “They’re referred to as ‘suicide headaches’ because the pain is so severe that patients often report they think about killing themselves to get rid of the pain,” said Dr. Obermann.

The cause is unclear, although there is some evidence that the hypothalamus is involved. The headaches sometimes follow a “strict circadian pattern,” said Dr. Obermann. He noted that the attacks might occur over a few weeks or months and then not return for months or even years.

An estimated 1 in 1,000 people experience cluster headache, but the condition is underrecognized, and research is scarce and poorly funded. Previous research does show that the calcium channel blocker verapamil, which is used to treat high blood pressure, is effective in cluster headache. However, it takes about 14 days to work and has to be slowly titrated because of cardiac side effects, said Dr. Obermann. For these reasons, international guidelines recommend initiating short-term preventive treatment with corticosteroids to suppress, or at least lessen, cluster headache attacks until long-term prevention is effective.

Although some clinicians treat cluster headaches with corticosteroids, others don’t because of a lack of evidence that shows they are effective. “There’s no evidence whatsoever on what the correct dose is or whether it helps at all. This is the gap we wanted to close,” said Dr. Obermann.

The study included 116 adult patients with cluster headache from 10 centers who were experiencing a cluster headache episode and were not taking prophylactic medication.

The trial only included patients who had an attack within 30 days of their current episode. The investigators included this restriction to reduce the possibility of spontaneous remission, which is “a big problem” in cluster headache trials, he said. To confirm that episodes were cluster headache attacks, patients were also required to have moderate to severe pain, indicated by a score of at least 5 on a numerical rating scale in which 0 indicates no pain and 10 indicates the worse imaginable pain.

Participants were allowed to use treatments for acute attack, but these therapies were limited to triptans, high-flow oxygen, intranasal lidocaine, ergotamine, and oral analgesics.
 

Debilitating pain

Patients were randomly assigned to receive oral prednisone (n = 53) or placebo (n = 56). The study groups were matched with respect to demographic and clinical characteristics. Prednisone was initiated at 100 mg/d for 5 days and was then tapered by 20 mg every 3 days in the active-treatment group. All patients also received oral verapamil at a starting dose of 40 mg three times per day. The dose was increased every 3 days by 40 mg to a maximum of 360 mg/d.

All participants received pantoprazole 20 mg to prevent the gastric side effects of prednisone. An attack was defined as a unilateral headache of moderate to severe intensity. The study lasted 28 days.

The study’s primary outcome was the mean number of cluster headache attacks during the first week of treatment with prednisone versus placebo.

The mean number of attacks during the first week of treatment was 7.1 in the prednisone group and 9.5 in the placebo group, for a difference of –2.4 attacks (95% confidence interval, –4.8 to –0.03; P = .002). “This might not sound like much,” but reducing the number of daily attacks from, say, eight to six “really makes a difference because the attacks are so painful,” said Dr. Obermann.

The prednisone group also came out on top for a number secondary outcomes. After the first 7 days, attacks ceased in 35% of the prednisone group versus 7% in the placebo group.
 

‘Clear evidence’ of efficacy

About 49% of patients who took prednisone reported a reduction of at least 50% in attack frequency at day 7. By comparison, 15% of patients who received placebo reported such a reduction. The number of cluster attacks at day 28 was less in the prednisone group than in the patients who received placebo.

With respect to treatment effect, the difference between prednisone and placebo gradually lessened over time “in parallel to the verapamil dose reaching its therapeutic effect,” the investigators noted. “Therefore, attack frequency reduction slowly converged between groups,” they added.

The study results provide “clear evidence” and should reassure clinicians that short-term prednisone early in a cluster headache attack is effective, said Dr. Obermann.

Adverse events, which included headache, palpitations, dizziness, and nausea, were as expected and were similar in the two groups. There were only two severe adverse events, both of which occurred in participants in the placebo group.

Dr. Obermann said the investigators were surprised that so many patients in the study were taking analgesics. “Analgesics don’t work in cluster headache; they just don’t work in this kind of pain.”

He noted that prednisone exposure of study patients spanned only 19 days and amounted to only 1,100 mg, which he believes is safe.

The prednisone dose used in the study is “what most clinicians use in clinical practice,” although there have been reports of success using 500 mg of IV prednisone over 5 days, said Dr. Obermann. He added that it would be “interesting to see if 50 mg would be just as good” as a starting dose.

Potential limitations of the study include the fact that the majority of participants were White, so the findings may not be generalizable to other populations.
 

Long-awaited results

In an accompanying editorial, Anne Ducros, MD, PhD, professor of neurology and director of the Headache Center, Montpellier (France) University Hospital, said the study provides “strong and long-awaited evidence supporting the use of oral steroids as a transitional treatment option.”

The trial “raises many topics for future research,” one of which is the long-term safety of prednisone for patients with cluster headache, said Dr. Ducros. She noted that use of high-dose steroids once or twice a year for 15 years or more “has the potential for severe systemic toxic effects,” such as corticosteroid-induced osteonecrosis of the femoral head.

Other questions about corticosteroid use for patients with cluster headache remain. These include understanding whether these agents provide better efficacy than occipital nerve injections and determining the optimal verapamil regimen, she noted.

In addition, the risk for oral steroid misuse needs to be studied, she said. She noted that drug misuse is common among patients with cluster headache.

Despite these questions, the results of this new study “provide an important step forward for patients with cluster headache, for whom safe and effective transitional therapies are much needed,” Dr. Ducros wrote.


Dr. Obermann has received fees from Sanofi, Biogen, Novartis, Teva Pharmaceuticals, and Eli Lilly and grants from Allergan and Heel Pharmaceuticals outside of this work. Dr. Ducros has received fees from Amgen, Novartis, Teva, and Eli Lilly; grants from the Programme Hospitalier de Recherche Clinique and from the Appel d’Offre Interne of Montpellier University Hospital; and nonfinancial support from SOS Oxygene.

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

Adjunctive oral prednisone appears to significantly reduce cluster headache attacks, new research shows. Results of the multicenter, randomized, double-blind trial show that patients who received the steroid had 25% fewer attacks in the first week of therapy, compared with their counterparts who received placebo.

In addition, more than a third of patients in the prednisone group were pain free, and for almost half, headache frequency was reduced by at least 50% at day 7 of treatment.

These findings provide clear evidence that prednisone, in conjunction with the use of verapamil, is effective in cluster headache, said lead author Mark Obermann, MD, director, Center for Neurology, Asklepios Hospitals Seesen (Germany), and associate professor, University of Duisburg-Essen (Germany).

The key message, he added, is that all patients with cluster headache should receive prednisone at the start of an episode.

The study was published online Nov. 24 in the Lancet Neurology.
 

‘Suicide headaches’

Cluster headaches are intense unilateral attacks of facial and head pain. They last 15-180 minutes and predominantly affect men. They are accompanied by trigeminal autonomic symptoms and are extremely painful. “They’re referred to as ‘suicide headaches’ because the pain is so severe that patients often report they think about killing themselves to get rid of the pain,” said Dr. Obermann.

The cause is unclear, although there is some evidence that the hypothalamus is involved. The headaches sometimes follow a “strict circadian pattern,” said Dr. Obermann. He noted that the attacks might occur over a few weeks or months and then not return for months or even years.

An estimated 1 in 1,000 people experience cluster headache, but the condition is underrecognized, and research is scarce and poorly funded. Previous research does show that the calcium channel blocker verapamil, which is used to treat high blood pressure, is effective in cluster headache. However, it takes about 14 days to work and has to be slowly titrated because of cardiac side effects, said Dr. Obermann. For these reasons, international guidelines recommend initiating short-term preventive treatment with corticosteroids to suppress, or at least lessen, cluster headache attacks until long-term prevention is effective.

Although some clinicians treat cluster headaches with corticosteroids, others don’t because of a lack of evidence that shows they are effective. “There’s no evidence whatsoever on what the correct dose is or whether it helps at all. This is the gap we wanted to close,” said Dr. Obermann.

The study included 116 adult patients with cluster headache from 10 centers who were experiencing a cluster headache episode and were not taking prophylactic medication.

The trial only included patients who had an attack within 30 days of their current episode. The investigators included this restriction to reduce the possibility of spontaneous remission, which is “a big problem” in cluster headache trials, he said. To confirm that episodes were cluster headache attacks, patients were also required to have moderate to severe pain, indicated by a score of at least 5 on a numerical rating scale in which 0 indicates no pain and 10 indicates the worse imaginable pain.

Participants were allowed to use treatments for acute attack, but these therapies were limited to triptans, high-flow oxygen, intranasal lidocaine, ergotamine, and oral analgesics.
 

Debilitating pain

Patients were randomly assigned to receive oral prednisone (n = 53) or placebo (n = 56). The study groups were matched with respect to demographic and clinical characteristics. Prednisone was initiated at 100 mg/d for 5 days and was then tapered by 20 mg every 3 days in the active-treatment group. All patients also received oral verapamil at a starting dose of 40 mg three times per day. The dose was increased every 3 days by 40 mg to a maximum of 360 mg/d.

All participants received pantoprazole 20 mg to prevent the gastric side effects of prednisone. An attack was defined as a unilateral headache of moderate to severe intensity. The study lasted 28 days.

The study’s primary outcome was the mean number of cluster headache attacks during the first week of treatment with prednisone versus placebo.

The mean number of attacks during the first week of treatment was 7.1 in the prednisone group and 9.5 in the placebo group, for a difference of –2.4 attacks (95% confidence interval, –4.8 to –0.03; P = .002). “This might not sound like much,” but reducing the number of daily attacks from, say, eight to six “really makes a difference because the attacks are so painful,” said Dr. Obermann.

The prednisone group also came out on top for a number secondary outcomes. After the first 7 days, attacks ceased in 35% of the prednisone group versus 7% in the placebo group.
 

‘Clear evidence’ of efficacy

About 49% of patients who took prednisone reported a reduction of at least 50% in attack frequency at day 7. By comparison, 15% of patients who received placebo reported such a reduction. The number of cluster attacks at day 28 was less in the prednisone group than in the patients who received placebo.

With respect to treatment effect, the difference between prednisone and placebo gradually lessened over time “in parallel to the verapamil dose reaching its therapeutic effect,” the investigators noted. “Therefore, attack frequency reduction slowly converged between groups,” they added.

The study results provide “clear evidence” and should reassure clinicians that short-term prednisone early in a cluster headache attack is effective, said Dr. Obermann.

Adverse events, which included headache, palpitations, dizziness, and nausea, were as expected and were similar in the two groups. There were only two severe adverse events, both of which occurred in participants in the placebo group.

Dr. Obermann said the investigators were surprised that so many patients in the study were taking analgesics. “Analgesics don’t work in cluster headache; they just don’t work in this kind of pain.”

He noted that prednisone exposure of study patients spanned only 19 days and amounted to only 1,100 mg, which he believes is safe.

The prednisone dose used in the study is “what most clinicians use in clinical practice,” although there have been reports of success using 500 mg of IV prednisone over 5 days, said Dr. Obermann. He added that it would be “interesting to see if 50 mg would be just as good” as a starting dose.

Potential limitations of the study include the fact that the majority of participants were White, so the findings may not be generalizable to other populations.
 

Long-awaited results

In an accompanying editorial, Anne Ducros, MD, PhD, professor of neurology and director of the Headache Center, Montpellier (France) University Hospital, said the study provides “strong and long-awaited evidence supporting the use of oral steroids as a transitional treatment option.”

The trial “raises many topics for future research,” one of which is the long-term safety of prednisone for patients with cluster headache, said Dr. Ducros. She noted that use of high-dose steroids once or twice a year for 15 years or more “has the potential for severe systemic toxic effects,” such as corticosteroid-induced osteonecrosis of the femoral head.

Other questions about corticosteroid use for patients with cluster headache remain. These include understanding whether these agents provide better efficacy than occipital nerve injections and determining the optimal verapamil regimen, she noted.

In addition, the risk for oral steroid misuse needs to be studied, she said. She noted that drug misuse is common among patients with cluster headache.

Despite these questions, the results of this new study “provide an important step forward for patients with cluster headache, for whom safe and effective transitional therapies are much needed,” Dr. Ducros wrote.


Dr. Obermann has received fees from Sanofi, Biogen, Novartis, Teva Pharmaceuticals, and Eli Lilly and grants from Allergan and Heel Pharmaceuticals outside of this work. Dr. Ducros has received fees from Amgen, Novartis, Teva, and Eli Lilly; grants from the Programme Hospitalier de Recherche Clinique and from the Appel d’Offre Interne of Montpellier University Hospital; and nonfinancial support from SOS Oxygene.

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

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A commonly used newborn hearing test shows promise in the early detection of autism spectrum disorder (ASD), new research shows.  

Results from one of the largest studies of its kind show the auditory brainstem response (ABR) test, which is carried out on most newborns, represents “a huge untapped potential” to detect autism, lead author Oren Miron, research associate, department of biomedical informatics, Harvard Medical School, Boston, and a PhD candidate at Ben Gurion University in Beersheba, Israel, said in an interview.

“The findings further reinforce our understanding that autism, in many cases, has a sensorial and auditory aspect to it,” said Mr. Miron, adding that an adverse response to sound is one of the earliest behavioral signs of autism.

The research was published online Oct. 31 in Autism Research.
 

Early intervention critical

Autism spectrum disorder (ASD), which involves problems in social communication and interaction, affects an estimated 1 in 59 children. Early identification and intervention are critical for improving outcomes and decreasing the economic burden associated with ASD.

The ABR test, which is used for Universal Newborn Hearing Screening (UNHS), uses surface electrodes to measure auditory nerve and brainstem responses to sound.

Previous studies identified abnormal ABR amplitude in children with ASD. However, it’s unclear whether healthy newborns who later develop autism also show ABR differences vs those who don’t develop the disorder.

Researchers used UNHS data, which allowed them to examine a larger, younger, and healthier sample compared with previous studies. The study included 321 newborns later diagnosed with ASD and 138,844 controls without a subsequent ASD diagnosis.

The mean ABR testing age was 1.76 days for newborns later diagnosed with ASD and 1.86 for those in the non-ASD group.

The ASD group was 77% male and the non-ASD group was 51% male. The rate of neonatal intensive care unit admission was 8% in the ASD group and 10% in the non-ASD group.

The hearing test involves placing an earpiece in the baby’s ear and delivering a click sound at 35 dB above normal hearing level (nHL) at a rate of 77 clicks per second in the right ear and 79 clicks per second in the left ear.
 

Brainstem abnormalities?

The clicks create electrical activity, which is recorded by a surface electrode and used to extract the ABR waveform. When a sound reaches the brain stem, it creates five consecutive waveforms – waves I, II, III, IV, and V.

Previous studies focused on wave V, which is easiest to detect. The current study used low intensity sound that resulted in a weaker signal.

To overcome this low intensity issue, researchers focused on the negative drop (latency) after the wave V (Vn), which is easier to detect, and on the ABR phase, or entire waveform. They illustrated the differences between the ASD and non-ASD groups in a series of graphs.

Results showed that the ABR phase in the right ear was significantly prolonged in the ASD vs non-ASD group (P < .001). ABR phase in the left ear was also significantly prolonged in the ASD group (P = .021)

Vn latency in the right ear was significantly prolonged in the ASD group compared with the non-ASD group (P = .048); however, this was not the case in the left ear.

The prolongation could mean that the V-negative wave might appear after 8 ms in normally developing children compared with 8.5 or 9 ms in children with autism, said Mr. Miron.

The new study is the first to show V-negative and phase abnormalities are associated with ASD, the authors note. The brainstem prolongation could be due to anatomical abnormalities in the brainstem in individuals with ASD, the researchers added.
 

Present before birth?

The presence of ABR biomarkers of ASD in the first weeks after birth suggests the disorder is likely present before birth in a large group of these individuals, the researchers note.

It’s possible the ABR test could be modified to use lower intensities not only to detect hearing impairment but autism risk, said Mr. Miron. “The test has been optimized to detect hearing impairment, and it does so brilliantly and helps thousands of children. We want to do the same kind of optimization for autism.”

This could lead to earlier behavioral diagnoses, which, in turn, could lead to earlier treatment and better outcomes for children with ASD, said Mr. Miron.

At this time, the level of prolongation to detect ASD is unclear. “I would think a lot of people would want to make it one standard deviation, but it depends on a lot of factors, including for example, whether a baby is preterm,” said Mr. Miron.

More research and better accuracy and specificity are needed before the newborn hearing test is clinically useful.

He noted that the hearing test is only one marker of autism and that it could potentially be combined with other behavioral signs and genetic markers to facilitate earlier diagnosis and treatment and improve outcomes for patients with ASD.

Future research by his group will investigate whether the degree of auditory prolongation relates to autism severity. They also plan to research ASD subgroups including children with comorbid epilepsy.
 

Terrific, clever research

Jeremy Veenstra-VanderWeele, MD, professor, child and adolescent psychiatry, Columbia University, New York, said in an interview that the study is “terrific” and a “clever use” of an existing dataset.

“They showed a difference between a large group of kids with autism and a large group of kids without.”

However, he added, more research is needed before the test can be used as an autism screening tool.

“In order for this to be a screening test that could be broadly applied you would need to identify a cutoff where you’d think a child was at risk for autism, and if you look at the graphs in the article, there are no clear cutoffs,” said Dr. Veenstra-VanderWeele.

To turn this into a useful test, “you would have to establish sensitivity and specificity, you would have to look not just at the comparison of kids with autism and kids without but apply it in a predictive way in a second population.”

The study authors and Dr. Veenstra-VanderWeele have reported no relevant financial relationships. Veenstra-VanderWeele is an associate editor at Autism Research, which published the article, but he did not handle or view it before being interviewed.

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

A commonly used newborn hearing test shows promise in the early detection of autism spectrum disorder (ASD), new research shows.  

Results from one of the largest studies of its kind show the auditory brainstem response (ABR) test, which is carried out on most newborns, represents “a huge untapped potential” to detect autism, lead author Oren Miron, research associate, department of biomedical informatics, Harvard Medical School, Boston, and a PhD candidate at Ben Gurion University in Beersheba, Israel, said in an interview.

“The findings further reinforce our understanding that autism, in many cases, has a sensorial and auditory aspect to it,” said Mr. Miron, adding that an adverse response to sound is one of the earliest behavioral signs of autism.

The research was published online Oct. 31 in Autism Research.
 

Early intervention critical

Autism spectrum disorder (ASD), which involves problems in social communication and interaction, affects an estimated 1 in 59 children. Early identification and intervention are critical for improving outcomes and decreasing the economic burden associated with ASD.

The ABR test, which is used for Universal Newborn Hearing Screening (UNHS), uses surface electrodes to measure auditory nerve and brainstem responses to sound.

Previous studies identified abnormal ABR amplitude in children with ASD. However, it’s unclear whether healthy newborns who later develop autism also show ABR differences vs those who don’t develop the disorder.

Researchers used UNHS data, which allowed them to examine a larger, younger, and healthier sample compared with previous studies. The study included 321 newborns later diagnosed with ASD and 138,844 controls without a subsequent ASD diagnosis.

The mean ABR testing age was 1.76 days for newborns later diagnosed with ASD and 1.86 for those in the non-ASD group.

The ASD group was 77% male and the non-ASD group was 51% male. The rate of neonatal intensive care unit admission was 8% in the ASD group and 10% in the non-ASD group.

The hearing test involves placing an earpiece in the baby’s ear and delivering a click sound at 35 dB above normal hearing level (nHL) at a rate of 77 clicks per second in the right ear and 79 clicks per second in the left ear.
 

Brainstem abnormalities?

The clicks create electrical activity, which is recorded by a surface electrode and used to extract the ABR waveform. When a sound reaches the brain stem, it creates five consecutive waveforms – waves I, II, III, IV, and V.

Previous studies focused on wave V, which is easiest to detect. The current study used low intensity sound that resulted in a weaker signal.

To overcome this low intensity issue, researchers focused on the negative drop (latency) after the wave V (Vn), which is easier to detect, and on the ABR phase, or entire waveform. They illustrated the differences between the ASD and non-ASD groups in a series of graphs.

Results showed that the ABR phase in the right ear was significantly prolonged in the ASD vs non-ASD group (P < .001). ABR phase in the left ear was also significantly prolonged in the ASD group (P = .021)

Vn latency in the right ear was significantly prolonged in the ASD group compared with the non-ASD group (P = .048); however, this was not the case in the left ear.

The prolongation could mean that the V-negative wave might appear after 8 ms in normally developing children compared with 8.5 or 9 ms in children with autism, said Mr. Miron.

The new study is the first to show V-negative and phase abnormalities are associated with ASD, the authors note. The brainstem prolongation could be due to anatomical abnormalities in the brainstem in individuals with ASD, the researchers added.
 

Present before birth?

The presence of ABR biomarkers of ASD in the first weeks after birth suggests the disorder is likely present before birth in a large group of these individuals, the researchers note.

It’s possible the ABR test could be modified to use lower intensities not only to detect hearing impairment but autism risk, said Mr. Miron. “The test has been optimized to detect hearing impairment, and it does so brilliantly and helps thousands of children. We want to do the same kind of optimization for autism.”

This could lead to earlier behavioral diagnoses, which, in turn, could lead to earlier treatment and better outcomes for children with ASD, said Mr. Miron.

At this time, the level of prolongation to detect ASD is unclear. “I would think a lot of people would want to make it one standard deviation, but it depends on a lot of factors, including for example, whether a baby is preterm,” said Mr. Miron.

More research and better accuracy and specificity are needed before the newborn hearing test is clinically useful.

He noted that the hearing test is only one marker of autism and that it could potentially be combined with other behavioral signs and genetic markers to facilitate earlier diagnosis and treatment and improve outcomes for patients with ASD.

Future research by his group will investigate whether the degree of auditory prolongation relates to autism severity. They also plan to research ASD subgroups including children with comorbid epilepsy.
 

Terrific, clever research

Jeremy Veenstra-VanderWeele, MD, professor, child and adolescent psychiatry, Columbia University, New York, said in an interview that the study is “terrific” and a “clever use” of an existing dataset.

“They showed a difference between a large group of kids with autism and a large group of kids without.”

However, he added, more research is needed before the test can be used as an autism screening tool.

“In order for this to be a screening test that could be broadly applied you would need to identify a cutoff where you’d think a child was at risk for autism, and if you look at the graphs in the article, there are no clear cutoffs,” said Dr. Veenstra-VanderWeele.

To turn this into a useful test, “you would have to establish sensitivity and specificity, you would have to look not just at the comparison of kids with autism and kids without but apply it in a predictive way in a second population.”

The study authors and Dr. Veenstra-VanderWeele have reported no relevant financial relationships. Veenstra-VanderWeele is an associate editor at Autism Research, which published the article, but he did not handle or view it before being interviewed.

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

A commonly used newborn hearing test shows promise in the early detection of autism spectrum disorder (ASD), new research shows.  

Results from one of the largest studies of its kind show the auditory brainstem response (ABR) test, which is carried out on most newborns, represents “a huge untapped potential” to detect autism, lead author Oren Miron, research associate, department of biomedical informatics, Harvard Medical School, Boston, and a PhD candidate at Ben Gurion University in Beersheba, Israel, said in an interview.

“The findings further reinforce our understanding that autism, in many cases, has a sensorial and auditory aspect to it,” said Mr. Miron, adding that an adverse response to sound is one of the earliest behavioral signs of autism.

The research was published online Oct. 31 in Autism Research.
 

Early intervention critical

Autism spectrum disorder (ASD), which involves problems in social communication and interaction, affects an estimated 1 in 59 children. Early identification and intervention are critical for improving outcomes and decreasing the economic burden associated with ASD.

The ABR test, which is used for Universal Newborn Hearing Screening (UNHS), uses surface electrodes to measure auditory nerve and brainstem responses to sound.

Previous studies identified abnormal ABR amplitude in children with ASD. However, it’s unclear whether healthy newborns who later develop autism also show ABR differences vs those who don’t develop the disorder.

Researchers used UNHS data, which allowed them to examine a larger, younger, and healthier sample compared with previous studies. The study included 321 newborns later diagnosed with ASD and 138,844 controls without a subsequent ASD diagnosis.

The mean ABR testing age was 1.76 days for newborns later diagnosed with ASD and 1.86 for those in the non-ASD group.

The ASD group was 77% male and the non-ASD group was 51% male. The rate of neonatal intensive care unit admission was 8% in the ASD group and 10% in the non-ASD group.

The hearing test involves placing an earpiece in the baby’s ear and delivering a click sound at 35 dB above normal hearing level (nHL) at a rate of 77 clicks per second in the right ear and 79 clicks per second in the left ear.
 

Brainstem abnormalities?

The clicks create electrical activity, which is recorded by a surface electrode and used to extract the ABR waveform. When a sound reaches the brain stem, it creates five consecutive waveforms – waves I, II, III, IV, and V.

Previous studies focused on wave V, which is easiest to detect. The current study used low intensity sound that resulted in a weaker signal.

To overcome this low intensity issue, researchers focused on the negative drop (latency) after the wave V (Vn), which is easier to detect, and on the ABR phase, or entire waveform. They illustrated the differences between the ASD and non-ASD groups in a series of graphs.

Results showed that the ABR phase in the right ear was significantly prolonged in the ASD vs non-ASD group (P < .001). ABR phase in the left ear was also significantly prolonged in the ASD group (P = .021)

Vn latency in the right ear was significantly prolonged in the ASD group compared with the non-ASD group (P = .048); however, this was not the case in the left ear.

The prolongation could mean that the V-negative wave might appear after 8 ms in normally developing children compared with 8.5 or 9 ms in children with autism, said Mr. Miron.

The new study is the first to show V-negative and phase abnormalities are associated with ASD, the authors note. The brainstem prolongation could be due to anatomical abnormalities in the brainstem in individuals with ASD, the researchers added.
 

Present before birth?

The presence of ABR biomarkers of ASD in the first weeks after birth suggests the disorder is likely present before birth in a large group of these individuals, the researchers note.

It’s possible the ABR test could be modified to use lower intensities not only to detect hearing impairment but autism risk, said Mr. Miron. “The test has been optimized to detect hearing impairment, and it does so brilliantly and helps thousands of children. We want to do the same kind of optimization for autism.”

This could lead to earlier behavioral diagnoses, which, in turn, could lead to earlier treatment and better outcomes for children with ASD, said Mr. Miron.

At this time, the level of prolongation to detect ASD is unclear. “I would think a lot of people would want to make it one standard deviation, but it depends on a lot of factors, including for example, whether a baby is preterm,” said Mr. Miron.

More research and better accuracy and specificity are needed before the newborn hearing test is clinically useful.

He noted that the hearing test is only one marker of autism and that it could potentially be combined with other behavioral signs and genetic markers to facilitate earlier diagnosis and treatment and improve outcomes for patients with ASD.

Future research by his group will investigate whether the degree of auditory prolongation relates to autism severity. They also plan to research ASD subgroups including children with comorbid epilepsy.
 

Terrific, clever research

Jeremy Veenstra-VanderWeele, MD, professor, child and adolescent psychiatry, Columbia University, New York, said in an interview that the study is “terrific” and a “clever use” of an existing dataset.

“They showed a difference between a large group of kids with autism and a large group of kids without.”

However, he added, more research is needed before the test can be used as an autism screening tool.

“In order for this to be a screening test that could be broadly applied you would need to identify a cutoff where you’d think a child was at risk for autism, and if you look at the graphs in the article, there are no clear cutoffs,” said Dr. Veenstra-VanderWeele.

To turn this into a useful test, “you would have to establish sensitivity and specificity, you would have to look not just at the comparison of kids with autism and kids without but apply it in a predictive way in a second population.”

The study authors and Dr. Veenstra-VanderWeele have reported no relevant financial relationships. Veenstra-VanderWeele is an associate editor at Autism Research, which published the article, but he did not handle or view it before being interviewed.

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

The first blood test to detect the presence of amyloid, a hallmark of Alzheimer’s disease, is now available for clinical use, according to C2N Diagnostics, the company behind the test’s development. The availability of the noninvasive, easily administered test is being called a milestone in the early detection and diagnosis of Alzheimer’s disease.

The blood test “introduces a new option for patients, families, and the medical community that have eagerly awaited innovative tools to address Alzheimer’s troubling problems,” Joel B. Braunstein, MD, MBA, CEO of C2N Diagnostics, said in a press release.

“This is really an important advance,” said Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation (ADDF), which partially funded the development of the test, in a separate press release.

“You can now walk into your doctor’s office to get a blood test to help detect Alzheimer’s disease,” said Dr. Fillit. “This test answers a critical need for less costly and accessible diagnostic testing in memory and dementia care.”
 

A word of caution

However, Maria C. Carrillo, PhD, chief science officer, Alzheimer’s Association, highlighted the need for caution. The test is “very new,” experts have only “limited information” about it, and it is only available by prescription from a healthcare provider for patients with cognitive impairment, said Dr. Carrillo.

“The test is not [Food and Drug Administration] approved and it does not, on its own, diagnose Alzheimer’s disease,” added Dr. Carrillo. “Without FDA review, healthcare providers lack the agency’s guidance for how to use it when making decisions about a person’s health or treatment.”

Dr. Carrillo also noted that the test has only been studied in a limited number of individuals and that few data are available regarding underrepresented populations.

“As a result, it is not clear how accurate or generalizable the results are for all individuals and populations,” she noted.

Another factor to consider, said Dr. Carrillo, is that the test is not covered by insurance, including Medicare and Medicaid.
 

How it works

The test (PrecivityAD) is for use in patients with cognitive impairment. It requires a very small blood sample – as little as a teaspoon – from the patient’s forearm. The physician sends the sample to C2N Diagnostic’s specialized laboratory, where it is analyzed using mass spectrometry to measure concentrations of amyloid beta 42 and 40 and to detect the presence of apolipoprotein E isoforms.

The lab report, which is sent to the patient’s physician, details biomarker levels and provides an overall combined score, known as the Amyloid Probability Score, to assess the likelihood of low, intermediate, or high levels of amyloid plaque in the brain.

The company reports that, on the basis of data from 686 patients older than 60 years who had subjective cognitive impairment or dementia, the test correctly identified brain amyloid plaque status, as determined by quantitative amyloid positron-emission tomography (PET) scans, in 86% of the patients. In the analysis, the area under the curve for the receiver operating characteristic was 0.88.

The company notes that the test, the results of which require interpretation by a health care provider, is an important new tool to aid physicians in the evaluation process.

The new blood test is currently available in 45 states, the District of Columbia, and Puerto Rico.

C2N Diagnostics is moving ahead with development of a brain health panel to detect multiple blood-based markers for Alzheimer’s disease to aid in disease staging, treatment monitoring, and differential diagnosis.

The ADDF believes the path to approval of treatments of Alzheimer’s disease starts with a better diagnosis, Dr. Fillit said in his organization’s press release.

“Investing in biomarker research has been a core goal for the ADDF because reliable, accessible, and affordable biomarkers for Alzheimer’s diagnosis are critical to our ability to find drugs to prevent, slow, and even cure the disease. Our funding helped bring the first PET scan to market and now has helped bring the first blood test to market,” he said.

In addition to the ADDF, the National Institutes of Health, the GHR Foundation, and the BrightFocus Foundation contributed funding for the development of the amyloid blood test.

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

The first blood test to detect the presence of amyloid, a hallmark of Alzheimer’s disease, is now available for clinical use, according to C2N Diagnostics, the company behind the test’s development. The availability of the noninvasive, easily administered test is being called a milestone in the early detection and diagnosis of Alzheimer’s disease.

The blood test “introduces a new option for patients, families, and the medical community that have eagerly awaited innovative tools to address Alzheimer’s troubling problems,” Joel B. Braunstein, MD, MBA, CEO of C2N Diagnostics, said in a press release.

“This is really an important advance,” said Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation (ADDF), which partially funded the development of the test, in a separate press release.

“You can now walk into your doctor’s office to get a blood test to help detect Alzheimer’s disease,” said Dr. Fillit. “This test answers a critical need for less costly and accessible diagnostic testing in memory and dementia care.”
 

A word of caution

However, Maria C. Carrillo, PhD, chief science officer, Alzheimer’s Association, highlighted the need for caution. The test is “very new,” experts have only “limited information” about it, and it is only available by prescription from a healthcare provider for patients with cognitive impairment, said Dr. Carrillo.

“The test is not [Food and Drug Administration] approved and it does not, on its own, diagnose Alzheimer’s disease,” added Dr. Carrillo. “Without FDA review, healthcare providers lack the agency’s guidance for how to use it when making decisions about a person’s health or treatment.”

Dr. Carrillo also noted that the test has only been studied in a limited number of individuals and that few data are available regarding underrepresented populations.

“As a result, it is not clear how accurate or generalizable the results are for all individuals and populations,” she noted.

Another factor to consider, said Dr. Carrillo, is that the test is not covered by insurance, including Medicare and Medicaid.
 

How it works

The test (PrecivityAD) is for use in patients with cognitive impairment. It requires a very small blood sample – as little as a teaspoon – from the patient’s forearm. The physician sends the sample to C2N Diagnostic’s specialized laboratory, where it is analyzed using mass spectrometry to measure concentrations of amyloid beta 42 and 40 and to detect the presence of apolipoprotein E isoforms.

The lab report, which is sent to the patient’s physician, details biomarker levels and provides an overall combined score, known as the Amyloid Probability Score, to assess the likelihood of low, intermediate, or high levels of amyloid plaque in the brain.

The company reports that, on the basis of data from 686 patients older than 60 years who had subjective cognitive impairment or dementia, the test correctly identified brain amyloid plaque status, as determined by quantitative amyloid positron-emission tomography (PET) scans, in 86% of the patients. In the analysis, the area under the curve for the receiver operating characteristic was 0.88.

The company notes that the test, the results of which require interpretation by a health care provider, is an important new tool to aid physicians in the evaluation process.

The new blood test is currently available in 45 states, the District of Columbia, and Puerto Rico.

C2N Diagnostics is moving ahead with development of a brain health panel to detect multiple blood-based markers for Alzheimer’s disease to aid in disease staging, treatment monitoring, and differential diagnosis.

The ADDF believes the path to approval of treatments of Alzheimer’s disease starts with a better diagnosis, Dr. Fillit said in his organization’s press release.

“Investing in biomarker research has been a core goal for the ADDF because reliable, accessible, and affordable biomarkers for Alzheimer’s diagnosis are critical to our ability to find drugs to prevent, slow, and even cure the disease. Our funding helped bring the first PET scan to market and now has helped bring the first blood test to market,” he said.

In addition to the ADDF, the National Institutes of Health, the GHR Foundation, and the BrightFocus Foundation contributed funding for the development of the amyloid blood test.

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

The first blood test to detect the presence of amyloid, a hallmark of Alzheimer’s disease, is now available for clinical use, according to C2N Diagnostics, the company behind the test’s development. The availability of the noninvasive, easily administered test is being called a milestone in the early detection and diagnosis of Alzheimer’s disease.

The blood test “introduces a new option for patients, families, and the medical community that have eagerly awaited innovative tools to address Alzheimer’s troubling problems,” Joel B. Braunstein, MD, MBA, CEO of C2N Diagnostics, said in a press release.

“This is really an important advance,” said Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation (ADDF), which partially funded the development of the test, in a separate press release.

“You can now walk into your doctor’s office to get a blood test to help detect Alzheimer’s disease,” said Dr. Fillit. “This test answers a critical need for less costly and accessible diagnostic testing in memory and dementia care.”
 

A word of caution

However, Maria C. Carrillo, PhD, chief science officer, Alzheimer’s Association, highlighted the need for caution. The test is “very new,” experts have only “limited information” about it, and it is only available by prescription from a healthcare provider for patients with cognitive impairment, said Dr. Carrillo.

“The test is not [Food and Drug Administration] approved and it does not, on its own, diagnose Alzheimer’s disease,” added Dr. Carrillo. “Without FDA review, healthcare providers lack the agency’s guidance for how to use it when making decisions about a person’s health or treatment.”

Dr. Carrillo also noted that the test has only been studied in a limited number of individuals and that few data are available regarding underrepresented populations.

“As a result, it is not clear how accurate or generalizable the results are for all individuals and populations,” she noted.

Another factor to consider, said Dr. Carrillo, is that the test is not covered by insurance, including Medicare and Medicaid.
 

How it works

The test (PrecivityAD) is for use in patients with cognitive impairment. It requires a very small blood sample – as little as a teaspoon – from the patient’s forearm. The physician sends the sample to C2N Diagnostic’s specialized laboratory, where it is analyzed using mass spectrometry to measure concentrations of amyloid beta 42 and 40 and to detect the presence of apolipoprotein E isoforms.

The lab report, which is sent to the patient’s physician, details biomarker levels and provides an overall combined score, known as the Amyloid Probability Score, to assess the likelihood of low, intermediate, or high levels of amyloid plaque in the brain.

The company reports that, on the basis of data from 686 patients older than 60 years who had subjective cognitive impairment or dementia, the test correctly identified brain amyloid plaque status, as determined by quantitative amyloid positron-emission tomography (PET) scans, in 86% of the patients. In the analysis, the area under the curve for the receiver operating characteristic was 0.88.

The company notes that the test, the results of which require interpretation by a health care provider, is an important new tool to aid physicians in the evaluation process.

The new blood test is currently available in 45 states, the District of Columbia, and Puerto Rico.

C2N Diagnostics is moving ahead with development of a brain health panel to detect multiple blood-based markers for Alzheimer’s disease to aid in disease staging, treatment monitoring, and differential diagnosis.

The ADDF believes the path to approval of treatments of Alzheimer’s disease starts with a better diagnosis, Dr. Fillit said in his organization’s press release.

“Investing in biomarker research has been a core goal for the ADDF because reliable, accessible, and affordable biomarkers for Alzheimer’s diagnosis are critical to our ability to find drugs to prevent, slow, and even cure the disease. Our funding helped bring the first PET scan to market and now has helped bring the first blood test to market,” he said.

In addition to the ADDF, the National Institutes of Health, the GHR Foundation, and the BrightFocus Foundation contributed funding for the development of the amyloid blood test.

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

A novel program that strengthens bonds, boosts morale, and encourages supportive networks among US Air Force personnel cuts suicidal ideation and depressive symptoms after 1 month, new research shows.

The so-called Wingman-Connect initiative also had a beneficial impact on work performance, and the benefits were apparent at 6-month follow-up.

“This study suggests that group training can teach skills that help with occupational functioning and reduce the likelihood of experiencing elevated depression and suicidal ideation, at least in the short term,” lead author Peter A. Wyman, PhD, professor, department of psychiatry, University of Rochester, New York, told Medscape Medical News.

The study was published online Oct. 21 in JAMA Network Open.
 

Significant rise in suicide rates

Suicide rates among active duty military populations have increased “significantly” in the past 15 years and have exceeded rates for the general population when comparing groups of the same age and gender, said Wyman.

The study included new personnel who were taking classes at a single training center between October 2017 and October 2019.

Participants were randomly assigned to the Wingman-Connect program or to a stress management program.

The Wingman-Connect intervention involved three 2-hour blocks of group classes that focused on building skills in areas such as healthy relationships and maintaining balance. Group exercises emphasized cohesion, shared purpose, and the value of a healthy unit.

Participants in the stress management group received an overview of the stress response system, information on the effect of stress on health, and cognitive and behavioral strategies to reduce stress.

Primary outcomes included the scores on the suicide scale and the depression inventory of the Computerized Adaptive Test for Mental Health.

The study included 1,485 participants (82.3% men; mean age, 20.9 years). At the 1-month follow-up, participants in Wingman-Connect classes reported less severe suicidal ideation (effect size, −0.23; 95% confidence interval, −39 to −0.09; P = .001) and depressive symptoms (ES, −0.24; 95% CI, −0.41 to −0.08; P = .002).

Unlike most suicide prevention programs, the Wingman intervention didn’t target only high-risk participants. “You’d expect smaller effect sizes” because many people were already doing well, said Wyman.

He noted that the effects at 1 month were similar to other state-of-the-art prevention programs.

Another primary endpoint was self-reported occupational impairment. A poor outcome here, said Wyman, could mean having to repeat a class or falling short of expectations behaviorally or academically.

Investigators found a 50% reduction – from approximately 10% to 5% – among the participants in the Wingman-Connect group who had occupational problems or performance concerns, said Wyman.

About 84% of participants in both study arms participated in the 6-month follow-up. At this time point, Wingman-Connect participants reported significantly lower depressive symptoms (ES, −0.16; 95% CI, −0.34 to −0.02; P = .03), but suicidal ideation severity scores were not significantly lower (ES, −0.13; 95% CI, −0.29 to 0.01; P = .06).
 

Universally beneficial

A beneficial effect on occupational problems was not evident after 6 months. This suggests that this type of training should be continued in later stages of military careers, said Wyman.

“This is not a one-time inoculation that will likely prevent all future problems,” he said.

Study participants experienced improvements in protective factors such as cohesion, morale, and bonds to classmates. The program was also associated with reduced anxiety and anger.

Overall, the Wingman-Connect group was about 20% less likely than the stress management group to report elevated depression at either follow-up period. In addition, on average, participants in the active intervention group were 19% less likely to have elevated suicidal ideation scores, although the difference was not significant.

The “logical interpretation” of this lack of statistical significance is that because depression was more common than suicidal ideation, “the intervention could have a slightly larger and more lasting effect on depression,” said Wyman.

There was no indication that men or women or those who started out at higher risk experienced greater benefit.

“Overall, the effects seemed to be distributed across airmen, independent of how they started,” said Wyman.

Wyman emphasized the unique nature of the Wingman-Connect program. “It’s universal prevention for all airmen – for those thriving and those struggling,” he said.

“We don’t know who necessarily will become at risk later on, or 6 months later, so it’s important to provide this kind of training for everyone.”

The “key mechanism” by which the program may prevent mental health problems is use of “units of military people working together day to day,” said Wyman.

The study did not reveal whether the intervention reduced suicidal behavior. This, say the authors, will need to be determined in future studies, as will determining which personnel are most likely to benefit.
 

A ‘particular challenge’

In an accompanying editorial, Roy H. Perlis, MD, department of psychiatry, Massachusetts General Hospital and Harvard Medical School, both in Boston, and Stephan D. Fihn, MD, department of medicine, University of Washington, Seattle, noted that suicide represents a “particular challenge” in the military.

This is “because soldiers are placed in extremely stressful situations, often without adequate physical or emotional support.”

The new study “adds to a literature that group-based interventions are effective in reducing depressive symptoms and may have advantages in resource-constrained environments,” they write.

Perlis and Finn note that it remains to be seen whether targeted strategies to reduce suicide “are worthwhile, rather than simply developing better treatments for depression.”

Commenting on the study for Medscape Medical News, Elspeth Cameron Ritchie, MD, former military psychiatrist and chair of the department of psychiatry, Medstar Washington Hospital Center, Washington, D.C., said the study “is based on quite a sound premise.”

Ritchie referred to the “long history” of research “repeatedly showing that units with good cohesion and morale have fewer difficulties of all kinds.”

However, the current study didn’t investigate the “converse of that,” said Ritchie. “There’s a high likelihood for suicidal ideation among those who are expelled” from the unit for various reasons.

Ritchie noted that a variety of different prevention initiatives have been launched in all military services over the years.

“Often, they have worked for a little while when there’s a champion behind them and there’s a lot of enthusiasm, and then they kind of fade out,” she said.

Ritchie agreed that such initiatives should continue throughout a person’s military career. She noted that suicide risk is elevated during periods of transition, for example, “leaving training base and going to your first duty station,” as well as when approaching retirement.

She appreciated the universal nature of the approach used in the study.

“Often, suicides are in those who have not been identified as high risk,” she said. However, she questioned whether the study’s follow-up period was long enough.

The study was supported by the Office of the Assistant Secretary of Defense for Health Affairs. Wyman, Perlis, and Cameron have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A novel program that strengthens bonds, boosts morale, and encourages supportive networks among US Air Force personnel cuts suicidal ideation and depressive symptoms after 1 month, new research shows.

The so-called Wingman-Connect initiative also had a beneficial impact on work performance, and the benefits were apparent at 6-month follow-up.

“This study suggests that group training can teach skills that help with occupational functioning and reduce the likelihood of experiencing elevated depression and suicidal ideation, at least in the short term,” lead author Peter A. Wyman, PhD, professor, department of psychiatry, University of Rochester, New York, told Medscape Medical News.

The study was published online Oct. 21 in JAMA Network Open.
 

Significant rise in suicide rates

Suicide rates among active duty military populations have increased “significantly” in the past 15 years and have exceeded rates for the general population when comparing groups of the same age and gender, said Wyman.

The study included new personnel who were taking classes at a single training center between October 2017 and October 2019.

Participants were randomly assigned to the Wingman-Connect program or to a stress management program.

The Wingman-Connect intervention involved three 2-hour blocks of group classes that focused on building skills in areas such as healthy relationships and maintaining balance. Group exercises emphasized cohesion, shared purpose, and the value of a healthy unit.

Participants in the stress management group received an overview of the stress response system, information on the effect of stress on health, and cognitive and behavioral strategies to reduce stress.

Primary outcomes included the scores on the suicide scale and the depression inventory of the Computerized Adaptive Test for Mental Health.

The study included 1,485 participants (82.3% men; mean age, 20.9 years). At the 1-month follow-up, participants in Wingman-Connect classes reported less severe suicidal ideation (effect size, −0.23; 95% confidence interval, −39 to −0.09; P = .001) and depressive symptoms (ES, −0.24; 95% CI, −0.41 to −0.08; P = .002).

Unlike most suicide prevention programs, the Wingman intervention didn’t target only high-risk participants. “You’d expect smaller effect sizes” because many people were already doing well, said Wyman.

He noted that the effects at 1 month were similar to other state-of-the-art prevention programs.

Another primary endpoint was self-reported occupational impairment. A poor outcome here, said Wyman, could mean having to repeat a class or falling short of expectations behaviorally or academically.

Investigators found a 50% reduction – from approximately 10% to 5% – among the participants in the Wingman-Connect group who had occupational problems or performance concerns, said Wyman.

About 84% of participants in both study arms participated in the 6-month follow-up. At this time point, Wingman-Connect participants reported significantly lower depressive symptoms (ES, −0.16; 95% CI, −0.34 to −0.02; P = .03), but suicidal ideation severity scores were not significantly lower (ES, −0.13; 95% CI, −0.29 to 0.01; P = .06).
 

Universally beneficial

A beneficial effect on occupational problems was not evident after 6 months. This suggests that this type of training should be continued in later stages of military careers, said Wyman.

“This is not a one-time inoculation that will likely prevent all future problems,” he said.

Study participants experienced improvements in protective factors such as cohesion, morale, and bonds to classmates. The program was also associated with reduced anxiety and anger.

Overall, the Wingman-Connect group was about 20% less likely than the stress management group to report elevated depression at either follow-up period. In addition, on average, participants in the active intervention group were 19% less likely to have elevated suicidal ideation scores, although the difference was not significant.

The “logical interpretation” of this lack of statistical significance is that because depression was more common than suicidal ideation, “the intervention could have a slightly larger and more lasting effect on depression,” said Wyman.

There was no indication that men or women or those who started out at higher risk experienced greater benefit.

“Overall, the effects seemed to be distributed across airmen, independent of how they started,” said Wyman.

Wyman emphasized the unique nature of the Wingman-Connect program. “It’s universal prevention for all airmen – for those thriving and those struggling,” he said.

“We don’t know who necessarily will become at risk later on, or 6 months later, so it’s important to provide this kind of training for everyone.”

The “key mechanism” by which the program may prevent mental health problems is use of “units of military people working together day to day,” said Wyman.

The study did not reveal whether the intervention reduced suicidal behavior. This, say the authors, will need to be determined in future studies, as will determining which personnel are most likely to benefit.
 

A ‘particular challenge’

In an accompanying editorial, Roy H. Perlis, MD, department of psychiatry, Massachusetts General Hospital and Harvard Medical School, both in Boston, and Stephan D. Fihn, MD, department of medicine, University of Washington, Seattle, noted that suicide represents a “particular challenge” in the military.

This is “because soldiers are placed in extremely stressful situations, often without adequate physical or emotional support.”

The new study “adds to a literature that group-based interventions are effective in reducing depressive symptoms and may have advantages in resource-constrained environments,” they write.

Perlis and Finn note that it remains to be seen whether targeted strategies to reduce suicide “are worthwhile, rather than simply developing better treatments for depression.”

Commenting on the study for Medscape Medical News, Elspeth Cameron Ritchie, MD, former military psychiatrist and chair of the department of psychiatry, Medstar Washington Hospital Center, Washington, D.C., said the study “is based on quite a sound premise.”

Ritchie referred to the “long history” of research “repeatedly showing that units with good cohesion and morale have fewer difficulties of all kinds.”

However, the current study didn’t investigate the “converse of that,” said Ritchie. “There’s a high likelihood for suicidal ideation among those who are expelled” from the unit for various reasons.

Ritchie noted that a variety of different prevention initiatives have been launched in all military services over the years.

“Often, they have worked for a little while when there’s a champion behind them and there’s a lot of enthusiasm, and then they kind of fade out,” she said.

Ritchie agreed that such initiatives should continue throughout a person’s military career. She noted that suicide risk is elevated during periods of transition, for example, “leaving training base and going to your first duty station,” as well as when approaching retirement.

She appreciated the universal nature of the approach used in the study.

“Often, suicides are in those who have not been identified as high risk,” she said. However, she questioned whether the study’s follow-up period was long enough.

The study was supported by the Office of the Assistant Secretary of Defense for Health Affairs. Wyman, Perlis, and Cameron have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A novel program that strengthens bonds, boosts morale, and encourages supportive networks among US Air Force personnel cuts suicidal ideation and depressive symptoms after 1 month, new research shows.

The so-called Wingman-Connect initiative also had a beneficial impact on work performance, and the benefits were apparent at 6-month follow-up.

“This study suggests that group training can teach skills that help with occupational functioning and reduce the likelihood of experiencing elevated depression and suicidal ideation, at least in the short term,” lead author Peter A. Wyman, PhD, professor, department of psychiatry, University of Rochester, New York, told Medscape Medical News.

The study was published online Oct. 21 in JAMA Network Open.
 

Significant rise in suicide rates

Suicide rates among active duty military populations have increased “significantly” in the past 15 years and have exceeded rates for the general population when comparing groups of the same age and gender, said Wyman.

The study included new personnel who were taking classes at a single training center between October 2017 and October 2019.

Participants were randomly assigned to the Wingman-Connect program or to a stress management program.

The Wingman-Connect intervention involved three 2-hour blocks of group classes that focused on building skills in areas such as healthy relationships and maintaining balance. Group exercises emphasized cohesion, shared purpose, and the value of a healthy unit.

Participants in the stress management group received an overview of the stress response system, information on the effect of stress on health, and cognitive and behavioral strategies to reduce stress.

Primary outcomes included the scores on the suicide scale and the depression inventory of the Computerized Adaptive Test for Mental Health.

The study included 1,485 participants (82.3% men; mean age, 20.9 years). At the 1-month follow-up, participants in Wingman-Connect classes reported less severe suicidal ideation (effect size, −0.23; 95% confidence interval, −39 to −0.09; P = .001) and depressive symptoms (ES, −0.24; 95% CI, −0.41 to −0.08; P = .002).

Unlike most suicide prevention programs, the Wingman intervention didn’t target only high-risk participants. “You’d expect smaller effect sizes” because many people were already doing well, said Wyman.

He noted that the effects at 1 month were similar to other state-of-the-art prevention programs.

Another primary endpoint was self-reported occupational impairment. A poor outcome here, said Wyman, could mean having to repeat a class or falling short of expectations behaviorally or academically.

Investigators found a 50% reduction – from approximately 10% to 5% – among the participants in the Wingman-Connect group who had occupational problems or performance concerns, said Wyman.

About 84% of participants in both study arms participated in the 6-month follow-up. At this time point, Wingman-Connect participants reported significantly lower depressive symptoms (ES, −0.16; 95% CI, −0.34 to −0.02; P = .03), but suicidal ideation severity scores were not significantly lower (ES, −0.13; 95% CI, −0.29 to 0.01; P = .06).
 

Universally beneficial

A beneficial effect on occupational problems was not evident after 6 months. This suggests that this type of training should be continued in later stages of military careers, said Wyman.

“This is not a one-time inoculation that will likely prevent all future problems,” he said.

Study participants experienced improvements in protective factors such as cohesion, morale, and bonds to classmates. The program was also associated with reduced anxiety and anger.

Overall, the Wingman-Connect group was about 20% less likely than the stress management group to report elevated depression at either follow-up period. In addition, on average, participants in the active intervention group were 19% less likely to have elevated suicidal ideation scores, although the difference was not significant.

The “logical interpretation” of this lack of statistical significance is that because depression was more common than suicidal ideation, “the intervention could have a slightly larger and more lasting effect on depression,” said Wyman.

There was no indication that men or women or those who started out at higher risk experienced greater benefit.

“Overall, the effects seemed to be distributed across airmen, independent of how they started,” said Wyman.

Wyman emphasized the unique nature of the Wingman-Connect program. “It’s universal prevention for all airmen – for those thriving and those struggling,” he said.

“We don’t know who necessarily will become at risk later on, or 6 months later, so it’s important to provide this kind of training for everyone.”

The “key mechanism” by which the program may prevent mental health problems is use of “units of military people working together day to day,” said Wyman.

The study did not reveal whether the intervention reduced suicidal behavior. This, say the authors, will need to be determined in future studies, as will determining which personnel are most likely to benefit.
 

A ‘particular challenge’

In an accompanying editorial, Roy H. Perlis, MD, department of psychiatry, Massachusetts General Hospital and Harvard Medical School, both in Boston, and Stephan D. Fihn, MD, department of medicine, University of Washington, Seattle, noted that suicide represents a “particular challenge” in the military.

This is “because soldiers are placed in extremely stressful situations, often without adequate physical or emotional support.”

The new study “adds to a literature that group-based interventions are effective in reducing depressive symptoms and may have advantages in resource-constrained environments,” they write.

Perlis and Finn note that it remains to be seen whether targeted strategies to reduce suicide “are worthwhile, rather than simply developing better treatments for depression.”

Commenting on the study for Medscape Medical News, Elspeth Cameron Ritchie, MD, former military psychiatrist and chair of the department of psychiatry, Medstar Washington Hospital Center, Washington, D.C., said the study “is based on quite a sound premise.”

Ritchie referred to the “long history” of research “repeatedly showing that units with good cohesion and morale have fewer difficulties of all kinds.”

However, the current study didn’t investigate the “converse of that,” said Ritchie. “There’s a high likelihood for suicidal ideation among those who are expelled” from the unit for various reasons.

Ritchie noted that a variety of different prevention initiatives have been launched in all military services over the years.

“Often, they have worked for a little while when there’s a champion behind them and there’s a lot of enthusiasm, and then they kind of fade out,” she said.

Ritchie agreed that such initiatives should continue throughout a person’s military career. She noted that suicide risk is elevated during periods of transition, for example, “leaving training base and going to your first duty station,” as well as when approaching retirement.

She appreciated the universal nature of the approach used in the study.

“Often, suicides are in those who have not been identified as high risk,” she said. However, she questioned whether the study’s follow-up period was long enough.

The study was supported by the Office of the Assistant Secretary of Defense for Health Affairs. Wyman, Perlis, and Cameron have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

New research shows that about a quarter of police officers in one large force report past or present mental health problems.

Responding to a survey, 26% of police officers on the Dallas police department screened positive for depression, anxiety, PTSD, or symptoms of suicide ideation or self-harm.

Mental illness rates were particularly high among female officers, those who were divorced, widowed, or separated, and those with military experience.

The study also showed that concerns over confidentiality and stigma may prevent officers with mental illness from seeking treatment.

The results underscored the need to identify police officers with psychiatric problems and to connect them to the most appropriate individualized care, author Katelyn K. Jetelina, PhD, assistant professor in the department of epidemiology, human genetics, and environmental sciences, University of Texas Health Science Center, Dallas, said in an interview.

“This is a very hard-to-reach population, and because of that, we need to be innovative in reaching them for services,” she said.

The study was published online Oct. 7 in JAMA Network Open.

Dr. Jetelina and colleagues are investigating various aspects of police officers’ well-being, including their nutritional needs and their occupational, physical, and mental health.

The current study included 434 members of the Dallas police department, the ninth largest in the United States. The mean age of the participants was 37 years, 82% were men, and about half were White. The 434 officers represented 97% of those invited to participate (n = 446) and 31% of the total patrol population of the Dallas police department (n = 1,413).

These officers completed a short survey on their smartphone that asked about lifetime diagnoses of depression, anxiety, and PTSD. They were also asked whether they experienced suicidal ideation or self-harm during the previous 2 weeks.

Overall, 12% of survey respondents reported having been diagnosed with a mental illness. This, said Jetelina, is slightly lower than the rate reported in the general population.

Study participants who had not currently been diagnosed with a mental illness completed the Patient Health Questionnaire–2 (PHQ-2), the Generalized Anxiety Disorder–2 (GAD-2), and the Primary Care–Posttraumatic Stress Disorder (PC-PTSD).

Officers were considered to have a positive result if they had a score of 3 or more (PHQ-2, sensitivity of 83% and specificity of 92%; PC-PTSD-5, sensitivity of 93% and specificity of 85%; GAD-2, sensitivity of 86% and specificity of 83%).

About 26% of respondents had a positive screening for mental illness symptoms, mainly PTSD and depression, which Dr. Jetelina noted is a higher percentage than in the general population.

This rate of mental health symptoms is “high and concerning,” but not surprising because of the work of police officers, which could include attending to sometimes violent car crashes, domestic abuse situations, and armed conflicts, said Dr. Jetelina.

“They’re constantly exposed to traumatic calls for service; they see people on their worst day, 8 hours a day, 5 days a week. That stress and exposure will have a detrimental effect on mental health, and we have to pay more attention to that,” she said.

Dr. Jetelina pointed out that the surveys were completed in January and February 2020, before COVID-19 had become a cause of stress for everyone and before the increase in calls for defunding police amid a resurgence of Black Lives Matter demonstrations.

However, she stressed that racial biases and occupational stress among police officers are “nothing new for them.” For example, in 2016, five Dallas police officers were killed during Black Lives Matter protests because of their race/ethnicity.
 

More at risk

The study showed that certain subgroups of officers were more at risk for mental illness. After adjustment for confounders, including demographic characteristics, marital status, and educational level, the odds of being diagnosed with a mental illness during the course of one’s life were significantly higher among female officers than male officers (adjusted odds ratio, 3.20; 95% confidence interval, 1.18-8.68).

Officers who were divorced, widowed, or separated and those who had more experience and held a higher rank were also at greater risk for mental illness.

As well, military veterans had greater odds of being diagnosed with a mental health disorder, compared with nonveterans (aOR, 3.25; 95% CI, 1.38-7.67).

The study also asked participants about use of mental health care services over the past 12 months. About 35% of those who had a current mental health diagnosis and 17% of those who screened positive for mental health symptoms reported using such services.

The study also asked those who screened positive about their interest in seeking such services. After adjustments, officers with suicidal ideation or self-harm were significantly more likely to be interested in getting help, compared with officers who did not report suicidal ideation or self-harm (aOR, 7.66; 95% CI, 1.70-34.48).

Dr. Jetelina was impressed that so many officers were keen to seek help, which “is a big positive,” she said. “It’s just a matter of better detecting who needs the help and better connecting them to medical services that meet their needs.”
 

Mindfulness exercise

Dr. Jetelina and colleagues are conducting a pilot test of the use by police officers of smartwatches that monitor heart rate and oxygen levels. If measurements with these devices reach a predetermined threshold, the officers are “pinged” and are instructed to perform a mindfulness exercise in the field, she said.

Results so far “are really exciting,” said Dr. Jetelina. “Officers have found this extremely helpful and feasible, and so the next step is to test if this truly impacts mental illness over time.”

Routine mental health screening of officers might be beneficial, but only if it’s conducted in a manner “respectful of the officers’ needs and wants,” said Dr. Jetelina.

She pointed out that although psychological assessments are routinely carried out following an extreme traumatic call, such as one involving an officer-involved shooting, the “in-between” calls could have a more severe cumulative impact on mental health.

It’s important to provide officers with easy-to-access services tailored for their individual needs, said Dr. Jetelina.
 

‘Numb to it’

Eighteen patrol officers also participated in a focus group, during which several themes regarding the use of mental health care services emerged. One theme was the inability of officers to identify when they’re personally experiencing a mental health problem.

Participants said they had become “numb” to the traumatic events on the job, which is “concerning,” Dr. Jetelina said. “They think that having nightmares every week is completely normal, but it’s not, and this needs to be addressed.”

Other themes that emerged from focus groups included the belief that psychologists can’t relate to police stressors; concerns about confidentiality (one sentiment that was expressed was “you’re an idiot” if you “trust this department”); and stigma for officers who seek mental health care (participants talked about “reprisal” from seeing “a shrink,” including being labeled as “a nutter” and losing their job).

Dr. Jetelina noted that some “champion” officers revealed their mental health journey during focus groups, which tended to “open a Pandora’s box” for others to discuss their experience. She said these champions could be leveraged throughout the police department to help reduce stigma.

The study included participants from only one police department, although rigorous data collection allows for generalizability to the entire patrol department, say the authors. Although the study included only brief screens of mental illness symptoms, these short versions of screening tests have high sensitivity and specificity for mental illness in primary care, they noted.

The next step for the researchers is to study how mental illness and symptoms affect job performance, said Dr. Jetelina. “Does this impact excessive use of force? Does this impact workers’ compensation? Does this impact dispatch times, the time it takes for a police officer to respond to [a] 911 call?”
 

Possible underrepresentation

Anthony T. Ng, MD, regional medical director, East Region Hartford HealthCare Behavioral Health Network in Mansfield, Conn., and member of the American Psychiatric Association’s Council on Communications, found the study “helpful.”

However, the 26% who tested positive for mental illness may be an “underrepresentation” of the true picture, inasmuch as police officers might minimize or be less than truthful about their mental health status, said Dr. Ng.

Law enforcement has “never been easy,” but stressors may have escalated recently as police forces deal with shortages of staff and jails, said Dr. Ng.

He also noted that officers might face stressors at home. “Evidence shows that domestic violence is quite high – or higher than average – among law enforcement,” he said. “All these things add up.”

Psychiatrists and other mental health professionals should be “aware of the unique challenges” that police officers face and be “proactively involved” in providing guidance and education on mitigating stress, said Dr. Ng.

“You have police officers wearing body armor, so why can’t you give them some training to learn how to have psychiatric or psychological body armor?” he said. But it’s a two-way street; police forces should be open to outreach from mental health professionals. “We have to meet halfway.”
 

Compassion fatigue

In an accompanying commentary, John M. Violanti, PhD, of the department of epidemiology and environmental health at the State University of New York at Buffalo, said the article helps bring “to the forefront” the issue of the psychological dangers of police work.

There is conjecture as to why police experience mental distress, said Dr. Violanti, who pointed to a study of New York City police suicides during the 1930s that suggested that police have a “social license” for aggressive behavior but are restrained as part of public trust, placing them in a position of “psychological strain.”

“This situation may be reflective of the same situation police find themselves today,” said Dr. Violanti.

“Compassion fatigue,” a feeling of mental exhaustion caused by the inability to care for all persons in trouble, may also be a factor, as could the constant stress that leaves police officers feeling “cynical and isolated from others,” he wrote.

“The socialization process of becoming a police officer is associated with constrictive reasoning, viewing the world as either right or wrong, which leaves no middle ground for alternatives to deal with mental distress,” Dr. Violanti said.

He noted that police officers may abuse alcohol because of stress, peer pressure, isolation, and a culture that approves of alcohol use. “Officers tend to drink together and reinforce their own values.”.

Although no prospective studies have linked police mental health problems with childhood abuse or neglect, some mental health professionals estimate that about 25% of their police clients have a history of childhood abuse or neglect, said Dr. Violanti.

He agreed that mindfulness may help manage stress and increase cognitive flexibility in dealing with trauma and crises.

A possible way to ensure confidentiality is a peer support program that allows distressed officers to first talk privately with a trained and trusted peer officer and to then seek professional help if necessary, said Dr. Violanti.

The study was funded by a grant from the National Institute of Occupational Health and Safety. Dr. Jetelina, Dr. Ng, and Dr. Violanti disclosed no relevant financial relationships.

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

New research shows that about a quarter of police officers in one large force report past or present mental health problems.

Responding to a survey, 26% of police officers on the Dallas police department screened positive for depression, anxiety, PTSD, or symptoms of suicide ideation or self-harm.

Mental illness rates were particularly high among female officers, those who were divorced, widowed, or separated, and those with military experience.

The study also showed that concerns over confidentiality and stigma may prevent officers with mental illness from seeking treatment.

The results underscored the need to identify police officers with psychiatric problems and to connect them to the most appropriate individualized care, author Katelyn K. Jetelina, PhD, assistant professor in the department of epidemiology, human genetics, and environmental sciences, University of Texas Health Science Center, Dallas, said in an interview.

“This is a very hard-to-reach population, and because of that, we need to be innovative in reaching them for services,” she said.

The study was published online Oct. 7 in JAMA Network Open.

Dr. Jetelina and colleagues are investigating various aspects of police officers’ well-being, including their nutritional needs and their occupational, physical, and mental health.

The current study included 434 members of the Dallas police department, the ninth largest in the United States. The mean age of the participants was 37 years, 82% were men, and about half were White. The 434 officers represented 97% of those invited to participate (n = 446) and 31% of the total patrol population of the Dallas police department (n = 1,413).

These officers completed a short survey on their smartphone that asked about lifetime diagnoses of depression, anxiety, and PTSD. They were also asked whether they experienced suicidal ideation or self-harm during the previous 2 weeks.

Overall, 12% of survey respondents reported having been diagnosed with a mental illness. This, said Jetelina, is slightly lower than the rate reported in the general population.

Study participants who had not currently been diagnosed with a mental illness completed the Patient Health Questionnaire–2 (PHQ-2), the Generalized Anxiety Disorder–2 (GAD-2), and the Primary Care–Posttraumatic Stress Disorder (PC-PTSD).

Officers were considered to have a positive result if they had a score of 3 or more (PHQ-2, sensitivity of 83% and specificity of 92%; PC-PTSD-5, sensitivity of 93% and specificity of 85%; GAD-2, sensitivity of 86% and specificity of 83%).

About 26% of respondents had a positive screening for mental illness symptoms, mainly PTSD and depression, which Dr. Jetelina noted is a higher percentage than in the general population.

This rate of mental health symptoms is “high and concerning,” but not surprising because of the work of police officers, which could include attending to sometimes violent car crashes, domestic abuse situations, and armed conflicts, said Dr. Jetelina.

“They’re constantly exposed to traumatic calls for service; they see people on their worst day, 8 hours a day, 5 days a week. That stress and exposure will have a detrimental effect on mental health, and we have to pay more attention to that,” she said.

Dr. Jetelina pointed out that the surveys were completed in January and February 2020, before COVID-19 had become a cause of stress for everyone and before the increase in calls for defunding police amid a resurgence of Black Lives Matter demonstrations.

However, she stressed that racial biases and occupational stress among police officers are “nothing new for them.” For example, in 2016, five Dallas police officers were killed during Black Lives Matter protests because of their race/ethnicity.
 

More at risk

The study showed that certain subgroups of officers were more at risk for mental illness. After adjustment for confounders, including demographic characteristics, marital status, and educational level, the odds of being diagnosed with a mental illness during the course of one’s life were significantly higher among female officers than male officers (adjusted odds ratio, 3.20; 95% confidence interval, 1.18-8.68).

Officers who were divorced, widowed, or separated and those who had more experience and held a higher rank were also at greater risk for mental illness.

As well, military veterans had greater odds of being diagnosed with a mental health disorder, compared with nonveterans (aOR, 3.25; 95% CI, 1.38-7.67).

The study also asked participants about use of mental health care services over the past 12 months. About 35% of those who had a current mental health diagnosis and 17% of those who screened positive for mental health symptoms reported using such services.

The study also asked those who screened positive about their interest in seeking such services. After adjustments, officers with suicidal ideation or self-harm were significantly more likely to be interested in getting help, compared with officers who did not report suicidal ideation or self-harm (aOR, 7.66; 95% CI, 1.70-34.48).

Dr. Jetelina was impressed that so many officers were keen to seek help, which “is a big positive,” she said. “It’s just a matter of better detecting who needs the help and better connecting them to medical services that meet their needs.”
 

Mindfulness exercise

Dr. Jetelina and colleagues are conducting a pilot test of the use by police officers of smartwatches that monitor heart rate and oxygen levels. If measurements with these devices reach a predetermined threshold, the officers are “pinged” and are instructed to perform a mindfulness exercise in the field, she said.

Results so far “are really exciting,” said Dr. Jetelina. “Officers have found this extremely helpful and feasible, and so the next step is to test if this truly impacts mental illness over time.”

Routine mental health screening of officers might be beneficial, but only if it’s conducted in a manner “respectful of the officers’ needs and wants,” said Dr. Jetelina.

She pointed out that although psychological assessments are routinely carried out following an extreme traumatic call, such as one involving an officer-involved shooting, the “in-between” calls could have a more severe cumulative impact on mental health.

It’s important to provide officers with easy-to-access services tailored for their individual needs, said Dr. Jetelina.
 

‘Numb to it’

Eighteen patrol officers also participated in a focus group, during which several themes regarding the use of mental health care services emerged. One theme was the inability of officers to identify when they’re personally experiencing a mental health problem.

Participants said they had become “numb” to the traumatic events on the job, which is “concerning,” Dr. Jetelina said. “They think that having nightmares every week is completely normal, but it’s not, and this needs to be addressed.”

Other themes that emerged from focus groups included the belief that psychologists can’t relate to police stressors; concerns about confidentiality (one sentiment that was expressed was “you’re an idiot” if you “trust this department”); and stigma for officers who seek mental health care (participants talked about “reprisal” from seeing “a shrink,” including being labeled as “a nutter” and losing their job).

Dr. Jetelina noted that some “champion” officers revealed their mental health journey during focus groups, which tended to “open a Pandora’s box” for others to discuss their experience. She said these champions could be leveraged throughout the police department to help reduce stigma.

The study included participants from only one police department, although rigorous data collection allows for generalizability to the entire patrol department, say the authors. Although the study included only brief screens of mental illness symptoms, these short versions of screening tests have high sensitivity and specificity for mental illness in primary care, they noted.

The next step for the researchers is to study how mental illness and symptoms affect job performance, said Dr. Jetelina. “Does this impact excessive use of force? Does this impact workers’ compensation? Does this impact dispatch times, the time it takes for a police officer to respond to [a] 911 call?”
 

Possible underrepresentation

Anthony T. Ng, MD, regional medical director, East Region Hartford HealthCare Behavioral Health Network in Mansfield, Conn., and member of the American Psychiatric Association’s Council on Communications, found the study “helpful.”

However, the 26% who tested positive for mental illness may be an “underrepresentation” of the true picture, inasmuch as police officers might minimize or be less than truthful about their mental health status, said Dr. Ng.

Law enforcement has “never been easy,” but stressors may have escalated recently as police forces deal with shortages of staff and jails, said Dr. Ng.

He also noted that officers might face stressors at home. “Evidence shows that domestic violence is quite high – or higher than average – among law enforcement,” he said. “All these things add up.”

Psychiatrists and other mental health professionals should be “aware of the unique challenges” that police officers face and be “proactively involved” in providing guidance and education on mitigating stress, said Dr. Ng.

“You have police officers wearing body armor, so why can’t you give them some training to learn how to have psychiatric or psychological body armor?” he said. But it’s a two-way street; police forces should be open to outreach from mental health professionals. “We have to meet halfway.”
 

Compassion fatigue

In an accompanying commentary, John M. Violanti, PhD, of the department of epidemiology and environmental health at the State University of New York at Buffalo, said the article helps bring “to the forefront” the issue of the psychological dangers of police work.

There is conjecture as to why police experience mental distress, said Dr. Violanti, who pointed to a study of New York City police suicides during the 1930s that suggested that police have a “social license” for aggressive behavior but are restrained as part of public trust, placing them in a position of “psychological strain.”

“This situation may be reflective of the same situation police find themselves today,” said Dr. Violanti.

“Compassion fatigue,” a feeling of mental exhaustion caused by the inability to care for all persons in trouble, may also be a factor, as could the constant stress that leaves police officers feeling “cynical and isolated from others,” he wrote.

“The socialization process of becoming a police officer is associated with constrictive reasoning, viewing the world as either right or wrong, which leaves no middle ground for alternatives to deal with mental distress,” Dr. Violanti said.

He noted that police officers may abuse alcohol because of stress, peer pressure, isolation, and a culture that approves of alcohol use. “Officers tend to drink together and reinforce their own values.”.

Although no prospective studies have linked police mental health problems with childhood abuse or neglect, some mental health professionals estimate that about 25% of their police clients have a history of childhood abuse or neglect, said Dr. Violanti.

He agreed that mindfulness may help manage stress and increase cognitive flexibility in dealing with trauma and crises.

A possible way to ensure confidentiality is a peer support program that allows distressed officers to first talk privately with a trained and trusted peer officer and to then seek professional help if necessary, said Dr. Violanti.

The study was funded by a grant from the National Institute of Occupational Health and Safety. Dr. Jetelina, Dr. Ng, and Dr. Violanti disclosed no relevant financial relationships.

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

New research shows that about a quarter of police officers in one large force report past or present mental health problems.

Responding to a survey, 26% of police officers on the Dallas police department screened positive for depression, anxiety, PTSD, or symptoms of suicide ideation or self-harm.

Mental illness rates were particularly high among female officers, those who were divorced, widowed, or separated, and those with military experience.

The study also showed that concerns over confidentiality and stigma may prevent officers with mental illness from seeking treatment.

The results underscored the need to identify police officers with psychiatric problems and to connect them to the most appropriate individualized care, author Katelyn K. Jetelina, PhD, assistant professor in the department of epidemiology, human genetics, and environmental sciences, University of Texas Health Science Center, Dallas, said in an interview.

“This is a very hard-to-reach population, and because of that, we need to be innovative in reaching them for services,” she said.

The study was published online Oct. 7 in JAMA Network Open.

Dr. Jetelina and colleagues are investigating various aspects of police officers’ well-being, including their nutritional needs and their occupational, physical, and mental health.

The current study included 434 members of the Dallas police department, the ninth largest in the United States. The mean age of the participants was 37 years, 82% were men, and about half were White. The 434 officers represented 97% of those invited to participate (n = 446) and 31% of the total patrol population of the Dallas police department (n = 1,413).

These officers completed a short survey on their smartphone that asked about lifetime diagnoses of depression, anxiety, and PTSD. They were also asked whether they experienced suicidal ideation or self-harm during the previous 2 weeks.

Overall, 12% of survey respondents reported having been diagnosed with a mental illness. This, said Jetelina, is slightly lower than the rate reported in the general population.

Study participants who had not currently been diagnosed with a mental illness completed the Patient Health Questionnaire–2 (PHQ-2), the Generalized Anxiety Disorder–2 (GAD-2), and the Primary Care–Posttraumatic Stress Disorder (PC-PTSD).

Officers were considered to have a positive result if they had a score of 3 or more (PHQ-2, sensitivity of 83% and specificity of 92%; PC-PTSD-5, sensitivity of 93% and specificity of 85%; GAD-2, sensitivity of 86% and specificity of 83%).

About 26% of respondents had a positive screening for mental illness symptoms, mainly PTSD and depression, which Dr. Jetelina noted is a higher percentage than in the general population.

This rate of mental health symptoms is “high and concerning,” but not surprising because of the work of police officers, which could include attending to sometimes violent car crashes, domestic abuse situations, and armed conflicts, said Dr. Jetelina.

“They’re constantly exposed to traumatic calls for service; they see people on their worst day, 8 hours a day, 5 days a week. That stress and exposure will have a detrimental effect on mental health, and we have to pay more attention to that,” she said.

Dr. Jetelina pointed out that the surveys were completed in January and February 2020, before COVID-19 had become a cause of stress for everyone and before the increase in calls for defunding police amid a resurgence of Black Lives Matter demonstrations.

However, she stressed that racial biases and occupational stress among police officers are “nothing new for them.” For example, in 2016, five Dallas police officers were killed during Black Lives Matter protests because of their race/ethnicity.
 

More at risk

The study showed that certain subgroups of officers were more at risk for mental illness. After adjustment for confounders, including demographic characteristics, marital status, and educational level, the odds of being diagnosed with a mental illness during the course of one’s life were significantly higher among female officers than male officers (adjusted odds ratio, 3.20; 95% confidence interval, 1.18-8.68).

Officers who were divorced, widowed, or separated and those who had more experience and held a higher rank were also at greater risk for mental illness.

As well, military veterans had greater odds of being diagnosed with a mental health disorder, compared with nonveterans (aOR, 3.25; 95% CI, 1.38-7.67).

The study also asked participants about use of mental health care services over the past 12 months. About 35% of those who had a current mental health diagnosis and 17% of those who screened positive for mental health symptoms reported using such services.

The study also asked those who screened positive about their interest in seeking such services. After adjustments, officers with suicidal ideation or self-harm were significantly more likely to be interested in getting help, compared with officers who did not report suicidal ideation or self-harm (aOR, 7.66; 95% CI, 1.70-34.48).

Dr. Jetelina was impressed that so many officers were keen to seek help, which “is a big positive,” she said. “It’s just a matter of better detecting who needs the help and better connecting them to medical services that meet their needs.”
 

Mindfulness exercise

Dr. Jetelina and colleagues are conducting a pilot test of the use by police officers of smartwatches that monitor heart rate and oxygen levels. If measurements with these devices reach a predetermined threshold, the officers are “pinged” and are instructed to perform a mindfulness exercise in the field, she said.

Results so far “are really exciting,” said Dr. Jetelina. “Officers have found this extremely helpful and feasible, and so the next step is to test if this truly impacts mental illness over time.”

Routine mental health screening of officers might be beneficial, but only if it’s conducted in a manner “respectful of the officers’ needs and wants,” said Dr. Jetelina.

She pointed out that although psychological assessments are routinely carried out following an extreme traumatic call, such as one involving an officer-involved shooting, the “in-between” calls could have a more severe cumulative impact on mental health.

It’s important to provide officers with easy-to-access services tailored for their individual needs, said Dr. Jetelina.
 

‘Numb to it’

Eighteen patrol officers also participated in a focus group, during which several themes regarding the use of mental health care services emerged. One theme was the inability of officers to identify when they’re personally experiencing a mental health problem.

Participants said they had become “numb” to the traumatic events on the job, which is “concerning,” Dr. Jetelina said. “They think that having nightmares every week is completely normal, but it’s not, and this needs to be addressed.”

Other themes that emerged from focus groups included the belief that psychologists can’t relate to police stressors; concerns about confidentiality (one sentiment that was expressed was “you’re an idiot” if you “trust this department”); and stigma for officers who seek mental health care (participants talked about “reprisal” from seeing “a shrink,” including being labeled as “a nutter” and losing their job).

Dr. Jetelina noted that some “champion” officers revealed their mental health journey during focus groups, which tended to “open a Pandora’s box” for others to discuss their experience. She said these champions could be leveraged throughout the police department to help reduce stigma.

The study included participants from only one police department, although rigorous data collection allows for generalizability to the entire patrol department, say the authors. Although the study included only brief screens of mental illness symptoms, these short versions of screening tests have high sensitivity and specificity for mental illness in primary care, they noted.

The next step for the researchers is to study how mental illness and symptoms affect job performance, said Dr. Jetelina. “Does this impact excessive use of force? Does this impact workers’ compensation? Does this impact dispatch times, the time it takes for a police officer to respond to [a] 911 call?”
 

Possible underrepresentation

Anthony T. Ng, MD, regional medical director, East Region Hartford HealthCare Behavioral Health Network in Mansfield, Conn., and member of the American Psychiatric Association’s Council on Communications, found the study “helpful.”

However, the 26% who tested positive for mental illness may be an “underrepresentation” of the true picture, inasmuch as police officers might minimize or be less than truthful about their mental health status, said Dr. Ng.

Law enforcement has “never been easy,” but stressors may have escalated recently as police forces deal with shortages of staff and jails, said Dr. Ng.

He also noted that officers might face stressors at home. “Evidence shows that domestic violence is quite high – or higher than average – among law enforcement,” he said. “All these things add up.”

Psychiatrists and other mental health professionals should be “aware of the unique challenges” that police officers face and be “proactively involved” in providing guidance and education on mitigating stress, said Dr. Ng.

“You have police officers wearing body armor, so why can’t you give them some training to learn how to have psychiatric or psychological body armor?” he said. But it’s a two-way street; police forces should be open to outreach from mental health professionals. “We have to meet halfway.”
 

Compassion fatigue

In an accompanying commentary, John M. Violanti, PhD, of the department of epidemiology and environmental health at the State University of New York at Buffalo, said the article helps bring “to the forefront” the issue of the psychological dangers of police work.

There is conjecture as to why police experience mental distress, said Dr. Violanti, who pointed to a study of New York City police suicides during the 1930s that suggested that police have a “social license” for aggressive behavior but are restrained as part of public trust, placing them in a position of “psychological strain.”

“This situation may be reflective of the same situation police find themselves today,” said Dr. Violanti.

“Compassion fatigue,” a feeling of mental exhaustion caused by the inability to care for all persons in trouble, may also be a factor, as could the constant stress that leaves police officers feeling “cynical and isolated from others,” he wrote.

“The socialization process of becoming a police officer is associated with constrictive reasoning, viewing the world as either right or wrong, which leaves no middle ground for alternatives to deal with mental distress,” Dr. Violanti said.

He noted that police officers may abuse alcohol because of stress, peer pressure, isolation, and a culture that approves of alcohol use. “Officers tend to drink together and reinforce their own values.”.

Although no prospective studies have linked police mental health problems with childhood abuse or neglect, some mental health professionals estimate that about 25% of their police clients have a history of childhood abuse or neglect, said Dr. Violanti.

He agreed that mindfulness may help manage stress and increase cognitive flexibility in dealing with trauma and crises.

A possible way to ensure confidentiality is a peer support program that allows distressed officers to first talk privately with a trained and trusted peer officer and to then seek professional help if necessary, said Dr. Violanti.

The study was funded by a grant from the National Institute of Occupational Health and Safety. Dr. Jetelina, Dr. Ng, and Dr. Violanti disclosed no relevant financial relationships.

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

The long-awaited postmarketing studies of the abuse-deterrent formulation (ADF) of OxyContin (Perdue Pharma) received mixed reviews from a Food and Drug Administration joint advisory committee.

After a 2-day discussion of new research submitted by Perdue, as well as other relevant published data, most members of the Drug Safety and Risk Management and Anesthetic and Analgesic Drug Products advisory committees came to the conclusion that the reformulated drug “meaningfully” reduced abuse via intranasal administration and intravenous injection, but not overall opioid abuse or overdose.

The reformulated OxyContin “was the first out of the gate,” and “has the greatest market penetration of any ADF” so “it gives us the greatest opportunity to measure change before and after reformulation,” said committee member Traci C. Green, PhD, MSc, professor and director of the Opioid Policy Research Collaborative at Brandeis University, Waltham, Mass.

The FDA approved the original formulation of OxyContin (oxycodone hydrochloride), a mu-receptor opioid agonist, in December 1995 for the management of pain requiring daily round-the-clock opioid treatment in cases where other treatments were inadequate. It approved an ADF version of the product in April 2010.

The updated formulation incorporates polyethylene oxide, an inactive polymer that makes the tablet harder and more crush resistant. The tablet turns into a gel or glue-like substance when wet.

The new formulation is bioequivalent to the original formulation, so no additional clinical efficacy and safety studies were conducted.

At the request of the FDA, the company carried out four postmarketing studies, which the FDA also reviewed.

• A National Addictions Vigilance Intervention and Prevention Program study that included 66,897 assessments in patients undergoing evaluation for substance use or entering an opioid addiction program. Results showed a drop in up to 52% of self-reported past 30-day OxyContin injection and snorting versus comparators, including extended-release morphine and immediate-release hydrocodone.
• An analysis of 308,465 calls to U.S. poison centers showing a reduction of up to 28% for calls regarding intentional OxyContin-related exposures immediately following the drug’s reformulation. However, the FDA analysis concluded it is unclear whether the decline was attributable to the drug’s reformulation or co-occurring trends.
• A study of 63,528 individuals entering methadone clinics or treatment programs that showed a reduction of up to 27% in OxyContin abuse versus comparators. There was no information on route of abuse. Here, the FDA analysis determined the results were mixed and didn’t provide compelling evidence.
• A claims-based analysis of patients who were dispensed an opioid (297,836 OxyContin; 659,673 a comparator) that showed no evidence that the updated product affected the rate of fatal and nonfatal opioid overdoses.

During the meeting, committee members heard that opioid use in the United States peaked in 2012, with 260 million prescriptions dispensed, then declined by 41% by 2019. ADFs accounted for only 2% of prescriptions in 2019. They also heard that results of a wide variety of studies and surveys support the conclusion that misuse, abuse, and diversion of OxyContin decreased after it was reformulated.

Ultimately, the joint committee voted 20 to 7 (with 1 abstention) that the reformulated drug reduced nonoral abuse. Most members who voted in favor cited the NAVIPPRO study as a reason for their decision, but few found the strength of the evidence better than moderate.

Meeting chair Sonia Hernandez-Diaz, MD, professor of epidemiology, Harvard School of Public Health, Boston, noted the reduction in abuse may, in part, be a result of the overall reduction in opioid use.

Jon E. Zibbell, PhD, senior public health scientist, behavioral health research division, RTI International, Atlanta, who voted “no,” was disappointed there was not more data.

“We had a bunch of years for this and so many of us could have done some amazing studies” related to how abuse changed post reformulation, he said.

As for overall abuse deterrence, the committee believed the evidence was less compelling. Only two members voted that the reformulated version of the drug reduced overall abuse and only one member voted that the reformulated tablets reduced opioid overdose.

Members generally agreed that all of the studies had limitations, including retrospective designs, confounding, and potential misclassifications. Many noted the challenge of assessing abuse pre- and post reformulation given the evolving situation.

For instance, at the time the reformulated drug was launched, public health initiatives targeting opioid abuse were introduced, more treatment centers were opening, and there was a crackdown on “pill-mill” doctors.

In addition, prescribing and consumption habits were changing. Some doctors may have switched only “at-risk” patients to the reformulated opioid and there may have been “self-selection” among patients – with some potentially opting for another drug such as immediate-release oxycodone.

During the meeting, there was discussion about how to interpret a “meaningful” abuse reduction. However, there was no consensus of a percentage the reduction had to reach in order to be deemed meaningful.

Another issue discussed was the term “abuse deterrent,” which some members believed was stigmatizing and should be changed to crush resistant.

There was also concern that prescribers might consider the ADF a “safe” or less addictive opioid. Michael Sprintz, DO, clinical assistant professor, division of geriatric and palliative medicine, University of Texas Health Science Center, Houston, said ADFs might provide physicians with “a false sense of security.”

Dr. Sprintz, also founder of the Sprintz Center for Pain and Recovery, noted the importance of pain medicine physicians understanding addiction and addiction specialists understanding pain management.

Other committee members voiced concern that the reformulation results in patients switching from intravenous and intranasal abuse to oral abuse. Committed abusers can still swallow multiple pills.

Some members noted that reformulated OxyContin coincided with increased transition to heroin, which is relatively cheap and readily available. However, they recognized that proving causality is difficult.

The committee was reminded that the reformulated drug provides a significant barrier against, but doesn’t altogether eliminate, opioid abuse. With hot water and the right tools, the tablets can still be manipulated.

In addition, the reformulated drug will not solve the U.S. opioid epidemic, which requires a multifaceted approach. The opioid crisis, said Wilson Compton, MD, deputy director at the National Institute on Drug Abuse, has resulted in a “skyrocketing” of deaths linked to “tremendously potent” forms of fentanyl, emerging stimulant use issues, and the possible increase in drug overdoses linked to COVID-19.

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

The long-awaited postmarketing studies of the abuse-deterrent formulation (ADF) of OxyContin (Perdue Pharma) received mixed reviews from a Food and Drug Administration joint advisory committee.

After a 2-day discussion of new research submitted by Perdue, as well as other relevant published data, most members of the Drug Safety and Risk Management and Anesthetic and Analgesic Drug Products advisory committees came to the conclusion that the reformulated drug “meaningfully” reduced abuse via intranasal administration and intravenous injection, but not overall opioid abuse or overdose.

The reformulated OxyContin “was the first out of the gate,” and “has the greatest market penetration of any ADF” so “it gives us the greatest opportunity to measure change before and after reformulation,” said committee member Traci C. Green, PhD, MSc, professor and director of the Opioid Policy Research Collaborative at Brandeis University, Waltham, Mass.

The FDA approved the original formulation of OxyContin (oxycodone hydrochloride), a mu-receptor opioid agonist, in December 1995 for the management of pain requiring daily round-the-clock opioid treatment in cases where other treatments were inadequate. It approved an ADF version of the product in April 2010.

The updated formulation incorporates polyethylene oxide, an inactive polymer that makes the tablet harder and more crush resistant. The tablet turns into a gel or glue-like substance when wet.

The new formulation is bioequivalent to the original formulation, so no additional clinical efficacy and safety studies were conducted.

At the request of the FDA, the company carried out four postmarketing studies, which the FDA also reviewed.

• A National Addictions Vigilance Intervention and Prevention Program study that included 66,897 assessments in patients undergoing evaluation for substance use or entering an opioid addiction program. Results showed a drop in up to 52% of self-reported past 30-day OxyContin injection and snorting versus comparators, including extended-release morphine and immediate-release hydrocodone.
• An analysis of 308,465 calls to U.S. poison centers showing a reduction of up to 28% for calls regarding intentional OxyContin-related exposures immediately following the drug’s reformulation. However, the FDA analysis concluded it is unclear whether the decline was attributable to the drug’s reformulation or co-occurring trends.
• A study of 63,528 individuals entering methadone clinics or treatment programs that showed a reduction of up to 27% in OxyContin abuse versus comparators. There was no information on route of abuse. Here, the FDA analysis determined the results were mixed and didn’t provide compelling evidence.
• A claims-based analysis of patients who were dispensed an opioid (297,836 OxyContin; 659,673 a comparator) that showed no evidence that the updated product affected the rate of fatal and nonfatal opioid overdoses.

During the meeting, committee members heard that opioid use in the United States peaked in 2012, with 260 million prescriptions dispensed, then declined by 41% by 2019. ADFs accounted for only 2% of prescriptions in 2019. They also heard that results of a wide variety of studies and surveys support the conclusion that misuse, abuse, and diversion of OxyContin decreased after it was reformulated.

Ultimately, the joint committee voted 20 to 7 (with 1 abstention) that the reformulated drug reduced nonoral abuse. Most members who voted in favor cited the NAVIPPRO study as a reason for their decision, but few found the strength of the evidence better than moderate.

Meeting chair Sonia Hernandez-Diaz, MD, professor of epidemiology, Harvard School of Public Health, Boston, noted the reduction in abuse may, in part, be a result of the overall reduction in opioid use.

Jon E. Zibbell, PhD, senior public health scientist, behavioral health research division, RTI International, Atlanta, who voted “no,” was disappointed there was not more data.

“We had a bunch of years for this and so many of us could have done some amazing studies” related to how abuse changed post reformulation, he said.

As for overall abuse deterrence, the committee believed the evidence was less compelling. Only two members voted that the reformulated version of the drug reduced overall abuse and only one member voted that the reformulated tablets reduced opioid overdose.

Members generally agreed that all of the studies had limitations, including retrospective designs, confounding, and potential misclassifications. Many noted the challenge of assessing abuse pre- and post reformulation given the evolving situation.

For instance, at the time the reformulated drug was launched, public health initiatives targeting opioid abuse were introduced, more treatment centers were opening, and there was a crackdown on “pill-mill” doctors.

In addition, prescribing and consumption habits were changing. Some doctors may have switched only “at-risk” patients to the reformulated opioid and there may have been “self-selection” among patients – with some potentially opting for another drug such as immediate-release oxycodone.

During the meeting, there was discussion about how to interpret a “meaningful” abuse reduction. However, there was no consensus of a percentage the reduction had to reach in order to be deemed meaningful.

Another issue discussed was the term “abuse deterrent,” which some members believed was stigmatizing and should be changed to crush resistant.

There was also concern that prescribers might consider the ADF a “safe” or less addictive opioid. Michael Sprintz, DO, clinical assistant professor, division of geriatric and palliative medicine, University of Texas Health Science Center, Houston, said ADFs might provide physicians with “a false sense of security.”

Dr. Sprintz, also founder of the Sprintz Center for Pain and Recovery, noted the importance of pain medicine physicians understanding addiction and addiction specialists understanding pain management.

Other committee members voiced concern that the reformulation results in patients switching from intravenous and intranasal abuse to oral abuse. Committed abusers can still swallow multiple pills.

Some members noted that reformulated OxyContin coincided with increased transition to heroin, which is relatively cheap and readily available. However, they recognized that proving causality is difficult.

The committee was reminded that the reformulated drug provides a significant barrier against, but doesn’t altogether eliminate, opioid abuse. With hot water and the right tools, the tablets can still be manipulated.

In addition, the reformulated drug will not solve the U.S. opioid epidemic, which requires a multifaceted approach. The opioid crisis, said Wilson Compton, MD, deputy director at the National Institute on Drug Abuse, has resulted in a “skyrocketing” of deaths linked to “tremendously potent” forms of fentanyl, emerging stimulant use issues, and the possible increase in drug overdoses linked to COVID-19.

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

The long-awaited postmarketing studies of the abuse-deterrent formulation (ADF) of OxyContin (Perdue Pharma) received mixed reviews from a Food and Drug Administration joint advisory committee.

After a 2-day discussion of new research submitted by Perdue, as well as other relevant published data, most members of the Drug Safety and Risk Management and Anesthetic and Analgesic Drug Products advisory committees came to the conclusion that the reformulated drug “meaningfully” reduced abuse via intranasal administration and intravenous injection, but not overall opioid abuse or overdose.

The reformulated OxyContin “was the first out of the gate,” and “has the greatest market penetration of any ADF” so “it gives us the greatest opportunity to measure change before and after reformulation,” said committee member Traci C. Green, PhD, MSc, professor and director of the Opioid Policy Research Collaborative at Brandeis University, Waltham, Mass.

The FDA approved the original formulation of OxyContin (oxycodone hydrochloride), a mu-receptor opioid agonist, in December 1995 for the management of pain requiring daily round-the-clock opioid treatment in cases where other treatments were inadequate. It approved an ADF version of the product in April 2010.

The updated formulation incorporates polyethylene oxide, an inactive polymer that makes the tablet harder and more crush resistant. The tablet turns into a gel or glue-like substance when wet.

The new formulation is bioequivalent to the original formulation, so no additional clinical efficacy and safety studies were conducted.

At the request of the FDA, the company carried out four postmarketing studies, which the FDA also reviewed.

• A National Addictions Vigilance Intervention and Prevention Program study that included 66,897 assessments in patients undergoing evaluation for substance use or entering an opioid addiction program. Results showed a drop in up to 52% of self-reported past 30-day OxyContin injection and snorting versus comparators, including extended-release morphine and immediate-release hydrocodone.
• An analysis of 308,465 calls to U.S. poison centers showing a reduction of up to 28% for calls regarding intentional OxyContin-related exposures immediately following the drug’s reformulation. However, the FDA analysis concluded it is unclear whether the decline was attributable to the drug’s reformulation or co-occurring trends.
• A study of 63,528 individuals entering methadone clinics or treatment programs that showed a reduction of up to 27% in OxyContin abuse versus comparators. There was no information on route of abuse. Here, the FDA analysis determined the results were mixed and didn’t provide compelling evidence.
• A claims-based analysis of patients who were dispensed an opioid (297,836 OxyContin; 659,673 a comparator) that showed no evidence that the updated product affected the rate of fatal and nonfatal opioid overdoses.

During the meeting, committee members heard that opioid use in the United States peaked in 2012, with 260 million prescriptions dispensed, then declined by 41% by 2019. ADFs accounted for only 2% of prescriptions in 2019. They also heard that results of a wide variety of studies and surveys support the conclusion that misuse, abuse, and diversion of OxyContin decreased after it was reformulated.

Ultimately, the joint committee voted 20 to 7 (with 1 abstention) that the reformulated drug reduced nonoral abuse. Most members who voted in favor cited the NAVIPPRO study as a reason for their decision, but few found the strength of the evidence better than moderate.

Meeting chair Sonia Hernandez-Diaz, MD, professor of epidemiology, Harvard School of Public Health, Boston, noted the reduction in abuse may, in part, be a result of the overall reduction in opioid use.

Jon E. Zibbell, PhD, senior public health scientist, behavioral health research division, RTI International, Atlanta, who voted “no,” was disappointed there was not more data.

“We had a bunch of years for this and so many of us could have done some amazing studies” related to how abuse changed post reformulation, he said.

As for overall abuse deterrence, the committee believed the evidence was less compelling. Only two members voted that the reformulated version of the drug reduced overall abuse and only one member voted that the reformulated tablets reduced opioid overdose.

Members generally agreed that all of the studies had limitations, including retrospective designs, confounding, and potential misclassifications. Many noted the challenge of assessing abuse pre- and post reformulation given the evolving situation.

For instance, at the time the reformulated drug was launched, public health initiatives targeting opioid abuse were introduced, more treatment centers were opening, and there was a crackdown on “pill-mill” doctors.

In addition, prescribing and consumption habits were changing. Some doctors may have switched only “at-risk” patients to the reformulated opioid and there may have been “self-selection” among patients – with some potentially opting for another drug such as immediate-release oxycodone.

During the meeting, there was discussion about how to interpret a “meaningful” abuse reduction. However, there was no consensus of a percentage the reduction had to reach in order to be deemed meaningful.

Another issue discussed was the term “abuse deterrent,” which some members believed was stigmatizing and should be changed to crush resistant.

There was also concern that prescribers might consider the ADF a “safe” or less addictive opioid. Michael Sprintz, DO, clinical assistant professor, division of geriatric and palliative medicine, University of Texas Health Science Center, Houston, said ADFs might provide physicians with “a false sense of security.”

Dr. Sprintz, also founder of the Sprintz Center for Pain and Recovery, noted the importance of pain medicine physicians understanding addiction and addiction specialists understanding pain management.

Other committee members voiced concern that the reformulation results in patients switching from intravenous and intranasal abuse to oral abuse. Committed abusers can still swallow multiple pills.

Some members noted that reformulated OxyContin coincided with increased transition to heroin, which is relatively cheap and readily available. However, they recognized that proving causality is difficult.

The committee was reminded that the reformulated drug provides a significant barrier against, but doesn’t altogether eliminate, opioid abuse. With hot water and the right tools, the tablets can still be manipulated.

In addition, the reformulated drug will not solve the U.S. opioid epidemic, which requires a multifaceted approach. The opioid crisis, said Wilson Compton, MD, deputy director at the National Institute on Drug Abuse, has resulted in a “skyrocketing” of deaths linked to “tremendously potent” forms of fentanyl, emerging stimulant use issues, and the possible increase in drug overdoses linked to COVID-19.

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