Clinical Psychiatry News

In 2019, the U.S. suicide rate dropped for the first time in 14 years, driven largely by a significant decline in firearm-related deaths, according to a new analysis of National Vital Statistics System data.

Since firearms are the “most common and most lethal” mechanism of suicide, the drop in deaths is “particularly encouraging,” Deborah M. Stone, ScD, MSW, MPH, and associates wrote in the Morbidity and Mortality Weekly Report.

The national suicide rate decreased from 14.2 per 100,000 population in 2018 to 13.9 per 100,000 in 2019, a statistically significant drop of 2.1% that reversed a 20-year trend that saw the rate increase by 33% since 1999, they said.

The rate for firearm use, which is involved in half of all suicides, declined from 7.0 per 100,000 to 6.8, for a significant change of 2.9%, said Dr. Stone and associates at the Centers for Disease Control and Prevention’s National Center for Injury Prevention and Control.

The only other method with a drop in suicide rate from 2018 to 2019 was suffocation – the second most common mechanism of injury – but the relative change of 2.3% was not significant, they noted.

Significant declines also occurred in several subgroups: Whites; those aged 15-24, 55-64, and 65-74 years; and those living in counties classified as large fringe metropolitan or micropolitan (urban cluster of ≥ 10,000 but less than 50,000 population), they said, based on data from the National Vital Statistics System.

“These declines, although encouraging, were not uniform, and several states experienced significant rate increases,” the investigators wrote.

The states with significant increases were Hawaii (30.3%) and Nebraska (20.1%), while declines in the suicide rate were significant in five states – Idaho, Indiana, Massachusetts, North Carolina, and Virginia, Dr. Stone and associates reported. Altogether, the rate fell in 31 states, increased in 18, and did not change in 2.

The significance of those changes varied between males and females. Declines were significant for females in Indiana, Massachusetts, and Washington, and for males in Florida, Kentucky, Massachusetts, North Carolina, and West Virginia. Minnesota was the only state with a significant increase among females, with Hawaii and Wyoming posting increases for males, they said.

As the response to the COVID-19 pandemic continues, the investigators pointed out, “prevention is more important than ever. Past research indicates that suicide rates remain stable or decline during infrastructure disruption (e.g., natural disasters), only to rise afterwards as the longer-term sequelae unfold in persons, families, and communities.”

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In 2019, the U.S. suicide rate dropped for the first time in 14 years, driven largely by a significant decline in firearm-related deaths, according to a new analysis of National Vital Statistics System data.

Since firearms are the “most common and most lethal” mechanism of suicide, the drop in deaths is “particularly encouraging,” Deborah M. Stone, ScD, MSW, MPH, and associates wrote in the Morbidity and Mortality Weekly Report.

The national suicide rate decreased from 14.2 per 100,000 population in 2018 to 13.9 per 100,000 in 2019, a statistically significant drop of 2.1% that reversed a 20-year trend that saw the rate increase by 33% since 1999, they said.

The rate for firearm use, which is involved in half of all suicides, declined from 7.0 per 100,000 to 6.8, for a significant change of 2.9%, said Dr. Stone and associates at the Centers for Disease Control and Prevention’s National Center for Injury Prevention and Control.

The only other method with a drop in suicide rate from 2018 to 2019 was suffocation – the second most common mechanism of injury – but the relative change of 2.3% was not significant, they noted.

Significant declines also occurred in several subgroups: Whites; those aged 15-24, 55-64, and 65-74 years; and those living in counties classified as large fringe metropolitan or micropolitan (urban cluster of ≥ 10,000 but less than 50,000 population), they said, based on data from the National Vital Statistics System.

“These declines, although encouraging, were not uniform, and several states experienced significant rate increases,” the investigators wrote.

The states with significant increases were Hawaii (30.3%) and Nebraska (20.1%), while declines in the suicide rate were significant in five states – Idaho, Indiana, Massachusetts, North Carolina, and Virginia, Dr. Stone and associates reported. Altogether, the rate fell in 31 states, increased in 18, and did not change in 2.

The significance of those changes varied between males and females. Declines were significant for females in Indiana, Massachusetts, and Washington, and for males in Florida, Kentucky, Massachusetts, North Carolina, and West Virginia. Minnesota was the only state with a significant increase among females, with Hawaii and Wyoming posting increases for males, they said.

As the response to the COVID-19 pandemic continues, the investigators pointed out, “prevention is more important than ever. Past research indicates that suicide rates remain stable or decline during infrastructure disruption (e.g., natural disasters), only to rise afterwards as the longer-term sequelae unfold in persons, families, and communities.”

[email protected]

In 2019, the U.S. suicide rate dropped for the first time in 14 years, driven largely by a significant decline in firearm-related deaths, according to a new analysis of National Vital Statistics System data.

Since firearms are the “most common and most lethal” mechanism of suicide, the drop in deaths is “particularly encouraging,” Deborah M. Stone, ScD, MSW, MPH, and associates wrote in the Morbidity and Mortality Weekly Report.

The national suicide rate decreased from 14.2 per 100,000 population in 2018 to 13.9 per 100,000 in 2019, a statistically significant drop of 2.1% that reversed a 20-year trend that saw the rate increase by 33% since 1999, they said.

The rate for firearm use, which is involved in half of all suicides, declined from 7.0 per 100,000 to 6.8, for a significant change of 2.9%, said Dr. Stone and associates at the Centers for Disease Control and Prevention’s National Center for Injury Prevention and Control.

The only other method with a drop in suicide rate from 2018 to 2019 was suffocation – the second most common mechanism of injury – but the relative change of 2.3% was not significant, they noted.

Significant declines also occurred in several subgroups: Whites; those aged 15-24, 55-64, and 65-74 years; and those living in counties classified as large fringe metropolitan or micropolitan (urban cluster of ≥ 10,000 but less than 50,000 population), they said, based on data from the National Vital Statistics System.

“These declines, although encouraging, were not uniform, and several states experienced significant rate increases,” the investigators wrote.

The states with significant increases were Hawaii (30.3%) and Nebraska (20.1%), while declines in the suicide rate were significant in five states – Idaho, Indiana, Massachusetts, North Carolina, and Virginia, Dr. Stone and associates reported. Altogether, the rate fell in 31 states, increased in 18, and did not change in 2.

The significance of those changes varied between males and females. Declines were significant for females in Indiana, Massachusetts, and Washington, and for males in Florida, Kentucky, Massachusetts, North Carolina, and West Virginia. Minnesota was the only state with a significant increase among females, with Hawaii and Wyoming posting increases for males, they said.

As the response to the COVID-19 pandemic continues, the investigators pointed out, “prevention is more important than ever. Past research indicates that suicide rates remain stable or decline during infrastructure disruption (e.g., natural disasters), only to rise afterwards as the longer-term sequelae unfold in persons, families, and communities.”

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Contrary to previous findings, selective serotonin reuptake inhibitors are not associated with an increased risk of intracerebral hemorrhage (ICH), results of a large observational study show. However, at least one expert urged caution in interpreting the finding.

“These findings are important, especially since depression is common after stroke and SSRIs are some of the first drugs considered for people,” Mithilesh Siddu, MD, of the University of Miami/Jackson Memorial Hospital, also in Miami, said in a statement.

However, Dr. Siddu said “more research is needed to confirm our findings and to also examine if SSRIs prescribed after a stroke may be linked to risk of a second stroke.”

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Widely prescribed

SSRIs, the most widely prescribed antidepressant in the United States, have previously been linked to an increased risk of ICH, possibly as a result of impaired platelet function.

To investigate further, the researchers analyzed data from the Florida Stroke Registry (FSR). They identified 127,915 patients who suffered ICH from January 2010 to December 2019 and for whom information on antidepressant use was available.

They analyzed the proportion of cases presenting with ICH among antidepressant users and the rate of SSRI prescription among stroke patients discharged on antidepressant therapy.

The researchers found that 11% of those who had been prescribed antidepressants had an ICH, compared with 14% of those who had not.

Antidepressant users were more likely to be female; non-Hispanic White; have hypertension; have diabetes; and use oral anticoagulants, antiplatelets, and statins prior to hospital presentation for ICH.

In multivariable analyses adjusting for age, race, prior history of hypertension, diabetes and prior oral anticoagulant, antiplatelet and statin use, antidepressant users were just as likely to present with spontaneous ICH as nonantidepressant users (odds ratio, 0.92; 95% confidence interval, 0.85-1.01).

A total of 3.4% of all ICH patients and 9% of those in whom specific antidepressant information was available were discharged home on an antidepressant, most commonly an SSRI (74%).

The authors noted a key limitation of the study: Some details regarding the length, dosage, and type of antidepressants were not available.
 

Interpret with caution

In a comment, Shaheen Lakhan, MD, PhD, a neurologist in Newton, Mass., and executive director of the Global Neuroscience Initiative Foundation, urged caution in making any firm conclusions based on this study.

“We have two questions here: One, is SSRI use a risk factor for first-time intracerebral hemorrhage, and two, is SSRI use after an ICH a risk factor for additional hemorrhages,” said Dr. Lakhan, who was not involved with the study.

“This study incompletely addresses the first because it is known that SSRIs have a variety of potencies. For instance, paroxetine is a strong inhibitor of serotonin reuptake, whereas bupropion is weak. Hypothetically, the former has a greater risk of ICH. Because this study did not stratify by type of antidepressant, it is not possible to tease these out,” Dr. Lakhan said.

“The second question is completely unaddressed by this study and is the real concern in clinical practice, because the chance of rebleed is much higher than the risk of first-time ICH in the general population,” he added.

The study had no specific funding. Dr. Siddu and Dr. Lakhan disclosed no relevant financial relationships.

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

Contrary to previous findings, selective serotonin reuptake inhibitors are not associated with an increased risk of intracerebral hemorrhage (ICH), results of a large observational study show. However, at least one expert urged caution in interpreting the finding.

“These findings are important, especially since depression is common after stroke and SSRIs are some of the first drugs considered for people,” Mithilesh Siddu, MD, of the University of Miami/Jackson Memorial Hospital, also in Miami, said in a statement.

However, Dr. Siddu said “more research is needed to confirm our findings and to also examine if SSRIs prescribed after a stroke may be linked to risk of a second stroke.”

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Widely prescribed

SSRIs, the most widely prescribed antidepressant in the United States, have previously been linked to an increased risk of ICH, possibly as a result of impaired platelet function.

To investigate further, the researchers analyzed data from the Florida Stroke Registry (FSR). They identified 127,915 patients who suffered ICH from January 2010 to December 2019 and for whom information on antidepressant use was available.

They analyzed the proportion of cases presenting with ICH among antidepressant users and the rate of SSRI prescription among stroke patients discharged on antidepressant therapy.

The researchers found that 11% of those who had been prescribed antidepressants had an ICH, compared with 14% of those who had not.

Antidepressant users were more likely to be female; non-Hispanic White; have hypertension; have diabetes; and use oral anticoagulants, antiplatelets, and statins prior to hospital presentation for ICH.

In multivariable analyses adjusting for age, race, prior history of hypertension, diabetes and prior oral anticoagulant, antiplatelet and statin use, antidepressant users were just as likely to present with spontaneous ICH as nonantidepressant users (odds ratio, 0.92; 95% confidence interval, 0.85-1.01).

A total of 3.4% of all ICH patients and 9% of those in whom specific antidepressant information was available were discharged home on an antidepressant, most commonly an SSRI (74%).

The authors noted a key limitation of the study: Some details regarding the length, dosage, and type of antidepressants were not available.
 

Interpret with caution

In a comment, Shaheen Lakhan, MD, PhD, a neurologist in Newton, Mass., and executive director of the Global Neuroscience Initiative Foundation, urged caution in making any firm conclusions based on this study.

“We have two questions here: One, is SSRI use a risk factor for first-time intracerebral hemorrhage, and two, is SSRI use after an ICH a risk factor for additional hemorrhages,” said Dr. Lakhan, who was not involved with the study.

“This study incompletely addresses the first because it is known that SSRIs have a variety of potencies. For instance, paroxetine is a strong inhibitor of serotonin reuptake, whereas bupropion is weak. Hypothetically, the former has a greater risk of ICH. Because this study did not stratify by type of antidepressant, it is not possible to tease these out,” Dr. Lakhan said.

“The second question is completely unaddressed by this study and is the real concern in clinical practice, because the chance of rebleed is much higher than the risk of first-time ICH in the general population,” he added.

The study had no specific funding. Dr. Siddu and Dr. Lakhan disclosed no relevant financial relationships.

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

Contrary to previous findings, selective serotonin reuptake inhibitors are not associated with an increased risk of intracerebral hemorrhage (ICH), results of a large observational study show. However, at least one expert urged caution in interpreting the finding.

“These findings are important, especially since depression is common after stroke and SSRIs are some of the first drugs considered for people,” Mithilesh Siddu, MD, of the University of Miami/Jackson Memorial Hospital, also in Miami, said in a statement.

However, Dr. Siddu said “more research is needed to confirm our findings and to also examine if SSRIs prescribed after a stroke may be linked to risk of a second stroke.”

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Widely prescribed

SSRIs, the most widely prescribed antidepressant in the United States, have previously been linked to an increased risk of ICH, possibly as a result of impaired platelet function.

To investigate further, the researchers analyzed data from the Florida Stroke Registry (FSR). They identified 127,915 patients who suffered ICH from January 2010 to December 2019 and for whom information on antidepressant use was available.

They analyzed the proportion of cases presenting with ICH among antidepressant users and the rate of SSRI prescription among stroke patients discharged on antidepressant therapy.

The researchers found that 11% of those who had been prescribed antidepressants had an ICH, compared with 14% of those who had not.

Antidepressant users were more likely to be female; non-Hispanic White; have hypertension; have diabetes; and use oral anticoagulants, antiplatelets, and statins prior to hospital presentation for ICH.

In multivariable analyses adjusting for age, race, prior history of hypertension, diabetes and prior oral anticoagulant, antiplatelet and statin use, antidepressant users were just as likely to present with spontaneous ICH as nonantidepressant users (odds ratio, 0.92; 95% confidence interval, 0.85-1.01).

A total of 3.4% of all ICH patients and 9% of those in whom specific antidepressant information was available were discharged home on an antidepressant, most commonly an SSRI (74%).

The authors noted a key limitation of the study: Some details regarding the length, dosage, and type of antidepressants were not available.
 

Interpret with caution

In a comment, Shaheen Lakhan, MD, PhD, a neurologist in Newton, Mass., and executive director of the Global Neuroscience Initiative Foundation, urged caution in making any firm conclusions based on this study.

“We have two questions here: One, is SSRI use a risk factor for first-time intracerebral hemorrhage, and two, is SSRI use after an ICH a risk factor for additional hemorrhages,” said Dr. Lakhan, who was not involved with the study.

“This study incompletely addresses the first because it is known that SSRIs have a variety of potencies. For instance, paroxetine is a strong inhibitor of serotonin reuptake, whereas bupropion is weak. Hypothetically, the former has a greater risk of ICH. Because this study did not stratify by type of antidepressant, it is not possible to tease these out,” Dr. Lakhan said.

“The second question is completely unaddressed by this study and is the real concern in clinical practice, because the chance of rebleed is much higher than the risk of first-time ICH in the general population,” he added.

The study had no specific funding. Dr. Siddu and Dr. Lakhan disclosed no relevant financial relationships.

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

One of the biggest conundrums of the COVID-19 pandemic has been the simultaneous panic-hiring of medical professionals in hot spots and significant downsizing of staff across the country. From huge hospital systems to private practices, the stoppage of breast reductions and knee replacements, not to mention the drops in motor vehicle accidents and bar fights, have quieted operating rooms and emergency departments and put doctors’ jobs on the chopping block. A widely cited survey suggests that 21% of doctors have had a work reduction due to COVID-19.

For many American doctors, this is their first extended period of unemployment. Unlike engineers or those with MBAs who might see their fortunes rise and fall with the whims of recessions and boom times, physicians are not exactly accustomed to being laid off. However, doctors were already smarting for years due to falling salaries and decreased autonomy, punctuated by endless clicks on electronic medical records software.

Now, the twin shock of income loss and feeling unwanted in a pandemic – when, you know, medicine might seem especially essential – has doctors resorting to a bizarre array of side gigs, “fun-employment” activities, or outright career overhauls.

Stephanie Eschenbach Morgan, MD, a breast radiologist in North Carolina, trained for 10 years after college before earning a true physician’s salary.

“Being furloughed was awful. Initially, it was only going to be 2 weeks, and then it turned into 2 months with no pay,” she reflected.

Dr. Eschenbach Morgan and her surgeon husband, who lost a full quarter’s salary, had to ask for grace periods on their credit card and mortgage payments because they had paid a large tax bill right before the pandemic began. “We couldn’t get any stimulus help, so that added insult to injury,” she said.

With her time spent waiting in a holding pattern, Dr. Eschenbach Morgan homeschooled her two young children and started putting a home gym together. She went on a home organizing spree, started a garden, and, perhaps most impressively, caught up with 5 years of photo albums.

A bonus she noted: “I didn’t set an alarm for 2 months.”

Shella Farooki, MD, a radiologist in California, was also focused on homeschooling, itself a demanding job, and veered toward retirement. When one of her work contracts furloughed her (“at one point, I made $30K a month for [their business]”), she started saving money at home, teaching the kids, and applied for a Paycheck Protection Program loan. Her husband, a hospitalist, had had his shifts cut. Dr. Farooki tried a radiology artificial intelligence firm but backed out when she was asked to read 9,200 studies for them for $2,000 per month.

Now, she thinks about leaving medicine “every day.”

Some doctors are questioning whether they should be in medicine in the first place. Family medicine physician Jonathan Polak, MD, faced with his own pink slip, turned to pink T-shirts instead. His girlfriend manages an outlet of the teen fashion retailer Justice. Dr. Polak, who finished his residency just 2 years ago, didn’t hesitate to take a $10-an-hour gig as a stock doc, once even finding himself delivering a shelving unit from the shuttering store to a physician fleeing the city for rural New Hampshire to “escape.”

There’s no escape for him – yet. Saddled with “astronomical” student loans, he had considered grocery store work as well. Dr. Polak knows he can’t work part time or go into teaching long term, as he might like.

Even so, he’s doing everything he can to not be in patient care for the long haul – it’s just not what he thought it would be.

“The culture of medicine, bureaucracy, endless paperwork and charting, and threat of litigation sucks a lot of the joy out of it to the point that I don’t see myself doing it forever when imagining myself 5-10 years into it.”

Still, he recently took an 18-month hospital contract that will force him to move to Florida, but he’s also been turning himself into a veritable Renaissance man; composing music, training for an ultramarathon, studying the latest medical findings, roadtripping, and launching a podcast about dog grooming with a master groomer. “We found parallels between medicine and dog grooming,” he says, somewhat convincingly.

Also working the ruff life is Jen Tserng, MD, a former forensic pathologist who landed on news websites in recent years for becoming a professional dogwalker and housesitter without a permanent home. Dr. Tserng knows doctors were restless and unhappy before COVID-19, their thoughts wandering where the grass might be greener.

As her profile grew, she found her inbox gathering messages from disaffected medical minions: students with a fear of failing or staring down residency application season and employed doctors sick of the constant grind. As she recounted those de facto life coach conversations (“What do you really enjoy?” “Do you really like dogs?”) by phone from New York, she said matter-of-factly, “They don’t call because of COVID. They call because they hate their lives.”

Michelle Mudge-Riley, MD, a physician in Texas, has been seeing this shift for some time as well. She recently held a virtual version of her Physicians Helping Physicians conference, where doctors hear from their peers working successfully in fields like pharmaceuticals and real estate investing.

When COVID-19 hit, Dr. Mudge-Riley quickly pivoted to a virtual platform, where the MDs and DOs huddled in breakout rooms having honest chats about their fears and tentative hopes about their new careers.

“There has been increased interest in nonclinical exploration into full- and part-time careers, as well as side hustles, since COVID began,” she said. “Many physicians have had their hours or pay cut, and some have been laid off. Others are furloughed. Some just want out of an environment where they don’t feel safe.”

An ear, nose, and throat surgeon, Maansi Doshi, MD, from central California, didn’t feel safe – so she left. She had returned from India sick with a mystery virus right as the pandemic began (she said her COVID-19 tests were all negative) and was waiting to get well enough to go back to her private practice job. However, she said she clashed with Trump-supporting colleagues she feared might not be taking the pandemic seriously enough.

Finally getting over a relapse of her mystery virus, Dr. Doshi emailed her resignation in May. Her husband, family practice doctor Mark Mangiapane, MD, gave his job notice weeks later in solidarity because he worked in the same building. Together, they have embraced gardening, a Peloton splurge, and learning business skills to open private practices – solo primary care for him; ENT with a focus on her favorite surgery, rhinoplasty, for her.

Dr. Mangiapane had considered editing medical brochures and also tried to apply for a job as a county public health officer in rural California, but he received his own shock when he learned the county intended to open schools in the midst of the pandemic despite advisement to the contrary by the former health officer.

He retreated from job listings altogether after hearing his would-be peers were getting death threats – targeting their children.

Both doctors felt COVID-19 pushed them beyond their comfort zones. “If COVID hadn’t happened, I would be working. ... Be ‘owned.’ In a weird way, COVID made me more independent and take a risk with my career.”

Obstetrician Kwandaa Roberts, MD, certainly did; she took a budding interest in decorating dollhouses straight to Instagram and national news fame, and she is now a TV-show expert on “Sell This House.”

Like Dr. Doshi and Dr. Mangiapane, Dr. Polak wants to be more in control of his future – even if selling T-shirts at a mall means a certain loss of status along the way.

“Aside from my passion to learn and to have that connection with people, I went into medicine ... because of the job security I thought existed,” he said. “I would say that my getting furloughed has changed my view of the United States in a dramatic way. I do not feel as confident in the U.S. economy and general way of life as I did a year ago. And I am taking a number of steps to put myself in a more fluid, adaptable position in case another crisis like this occurs or if the current state of things worsens.”

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

One of the biggest conundrums of the COVID-19 pandemic has been the simultaneous panic-hiring of medical professionals in hot spots and significant downsizing of staff across the country. From huge hospital systems to private practices, the stoppage of breast reductions and knee replacements, not to mention the drops in motor vehicle accidents and bar fights, have quieted operating rooms and emergency departments and put doctors’ jobs on the chopping block. A widely cited survey suggests that 21% of doctors have had a work reduction due to COVID-19.

For many American doctors, this is their first extended period of unemployment. Unlike engineers or those with MBAs who might see their fortunes rise and fall with the whims of recessions and boom times, physicians are not exactly accustomed to being laid off. However, doctors were already smarting for years due to falling salaries and decreased autonomy, punctuated by endless clicks on electronic medical records software.

Now, the twin shock of income loss and feeling unwanted in a pandemic – when, you know, medicine might seem especially essential – has doctors resorting to a bizarre array of side gigs, “fun-employment” activities, or outright career overhauls.

Stephanie Eschenbach Morgan, MD, a breast radiologist in North Carolina, trained for 10 years after college before earning a true physician’s salary.

“Being furloughed was awful. Initially, it was only going to be 2 weeks, and then it turned into 2 months with no pay,” she reflected.

Dr. Eschenbach Morgan and her surgeon husband, who lost a full quarter’s salary, had to ask for grace periods on their credit card and mortgage payments because they had paid a large tax bill right before the pandemic began. “We couldn’t get any stimulus help, so that added insult to injury,” she said.

With her time spent waiting in a holding pattern, Dr. Eschenbach Morgan homeschooled her two young children and started putting a home gym together. She went on a home organizing spree, started a garden, and, perhaps most impressively, caught up with 5 years of photo albums.

A bonus she noted: “I didn’t set an alarm for 2 months.”

Shella Farooki, MD, a radiologist in California, was also focused on homeschooling, itself a demanding job, and veered toward retirement. When one of her work contracts furloughed her (“at one point, I made $30K a month for [their business]”), she started saving money at home, teaching the kids, and applied for a Paycheck Protection Program loan. Her husband, a hospitalist, had had his shifts cut. Dr. Farooki tried a radiology artificial intelligence firm but backed out when she was asked to read 9,200 studies for them for $2,000 per month.

Now, she thinks about leaving medicine “every day.”

Some doctors are questioning whether they should be in medicine in the first place. Family medicine physician Jonathan Polak, MD, faced with his own pink slip, turned to pink T-shirts instead. His girlfriend manages an outlet of the teen fashion retailer Justice. Dr. Polak, who finished his residency just 2 years ago, didn’t hesitate to take a $10-an-hour gig as a stock doc, once even finding himself delivering a shelving unit from the shuttering store to a physician fleeing the city for rural New Hampshire to “escape.”

There’s no escape for him – yet. Saddled with “astronomical” student loans, he had considered grocery store work as well. Dr. Polak knows he can’t work part time or go into teaching long term, as he might like.

Even so, he’s doing everything he can to not be in patient care for the long haul – it’s just not what he thought it would be.

“The culture of medicine, bureaucracy, endless paperwork and charting, and threat of litigation sucks a lot of the joy out of it to the point that I don’t see myself doing it forever when imagining myself 5-10 years into it.”

Still, he recently took an 18-month hospital contract that will force him to move to Florida, but he’s also been turning himself into a veritable Renaissance man; composing music, training for an ultramarathon, studying the latest medical findings, roadtripping, and launching a podcast about dog grooming with a master groomer. “We found parallels between medicine and dog grooming,” he says, somewhat convincingly.

Also working the ruff life is Jen Tserng, MD, a former forensic pathologist who landed on news websites in recent years for becoming a professional dogwalker and housesitter without a permanent home. Dr. Tserng knows doctors were restless and unhappy before COVID-19, their thoughts wandering where the grass might be greener.

As her profile grew, she found her inbox gathering messages from disaffected medical minions: students with a fear of failing or staring down residency application season and employed doctors sick of the constant grind. As she recounted those de facto life coach conversations (“What do you really enjoy?” “Do you really like dogs?”) by phone from New York, she said matter-of-factly, “They don’t call because of COVID. They call because they hate their lives.”

Michelle Mudge-Riley, MD, a physician in Texas, has been seeing this shift for some time as well. She recently held a virtual version of her Physicians Helping Physicians conference, where doctors hear from their peers working successfully in fields like pharmaceuticals and real estate investing.

When COVID-19 hit, Dr. Mudge-Riley quickly pivoted to a virtual platform, where the MDs and DOs huddled in breakout rooms having honest chats about their fears and tentative hopes about their new careers.

“There has been increased interest in nonclinical exploration into full- and part-time careers, as well as side hustles, since COVID began,” she said. “Many physicians have had their hours or pay cut, and some have been laid off. Others are furloughed. Some just want out of an environment where they don’t feel safe.”

An ear, nose, and throat surgeon, Maansi Doshi, MD, from central California, didn’t feel safe – so she left. She had returned from India sick with a mystery virus right as the pandemic began (she said her COVID-19 tests were all negative) and was waiting to get well enough to go back to her private practice job. However, she said she clashed with Trump-supporting colleagues she feared might not be taking the pandemic seriously enough.

Finally getting over a relapse of her mystery virus, Dr. Doshi emailed her resignation in May. Her husband, family practice doctor Mark Mangiapane, MD, gave his job notice weeks later in solidarity because he worked in the same building. Together, they have embraced gardening, a Peloton splurge, and learning business skills to open private practices – solo primary care for him; ENT with a focus on her favorite surgery, rhinoplasty, for her.

Dr. Mangiapane had considered editing medical brochures and also tried to apply for a job as a county public health officer in rural California, but he received his own shock when he learned the county intended to open schools in the midst of the pandemic despite advisement to the contrary by the former health officer.

He retreated from job listings altogether after hearing his would-be peers were getting death threats – targeting their children.

Both doctors felt COVID-19 pushed them beyond their comfort zones. “If COVID hadn’t happened, I would be working. ... Be ‘owned.’ In a weird way, COVID made me more independent and take a risk with my career.”

Obstetrician Kwandaa Roberts, MD, certainly did; she took a budding interest in decorating dollhouses straight to Instagram and national news fame, and she is now a TV-show expert on “Sell This House.”

Like Dr. Doshi and Dr. Mangiapane, Dr. Polak wants to be more in control of his future – even if selling T-shirts at a mall means a certain loss of status along the way.

“Aside from my passion to learn and to have that connection with people, I went into medicine ... because of the job security I thought existed,” he said. “I would say that my getting furloughed has changed my view of the United States in a dramatic way. I do not feel as confident in the U.S. economy and general way of life as I did a year ago. And I am taking a number of steps to put myself in a more fluid, adaptable position in case another crisis like this occurs or if the current state of things worsens.”

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

One of the biggest conundrums of the COVID-19 pandemic has been the simultaneous panic-hiring of medical professionals in hot spots and significant downsizing of staff across the country. From huge hospital systems to private practices, the stoppage of breast reductions and knee replacements, not to mention the drops in motor vehicle accidents and bar fights, have quieted operating rooms and emergency departments and put doctors’ jobs on the chopping block. A widely cited survey suggests that 21% of doctors have had a work reduction due to COVID-19.

For many American doctors, this is their first extended period of unemployment. Unlike engineers or those with MBAs who might see their fortunes rise and fall with the whims of recessions and boom times, physicians are not exactly accustomed to being laid off. However, doctors were already smarting for years due to falling salaries and decreased autonomy, punctuated by endless clicks on electronic medical records software.

Now, the twin shock of income loss and feeling unwanted in a pandemic – when, you know, medicine might seem especially essential – has doctors resorting to a bizarre array of side gigs, “fun-employment” activities, or outright career overhauls.

Stephanie Eschenbach Morgan, MD, a breast radiologist in North Carolina, trained for 10 years after college before earning a true physician’s salary.

“Being furloughed was awful. Initially, it was only going to be 2 weeks, and then it turned into 2 months with no pay,” she reflected.

Dr. Eschenbach Morgan and her surgeon husband, who lost a full quarter’s salary, had to ask for grace periods on their credit card and mortgage payments because they had paid a large tax bill right before the pandemic began. “We couldn’t get any stimulus help, so that added insult to injury,” she said.

With her time spent waiting in a holding pattern, Dr. Eschenbach Morgan homeschooled her two young children and started putting a home gym together. She went on a home organizing spree, started a garden, and, perhaps most impressively, caught up with 5 years of photo albums.

A bonus she noted: “I didn’t set an alarm for 2 months.”

Shella Farooki, MD, a radiologist in California, was also focused on homeschooling, itself a demanding job, and veered toward retirement. When one of her work contracts furloughed her (“at one point, I made $30K a month for [their business]”), she started saving money at home, teaching the kids, and applied for a Paycheck Protection Program loan. Her husband, a hospitalist, had had his shifts cut. Dr. Farooki tried a radiology artificial intelligence firm but backed out when she was asked to read 9,200 studies for them for $2,000 per month.

Now, she thinks about leaving medicine “every day.”

Some doctors are questioning whether they should be in medicine in the first place. Family medicine physician Jonathan Polak, MD, faced with his own pink slip, turned to pink T-shirts instead. His girlfriend manages an outlet of the teen fashion retailer Justice. Dr. Polak, who finished his residency just 2 years ago, didn’t hesitate to take a $10-an-hour gig as a stock doc, once even finding himself delivering a shelving unit from the shuttering store to a physician fleeing the city for rural New Hampshire to “escape.”

There’s no escape for him – yet. Saddled with “astronomical” student loans, he had considered grocery store work as well. Dr. Polak knows he can’t work part time or go into teaching long term, as he might like.

Even so, he’s doing everything he can to not be in patient care for the long haul – it’s just not what he thought it would be.

“The culture of medicine, bureaucracy, endless paperwork and charting, and threat of litigation sucks a lot of the joy out of it to the point that I don’t see myself doing it forever when imagining myself 5-10 years into it.”

Still, he recently took an 18-month hospital contract that will force him to move to Florida, but he’s also been turning himself into a veritable Renaissance man; composing music, training for an ultramarathon, studying the latest medical findings, roadtripping, and launching a podcast about dog grooming with a master groomer. “We found parallels between medicine and dog grooming,” he says, somewhat convincingly.

Also working the ruff life is Jen Tserng, MD, a former forensic pathologist who landed on news websites in recent years for becoming a professional dogwalker and housesitter without a permanent home. Dr. Tserng knows doctors were restless and unhappy before COVID-19, their thoughts wandering where the grass might be greener.

As her profile grew, she found her inbox gathering messages from disaffected medical minions: students with a fear of failing or staring down residency application season and employed doctors sick of the constant grind. As she recounted those de facto life coach conversations (“What do you really enjoy?” “Do you really like dogs?”) by phone from New York, she said matter-of-factly, “They don’t call because of COVID. They call because they hate their lives.”

Michelle Mudge-Riley, MD, a physician in Texas, has been seeing this shift for some time as well. She recently held a virtual version of her Physicians Helping Physicians conference, where doctors hear from their peers working successfully in fields like pharmaceuticals and real estate investing.

When COVID-19 hit, Dr. Mudge-Riley quickly pivoted to a virtual platform, where the MDs and DOs huddled in breakout rooms having honest chats about their fears and tentative hopes about their new careers.

“There has been increased interest in nonclinical exploration into full- and part-time careers, as well as side hustles, since COVID began,” she said. “Many physicians have had their hours or pay cut, and some have been laid off. Others are furloughed. Some just want out of an environment where they don’t feel safe.”

An ear, nose, and throat surgeon, Maansi Doshi, MD, from central California, didn’t feel safe – so she left. She had returned from India sick with a mystery virus right as the pandemic began (she said her COVID-19 tests were all negative) and was waiting to get well enough to go back to her private practice job. However, she said she clashed with Trump-supporting colleagues she feared might not be taking the pandemic seriously enough.

Finally getting over a relapse of her mystery virus, Dr. Doshi emailed her resignation in May. Her husband, family practice doctor Mark Mangiapane, MD, gave his job notice weeks later in solidarity because he worked in the same building. Together, they have embraced gardening, a Peloton splurge, and learning business skills to open private practices – solo primary care for him; ENT with a focus on her favorite surgery, rhinoplasty, for her.

Dr. Mangiapane had considered editing medical brochures and also tried to apply for a job as a county public health officer in rural California, but he received his own shock when he learned the county intended to open schools in the midst of the pandemic despite advisement to the contrary by the former health officer.

He retreated from job listings altogether after hearing his would-be peers were getting death threats – targeting their children.

Both doctors felt COVID-19 pushed them beyond their comfort zones. “If COVID hadn’t happened, I would be working. ... Be ‘owned.’ In a weird way, COVID made me more independent and take a risk with my career.”

Obstetrician Kwandaa Roberts, MD, certainly did; she took a budding interest in decorating dollhouses straight to Instagram and national news fame, and she is now a TV-show expert on “Sell This House.”

Like Dr. Doshi and Dr. Mangiapane, Dr. Polak wants to be more in control of his future – even if selling T-shirts at a mall means a certain loss of status along the way.

“Aside from my passion to learn and to have that connection with people, I went into medicine ... because of the job security I thought existed,” he said. “I would say that my getting furloughed has changed my view of the United States in a dramatic way. I do not feel as confident in the U.S. economy and general way of life as I did a year ago. And I am taking a number of steps to put myself in a more fluid, adaptable position in case another crisis like this occurs or if the current state of things worsens.”

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

Have you ever had a really good idea about how to improve the delivery of mental health services? An idea that would help people, but that would require passion, innovation, and hard work to implement, and one that immediately is beset with a list of reasons why it can not be implemented?

Mona Masood, DO, had an idea. The Pennsylvania psychiatrist was asked to help moderate a Facebook group started by one of her infectious disease colleagues last winter – a private Facebook group for physicians working with COVID-19 patients.

“The group was getting posts from frontline workers about how depressed and hopeless they were feeling.” Dr. Masood said. “People were posting about how they were having escape fantasies and how they regretted becoming physicians. It became clear that there was a need for more support.”

She could pinpoint the day – March 22, 2020 – when she came up with the idea to start a peer-to-peer physician support hotline: psychiatrist volunteers would take calls from physicians who needed someone to talk to – the psychiatrist would provide a sympathetic ear and have a list of resources, but this would be support, not treatment. There would be no prescriptions, no treatment relationship, no reporting to licensing boards or employers. The calls would be anonymous.

She posted her idea on the Facebook group, and the response was immediate. “There were a lot of emails – 200 psychiatrists responded saying: “Sign me up.” A Zoom meeting was set up, and the process was set in motion.

Dr. Masood used a Google document for weekly sign-ups so the volunteer psychiatrists could choose times. “We had to pay for an upgraded Google suite package for that many users. Getting this up and running was like the saying about building a plane as you fly it,” Dr. Masood said. “It forced so much so quickly because there was this acknowledgment that the need was there.”

Initially, the support line launched with a telehealth platform, but there was a problem. “Many doctors don’t want to be seen; they worry about being recognized.” Dr. Masood researched hotline phone services and was able to get one for a reduced fee. The volunteers have an App on their smartphones that enables them to log in at the start of their shifts and log out at the end. In addition to the logistics of coordinating the volunteers – now numbering over 700 – the group found a health care law firm that provided pro bono services to review the policies and procedures.

Now that the support line is running, Dr. Masood is able to set up the day’s volunteers for the support line connection in a few minutes each morning, but the beginning was not easy. Her private practice transitioned to telemedicine, and her two children were home with one in virtual school. “At first, it was like another full-time job.” She still remains available for trouble-shooting during the day. It’s a project she has taken on with passion.

The support line began as a response to watching colleagues struggle with COVID. Since it launched, there have been approximately 2,000 calls. Calls typically last for 20 to 90 minutes, and no one has called with a suicidal crisis. It is now open to doctors and medical students looking for support for any reason. “Physicians call with all kinds of issues. In the first 3 months, it was COVID, but then they called with other concerns – there were doctors who called with election anxiety, really anything that affects the general public also affects us.”

The group has also offered Saturday didactic sessions for volunteers and weekly debriefing sessions. Dr. Masood has been approached by Vibrant Emotional Health, the administrator of the National Suicide Prevention Lifeline, about resources to help with funding – until now, this endeavor has had no financing – and she is hopeful that their financial support will allow the support line to sustain itself and grow. Future directions include advocating for systemic change in how physician mental health and wellness issues are addressed.

The Physician Support Line was one psychiatrist’s vision for how to address a problem. Like so many things related to this pandemic, it happened quickly and with surprising efficiency. Implementing this service, however, was not easy – it required hard work, innovative thinking, and passion. Those looking for someone to listen can call 1-888-409-0141 and psychiatrists who wish to volunteer can sign up at physiciansupportline.com/volunteer-info.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2018). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, both in Baltimore.

Have you ever had a really good idea about how to improve the delivery of mental health services? An idea that would help people, but that would require passion, innovation, and hard work to implement, and one that immediately is beset with a list of reasons why it can not be implemented?

Mona Masood, DO, had an idea. The Pennsylvania psychiatrist was asked to help moderate a Facebook group started by one of her infectious disease colleagues last winter – a private Facebook group for physicians working with COVID-19 patients.

“The group was getting posts from frontline workers about how depressed and hopeless they were feeling.” Dr. Masood said. “People were posting about how they were having escape fantasies and how they regretted becoming physicians. It became clear that there was a need for more support.”

She could pinpoint the day – March 22, 2020 – when she came up with the idea to start a peer-to-peer physician support hotline: psychiatrist volunteers would take calls from physicians who needed someone to talk to – the psychiatrist would provide a sympathetic ear and have a list of resources, but this would be support, not treatment. There would be no prescriptions, no treatment relationship, no reporting to licensing boards or employers. The calls would be anonymous.

She posted her idea on the Facebook group, and the response was immediate. “There were a lot of emails – 200 psychiatrists responded saying: “Sign me up.” A Zoom meeting was set up, and the process was set in motion.

Dr. Masood used a Google document for weekly sign-ups so the volunteer psychiatrists could choose times. “We had to pay for an upgraded Google suite package for that many users. Getting this up and running was like the saying about building a plane as you fly it,” Dr. Masood said. “It forced so much so quickly because there was this acknowledgment that the need was there.”

Initially, the support line launched with a telehealth platform, but there was a problem. “Many doctors don’t want to be seen; they worry about being recognized.” Dr. Masood researched hotline phone services and was able to get one for a reduced fee. The volunteers have an App on their smartphones that enables them to log in at the start of their shifts and log out at the end. In addition to the logistics of coordinating the volunteers – now numbering over 700 – the group found a health care law firm that provided pro bono services to review the policies and procedures.

Now that the support line is running, Dr. Masood is able to set up the day’s volunteers for the support line connection in a few minutes each morning, but the beginning was not easy. Her private practice transitioned to telemedicine, and her two children were home with one in virtual school. “At first, it was like another full-time job.” She still remains available for trouble-shooting during the day. It’s a project she has taken on with passion.

The support line began as a response to watching colleagues struggle with COVID. Since it launched, there have been approximately 2,000 calls. Calls typically last for 20 to 90 minutes, and no one has called with a suicidal crisis. It is now open to doctors and medical students looking for support for any reason. “Physicians call with all kinds of issues. In the first 3 months, it was COVID, but then they called with other concerns – there were doctors who called with election anxiety, really anything that affects the general public also affects us.”

The group has also offered Saturday didactic sessions for volunteers and weekly debriefing sessions. Dr. Masood has been approached by Vibrant Emotional Health, the administrator of the National Suicide Prevention Lifeline, about resources to help with funding – until now, this endeavor has had no financing – and she is hopeful that their financial support will allow the support line to sustain itself and grow. Future directions include advocating for systemic change in how physician mental health and wellness issues are addressed.

The Physician Support Line was one psychiatrist’s vision for how to address a problem. Like so many things related to this pandemic, it happened quickly and with surprising efficiency. Implementing this service, however, was not easy – it required hard work, innovative thinking, and passion. Those looking for someone to listen can call 1-888-409-0141 and psychiatrists who wish to volunteer can sign up at physiciansupportline.com/volunteer-info.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2018). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, both in Baltimore.

Have you ever had a really good idea about how to improve the delivery of mental health services? An idea that would help people, but that would require passion, innovation, and hard work to implement, and one that immediately is beset with a list of reasons why it can not be implemented?

Mona Masood, DO, had an idea. The Pennsylvania psychiatrist was asked to help moderate a Facebook group started by one of her infectious disease colleagues last winter – a private Facebook group for physicians working with COVID-19 patients.

“The group was getting posts from frontline workers about how depressed and hopeless they were feeling.” Dr. Masood said. “People were posting about how they were having escape fantasies and how they regretted becoming physicians. It became clear that there was a need for more support.”

She could pinpoint the day – March 22, 2020 – when she came up with the idea to start a peer-to-peer physician support hotline: psychiatrist volunteers would take calls from physicians who needed someone to talk to – the psychiatrist would provide a sympathetic ear and have a list of resources, but this would be support, not treatment. There would be no prescriptions, no treatment relationship, no reporting to licensing boards or employers. The calls would be anonymous.

She posted her idea on the Facebook group, and the response was immediate. “There were a lot of emails – 200 psychiatrists responded saying: “Sign me up.” A Zoom meeting was set up, and the process was set in motion.

Dr. Masood used a Google document for weekly sign-ups so the volunteer psychiatrists could choose times. “We had to pay for an upgraded Google suite package for that many users. Getting this up and running was like the saying about building a plane as you fly it,” Dr. Masood said. “It forced so much so quickly because there was this acknowledgment that the need was there.”

Initially, the support line launched with a telehealth platform, but there was a problem. “Many doctors don’t want to be seen; they worry about being recognized.” Dr. Masood researched hotline phone services and was able to get one for a reduced fee. The volunteers have an App on their smartphones that enables them to log in at the start of their shifts and log out at the end. In addition to the logistics of coordinating the volunteers – now numbering over 700 – the group found a health care law firm that provided pro bono services to review the policies and procedures.

Now that the support line is running, Dr. Masood is able to set up the day’s volunteers for the support line connection in a few minutes each morning, but the beginning was not easy. Her private practice transitioned to telemedicine, and her two children were home with one in virtual school. “At first, it was like another full-time job.” She still remains available for trouble-shooting during the day. It’s a project she has taken on with passion.

The support line began as a response to watching colleagues struggle with COVID. Since it launched, there have been approximately 2,000 calls. Calls typically last for 20 to 90 minutes, and no one has called with a suicidal crisis. It is now open to doctors and medical students looking for support for any reason. “Physicians call with all kinds of issues. In the first 3 months, it was COVID, but then they called with other concerns – there were doctors who called with election anxiety, really anything that affects the general public also affects us.”

The group has also offered Saturday didactic sessions for volunteers and weekly debriefing sessions. Dr. Masood has been approached by Vibrant Emotional Health, the administrator of the National Suicide Prevention Lifeline, about resources to help with funding – until now, this endeavor has had no financing – and she is hopeful that their financial support will allow the support line to sustain itself and grow. Future directions include advocating for systemic change in how physician mental health and wellness issues are addressed.

The Physician Support Line was one psychiatrist’s vision for how to address a problem. Like so many things related to this pandemic, it happened quickly and with surprising efficiency. Implementing this service, however, was not easy – it required hard work, innovative thinking, and passion. Those looking for someone to listen can call 1-888-409-0141 and psychiatrists who wish to volunteer can sign up at physiciansupportline.com/volunteer-info.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2018). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, both in Baltimore.

This transcript has been edited for clarity.

I’m Dr. Gregory Scott Brown, an Austin (Tex.)-based psychiatrist and an affiliate faculty member at the University of Texas Dell Medical School.

Recently, a patient of mine told me that, because of the political environment we find ourselves in, he’s avoiding conversations with some of his longtime friends. Because of this, he’s feeling even more isolated than before.

We’re all coming off the heels of a tough year, and many of us expected that when we entered 2021 we’d quickly turn the page and life would get a whole lot easier. Since the reality is that we’re still dealing with deep divisions, social injustices, and the politicization of evidence-based medicine, emotions are naturally running high.

In listening to my patients over the past few weeks, there’s definitely a sense of optimism about coronavirus vaccines and getting back to life as usual. But there’s also a lingering sense of uncertainty and fear, especially when it comes to the possibility of saying the wrong thing, offending our friends, or just having conversations with people we may disagree with. I’m hearing concerns from my patients that 2020 exposed a dormant hatred that was brewing in the underbelly of our society, in our politics, and in our institutions. Patients are telling me that these concerns are making them anxious and some are avoiding interacting with people they may disagree with altogether because they’re afraid of the difficult conversations that may follow.

Since, like many of my patients as well as many of you, I follow the news, including stories of COVID-related deaths, economic hardships, peaceful protests gone bad, and political vitriol, I’ve had to remind myself about the importance of intentional kindness for effective communication and for supporting mental health.

I was reminded of the paper “Hate in the Counter-Transference” by the well-known pediatrician and psychoanalyst Donald Winnicott. He focuses on how to manage and sort through the strong emotions that may be experienced even during an encounter between a therapist and a patient. Although some of what he has to say doesn’t translate well to modern times, his recommendation that we acknowledge and try to normalize some of our feelings does. And this is how I’ve been starting a conversation with my patients – just by normalizing things a bit.

The past year or so has brought with it a range of intense emotions, including frustration, exhaustion, and some degree of sadness for most of us. When we’re self-aware about our feelings, we can make sense of them early on so that they don’t evolve into maladaptive ones like unhinged anger or hatred. My patients and I actively discuss how our feelings don’t have to get in the way of our ability to live and to interact with each other as we’d like to.

Considering the basic tenets of kindness is a good place to start. I recently spoke with Kelli Harding, MD, a psychiatrist and author of The Rabbit Effect: Live Longer, Happier, and Healthier with the Groundbreaking Science of Kindness. She pointed to research suggesting that kindness can benefit multiple areas of our health, from reducing cardiovascular events to improving mood and anxiety. In her book, she notes that the major contributor to outcomes in health isn’t our genetics, as we might think, it’s other determinants, like our political and social environment.

I tell my patients that we can’t always change our environment, but we can definitely change how we respond to it. This doesn’t mean it’s always an easy process, but there are things we can do. First, we have to acknowledge that some degree of conflict or cordial disagreement is inevitable and it doesn’t have to disrupt our mood.

An interesting study on conflict management pointed out that healthy conflict is actually beneficial in some cases. For instance, in the work environment, conflict can help with team development and better group decision-making. But it’s rigid personality differences, poor communication, emotional stress, and lack of candor that may contribute to so-called high-tension events, and this is where conflict can go awry. These are the areas that we can all focus on improving, not only for performance benefits but for our overall health and well-being as well.

The authors also recommend an active style of engagement as a technique to manage conflict, but in a way that feels both natural and safe. Other authors agree that so-called engaged coping is associated with a higher sense of control and overall improved psychological well-being. What this means is that avoidance may be necessary in the short term, but over time it may lead to more emotional stress and anxiety.

Overcoming the tendency to avoid requires both motivation and self-awareness. We need to know about patterns in our own behavior and how the behavior of others can push our buttons and spiral a healthy disagreement into a heated argument.

I like to recommend the hunger, angry, lonely, tired (HALT) model, which is often used as a self-care gauge in addiction treatment and to reduce medication errors. But I think it’s also a useful way to assess personal readiness for having a difficult conversation. I tell my patients to ask themselves in this moment: “Am I hungry, angry, lonely, or tired?” And if they are, perhaps it’s not the best time for the conversation.

Because 2020 brought with it a new set of challenges, it also forced many of us to focus on things that we just didn’t pay as much attention to before, including checking in on our feelings and the feelings of those around us. It also taught us to pay attention to the way and manner in which we communicate. I think that kindness is much easier to carry into difficult conversations if we approach them with a sense of curiosity before judgment. Ultimately, kindness is one of the best tools for balancing the intense emotions that many of us are feeling right now.

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

This transcript has been edited for clarity.

I’m Dr. Gregory Scott Brown, an Austin (Tex.)-based psychiatrist and an affiliate faculty member at the University of Texas Dell Medical School.

Recently, a patient of mine told me that, because of the political environment we find ourselves in, he’s avoiding conversations with some of his longtime friends. Because of this, he’s feeling even more isolated than before.

We’re all coming off the heels of a tough year, and many of us expected that when we entered 2021 we’d quickly turn the page and life would get a whole lot easier. Since the reality is that we’re still dealing with deep divisions, social injustices, and the politicization of evidence-based medicine, emotions are naturally running high.

In listening to my patients over the past few weeks, there’s definitely a sense of optimism about coronavirus vaccines and getting back to life as usual. But there’s also a lingering sense of uncertainty and fear, especially when it comes to the possibility of saying the wrong thing, offending our friends, or just having conversations with people we may disagree with. I’m hearing concerns from my patients that 2020 exposed a dormant hatred that was brewing in the underbelly of our society, in our politics, and in our institutions. Patients are telling me that these concerns are making them anxious and some are avoiding interacting with people they may disagree with altogether because they’re afraid of the difficult conversations that may follow.

Since, like many of my patients as well as many of you, I follow the news, including stories of COVID-related deaths, economic hardships, peaceful protests gone bad, and political vitriol, I’ve had to remind myself about the importance of intentional kindness for effective communication and for supporting mental health.

I was reminded of the paper “Hate in the Counter-Transference” by the well-known pediatrician and psychoanalyst Donald Winnicott. He focuses on how to manage and sort through the strong emotions that may be experienced even during an encounter between a therapist and a patient. Although some of what he has to say doesn’t translate well to modern times, his recommendation that we acknowledge and try to normalize some of our feelings does. And this is how I’ve been starting a conversation with my patients – just by normalizing things a bit.

The past year or so has brought with it a range of intense emotions, including frustration, exhaustion, and some degree of sadness for most of us. When we’re self-aware about our feelings, we can make sense of them early on so that they don’t evolve into maladaptive ones like unhinged anger or hatred. My patients and I actively discuss how our feelings don’t have to get in the way of our ability to live and to interact with each other as we’d like to.

Considering the basic tenets of kindness is a good place to start. I recently spoke with Kelli Harding, MD, a psychiatrist and author of The Rabbit Effect: Live Longer, Happier, and Healthier with the Groundbreaking Science of Kindness. She pointed to research suggesting that kindness can benefit multiple areas of our health, from reducing cardiovascular events to improving mood and anxiety. In her book, she notes that the major contributor to outcomes in health isn’t our genetics, as we might think, it’s other determinants, like our political and social environment.

I tell my patients that we can’t always change our environment, but we can definitely change how we respond to it. This doesn’t mean it’s always an easy process, but there are things we can do. First, we have to acknowledge that some degree of conflict or cordial disagreement is inevitable and it doesn’t have to disrupt our mood.

An interesting study on conflict management pointed out that healthy conflict is actually beneficial in some cases. For instance, in the work environment, conflict can help with team development and better group decision-making. But it’s rigid personality differences, poor communication, emotional stress, and lack of candor that may contribute to so-called high-tension events, and this is where conflict can go awry. These are the areas that we can all focus on improving, not only for performance benefits but for our overall health and well-being as well.

The authors also recommend an active style of engagement as a technique to manage conflict, but in a way that feels both natural and safe. Other authors agree that so-called engaged coping is associated with a higher sense of control and overall improved psychological well-being. What this means is that avoidance may be necessary in the short term, but over time it may lead to more emotional stress and anxiety.

Overcoming the tendency to avoid requires both motivation and self-awareness. We need to know about patterns in our own behavior and how the behavior of others can push our buttons and spiral a healthy disagreement into a heated argument.

I like to recommend the hunger, angry, lonely, tired (HALT) model, which is often used as a self-care gauge in addiction treatment and to reduce medication errors. But I think it’s also a useful way to assess personal readiness for having a difficult conversation. I tell my patients to ask themselves in this moment: “Am I hungry, angry, lonely, or tired?” And if they are, perhaps it’s not the best time for the conversation.

Because 2020 brought with it a new set of challenges, it also forced many of us to focus on things that we just didn’t pay as much attention to before, including checking in on our feelings and the feelings of those around us. It also taught us to pay attention to the way and manner in which we communicate. I think that kindness is much easier to carry into difficult conversations if we approach them with a sense of curiosity before judgment. Ultimately, kindness is one of the best tools for balancing the intense emotions that many of us are feeling right now.

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

This transcript has been edited for clarity.

I’m Dr. Gregory Scott Brown, an Austin (Tex.)-based psychiatrist and an affiliate faculty member at the University of Texas Dell Medical School.

Recently, a patient of mine told me that, because of the political environment we find ourselves in, he’s avoiding conversations with some of his longtime friends. Because of this, he’s feeling even more isolated than before.

We’re all coming off the heels of a tough year, and many of us expected that when we entered 2021 we’d quickly turn the page and life would get a whole lot easier. Since the reality is that we’re still dealing with deep divisions, social injustices, and the politicization of evidence-based medicine, emotions are naturally running high.

In listening to my patients over the past few weeks, there’s definitely a sense of optimism about coronavirus vaccines and getting back to life as usual. But there’s also a lingering sense of uncertainty and fear, especially when it comes to the possibility of saying the wrong thing, offending our friends, or just having conversations with people we may disagree with. I’m hearing concerns from my patients that 2020 exposed a dormant hatred that was brewing in the underbelly of our society, in our politics, and in our institutions. Patients are telling me that these concerns are making them anxious and some are avoiding interacting with people they may disagree with altogether because they’re afraid of the difficult conversations that may follow.

Since, like many of my patients as well as many of you, I follow the news, including stories of COVID-related deaths, economic hardships, peaceful protests gone bad, and political vitriol, I’ve had to remind myself about the importance of intentional kindness for effective communication and for supporting mental health.

I was reminded of the paper “Hate in the Counter-Transference” by the well-known pediatrician and psychoanalyst Donald Winnicott. He focuses on how to manage and sort through the strong emotions that may be experienced even during an encounter between a therapist and a patient. Although some of what he has to say doesn’t translate well to modern times, his recommendation that we acknowledge and try to normalize some of our feelings does. And this is how I’ve been starting a conversation with my patients – just by normalizing things a bit.

The past year or so has brought with it a range of intense emotions, including frustration, exhaustion, and some degree of sadness for most of us. When we’re self-aware about our feelings, we can make sense of them early on so that they don’t evolve into maladaptive ones like unhinged anger or hatred. My patients and I actively discuss how our feelings don’t have to get in the way of our ability to live and to interact with each other as we’d like to.

Considering the basic tenets of kindness is a good place to start. I recently spoke with Kelli Harding, MD, a psychiatrist and author of The Rabbit Effect: Live Longer, Happier, and Healthier with the Groundbreaking Science of Kindness. She pointed to research suggesting that kindness can benefit multiple areas of our health, from reducing cardiovascular events to improving mood and anxiety. In her book, she notes that the major contributor to outcomes in health isn’t our genetics, as we might think, it’s other determinants, like our political and social environment.

I tell my patients that we can’t always change our environment, but we can definitely change how we respond to it. This doesn’t mean it’s always an easy process, but there are things we can do. First, we have to acknowledge that some degree of conflict or cordial disagreement is inevitable and it doesn’t have to disrupt our mood.

An interesting study on conflict management pointed out that healthy conflict is actually beneficial in some cases. For instance, in the work environment, conflict can help with team development and better group decision-making. But it’s rigid personality differences, poor communication, emotional stress, and lack of candor that may contribute to so-called high-tension events, and this is where conflict can go awry. These are the areas that we can all focus on improving, not only for performance benefits but for our overall health and well-being as well.

The authors also recommend an active style of engagement as a technique to manage conflict, but in a way that feels both natural and safe. Other authors agree that so-called engaged coping is associated with a higher sense of control and overall improved psychological well-being. What this means is that avoidance may be necessary in the short term, but over time it may lead to more emotional stress and anxiety.

Overcoming the tendency to avoid requires both motivation and self-awareness. We need to know about patterns in our own behavior and how the behavior of others can push our buttons and spiral a healthy disagreement into a heated argument.

I like to recommend the hunger, angry, lonely, tired (HALT) model, which is often used as a self-care gauge in addiction treatment and to reduce medication errors. But I think it’s also a useful way to assess personal readiness for having a difficult conversation. I tell my patients to ask themselves in this moment: “Am I hungry, angry, lonely, or tired?” And if they are, perhaps it’s not the best time for the conversation.

Because 2020 brought with it a new set of challenges, it also forced many of us to focus on things that we just didn’t pay as much attention to before, including checking in on our feelings and the feelings of those around us. It also taught us to pay attention to the way and manner in which we communicate. I think that kindness is much easier to carry into difficult conversations if we approach them with a sense of curiosity before judgment. Ultimately, kindness is one of the best tools for balancing the intense emotions that many of us are feeling right now.

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

A novel therapy that combines a muscarinic receptor agonist with an anticholinergic agent is associated with a greater reduction in psychosis symptoms, compared with placebo, new research shows.

In a randomized, phase 2 trial composed of nearly 200 participants, xanomeline-trospium (KarXT) was generally well tolerated and had none of the common side effects linked to current antipsychotics, including weight gain and extrapyramidal symptoms such as dystonia, parkinsonism, and tardive dyskinesia.

“The results showing robust therapeutic efficacy of a non–dopamine targeting antipsychotic drug is an important milestone in the advance of the therapeutics of schizophrenia and other psychotic disorders,” coinvestigator Jeffrey A. Lieberman, MD, professor and chairman in the department of psychiatry, Columbia University, New York, said in an interview.

If approved, the new agent will be a “landmark” drug, Dr. Lieberman added.

The study was published in the Feb. 25, 2021, issue of the New England Journal of Medicine.
 

Long journey

The journey to develop an effective schizophrenia drug that reduces psychosis symptoms without onerous side effects has been a long one full of excitement and disappointment.

First-generation antipsychotics, dating back to the 1950s, targeted the postsynaptic dopamine-2 (D2) receptor. At the time, it was a “breakthrough” similar in scope to insulin for diabetes or antibiotics for infections, said Dr. Lieberman.

That was followed by development of numerous “me too” drugs with the same mechanism of action. However, these drugs had significant side effects, especially neurologic adverse events such as parkinsonism.

In 1989, second-generation antipsychotics were introduced, beginning with clozapine. They still targeted the D2 receptor but were “kinder and gentler,” Dr. Lieberman noted. “They didn’t bind to [the receptor] with such affinity that it shut things down completely, so had fewer neurologic side effects.”

However, these agents had other adverse consequences, such as weight gain and other metabolic effects including hyperglycemia and hyperlipidemia.

Today, about 20%-33% of patients with schizophrenia still do not respond to conventional treatments. Many have poor functional status and quality of life despite lifelong treatment with current antipsychotic agents.

“The pharmaceutical industry, biotech industry, and academic psychiatric community have been desperately trying to find novel strategies for antipsychotic drug development and asking, ‘Is D2 the only holy grail or are there other ways of treating psychotic symptoms of schizophrenia?’ ” Dr. Lieberman said.

Enter KarXT – a novel combination of xanomeline with trospium.
 

An ‘ingenious’ combination

Xanomeline, an oral muscarinic cholinergic receptor agonist, does not have direct effects on the dopamine receptor. Evidence suggests the muscarinic cholinergic system is involved in the pathophysiology of schizophrenia.

However, there may be dose-dependent adverse events with the medication, such as nausea, vomiting, diarrhea, sweating, and hypersalivation from stimulation of peripheral muscarinic cholinergic receptors.

That’s where trospium chloride, an oral panmuscarinic receptor antagonist approved for treating overactive bladder, comes in. It does not reach detectable levels in the cerebrospinal fluid and should avoid adverse central nervous system effects.

Dr. Lieberman said the idea of the drug combination is “ingenious.”

The new phase 2, multisite study included adult patients with a validated diagnosis of schizophrenia who were hospitalized with an acute exacerbation of psychosis, and who were free of antipsychotic medication for at least 2 weeks.

Participants were required to have a baseline Positive and Negative Syndrome Scale (PANSS) total score of 80 points or more.

In addition to seven positive symptom items, including delusions, hallucinations, and conceptual disorganization, the PANSS has seven negative symptom items. These include restricted emotional expression, paucity of speech, and diminished interest, social drive, and activity. Each item is scored from 1 to 7, with higher scores indicating more severe symptoms.

Patients also had to have a score on the Clinical Global Impression–Severity (CGI-S) scale of 4 or higher. Scores on the CGI-S range from 1 to 7, with higher scores indicating greater severity of illness.

The modified intention-to-treat analysis included patients randomly assigned to receive oral xanomeline-trospium (n = 83) or placebo (n = 87).

The dosing schedule was flexible, starting with 50 mg of xanomeline and 20 mg of trospium twice daily. The schedule increased to a maximum of 125 mg of xanomeline and 30 mg of trospium twice daily, with the option of lowering the dose if there were unacceptable side effects.

Mean scores at baseline for the treatment and placebo groups were 97.7 versus 96.6 for the PANSS total score, 26.4 versus 26.3 for the positive subscore, 22.6 versus 22.8 for the negative subscore, and 5.0 versus 4.9 in the CGI-S scale.
 

‘Impressively robust’ effect size

The primary endpoint was change in the PANSS total score at 5 weeks. Results showed a change of –17.4 points in the treatment group and –5.9 points in the placebo group (least-squares mean difference, –11.6 points; 95% confidence interval, –16.1 to –7.1; P < .001).

The effect size, which was almost 0.8 (0.75), was “impressively robust,” said Dr. Lieberman, adding that a moderate effect size in this patient population might be in the order of 0.4 or 0.5.

“That gives hope that this drug may not just be as effective as other antipsychotics, albeit acting in a novel way and in a way that has a less of side effect burden, but that it may actually have some elements of superior efficacy,” he said.

There were significant benefits on some secondary outcomes, including change in the PANSS positive symptom subscore (–5.6 points in the treatment group vs. –2.4 points in the placebo group; least-squares mean difference, –3.2 points; 95% CI, –4.8 to –1.7; P <  .001).

The active treatment also came out on top for CGI-S scores (P < .001), and PANSS negative symptom subscore (P < .001).

Because participants were hospitalized with an acute exacerbation of positive symptoms at time of study, it is difficult to determine “definitive efficacy” for negative symptoms, Dr. Lieberman noted. Negative symptoms may have improved simply because positive symptoms got better, he said.

Although the study included adults only, “there is nothing in the KarXT clinical profile that suggests it would be problematic for younger people,” Dr. Lieberman noted. This could include teenagers with first-episode psychosis.
 

Safety profile

Adverse events (AEs) were reported in 54% of the treatment group and 43% of the placebo group. AEs that were more common in the active treatment group included constipation (17% vs. 3%), nausea (17% vs. 4%), dry mouth (9% vs. 1%), dyspepsia (9% vs. 4%), and vomiting (9% vs. 4%). All AEs were rated as mild or moderate in severity and none resulted in discontinuation of treatment.

Rates of nausea, vomiting, and dry mouth were highest early in the trial and lower at the end, whereas constipation remained constant throughout the study.

Persistent constipation could affect the drug’s “utility” in elderly patients with cognitive issues but may be more of a “minor nuisance,” compared with other antipsychotics for those with schizophrenia, said Dr. Lieberman. He added that constipation might be mitigated with an over-the-counter treatment such as Metamucil. Importantly, there was no difference between groups in extrapyramidal symptoms.

In addition, participants receiving the active treatment did not have greater weight gain, which was about 3% versus 4% in the placebo group. The mean change in weight was 1.5 kg (3.3 lb) and 1.1 kg (2.4 lb), respectively.

Dr. Lieberman praised the manufacturer for undertaking the study.

“In an era when Big Pharma has retreated to a considerable degree from psychotropic drug development, it’s commendable that some companies have stayed the course and are succeeding in drug development,” he said.

Exciting mechanism

Commenting on the findings in an interview, Thomas Sedlak, MD, PhD, director of the Schizophrenia and Psychosis Consult Clinic and assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, called some aspects of the study “exciting.”

What’s especially important is that the novel agent “acts by a different mechanism than what we have been using for maybe 60 years,” said Dr. Sedlak, who was not involved with the research.

“There has been a lot of research in the last few decades into drugs that might act by alternate mechanisms of action, but nothing’s really gotten to market for schizophrenia,” he noted.

Another interesting aspect of the study is that it examined a combination drug that aims to maximize effects on the brain while minimizing periphery effects, Dr. Sedlak said.

In addition, he called the PANSS results “respectable.”

“It’s interesting that you get a big change in PANSS total score, but it’s not as big in the positive symptom score as you might have expected, and it’s not a huge drop in negative symptoms either,” said Dr. Sedlak.

It’s possible, he said, that the drug is targeting PANSS elements not captured in the main positive or negative symptom items; for example, anxiety, depression, guilt, attention, impulse control, disorientation, and judgment.

Dr. Sedlak noted that, while the new results are exciting, the enthusiasm may not be long-lasting. “When a new drug comes out, there’s often a lot of excitement about it, but once you start using it, expectations may deflate..

“More flexible ratios” of the two components of the drug might be useful to treat individual patients, he added.

In addition, using the components by themselves might be preferable for some clinicians. “I think a lot of physicians prefer using two separate drugs so they can alter the dose of each one independently and not be stuck with the ratio the manufacturer is providing,” Dr. Sedlak said.

However, he acknowledged that studying different choices of ratios would require much larger trials.

The study was supported by Karuna Therapeutics and the Wellcome Trust. Dr. Lieberman reported serving on an advisory board for Karuna Therapeutics and Intra-Cellular Therapies. Dr. Sedlak disclosed no relevant financial relationships.

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

A novel therapy that combines a muscarinic receptor agonist with an anticholinergic agent is associated with a greater reduction in psychosis symptoms, compared with placebo, new research shows.

In a randomized, phase 2 trial composed of nearly 200 participants, xanomeline-trospium (KarXT) was generally well tolerated and had none of the common side effects linked to current antipsychotics, including weight gain and extrapyramidal symptoms such as dystonia, parkinsonism, and tardive dyskinesia.

“The results showing robust therapeutic efficacy of a non–dopamine targeting antipsychotic drug is an important milestone in the advance of the therapeutics of schizophrenia and other psychotic disorders,” coinvestigator Jeffrey A. Lieberman, MD, professor and chairman in the department of psychiatry, Columbia University, New York, said in an interview.

If approved, the new agent will be a “landmark” drug, Dr. Lieberman added.

The study was published in the Feb. 25, 2021, issue of the New England Journal of Medicine.
 

Long journey

The journey to develop an effective schizophrenia drug that reduces psychosis symptoms without onerous side effects has been a long one full of excitement and disappointment.

First-generation antipsychotics, dating back to the 1950s, targeted the postsynaptic dopamine-2 (D2) receptor. At the time, it was a “breakthrough” similar in scope to insulin for diabetes or antibiotics for infections, said Dr. Lieberman.

That was followed by development of numerous “me too” drugs with the same mechanism of action. However, these drugs had significant side effects, especially neurologic adverse events such as parkinsonism.

In 1989, second-generation antipsychotics were introduced, beginning with clozapine. They still targeted the D2 receptor but were “kinder and gentler,” Dr. Lieberman noted. “They didn’t bind to [the receptor] with such affinity that it shut things down completely, so had fewer neurologic side effects.”

However, these agents had other adverse consequences, such as weight gain and other metabolic effects including hyperglycemia and hyperlipidemia.

Today, about 20%-33% of patients with schizophrenia still do not respond to conventional treatments. Many have poor functional status and quality of life despite lifelong treatment with current antipsychotic agents.

“The pharmaceutical industry, biotech industry, and academic psychiatric community have been desperately trying to find novel strategies for antipsychotic drug development and asking, ‘Is D2 the only holy grail or are there other ways of treating psychotic symptoms of schizophrenia?’ ” Dr. Lieberman said.

Enter KarXT – a novel combination of xanomeline with trospium.
 

An ‘ingenious’ combination

Xanomeline, an oral muscarinic cholinergic receptor agonist, does not have direct effects on the dopamine receptor. Evidence suggests the muscarinic cholinergic system is involved in the pathophysiology of schizophrenia.

However, there may be dose-dependent adverse events with the medication, such as nausea, vomiting, diarrhea, sweating, and hypersalivation from stimulation of peripheral muscarinic cholinergic receptors.

That’s where trospium chloride, an oral panmuscarinic receptor antagonist approved for treating overactive bladder, comes in. It does not reach detectable levels in the cerebrospinal fluid and should avoid adverse central nervous system effects.

Dr. Lieberman said the idea of the drug combination is “ingenious.”

The new phase 2, multisite study included adult patients with a validated diagnosis of schizophrenia who were hospitalized with an acute exacerbation of psychosis, and who were free of antipsychotic medication for at least 2 weeks.

Participants were required to have a baseline Positive and Negative Syndrome Scale (PANSS) total score of 80 points or more.

In addition to seven positive symptom items, including delusions, hallucinations, and conceptual disorganization, the PANSS has seven negative symptom items. These include restricted emotional expression, paucity of speech, and diminished interest, social drive, and activity. Each item is scored from 1 to 7, with higher scores indicating more severe symptoms.

Patients also had to have a score on the Clinical Global Impression–Severity (CGI-S) scale of 4 or higher. Scores on the CGI-S range from 1 to 7, with higher scores indicating greater severity of illness.

The modified intention-to-treat analysis included patients randomly assigned to receive oral xanomeline-trospium (n = 83) or placebo (n = 87).

The dosing schedule was flexible, starting with 50 mg of xanomeline and 20 mg of trospium twice daily. The schedule increased to a maximum of 125 mg of xanomeline and 30 mg of trospium twice daily, with the option of lowering the dose if there were unacceptable side effects.

Mean scores at baseline for the treatment and placebo groups were 97.7 versus 96.6 for the PANSS total score, 26.4 versus 26.3 for the positive subscore, 22.6 versus 22.8 for the negative subscore, and 5.0 versus 4.9 in the CGI-S scale.
 

‘Impressively robust’ effect size

The primary endpoint was change in the PANSS total score at 5 weeks. Results showed a change of –17.4 points in the treatment group and –5.9 points in the placebo group (least-squares mean difference, –11.6 points; 95% confidence interval, –16.1 to –7.1; P < .001).

The effect size, which was almost 0.8 (0.75), was “impressively robust,” said Dr. Lieberman, adding that a moderate effect size in this patient population might be in the order of 0.4 or 0.5.

“That gives hope that this drug may not just be as effective as other antipsychotics, albeit acting in a novel way and in a way that has a less of side effect burden, but that it may actually have some elements of superior efficacy,” he said.

There were significant benefits on some secondary outcomes, including change in the PANSS positive symptom subscore (–5.6 points in the treatment group vs. –2.4 points in the placebo group; least-squares mean difference, –3.2 points; 95% CI, –4.8 to –1.7; P <  .001).

The active treatment also came out on top for CGI-S scores (P < .001), and PANSS negative symptom subscore (P < .001).

Because participants were hospitalized with an acute exacerbation of positive symptoms at time of study, it is difficult to determine “definitive efficacy” for negative symptoms, Dr. Lieberman noted. Negative symptoms may have improved simply because positive symptoms got better, he said.

Although the study included adults only, “there is nothing in the KarXT clinical profile that suggests it would be problematic for younger people,” Dr. Lieberman noted. This could include teenagers with first-episode psychosis.
 

Safety profile

Adverse events (AEs) were reported in 54% of the treatment group and 43% of the placebo group. AEs that were more common in the active treatment group included constipation (17% vs. 3%), nausea (17% vs. 4%), dry mouth (9% vs. 1%), dyspepsia (9% vs. 4%), and vomiting (9% vs. 4%). All AEs were rated as mild or moderate in severity and none resulted in discontinuation of treatment.

Rates of nausea, vomiting, and dry mouth were highest early in the trial and lower at the end, whereas constipation remained constant throughout the study.

Persistent constipation could affect the drug’s “utility” in elderly patients with cognitive issues but may be more of a “minor nuisance,” compared with other antipsychotics for those with schizophrenia, said Dr. Lieberman. He added that constipation might be mitigated with an over-the-counter treatment such as Metamucil. Importantly, there was no difference between groups in extrapyramidal symptoms.

In addition, participants receiving the active treatment did not have greater weight gain, which was about 3% versus 4% in the placebo group. The mean change in weight was 1.5 kg (3.3 lb) and 1.1 kg (2.4 lb), respectively.

Dr. Lieberman praised the manufacturer for undertaking the study.

“In an era when Big Pharma has retreated to a considerable degree from psychotropic drug development, it’s commendable that some companies have stayed the course and are succeeding in drug development,” he said.

Exciting mechanism

Commenting on the findings in an interview, Thomas Sedlak, MD, PhD, director of the Schizophrenia and Psychosis Consult Clinic and assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, called some aspects of the study “exciting.”

What’s especially important is that the novel agent “acts by a different mechanism than what we have been using for maybe 60 years,” said Dr. Sedlak, who was not involved with the research.

“There has been a lot of research in the last few decades into drugs that might act by alternate mechanisms of action, but nothing’s really gotten to market for schizophrenia,” he noted.

Another interesting aspect of the study is that it examined a combination drug that aims to maximize effects on the brain while minimizing periphery effects, Dr. Sedlak said.

In addition, he called the PANSS results “respectable.”

“It’s interesting that you get a big change in PANSS total score, but it’s not as big in the positive symptom score as you might have expected, and it’s not a huge drop in negative symptoms either,” said Dr. Sedlak.

It’s possible, he said, that the drug is targeting PANSS elements not captured in the main positive or negative symptom items; for example, anxiety, depression, guilt, attention, impulse control, disorientation, and judgment.

Dr. Sedlak noted that, while the new results are exciting, the enthusiasm may not be long-lasting. “When a new drug comes out, there’s often a lot of excitement about it, but once you start using it, expectations may deflate..

“More flexible ratios” of the two components of the drug might be useful to treat individual patients, he added.

In addition, using the components by themselves might be preferable for some clinicians. “I think a lot of physicians prefer using two separate drugs so they can alter the dose of each one independently and not be stuck with the ratio the manufacturer is providing,” Dr. Sedlak said.

However, he acknowledged that studying different choices of ratios would require much larger trials.

The study was supported by Karuna Therapeutics and the Wellcome Trust. Dr. Lieberman reported serving on an advisory board for Karuna Therapeutics and Intra-Cellular Therapies. Dr. Sedlak disclosed no relevant financial relationships.

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

A novel therapy that combines a muscarinic receptor agonist with an anticholinergic agent is associated with a greater reduction in psychosis symptoms, compared with placebo, new research shows.

In a randomized, phase 2 trial composed of nearly 200 participants, xanomeline-trospium (KarXT) was generally well tolerated and had none of the common side effects linked to current antipsychotics, including weight gain and extrapyramidal symptoms such as dystonia, parkinsonism, and tardive dyskinesia.

“The results showing robust therapeutic efficacy of a non–dopamine targeting antipsychotic drug is an important milestone in the advance of the therapeutics of schizophrenia and other psychotic disorders,” coinvestigator Jeffrey A. Lieberman, MD, professor and chairman in the department of psychiatry, Columbia University, New York, said in an interview.

If approved, the new agent will be a “landmark” drug, Dr. Lieberman added.

The study was published in the Feb. 25, 2021, issue of the New England Journal of Medicine.
 

Long journey

The journey to develop an effective schizophrenia drug that reduces psychosis symptoms without onerous side effects has been a long one full of excitement and disappointment.

First-generation antipsychotics, dating back to the 1950s, targeted the postsynaptic dopamine-2 (D2) receptor. At the time, it was a “breakthrough” similar in scope to insulin for diabetes or antibiotics for infections, said Dr. Lieberman.

That was followed by development of numerous “me too” drugs with the same mechanism of action. However, these drugs had significant side effects, especially neurologic adverse events such as parkinsonism.

In 1989, second-generation antipsychotics were introduced, beginning with clozapine. They still targeted the D2 receptor but were “kinder and gentler,” Dr. Lieberman noted. “They didn’t bind to [the receptor] with such affinity that it shut things down completely, so had fewer neurologic side effects.”

However, these agents had other adverse consequences, such as weight gain and other metabolic effects including hyperglycemia and hyperlipidemia.

Today, about 20%-33% of patients with schizophrenia still do not respond to conventional treatments. Many have poor functional status and quality of life despite lifelong treatment with current antipsychotic agents.

“The pharmaceutical industry, biotech industry, and academic psychiatric community have been desperately trying to find novel strategies for antipsychotic drug development and asking, ‘Is D2 the only holy grail or are there other ways of treating psychotic symptoms of schizophrenia?’ ” Dr. Lieberman said.

Enter KarXT – a novel combination of xanomeline with trospium.
 

An ‘ingenious’ combination

Xanomeline, an oral muscarinic cholinergic receptor agonist, does not have direct effects on the dopamine receptor. Evidence suggests the muscarinic cholinergic system is involved in the pathophysiology of schizophrenia.

However, there may be dose-dependent adverse events with the medication, such as nausea, vomiting, diarrhea, sweating, and hypersalivation from stimulation of peripheral muscarinic cholinergic receptors.

That’s where trospium chloride, an oral panmuscarinic receptor antagonist approved for treating overactive bladder, comes in. It does not reach detectable levels in the cerebrospinal fluid and should avoid adverse central nervous system effects.

Dr. Lieberman said the idea of the drug combination is “ingenious.”

The new phase 2, multisite study included adult patients with a validated diagnosis of schizophrenia who were hospitalized with an acute exacerbation of psychosis, and who were free of antipsychotic medication for at least 2 weeks.

Participants were required to have a baseline Positive and Negative Syndrome Scale (PANSS) total score of 80 points or more.

In addition to seven positive symptom items, including delusions, hallucinations, and conceptual disorganization, the PANSS has seven negative symptom items. These include restricted emotional expression, paucity of speech, and diminished interest, social drive, and activity. Each item is scored from 1 to 7, with higher scores indicating more severe symptoms.

Patients also had to have a score on the Clinical Global Impression–Severity (CGI-S) scale of 4 or higher. Scores on the CGI-S range from 1 to 7, with higher scores indicating greater severity of illness.

The modified intention-to-treat analysis included patients randomly assigned to receive oral xanomeline-trospium (n = 83) or placebo (n = 87).

The dosing schedule was flexible, starting with 50 mg of xanomeline and 20 mg of trospium twice daily. The schedule increased to a maximum of 125 mg of xanomeline and 30 mg of trospium twice daily, with the option of lowering the dose if there were unacceptable side effects.

Mean scores at baseline for the treatment and placebo groups were 97.7 versus 96.6 for the PANSS total score, 26.4 versus 26.3 for the positive subscore, 22.6 versus 22.8 for the negative subscore, and 5.0 versus 4.9 in the CGI-S scale.
 

‘Impressively robust’ effect size

The primary endpoint was change in the PANSS total score at 5 weeks. Results showed a change of –17.4 points in the treatment group and –5.9 points in the placebo group (least-squares mean difference, –11.6 points; 95% confidence interval, –16.1 to –7.1; P < .001).

The effect size, which was almost 0.8 (0.75), was “impressively robust,” said Dr. Lieberman, adding that a moderate effect size in this patient population might be in the order of 0.4 or 0.5.

“That gives hope that this drug may not just be as effective as other antipsychotics, albeit acting in a novel way and in a way that has a less of side effect burden, but that it may actually have some elements of superior efficacy,” he said.

There were significant benefits on some secondary outcomes, including change in the PANSS positive symptom subscore (–5.6 points in the treatment group vs. –2.4 points in the placebo group; least-squares mean difference, –3.2 points; 95% CI, –4.8 to –1.7; P <  .001).

The active treatment also came out on top for CGI-S scores (P < .001), and PANSS negative symptom subscore (P < .001).

Because participants were hospitalized with an acute exacerbation of positive symptoms at time of study, it is difficult to determine “definitive efficacy” for negative symptoms, Dr. Lieberman noted. Negative symptoms may have improved simply because positive symptoms got better, he said.

Although the study included adults only, “there is nothing in the KarXT clinical profile that suggests it would be problematic for younger people,” Dr. Lieberman noted. This could include teenagers with first-episode psychosis.
 

Safety profile

Adverse events (AEs) were reported in 54% of the treatment group and 43% of the placebo group. AEs that were more common in the active treatment group included constipation (17% vs. 3%), nausea (17% vs. 4%), dry mouth (9% vs. 1%), dyspepsia (9% vs. 4%), and vomiting (9% vs. 4%). All AEs were rated as mild or moderate in severity and none resulted in discontinuation of treatment.

Rates of nausea, vomiting, and dry mouth were highest early in the trial and lower at the end, whereas constipation remained constant throughout the study.

Persistent constipation could affect the drug’s “utility” in elderly patients with cognitive issues but may be more of a “minor nuisance,” compared with other antipsychotics for those with schizophrenia, said Dr. Lieberman. He added that constipation might be mitigated with an over-the-counter treatment such as Metamucil. Importantly, there was no difference between groups in extrapyramidal symptoms.

In addition, participants receiving the active treatment did not have greater weight gain, which was about 3% versus 4% in the placebo group. The mean change in weight was 1.5 kg (3.3 lb) and 1.1 kg (2.4 lb), respectively.

Dr. Lieberman praised the manufacturer for undertaking the study.

“In an era when Big Pharma has retreated to a considerable degree from psychotropic drug development, it’s commendable that some companies have stayed the course and are succeeding in drug development,” he said.

Exciting mechanism

Commenting on the findings in an interview, Thomas Sedlak, MD, PhD, director of the Schizophrenia and Psychosis Consult Clinic and assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, called some aspects of the study “exciting.”

What’s especially important is that the novel agent “acts by a different mechanism than what we have been using for maybe 60 years,” said Dr. Sedlak, who was not involved with the research.

“There has been a lot of research in the last few decades into drugs that might act by alternate mechanisms of action, but nothing’s really gotten to market for schizophrenia,” he noted.

Another interesting aspect of the study is that it examined a combination drug that aims to maximize effects on the brain while minimizing periphery effects, Dr. Sedlak said.

In addition, he called the PANSS results “respectable.”

“It’s interesting that you get a big change in PANSS total score, but it’s not as big in the positive symptom score as you might have expected, and it’s not a huge drop in negative symptoms either,” said Dr. Sedlak.

It’s possible, he said, that the drug is targeting PANSS elements not captured in the main positive or negative symptom items; for example, anxiety, depression, guilt, attention, impulse control, disorientation, and judgment.

Dr. Sedlak noted that, while the new results are exciting, the enthusiasm may not be long-lasting. “When a new drug comes out, there’s often a lot of excitement about it, but once you start using it, expectations may deflate..

“More flexible ratios” of the two components of the drug might be useful to treat individual patients, he added.

In addition, using the components by themselves might be preferable for some clinicians. “I think a lot of physicians prefer using two separate drugs so they can alter the dose of each one independently and not be stuck with the ratio the manufacturer is providing,” Dr. Sedlak said.

However, he acknowledged that studying different choices of ratios would require much larger trials.

The study was supported by Karuna Therapeutics and the Wellcome Trust. Dr. Lieberman reported serving on an advisory board for Karuna Therapeutics and Intra-Cellular Therapies. Dr. Sedlak disclosed no relevant financial relationships.

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

In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.

“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”

Getting adequate sleep is especially challenging for patients with AD, and loss of sleep can have serious daytime consequences. In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).

In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
 

Behavioral, neurocognitive effects

In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.

In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.

In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).

“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
 

Impact on depression, anxiety

Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).

“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”

The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).

“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”

Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.

“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).

“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”

Dr. Bender reported having no financial disclosures.

[email protected]

In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.

“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”

Getting adequate sleep is especially challenging for patients with AD, and loss of sleep can have serious daytime consequences. In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).

In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
 

Behavioral, neurocognitive effects

In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.

In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.

In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).

“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
 

Impact on depression, anxiety

Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).

“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”

The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).

“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”

Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.

“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).

“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”

Dr. Bender reported having no financial disclosures.

[email protected]

In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.

“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”

Getting adequate sleep is especially challenging for patients with AD, and loss of sleep can have serious daytime consequences. In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).

In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
 

Behavioral, neurocognitive effects

In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.

In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.

In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).

“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
 

Impact on depression, anxiety

Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).

“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”

The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).

“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”

Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.

“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).

“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”

Dr. Bender reported having no financial disclosures.

[email protected]

When patients relay their fantasies during psychotherapy sessions, those visions are often rooted in frustration or wish fulfillment, according to Jessica Ferranti, MD.

“[Sigmund] Freud talked about how our fantasy life is invested with large amounts of energy and interest and conveys a true essence of our personality – a truth about what we’re thinking and who we are,” Dr. Ferranti, a forensic psychiatrist in the division of psychiatry and the law at the University of California, Davis, said during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“Fantasy life is one of the most important conveyances of information that we can get from our patients, whether in the general office or in the forensic realm – if we can access it, which is difficult, because fantasies are often intensely personal. They fall into the category of very high resistance topics with many patients.”

Psychiatrists routinely ask about violent thoughts and homicidal ideation, but violent fantasies – especially those that are sexually violent in nature – can be a warning sign of future danger. Dr. Ferranti defined violent fantasies as those depicting the use of physical force with the intent to injure another person or destroy property.

“This would be an individual who fantasizes about sadistically raping a woman, for instance,” said Dr. Ferranti, who directs the UC Davis Workplace Safety and Psychiatric Assessment Clinic. “That is an ominous and psychopathological sign in terms of the preoccupation with that kind of violent crime.”

Aggression, on the other hand, “is a very broad spectrum, with actions like assertion, interpersonal confrontation, or verbal expressions that are angry or hostile, but that do not necessarily lead to violence.”

Dr. Ferranti acknowledged that today’s rushed clinical environment makes it challenging for psychiatrists and psychologists to get patients to share detailed fantasies they may be harboring.

“It’s very difficult to get to deeper material with patients, unless potentially you have more intensive therapy going on, like a psychotherapeutic relationship where you see the patient frequently, an intensive treatment, [or] perhaps an inpatient hospitalization or a partial day program.” The key is that “the patient gets comfortable with relaying more of the truth about what they’re experiencing,” she said. “In some cases, this occurs during the forensic evaluation, because we have the luxury to do very lengthy evaluations. Under the stress of being with another person in the room for many hours, oftentimes the patient will disclose things eventually.

“I’ve been a forensic psychiatrist for the better part of 12 years, and I can tell you after hundreds of evaluations I’ve never had a person not speak. That’s a good thing, because a principle of the work we do, or talk therapy even, is that the things that we can put into words, we are less likely to act out. When we lose symbolism, the ability to represent things in our mind and speak about them, we are at greater risk of collapsing into the real and acting on the things we think about.”

Statutory reporting duties vary from state to state. In California, mandatory reporting duties include child abuse, elder abuse, abuse or neglect of developmentally disabled individuals, domestic violence, and victims of a gunshot wound. “Failing to report any of these crimes is a misdemeanor in California,” she said. “With all these statutory reporting duties, we have no legal obligation to inform the patient of the report. Under California law, patients do not have the right to refuse the report. These are reports we make in our best judgment, whether the patient is happy about that or not.”

What happens if your patient confesses to a past crime? “There’s no legal duty to report this,” Dr. Ferranti said. “The general rule is, unless there’s a current person who’s at risk, it would be violating confidentiality to report. This includes murder, bank robbery, and sexual assault. In addition, you cannot admit a patient to an inpatient setting to help them avoid arrest, even if you think the act in question was due to symptoms of a mental disorder, disease, or defect. You can actually be charged with aiding and abetting a criminal.”

In the 1976 landmark case Tarasoff v. the Regents of the University of California, the California Supreme Court ruled that psychiatrists and other therapists have a duty to do what is reasonably necessary to protect third parties if a patient presents a serious risk of violence to another person.

“Reasonable steps may include warning the third party, notifying police, detaining and hospitalizing the patient, intensifying the treatment to a higher level of care or more frequent outpatient appointments, removing weapons, and changing the medication therapy,” Dr. Ferranti said. “The more you can do of these, the better.”

She also discussed the concept of foreseeability, which she defined as the reasonable anticipation that harm or injury is likely to result from an act or omission to act.

“This is the malpractice standard for negligence,” she said. “In other words, was it foreseeable by a reasonable psychiatrist that this person was going to hurt someone else or themselves?” Another landmark case, Jablonski Pahls v. the United States broadened the reporting obligations of psychiatrists. In this 1983 case, the U.S. Court of Appeals 9th Circuit ruled that mental health professionals have to do more than warn foreseeable victims of an imminent danger of potential harm; they must involuntarily hospitalize the dangerous individual and consult that person’s prior records.

There is no sure-fire way to predict when an individual’s underlying violent fantasies are likely to be acted on, but Dr. Ferranti mentioned several behaviors that should raise alarm. One is a heightened physiological arousal when the person discusses the fantasy, such as rapid heartbeat, sweating; or physical posturing, such as clenching their fists or pounding their hands on an object as they tell you about it. You also want to determine the persistence of the fantasy.

“Can the patient think about it?” she asked. “Can they retain the ability to symbolize and separate themselves from necessarily doing whatever it is they think about?” You also want to determine the individual’s propensity for externalizing behaviors. “Here we’re talking about cluster B personality group patients – antisocial, narcissistic, and borderline patients who by virtue of their aggressivity titer and difficulties with anger, have a higher propensity for acting out and acting violently.”

Then there’s the concept of foreseeability. “Ask yourself, how likely is it that this could actually happen, based on the known risk factors and what you know about the patient?” Dr. Ferranti said. “Past history of violence is also very important. What people have done once before, they’re likely to do again.”

A good violence risk assessment can help you mitigate the potential for one of your patients to carry out harm to self or to others. Key risk factors include psychopathy, past violence, substance abuse, specific person/entity threatened, a history of impulsivity, unemployment, military history, gun possession, and the presence of paranoid and/or persecutory ideation or delusions.

“Know your specific state statutes and case law,” Dr. Ferranti concluded. “Delaying Tarasoff notification may indicate no need to violate confidentiality. If you think it’s warranted, do it without delay. Documentation is important when you’re consulting with therapists back and forth. You also want to attempt to obtain prior records and release only information that is required in a case of violence toward others. The details of the therapy or diagnosis are likely not relevant.”

Dr. Ferranti reported having no disclosures.

[email protected]

When patients relay their fantasies during psychotherapy sessions, those visions are often rooted in frustration or wish fulfillment, according to Jessica Ferranti, MD.

“[Sigmund] Freud talked about how our fantasy life is invested with large amounts of energy and interest and conveys a true essence of our personality – a truth about what we’re thinking and who we are,” Dr. Ferranti, a forensic psychiatrist in the division of psychiatry and the law at the University of California, Davis, said during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“Fantasy life is one of the most important conveyances of information that we can get from our patients, whether in the general office or in the forensic realm – if we can access it, which is difficult, because fantasies are often intensely personal. They fall into the category of very high resistance topics with many patients.”

Psychiatrists routinely ask about violent thoughts and homicidal ideation, but violent fantasies – especially those that are sexually violent in nature – can be a warning sign of future danger. Dr. Ferranti defined violent fantasies as those depicting the use of physical force with the intent to injure another person or destroy property.

“This would be an individual who fantasizes about sadistically raping a woman, for instance,” said Dr. Ferranti, who directs the UC Davis Workplace Safety and Psychiatric Assessment Clinic. “That is an ominous and psychopathological sign in terms of the preoccupation with that kind of violent crime.”

Aggression, on the other hand, “is a very broad spectrum, with actions like assertion, interpersonal confrontation, or verbal expressions that are angry or hostile, but that do not necessarily lead to violence.”

Dr. Ferranti acknowledged that today’s rushed clinical environment makes it challenging for psychiatrists and psychologists to get patients to share detailed fantasies they may be harboring.

“It’s very difficult to get to deeper material with patients, unless potentially you have more intensive therapy going on, like a psychotherapeutic relationship where you see the patient frequently, an intensive treatment, [or] perhaps an inpatient hospitalization or a partial day program.” The key is that “the patient gets comfortable with relaying more of the truth about what they’re experiencing,” she said. “In some cases, this occurs during the forensic evaluation, because we have the luxury to do very lengthy evaluations. Under the stress of being with another person in the room for many hours, oftentimes the patient will disclose things eventually.

“I’ve been a forensic psychiatrist for the better part of 12 years, and I can tell you after hundreds of evaluations I’ve never had a person not speak. That’s a good thing, because a principle of the work we do, or talk therapy even, is that the things that we can put into words, we are less likely to act out. When we lose symbolism, the ability to represent things in our mind and speak about them, we are at greater risk of collapsing into the real and acting on the things we think about.”

Statutory reporting duties vary from state to state. In California, mandatory reporting duties include child abuse, elder abuse, abuse or neglect of developmentally disabled individuals, domestic violence, and victims of a gunshot wound. “Failing to report any of these crimes is a misdemeanor in California,” she said. “With all these statutory reporting duties, we have no legal obligation to inform the patient of the report. Under California law, patients do not have the right to refuse the report. These are reports we make in our best judgment, whether the patient is happy about that or not.”

What happens if your patient confesses to a past crime? “There’s no legal duty to report this,” Dr. Ferranti said. “The general rule is, unless there’s a current person who’s at risk, it would be violating confidentiality to report. This includes murder, bank robbery, and sexual assault. In addition, you cannot admit a patient to an inpatient setting to help them avoid arrest, even if you think the act in question was due to symptoms of a mental disorder, disease, or defect. You can actually be charged with aiding and abetting a criminal.”

In the 1976 landmark case Tarasoff v. the Regents of the University of California, the California Supreme Court ruled that psychiatrists and other therapists have a duty to do what is reasonably necessary to protect third parties if a patient presents a serious risk of violence to another person.

“Reasonable steps may include warning the third party, notifying police, detaining and hospitalizing the patient, intensifying the treatment to a higher level of care or more frequent outpatient appointments, removing weapons, and changing the medication therapy,” Dr. Ferranti said. “The more you can do of these, the better.”

She also discussed the concept of foreseeability, which she defined as the reasonable anticipation that harm or injury is likely to result from an act or omission to act.

“This is the malpractice standard for negligence,” she said. “In other words, was it foreseeable by a reasonable psychiatrist that this person was going to hurt someone else or themselves?” Another landmark case, Jablonski Pahls v. the United States broadened the reporting obligations of psychiatrists. In this 1983 case, the U.S. Court of Appeals 9th Circuit ruled that mental health professionals have to do more than warn foreseeable victims of an imminent danger of potential harm; they must involuntarily hospitalize the dangerous individual and consult that person’s prior records.

There is no sure-fire way to predict when an individual’s underlying violent fantasies are likely to be acted on, but Dr. Ferranti mentioned several behaviors that should raise alarm. One is a heightened physiological arousal when the person discusses the fantasy, such as rapid heartbeat, sweating; or physical posturing, such as clenching their fists or pounding their hands on an object as they tell you about it. You also want to determine the persistence of the fantasy.

“Can the patient think about it?” she asked. “Can they retain the ability to symbolize and separate themselves from necessarily doing whatever it is they think about?” You also want to determine the individual’s propensity for externalizing behaviors. “Here we’re talking about cluster B personality group patients – antisocial, narcissistic, and borderline patients who by virtue of their aggressivity titer and difficulties with anger, have a higher propensity for acting out and acting violently.”

Then there’s the concept of foreseeability. “Ask yourself, how likely is it that this could actually happen, based on the known risk factors and what you know about the patient?” Dr. Ferranti said. “Past history of violence is also very important. What people have done once before, they’re likely to do again.”

A good violence risk assessment can help you mitigate the potential for one of your patients to carry out harm to self or to others. Key risk factors include psychopathy, past violence, substance abuse, specific person/entity threatened, a history of impulsivity, unemployment, military history, gun possession, and the presence of paranoid and/or persecutory ideation or delusions.

“Know your specific state statutes and case law,” Dr. Ferranti concluded. “Delaying Tarasoff notification may indicate no need to violate confidentiality. If you think it’s warranted, do it without delay. Documentation is important when you’re consulting with therapists back and forth. You also want to attempt to obtain prior records and release only information that is required in a case of violence toward others. The details of the therapy or diagnosis are likely not relevant.”

Dr. Ferranti reported having no disclosures.

[email protected]

When patients relay their fantasies during psychotherapy sessions, those visions are often rooted in frustration or wish fulfillment, according to Jessica Ferranti, MD.

“[Sigmund] Freud talked about how our fantasy life is invested with large amounts of energy and interest and conveys a true essence of our personality – a truth about what we’re thinking and who we are,” Dr. Ferranti, a forensic psychiatrist in the division of psychiatry and the law at the University of California, Davis, said during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“Fantasy life is one of the most important conveyances of information that we can get from our patients, whether in the general office or in the forensic realm – if we can access it, which is difficult, because fantasies are often intensely personal. They fall into the category of very high resistance topics with many patients.”

Psychiatrists routinely ask about violent thoughts and homicidal ideation, but violent fantasies – especially those that are sexually violent in nature – can be a warning sign of future danger. Dr. Ferranti defined violent fantasies as those depicting the use of physical force with the intent to injure another person or destroy property.

“This would be an individual who fantasizes about sadistically raping a woman, for instance,” said Dr. Ferranti, who directs the UC Davis Workplace Safety and Psychiatric Assessment Clinic. “That is an ominous and psychopathological sign in terms of the preoccupation with that kind of violent crime.”

Aggression, on the other hand, “is a very broad spectrum, with actions like assertion, interpersonal confrontation, or verbal expressions that are angry or hostile, but that do not necessarily lead to violence.”

Dr. Ferranti acknowledged that today’s rushed clinical environment makes it challenging for psychiatrists and psychologists to get patients to share detailed fantasies they may be harboring.

“It’s very difficult to get to deeper material with patients, unless potentially you have more intensive therapy going on, like a psychotherapeutic relationship where you see the patient frequently, an intensive treatment, [or] perhaps an inpatient hospitalization or a partial day program.” The key is that “the patient gets comfortable with relaying more of the truth about what they’re experiencing,” she said. “In some cases, this occurs during the forensic evaluation, because we have the luxury to do very lengthy evaluations. Under the stress of being with another person in the room for many hours, oftentimes the patient will disclose things eventually.

“I’ve been a forensic psychiatrist for the better part of 12 years, and I can tell you after hundreds of evaluations I’ve never had a person not speak. That’s a good thing, because a principle of the work we do, or talk therapy even, is that the things that we can put into words, we are less likely to act out. When we lose symbolism, the ability to represent things in our mind and speak about them, we are at greater risk of collapsing into the real and acting on the things we think about.”

Statutory reporting duties vary from state to state. In California, mandatory reporting duties include child abuse, elder abuse, abuse or neglect of developmentally disabled individuals, domestic violence, and victims of a gunshot wound. “Failing to report any of these crimes is a misdemeanor in California,” she said. “With all these statutory reporting duties, we have no legal obligation to inform the patient of the report. Under California law, patients do not have the right to refuse the report. These are reports we make in our best judgment, whether the patient is happy about that or not.”

What happens if your patient confesses to a past crime? “There’s no legal duty to report this,” Dr. Ferranti said. “The general rule is, unless there’s a current person who’s at risk, it would be violating confidentiality to report. This includes murder, bank robbery, and sexual assault. In addition, you cannot admit a patient to an inpatient setting to help them avoid arrest, even if you think the act in question was due to symptoms of a mental disorder, disease, or defect. You can actually be charged with aiding and abetting a criminal.”

In the 1976 landmark case Tarasoff v. the Regents of the University of California, the California Supreme Court ruled that psychiatrists and other therapists have a duty to do what is reasonably necessary to protect third parties if a patient presents a serious risk of violence to another person.

“Reasonable steps may include warning the third party, notifying police, detaining and hospitalizing the patient, intensifying the treatment to a higher level of care or more frequent outpatient appointments, removing weapons, and changing the medication therapy,” Dr. Ferranti said. “The more you can do of these, the better.”

She also discussed the concept of foreseeability, which she defined as the reasonable anticipation that harm or injury is likely to result from an act or omission to act.

“This is the malpractice standard for negligence,” she said. “In other words, was it foreseeable by a reasonable psychiatrist that this person was going to hurt someone else or themselves?” Another landmark case, Jablonski Pahls v. the United States broadened the reporting obligations of psychiatrists. In this 1983 case, the U.S. Court of Appeals 9th Circuit ruled that mental health professionals have to do more than warn foreseeable victims of an imminent danger of potential harm; they must involuntarily hospitalize the dangerous individual and consult that person’s prior records.

There is no sure-fire way to predict when an individual’s underlying violent fantasies are likely to be acted on, but Dr. Ferranti mentioned several behaviors that should raise alarm. One is a heightened physiological arousal when the person discusses the fantasy, such as rapid heartbeat, sweating; or physical posturing, such as clenching their fists or pounding their hands on an object as they tell you about it. You also want to determine the persistence of the fantasy.

“Can the patient think about it?” she asked. “Can they retain the ability to symbolize and separate themselves from necessarily doing whatever it is they think about?” You also want to determine the individual’s propensity for externalizing behaviors. “Here we’re talking about cluster B personality group patients – antisocial, narcissistic, and borderline patients who by virtue of their aggressivity titer and difficulties with anger, have a higher propensity for acting out and acting violently.”

Then there’s the concept of foreseeability. “Ask yourself, how likely is it that this could actually happen, based on the known risk factors and what you know about the patient?” Dr. Ferranti said. “Past history of violence is also very important. What people have done once before, they’re likely to do again.”

A good violence risk assessment can help you mitigate the potential for one of your patients to carry out harm to self or to others. Key risk factors include psychopathy, past violence, substance abuse, specific person/entity threatened, a history of impulsivity, unemployment, military history, gun possession, and the presence of paranoid and/or persecutory ideation or delusions.

“Know your specific state statutes and case law,” Dr. Ferranti concluded. “Delaying Tarasoff notification may indicate no need to violate confidentiality. If you think it’s warranted, do it without delay. Documentation is important when you’re consulting with therapists back and forth. You also want to attempt to obtain prior records and release only information that is required in a case of violence toward others. The details of the therapy or diagnosis are likely not relevant.”

Dr. Ferranti reported having no disclosures.

[email protected]

Patients with severe asthma and comorbid atopy, obesity, and depression/anxiety had fewer annual exacerbations after receiving mepolizumab, according to research from the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“Mepolizumab has clearly been shown to improve severe asthma control in many clinical trials, but atopy, obesity, and depression/anxiety affect patients with asthma at an increased rate,” Thomas B. Casale, MD, former AAAAI president and professor of medicine and pediatrics at the University of South Florida in Tampa, said in a presentation at the meeting. “Yet, few studies have examined whether asthma therapy with these comorbidities works.”

Dr. Casale and colleagues performed a retrospective analysis of patients in the United States from the MarketScan Commercial and Medicare Supplemental Database between November 2014 and December 2018 who had atopy, obesity, or depression/anxiety in addition to asthma and were receiving mepolizumab. Atopy in the study was defined as allergic rhinitis, anaphylaxis, atopic dermatitis, conjunctivitis, eosinophilic esophagitis, and food allergies. Patients were at least age 12 years, had at least one diagnosis for asthma, at least one diagnosis code for atopic disease, obesity, or depression/anxiety at baseline, and at least two administrations of mepolizumab within 180 days.

The researchers examined the number of exacerbations, oral corticosteroid (OCS) claims, and OCS bursts per year at 12-month follow-up, compared with baseline. They identified exacerbations by examining patients who had an emergency department or outpatient claim related to their asthma, and a claim for systemic corticosteroids made in the 4 days prior to or 5 days after a visit, or if their inpatient hospital admission contained a primary asthma diagnosis. Dr. Casale and colleagues measured OCS bursts as a pharmacy claim of at least 20 mg of prednisone per day for between 3 and 28 days plus a claim for an emergency department visit related to asthma in the 7 days prior or 6 days after the claim.

At baseline, patients across all groups were mean age 50.5-52.4 years with a Charleson Comorbidity Index score between 1.1 and 1.4, a majority were women (59.0%-72.0%) and nearly all were commercially insured (88.0%-90.0%). Patients who used biologics at baseline and/or used a biologic that wasn’t mepolizumab during the follow-up period were excluded.

Medication claims in the groups included inhaled corticosteroids (ICS) (36.8%-48.6%), ICS/long-acting beta-agonist (LABA) (60.2%-63.0%), LABA/ long-acting muscarinic antagonist (LAMA) (1.2%-3.5%), ICS/LABA/LAMA (21.2%-25.1%), short-acting beta-agonist (SABA) (83.2%-87.7%), LAMA alone (33.5%-42.1%), or leukotriene receptor antagonist (LTRA).

In the non–mutually exclusive group of patients with atopy (468 patients), 28.0% had comorbid obesity and 26.0% had comorbid depression/anxiety. For patients with obesity categorized in a non–mutually exclusive subgroup (171 patients), 79.0% had comorbid atopy and 32.0% had comorbid depression/anxiety. Among patients with non–mutually exclusive depression/anxiety (173 patients), 70.0% had comorbid atopy, while 32.0% had comorbid obesity.

The results showed the mean number of overall exacerbations decreased by 48% at 12 months in the atopic group (2.3 vs. 1.2; P < .001), 52% in the group with obesity (2.5 vs. 1.2; P < .001), and 38% in the depression/anxiety group (2.4 vs. 1.5; P < .001). The mean number of exacerbations leading to hospitalizations decreased by 64% in the atopic group (0.11 vs. 0.04; P < .001), 65% in the group with obesity (0.20 vs. 0.07; P < .001), and 68% in the group with depression/anxiety (0.22 vs. 0.07; P < .001).

The researchers also found the mean number of OCS claims and OCS bursts also significantly decreased over the 12-month follow-up period. Mean OCS claims decreased by 33% for patients in the atopic group (5.5 vs. 3.7; P < .001), by 38% in the group with obesity (6.1 vs. 3.8; P < .001), and by 31% in the group with depression/anxiety (6.2 vs. 4.3; P < .001).

The mean number of OCS bursts also significantly decreased by 40% in the atopic group (2.0 vs. 2.1; P < .001), 48% in the group with obesity (2.3 vs. 1.2; P < .001), and by 37% in the group with depression/anxiety (1.9 vs. 1.2; P < .001). In total, 69% of patients with comorbid atopy, 70.8% of patients with comorbid obesity, and 68.2% of patients with comorbid depression/anxiety experienced a mean decrease in their OCS dose over 12 months.

“These data demonstrate that patients with asthma and atopy, obesity, or depression and anxiety have significantly fewer exacerbations and reduced OCS use in a real-world setting with treatment of mepolizumab,” Dr. Casale said. “Thus, holistic patient care for severe asthma is critical, and mepolizumab provides tangible clinical benefit despite the complexities of medical comorbidities.”

This study was funded by GlaxoSmithKline, and the company also funded graphic design support of the poster. Dr. Casale reports he has received research funds from GlaxoSmithKline. Four authors report being current or former GlaxoSmithKline employees; three authors report holding stock and/or shares of GlaxoSmithKline. Three authors are IBM Watson Health employees, a company GlaxoSmithKline has provided research funding.

Patients with severe asthma and comorbid atopy, obesity, and depression/anxiety had fewer annual exacerbations after receiving mepolizumab, according to research from the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“Mepolizumab has clearly been shown to improve severe asthma control in many clinical trials, but atopy, obesity, and depression/anxiety affect patients with asthma at an increased rate,” Thomas B. Casale, MD, former AAAAI president and professor of medicine and pediatrics at the University of South Florida in Tampa, said in a presentation at the meeting. “Yet, few studies have examined whether asthma therapy with these comorbidities works.”

Dr. Casale and colleagues performed a retrospective analysis of patients in the United States from the MarketScan Commercial and Medicare Supplemental Database between November 2014 and December 2018 who had atopy, obesity, or depression/anxiety in addition to asthma and were receiving mepolizumab. Atopy in the study was defined as allergic rhinitis, anaphylaxis, atopic dermatitis, conjunctivitis, eosinophilic esophagitis, and food allergies. Patients were at least age 12 years, had at least one diagnosis for asthma, at least one diagnosis code for atopic disease, obesity, or depression/anxiety at baseline, and at least two administrations of mepolizumab within 180 days.

The researchers examined the number of exacerbations, oral corticosteroid (OCS) claims, and OCS bursts per year at 12-month follow-up, compared with baseline. They identified exacerbations by examining patients who had an emergency department or outpatient claim related to their asthma, and a claim for systemic corticosteroids made in the 4 days prior to or 5 days after a visit, or if their inpatient hospital admission contained a primary asthma diagnosis. Dr. Casale and colleagues measured OCS bursts as a pharmacy claim of at least 20 mg of prednisone per day for between 3 and 28 days plus a claim for an emergency department visit related to asthma in the 7 days prior or 6 days after the claim.

At baseline, patients across all groups were mean age 50.5-52.4 years with a Charleson Comorbidity Index score between 1.1 and 1.4, a majority were women (59.0%-72.0%) and nearly all were commercially insured (88.0%-90.0%). Patients who used biologics at baseline and/or used a biologic that wasn’t mepolizumab during the follow-up period were excluded.

Medication claims in the groups included inhaled corticosteroids (ICS) (36.8%-48.6%), ICS/long-acting beta-agonist (LABA) (60.2%-63.0%), LABA/ long-acting muscarinic antagonist (LAMA) (1.2%-3.5%), ICS/LABA/LAMA (21.2%-25.1%), short-acting beta-agonist (SABA) (83.2%-87.7%), LAMA alone (33.5%-42.1%), or leukotriene receptor antagonist (LTRA).

In the non–mutually exclusive group of patients with atopy (468 patients), 28.0% had comorbid obesity and 26.0% had comorbid depression/anxiety. For patients with obesity categorized in a non–mutually exclusive subgroup (171 patients), 79.0% had comorbid atopy and 32.0% had comorbid depression/anxiety. Among patients with non–mutually exclusive depression/anxiety (173 patients), 70.0% had comorbid atopy, while 32.0% had comorbid obesity.

The results showed the mean number of overall exacerbations decreased by 48% at 12 months in the atopic group (2.3 vs. 1.2; P < .001), 52% in the group with obesity (2.5 vs. 1.2; P < .001), and 38% in the depression/anxiety group (2.4 vs. 1.5; P < .001). The mean number of exacerbations leading to hospitalizations decreased by 64% in the atopic group (0.11 vs. 0.04; P < .001), 65% in the group with obesity (0.20 vs. 0.07; P < .001), and 68% in the group with depression/anxiety (0.22 vs. 0.07; P < .001).

The researchers also found the mean number of OCS claims and OCS bursts also significantly decreased over the 12-month follow-up period. Mean OCS claims decreased by 33% for patients in the atopic group (5.5 vs. 3.7; P < .001), by 38% in the group with obesity (6.1 vs. 3.8; P < .001), and by 31% in the group with depression/anxiety (6.2 vs. 4.3; P < .001).

The mean number of OCS bursts also significantly decreased by 40% in the atopic group (2.0 vs. 2.1; P < .001), 48% in the group with obesity (2.3 vs. 1.2; P < .001), and by 37% in the group with depression/anxiety (1.9 vs. 1.2; P < .001). In total, 69% of patients with comorbid atopy, 70.8% of patients with comorbid obesity, and 68.2% of patients with comorbid depression/anxiety experienced a mean decrease in their OCS dose over 12 months.

“These data demonstrate that patients with asthma and atopy, obesity, or depression and anxiety have significantly fewer exacerbations and reduced OCS use in a real-world setting with treatment of mepolizumab,” Dr. Casale said. “Thus, holistic patient care for severe asthma is critical, and mepolizumab provides tangible clinical benefit despite the complexities of medical comorbidities.”

This study was funded by GlaxoSmithKline, and the company also funded graphic design support of the poster. Dr. Casale reports he has received research funds from GlaxoSmithKline. Four authors report being current or former GlaxoSmithKline employees; three authors report holding stock and/or shares of GlaxoSmithKline. Three authors are IBM Watson Health employees, a company GlaxoSmithKline has provided research funding.

Patients with severe asthma and comorbid atopy, obesity, and depression/anxiety had fewer annual exacerbations after receiving mepolizumab, according to research from the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“Mepolizumab has clearly been shown to improve severe asthma control in many clinical trials, but atopy, obesity, and depression/anxiety affect patients with asthma at an increased rate,” Thomas B. Casale, MD, former AAAAI president and professor of medicine and pediatrics at the University of South Florida in Tampa, said in a presentation at the meeting. “Yet, few studies have examined whether asthma therapy with these comorbidities works.”

Dr. Casale and colleagues performed a retrospective analysis of patients in the United States from the MarketScan Commercial and Medicare Supplemental Database between November 2014 and December 2018 who had atopy, obesity, or depression/anxiety in addition to asthma and were receiving mepolizumab. Atopy in the study was defined as allergic rhinitis, anaphylaxis, atopic dermatitis, conjunctivitis, eosinophilic esophagitis, and food allergies. Patients were at least age 12 years, had at least one diagnosis for asthma, at least one diagnosis code for atopic disease, obesity, or depression/anxiety at baseline, and at least two administrations of mepolizumab within 180 days.

The researchers examined the number of exacerbations, oral corticosteroid (OCS) claims, and OCS bursts per year at 12-month follow-up, compared with baseline. They identified exacerbations by examining patients who had an emergency department or outpatient claim related to their asthma, and a claim for systemic corticosteroids made in the 4 days prior to or 5 days after a visit, or if their inpatient hospital admission contained a primary asthma diagnosis. Dr. Casale and colleagues measured OCS bursts as a pharmacy claim of at least 20 mg of prednisone per day for between 3 and 28 days plus a claim for an emergency department visit related to asthma in the 7 days prior or 6 days after the claim.

At baseline, patients across all groups were mean age 50.5-52.4 years with a Charleson Comorbidity Index score between 1.1 and 1.4, a majority were women (59.0%-72.0%) and nearly all were commercially insured (88.0%-90.0%). Patients who used biologics at baseline and/or used a biologic that wasn’t mepolizumab during the follow-up period were excluded.

Medication claims in the groups included inhaled corticosteroids (ICS) (36.8%-48.6%), ICS/long-acting beta-agonist (LABA) (60.2%-63.0%), LABA/ long-acting muscarinic antagonist (LAMA) (1.2%-3.5%), ICS/LABA/LAMA (21.2%-25.1%), short-acting beta-agonist (SABA) (83.2%-87.7%), LAMA alone (33.5%-42.1%), or leukotriene receptor antagonist (LTRA).

In the non–mutually exclusive group of patients with atopy (468 patients), 28.0% had comorbid obesity and 26.0% had comorbid depression/anxiety. For patients with obesity categorized in a non–mutually exclusive subgroup (171 patients), 79.0% had comorbid atopy and 32.0% had comorbid depression/anxiety. Among patients with non–mutually exclusive depression/anxiety (173 patients), 70.0% had comorbid atopy, while 32.0% had comorbid obesity.

The results showed the mean number of overall exacerbations decreased by 48% at 12 months in the atopic group (2.3 vs. 1.2; P < .001), 52% in the group with obesity (2.5 vs. 1.2; P < .001), and 38% in the depression/anxiety group (2.4 vs. 1.5; P < .001). The mean number of exacerbations leading to hospitalizations decreased by 64% in the atopic group (0.11 vs. 0.04; P < .001), 65% in the group with obesity (0.20 vs. 0.07; P < .001), and 68% in the group with depression/anxiety (0.22 vs. 0.07; P < .001).

The researchers also found the mean number of OCS claims and OCS bursts also significantly decreased over the 12-month follow-up period. Mean OCS claims decreased by 33% for patients in the atopic group (5.5 vs. 3.7; P < .001), by 38% in the group with obesity (6.1 vs. 3.8; P < .001), and by 31% in the group with depression/anxiety (6.2 vs. 4.3; P < .001).

The mean number of OCS bursts also significantly decreased by 40% in the atopic group (2.0 vs. 2.1; P < .001), 48% in the group with obesity (2.3 vs. 1.2; P < .001), and by 37% in the group with depression/anxiety (1.9 vs. 1.2; P < .001). In total, 69% of patients with comorbid atopy, 70.8% of patients with comorbid obesity, and 68.2% of patients with comorbid depression/anxiety experienced a mean decrease in their OCS dose over 12 months.

“These data demonstrate that patients with asthma and atopy, obesity, or depression and anxiety have significantly fewer exacerbations and reduced OCS use in a real-world setting with treatment of mepolizumab,” Dr. Casale said. “Thus, holistic patient care for severe asthma is critical, and mepolizumab provides tangible clinical benefit despite the complexities of medical comorbidities.”

This study was funded by GlaxoSmithKline, and the company also funded graphic design support of the poster. Dr. Casale reports he has received research funds from GlaxoSmithKline. Four authors report being current or former GlaxoSmithKline employees; three authors report holding stock and/or shares of GlaxoSmithKline. Three authors are IBM Watson Health employees, a company GlaxoSmithKline has provided research funding.

Stroke, dementias, and migraine cause the most disability among neurological disorders in the United States, according to new findings derived from the 2017 Global Burden of Disease study. 

The authors of the analysis, led by Valery Feigin, MD, PhD, of New Zealand’s National Institute for Stroke and Applied Neurosciences, and published in the February 2021 issue of JAMA Neurology, looked at prevalence, incidence, mortality, and disability-adjusted life years for 14 neurological disorders across 50 states between 1990 and 2017. The diseases included in the analysis were stroke, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, headaches, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.
 

Tracking the burden of neurologic diseases

Dr. Feigin and colleagues estimated that a full 60% of the U.S. population lives with one or more of these disorders, a figure much greater than previous estimates for neurological disease burden nationwide. Tension-type headache and migraine were the most prevalent in the analysis by Dr. Feigin and colleagues. During the study period, they found, prevalence, incidence, and disability burden of nearly all the included disorders increased, with the exception of brain and spinal cord injuries, meningitis, and encephalitis.

The researchers attributed most of the rise in noncommunicable neurological diseases to population aging. An age-standardized analysis found trends for stroke and Alzheimer’s disease and other dementias to be declining or flat. Age-standardized stroke incidence dropped by 16% from 1990 to 2017, while stroke mortality declined by nearly a third, and stroke disability by a quarter. Age-standardized incidence of Alzheimer’s disease and other dementias dropped by 12%, and their prevalence by 13%, during the study period, though dementia mortality and disability were seen increasing.

The authors surmised that the age-standardized declines in stroke and dementias could reflect that “primary prevention of these disorders are beginning to show an influence.” With dementia, which is linked to cognitive reserve and education, “improving educational levels of cohort reaching the age groups at greatest risk of disease may also be contributing to a modest decline over time,” Dr. Feigin and his colleagues wrote.

Parkinson’s disease and multiple sclerosis, meanwhile, were both seen rising in incidence, prevalence, and disability adjusted life years (DALYs) even with age-standardized figures. The United States saw comparatively more disability in 2017 from dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, and headache disorders, which together comprised 6.7% of DALYs, compared with 4.4% globally; these also accounted for a higher share of mortality in the U.S. than worldwide. The authors attributed at least some of the difference to better case ascertainment in the U.S.
 

Regional variations

The researchers also reported variations in disease burden by state and region. While previous studies have identified a “stroke belt” concentrated in North Carolina, South Carolina, and Georgia, the new findings point to stroke disability highest in Alabama, Arkansas, and Mississippi, and mortality highest in Alabama, Mississippi, and South Carolina. The researchers noted increases in dementia mortality in these states, “likely attributable to the reciprocal association between stroke and dementia.”

Northern states saw higher burdens of multiple sclerosis compared with the rest of the country, while eastern states had higher rates of Parkinson’s disease.

Such regional and state-by state variations, Dr. Feigin and colleagues wrote in their analysis, “may be associated with differences in the case ascertainment, as well as access to health care; racial/ethnic, genetic, and socioeconomic diversity; quality and comprehensiveness of preventive strategies; and risk factor distribution.”

The researchers noted as a limitation of their study that the 14 diseases captured were not an exhaustive list of neurological conditions; chronic lower back pain, a condition included in a previous major study of the burden of neurological disease in the United States, was omitted, as were restless legs syndrome and peripheral neuropathy. The researchers cited changes to coding practice in the U.S. and accuracy of medical claims data as potential limitations of their analysis. The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation, and several of Dr. Feigin’s coauthors reported financial relationships with industry.
 

Time to adjust the stroke belt?

Amelia Boehme, PhD, a stroke epidemiologist at Columbia University Mailman School of Public Health in New York, said in an interview that the current study added to recent findings showing surprising local variability in stroke prevalence, incidence, and mortality. “What we had always conceptually thought of as the ‘stroke belt’ isn’t necessarily the case,” Dr. Boehme said, but is rather subject to local, county-by-county variations. “Looking at the data here in conjunction with what previous authors have found, it raises some questions as to whether or not state-level data is giving a completely accurate picture, and whether we need to start looking at the county level and adjust for populations and age.” Importantly, Dr. Boehme said, data collected in the Global Burden of Disease study tends to be exceptionally rigorous and systematic, adding weight to Dr. Feigin and colleagues’ suggestions that prevention efforts may be making a dent in stroke and dementia. 

“More data is always needed before we start to say we’re seeing things change,” Dr. Boehme noted. “But any glimmer of optimism is welcome, especially with regard to interventions that have been put in place, to allow us to build on those interventions.”

Dr. Boehme disclosed no financial conflicts of interest.

Stroke, dementias, and migraine cause the most disability among neurological disorders in the United States, according to new findings derived from the 2017 Global Burden of Disease study. 

The authors of the analysis, led by Valery Feigin, MD, PhD, of New Zealand’s National Institute for Stroke and Applied Neurosciences, and published in the February 2021 issue of JAMA Neurology, looked at prevalence, incidence, mortality, and disability-adjusted life years for 14 neurological disorders across 50 states between 1990 and 2017. The diseases included in the analysis were stroke, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, headaches, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.
 

Tracking the burden of neurologic diseases

Dr. Feigin and colleagues estimated that a full 60% of the U.S. population lives with one or more of these disorders, a figure much greater than previous estimates for neurological disease burden nationwide. Tension-type headache and migraine were the most prevalent in the analysis by Dr. Feigin and colleagues. During the study period, they found, prevalence, incidence, and disability burden of nearly all the included disorders increased, with the exception of brain and spinal cord injuries, meningitis, and encephalitis.

The researchers attributed most of the rise in noncommunicable neurological diseases to population aging. An age-standardized analysis found trends for stroke and Alzheimer’s disease and other dementias to be declining or flat. Age-standardized stroke incidence dropped by 16% from 1990 to 2017, while stroke mortality declined by nearly a third, and stroke disability by a quarter. Age-standardized incidence of Alzheimer’s disease and other dementias dropped by 12%, and their prevalence by 13%, during the study period, though dementia mortality and disability were seen increasing.

The authors surmised that the age-standardized declines in stroke and dementias could reflect that “primary prevention of these disorders are beginning to show an influence.” With dementia, which is linked to cognitive reserve and education, “improving educational levels of cohort reaching the age groups at greatest risk of disease may also be contributing to a modest decline over time,” Dr. Feigin and his colleagues wrote.

Parkinson’s disease and multiple sclerosis, meanwhile, were both seen rising in incidence, prevalence, and disability adjusted life years (DALYs) even with age-standardized figures. The United States saw comparatively more disability in 2017 from dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, and headache disorders, which together comprised 6.7% of DALYs, compared with 4.4% globally; these also accounted for a higher share of mortality in the U.S. than worldwide. The authors attributed at least some of the difference to better case ascertainment in the U.S.
 

Regional variations

The researchers also reported variations in disease burden by state and region. While previous studies have identified a “stroke belt” concentrated in North Carolina, South Carolina, and Georgia, the new findings point to stroke disability highest in Alabama, Arkansas, and Mississippi, and mortality highest in Alabama, Mississippi, and South Carolina. The researchers noted increases in dementia mortality in these states, “likely attributable to the reciprocal association between stroke and dementia.”

Northern states saw higher burdens of multiple sclerosis compared with the rest of the country, while eastern states had higher rates of Parkinson’s disease.

Such regional and state-by state variations, Dr. Feigin and colleagues wrote in their analysis, “may be associated with differences in the case ascertainment, as well as access to health care; racial/ethnic, genetic, and socioeconomic diversity; quality and comprehensiveness of preventive strategies; and risk factor distribution.”

The researchers noted as a limitation of their study that the 14 diseases captured were not an exhaustive list of neurological conditions; chronic lower back pain, a condition included in a previous major study of the burden of neurological disease in the United States, was omitted, as were restless legs syndrome and peripheral neuropathy. The researchers cited changes to coding practice in the U.S. and accuracy of medical claims data as potential limitations of their analysis. The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation, and several of Dr. Feigin’s coauthors reported financial relationships with industry.
 

Time to adjust the stroke belt?

Amelia Boehme, PhD, a stroke epidemiologist at Columbia University Mailman School of Public Health in New York, said in an interview that the current study added to recent findings showing surprising local variability in stroke prevalence, incidence, and mortality. “What we had always conceptually thought of as the ‘stroke belt’ isn’t necessarily the case,” Dr. Boehme said, but is rather subject to local, county-by-county variations. “Looking at the data here in conjunction with what previous authors have found, it raises some questions as to whether or not state-level data is giving a completely accurate picture, and whether we need to start looking at the county level and adjust for populations and age.” Importantly, Dr. Boehme said, data collected in the Global Burden of Disease study tends to be exceptionally rigorous and systematic, adding weight to Dr. Feigin and colleagues’ suggestions that prevention efforts may be making a dent in stroke and dementia. 

“More data is always needed before we start to say we’re seeing things change,” Dr. Boehme noted. “But any glimmer of optimism is welcome, especially with regard to interventions that have been put in place, to allow us to build on those interventions.”

Dr. Boehme disclosed no financial conflicts of interest.

Stroke, dementias, and migraine cause the most disability among neurological disorders in the United States, according to new findings derived from the 2017 Global Burden of Disease study. 

The authors of the analysis, led by Valery Feigin, MD, PhD, of New Zealand’s National Institute for Stroke and Applied Neurosciences, and published in the February 2021 issue of JAMA Neurology, looked at prevalence, incidence, mortality, and disability-adjusted life years for 14 neurological disorders across 50 states between 1990 and 2017. The diseases included in the analysis were stroke, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, headaches, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.
 

Tracking the burden of neurologic diseases

Dr. Feigin and colleagues estimated that a full 60% of the U.S. population lives with one or more of these disorders, a figure much greater than previous estimates for neurological disease burden nationwide. Tension-type headache and migraine were the most prevalent in the analysis by Dr. Feigin and colleagues. During the study period, they found, prevalence, incidence, and disability burden of nearly all the included disorders increased, with the exception of brain and spinal cord injuries, meningitis, and encephalitis.

The researchers attributed most of the rise in noncommunicable neurological diseases to population aging. An age-standardized analysis found trends for stroke and Alzheimer’s disease and other dementias to be declining or flat. Age-standardized stroke incidence dropped by 16% from 1990 to 2017, while stroke mortality declined by nearly a third, and stroke disability by a quarter. Age-standardized incidence of Alzheimer’s disease and other dementias dropped by 12%, and their prevalence by 13%, during the study period, though dementia mortality and disability were seen increasing.

The authors surmised that the age-standardized declines in stroke and dementias could reflect that “primary prevention of these disorders are beginning to show an influence.” With dementia, which is linked to cognitive reserve and education, “improving educational levels of cohort reaching the age groups at greatest risk of disease may also be contributing to a modest decline over time,” Dr. Feigin and his colleagues wrote.

Parkinson’s disease and multiple sclerosis, meanwhile, were both seen rising in incidence, prevalence, and disability adjusted life years (DALYs) even with age-standardized figures. The United States saw comparatively more disability in 2017 from dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, and headache disorders, which together comprised 6.7% of DALYs, compared with 4.4% globally; these also accounted for a higher share of mortality in the U.S. than worldwide. The authors attributed at least some of the difference to better case ascertainment in the U.S.
 

Regional variations

The researchers also reported variations in disease burden by state and region. While previous studies have identified a “stroke belt” concentrated in North Carolina, South Carolina, and Georgia, the new findings point to stroke disability highest in Alabama, Arkansas, and Mississippi, and mortality highest in Alabama, Mississippi, and South Carolina. The researchers noted increases in dementia mortality in these states, “likely attributable to the reciprocal association between stroke and dementia.”

Northern states saw higher burdens of multiple sclerosis compared with the rest of the country, while eastern states had higher rates of Parkinson’s disease.

Such regional and state-by state variations, Dr. Feigin and colleagues wrote in their analysis, “may be associated with differences in the case ascertainment, as well as access to health care; racial/ethnic, genetic, and socioeconomic diversity; quality and comprehensiveness of preventive strategies; and risk factor distribution.”

The researchers noted as a limitation of their study that the 14 diseases captured were not an exhaustive list of neurological conditions; chronic lower back pain, a condition included in a previous major study of the burden of neurological disease in the United States, was omitted, as were restless legs syndrome and peripheral neuropathy. The researchers cited changes to coding practice in the U.S. and accuracy of medical claims data as potential limitations of their analysis. The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation, and several of Dr. Feigin’s coauthors reported financial relationships with industry.
 

Time to adjust the stroke belt?

Amelia Boehme, PhD, a stroke epidemiologist at Columbia University Mailman School of Public Health in New York, said in an interview that the current study added to recent findings showing surprising local variability in stroke prevalence, incidence, and mortality. “What we had always conceptually thought of as the ‘stroke belt’ isn’t necessarily the case,” Dr. Boehme said, but is rather subject to local, county-by-county variations. “Looking at the data here in conjunction with what previous authors have found, it raises some questions as to whether or not state-level data is giving a completely accurate picture, and whether we need to start looking at the county level and adjust for populations and age.” Importantly, Dr. Boehme said, data collected in the Global Burden of Disease study tends to be exceptionally rigorous and systematic, adding weight to Dr. Feigin and colleagues’ suggestions that prevention efforts may be making a dent in stroke and dementia. 

“More data is always needed before we start to say we’re seeing things change,” Dr. Boehme noted. “But any glimmer of optimism is welcome, especially with regard to interventions that have been put in place, to allow us to build on those interventions.”

Dr. Boehme disclosed no financial conflicts of interest.