Clinical Psychiatry News

The cumulative percentage of COVID-19 cases reported in children continues to climb, but “the history behind that cumulative number shows substantial change,” according to a new analysis of state health department data.

As of Sept. 10, the 549,432 cases in children represented 10.0% of all reported COVID-19 cases in the United States following a substantial rise over the course of the pandemic – the figure was 7.7% on July 16 and 3.2% on May 7, Blake Sisk, PhD, of the American Academy of Pediatrics and associates reported Sept. 29 in Pediatrics.

Unlike the cumulative number, the weekly proportion of cases in children fell early in the summer but then started climbing again in late July. “In the last 8 weeks, children represented between 12%-15.9% of new weekly reported cases,” Dr. Sisk and associates wrote.

Despite the increase, however, the proportion of pediatric COVID-19 cases is still well below children’s share of the overall population (22.6%). Also, “it is unclear how much of the increase in child cases is due to increased testing capacity, although CDC data from public and commercial laboratories show the share of all tests administered to children ages 0-17 has remained stable at 5%-7% since late April,” they said.

Data for the current report were drawn from 49 state health department websites (New York state does not report ages for COVID-19 cases), along with New York City, the District of Columbia, Puerto Rico, and Guam. Alabama changed its definition of a child case in August and was not included in the trend analysis (see graph), the investigators explained.

Those data show “substantial variation in case growth by region: in April, a preponderance of cases was in the Northeast. In June, cases surged in the South and West, followed by mid-July increases in the Midwest,” Dr. Sisk and associates said.

The increase among children in Midwest states is ongoing with the number of new cases reaching its highest level yet during the week ending Sept. 10, they reported.

[email protected]

SOURCE: Sisk B et al. Pediatrics. 2020 Sep 29. doi: 10.1542/peds.2020-027425.

The cumulative percentage of COVID-19 cases reported in children continues to climb, but “the history behind that cumulative number shows substantial change,” according to a new analysis of state health department data.

As of Sept. 10, the 549,432 cases in children represented 10.0% of all reported COVID-19 cases in the United States following a substantial rise over the course of the pandemic – the figure was 7.7% on July 16 and 3.2% on May 7, Blake Sisk, PhD, of the American Academy of Pediatrics and associates reported Sept. 29 in Pediatrics.

Unlike the cumulative number, the weekly proportion of cases in children fell early in the summer but then started climbing again in late July. “In the last 8 weeks, children represented between 12%-15.9% of new weekly reported cases,” Dr. Sisk and associates wrote.

Despite the increase, however, the proportion of pediatric COVID-19 cases is still well below children’s share of the overall population (22.6%). Also, “it is unclear how much of the increase in child cases is due to increased testing capacity, although CDC data from public and commercial laboratories show the share of all tests administered to children ages 0-17 has remained stable at 5%-7% since late April,” they said.

Data for the current report were drawn from 49 state health department websites (New York state does not report ages for COVID-19 cases), along with New York City, the District of Columbia, Puerto Rico, and Guam. Alabama changed its definition of a child case in August and was not included in the trend analysis (see graph), the investigators explained.

Those data show “substantial variation in case growth by region: in April, a preponderance of cases was in the Northeast. In June, cases surged in the South and West, followed by mid-July increases in the Midwest,” Dr. Sisk and associates said.

The increase among children in Midwest states is ongoing with the number of new cases reaching its highest level yet during the week ending Sept. 10, they reported.

[email protected]

SOURCE: Sisk B et al. Pediatrics. 2020 Sep 29. doi: 10.1542/peds.2020-027425.

The cumulative percentage of COVID-19 cases reported in children continues to climb, but “the history behind that cumulative number shows substantial change,” according to a new analysis of state health department data.

As of Sept. 10, the 549,432 cases in children represented 10.0% of all reported COVID-19 cases in the United States following a substantial rise over the course of the pandemic – the figure was 7.7% on July 16 and 3.2% on May 7, Blake Sisk, PhD, of the American Academy of Pediatrics and associates reported Sept. 29 in Pediatrics.

Unlike the cumulative number, the weekly proportion of cases in children fell early in the summer but then started climbing again in late July. “In the last 8 weeks, children represented between 12%-15.9% of new weekly reported cases,” Dr. Sisk and associates wrote.

Despite the increase, however, the proportion of pediatric COVID-19 cases is still well below children’s share of the overall population (22.6%). Also, “it is unclear how much of the increase in child cases is due to increased testing capacity, although CDC data from public and commercial laboratories show the share of all tests administered to children ages 0-17 has remained stable at 5%-7% since late April,” they said.

Data for the current report were drawn from 49 state health department websites (New York state does not report ages for COVID-19 cases), along with New York City, the District of Columbia, Puerto Rico, and Guam. Alabama changed its definition of a child case in August and was not included in the trend analysis (see graph), the investigators explained.

Those data show “substantial variation in case growth by region: in April, a preponderance of cases was in the Northeast. In June, cases surged in the South and West, followed by mid-July increases in the Midwest,” Dr. Sisk and associates said.

The increase among children in Midwest states is ongoing with the number of new cases reaching its highest level yet during the week ending Sept. 10, they reported.

[email protected]

SOURCE: Sisk B et al. Pediatrics. 2020 Sep 29. doi: 10.1542/peds.2020-027425.

Rural primary care doctors are facing a new set of obstacles to practicing in the COVID-19 pandemic. These include struggling with seeing patients virtually and treating patients who have politicized the virus. Additionally, the pandemic has exposed rural practices to greater financial difficulties.

Courtesy Dr. Jacqueline W. Fincher

Before the pandemic some rurally based primary care physicians were already working through big challenges, such as having few local medical colleagues to consult and working in small practices with lean budgets. In fact, data gathered by the National Rural Health Association showed that there are only 40 primary care physicians per 100,000 patients in rural regions, compared with 53 in urban areas – and the number of physicians overall is 13 per 10,000 in rural areas, compared with 31 in cities.

In the prepandemic world, for some doctors, the challenges were balanced by the benefits of practicing in these sparsely populated communities with scenic, low-traffic roads. Some perks of practicing in rural areas touted by doctors included having a fast commute, being able to swim in a lake near the office before work, having a low cost of living, and feeling like they are making a difference in their communities as they treat generations of the families they see around town.

But today, new hurdles to practicing medicine in rural America created by the COVID-19 pandemic have caused the hardships to feel heavier than the joys at times for some physicians interviewed by MDedge.

Many independent rural practices in need of assistance were not able to get much from the federal Provider Relief Funds, said John M. Westfall, MD, who is director of the Robert Graham Center for Policy Studies in Family Medicine and Primary Care, in an interview.

“Rural primary care doctors function independently or in smaller critical access hospitals and community health centers,” said Dr. Westfall, who previously practiced family medicine in a small town in Colorado. “Many of these have much less financial reserves so are at risk of cutbacks and closure.”

Jacqueline W. Fincher, MD, an internist based in a tiny Georgia community along the highway between Atlanta and Augusta, said her small practice works on really thin margins and doesn’t have much cushion. At the beginning of the pandemic, all visits were down, and her practice operated at a loss. To help, Dr. Fincher and her colleagues applied for funding from the Small Business Administration’s Paycheck Protection Program (PPP) through the CARES Act.

“COVID-19 has had a tremendous impact especially on primary care practices. We live and die by volume. … Our volume in mid-March to mid-May really dropped dramatically,” explained Dr. Fincher, who is also president of the American College of Physicians. “The PPP sustained us for 2 months, enabling us to pay our staff and to remain open and get us up and running on telehealth.”
 

Starting up telemedicine

Experiencing spotty or no access to broadband Internet is nothing new to rural physicians, but having this problem interfere with their ability to provide care to patients is.

As much of the American health system rapidly embraced telehealth during the pandemic, obtaining access to high-speed Internet has been a major challenge for rural patients, noted Dr. Westfall.

“Some practices were able to quickly adopt some telehealth capacity with phone and video. Changes in payment for telehealth helped. But in some rural communities there was not adequate Internet bandwidth for quality video connections. And some patients did not have the means for high-speed video connections,” Dr. Westfall said.

Indeed, according to a 2019 Pew Research Center survey, 63% of rural Americans say they can access the Internet through a broadband connection at home, compared with 75% and 79% in suburban and urban areas, respectively.

G&P Productions

In the Appalachian town of Zanesville, Ohio, for example, family physician Shelly L. Dunmyer, MD, and her colleagues discovered that many patients don’t have Internet access at home. Dr. Fincher has to go to the office to conduct telehealth visits because her own Internet access at home is unpredictable. As for patients, it may take 15 minutes for them to work out technical glitches and find good Internet reception, said Dr. Fincher. For internist Y. Ki Shin, MD, who practices in the coastal town of Montesano in Washington state, about 25% of his practice’s telehealth visits must be conducted by phone because of limitations on video, such as lack of high-speed access.

But telephone visits are often insufficient replacements for appointments via video, according to several rural physicians interviewed for this piece.

“Telehealth can be frustrating at times due to connectivity issues which can be difficult at times in the rural areas,” said Dr. Fincher. “In order for telehealth to be reasonably helpful to patients and physicians to care for people with chronic problems, the patients must have things like blood pressure monitors, glucometers, and scales to address problems like hypertension, diabetes myelitis, and congestive heart failure.”

“If you have the audio and video and the data from these devices, you’re good. If you don’t have these data, and/or don’t have the video you just can’t provide good care,” she explained.

G&P Productions

Dr. Dunmyer and her colleagues at Medical Home Primary Care Center in Zanesville, Ohio, found a way to get around the problem of patients not being able to access Internet to participate in video visits from their homes. This involved having her patients drive into her practice’s parking lot to participate in modified telehealth visits. Staffers gave iPads to patients in their cars, and Dr. Dunmyer conducted visits from her office, about 50 yards away.

“We were even doing Medicare wellness visits: Instead of asking them to get up and move around the room, we would sit at the window and wave at them, ask them to get out, walk around the car. We were able to check mobility and all kinds of things that we’d normally do in the office,” Dr. Dunmyer explained in an interview.

The family physician noted that her practice is now conducting fewer parking lot visits since her office is allowing in-person appointments, but that they’re still an option for her patients.
 

Treating political adversaries

Some rural physicians have experienced strained relationships with patients for reasons other than technology – stark differences in opinion over the pandemic itself. Certain patients are following President Trump’s lead and questioning everything from the pandemic death toll to preventive measures recommended by scientists and medical experts, physicians interviewed by MDedge said.

Patients everywhere share these viewpoints, of course, but research and election results confirm that rural areas are more receptive to conservative viewpoints. In 2018, a Pew Research Center survey reported that rural and urban areas are “becoming more polarized politically,” and “rural areas tend to have a higher concentration of Republicans and Republican-leaning independents.” For example, 40% of rural respondents reported “very warm” or “somewhat warm” feelings toward Donald Trump, compared with just 19% in urban areas.

Dr. Shin has struggled to cope with patients who want to argue about pandemic safety precautions like wearing masks and seem to question whether systemic racism exists.

“We are seeing a lot more people who feel that this pandemic is not real, that it’s a political and not-true infection,” he said in an interview. “We’ve had patients who were angry at us because we made them wear masks, and some were demanding hydroxychloroquine and wanted to have an argument because we’re not going to prescribe it for them.”

In one situation, which he found especially disturbing, Dr. Shin had to leave the exam room because a patient wouldn’t stop challenging him regarding the pandemic. Things have gotten so bad that Dr. Shin has even questioned whether he wants to continue his long career in his small town because of local political attitudes such as opposition to mask-wearing and social distancing.

“Mr. Trump’s misinformation on this pandemic made my job much more difficult. As a minority, I feel less safe in my community than ever,” said Dr. Shin, who described himself as Asian American.

Despite these new stressors, Dr. Shin has experienced some joyful moments while practicing medicine in the pandemic.

Courtesy Dr. Clara Shin

He said a recent home visit to a patient who had been hospitalized for over 3 months and nearly died helped him put political disputes with his patients into perspective.

“He was discharged home but is bedbound. He had gangrene on his toes, and I could not fully examine him using video,” Dr. Shin recalled. “It was tricky to find the house, but a very large Trump sign was very helpful in locating it. It was a good visit: He was happy to see me, and I was happy to see that he was doing okay at home.”

“I need to remind myself that supporting Mr. Trump does not always mean that my patient supports Mr. Trump’s view on the pandemic and the race issues in our country,” Dr. Shin added.

The Washington-based internist said he also tells himself that, even if his patients refuse to follow his strong advice regarding pandemic precautions, it does not mean he has failed as a doctor.

“I need to continue to educate patients about the dangers of COVID infection but cannot be angry if they don’t choose to follow my recommendations,” he noted.

Dr. Fincher says her close connection with patients has allowed her to smooth over politically charged claims about the pandemic in the town of Thomson, Georgia, with a population 6,800.

“I have a sense that, even though we may differ in our understanding of some basic facts, they appreciate what I say since we have a long-term relationship built on trust,” she said. This kind of trust, Dr. Fincher suggested, may be more common than in urban areas where there’s a larger supply of physicians, and patients don’t see the same doctors for long periods of time.

“It’s more meaningful when it comes from me, rather than doctors who are [new to patients] every year when their employer changes their insurance,” she noted.

Rural primary care doctors are facing a new set of obstacles to practicing in the COVID-19 pandemic. These include struggling with seeing patients virtually and treating patients who have politicized the virus. Additionally, the pandemic has exposed rural practices to greater financial difficulties.

Courtesy Dr. Jacqueline W. Fincher

Before the pandemic some rurally based primary care physicians were already working through big challenges, such as having few local medical colleagues to consult and working in small practices with lean budgets. In fact, data gathered by the National Rural Health Association showed that there are only 40 primary care physicians per 100,000 patients in rural regions, compared with 53 in urban areas – and the number of physicians overall is 13 per 10,000 in rural areas, compared with 31 in cities.

In the prepandemic world, for some doctors, the challenges were balanced by the benefits of practicing in these sparsely populated communities with scenic, low-traffic roads. Some perks of practicing in rural areas touted by doctors included having a fast commute, being able to swim in a lake near the office before work, having a low cost of living, and feeling like they are making a difference in their communities as they treat generations of the families they see around town.

But today, new hurdles to practicing medicine in rural America created by the COVID-19 pandemic have caused the hardships to feel heavier than the joys at times for some physicians interviewed by MDedge.

Many independent rural practices in need of assistance were not able to get much from the federal Provider Relief Funds, said John M. Westfall, MD, who is director of the Robert Graham Center for Policy Studies in Family Medicine and Primary Care, in an interview.

“Rural primary care doctors function independently or in smaller critical access hospitals and community health centers,” said Dr. Westfall, who previously practiced family medicine in a small town in Colorado. “Many of these have much less financial reserves so are at risk of cutbacks and closure.”

Jacqueline W. Fincher, MD, an internist based in a tiny Georgia community along the highway between Atlanta and Augusta, said her small practice works on really thin margins and doesn’t have much cushion. At the beginning of the pandemic, all visits were down, and her practice operated at a loss. To help, Dr. Fincher and her colleagues applied for funding from the Small Business Administration’s Paycheck Protection Program (PPP) through the CARES Act.

“COVID-19 has had a tremendous impact especially on primary care practices. We live and die by volume. … Our volume in mid-March to mid-May really dropped dramatically,” explained Dr. Fincher, who is also president of the American College of Physicians. “The PPP sustained us for 2 months, enabling us to pay our staff and to remain open and get us up and running on telehealth.”
 

Starting up telemedicine

Experiencing spotty or no access to broadband Internet is nothing new to rural physicians, but having this problem interfere with their ability to provide care to patients is.

As much of the American health system rapidly embraced telehealth during the pandemic, obtaining access to high-speed Internet has been a major challenge for rural patients, noted Dr. Westfall.

“Some practices were able to quickly adopt some telehealth capacity with phone and video. Changes in payment for telehealth helped. But in some rural communities there was not adequate Internet bandwidth for quality video connections. And some patients did not have the means for high-speed video connections,” Dr. Westfall said.

Indeed, according to a 2019 Pew Research Center survey, 63% of rural Americans say they can access the Internet through a broadband connection at home, compared with 75% and 79% in suburban and urban areas, respectively.

G&P Productions

In the Appalachian town of Zanesville, Ohio, for example, family physician Shelly L. Dunmyer, MD, and her colleagues discovered that many patients don’t have Internet access at home. Dr. Fincher has to go to the office to conduct telehealth visits because her own Internet access at home is unpredictable. As for patients, it may take 15 minutes for them to work out technical glitches and find good Internet reception, said Dr. Fincher. For internist Y. Ki Shin, MD, who practices in the coastal town of Montesano in Washington state, about 25% of his practice’s telehealth visits must be conducted by phone because of limitations on video, such as lack of high-speed access.

But telephone visits are often insufficient replacements for appointments via video, according to several rural physicians interviewed for this piece.

“Telehealth can be frustrating at times due to connectivity issues which can be difficult at times in the rural areas,” said Dr. Fincher. “In order for telehealth to be reasonably helpful to patients and physicians to care for people with chronic problems, the patients must have things like blood pressure monitors, glucometers, and scales to address problems like hypertension, diabetes myelitis, and congestive heart failure.”

“If you have the audio and video and the data from these devices, you’re good. If you don’t have these data, and/or don’t have the video you just can’t provide good care,” she explained.

G&P Productions

Dr. Dunmyer and her colleagues at Medical Home Primary Care Center in Zanesville, Ohio, found a way to get around the problem of patients not being able to access Internet to participate in video visits from their homes. This involved having her patients drive into her practice’s parking lot to participate in modified telehealth visits. Staffers gave iPads to patients in their cars, and Dr. Dunmyer conducted visits from her office, about 50 yards away.

“We were even doing Medicare wellness visits: Instead of asking them to get up and move around the room, we would sit at the window and wave at them, ask them to get out, walk around the car. We were able to check mobility and all kinds of things that we’d normally do in the office,” Dr. Dunmyer explained in an interview.

The family physician noted that her practice is now conducting fewer parking lot visits since her office is allowing in-person appointments, but that they’re still an option for her patients.
 

Treating political adversaries

Some rural physicians have experienced strained relationships with patients for reasons other than technology – stark differences in opinion over the pandemic itself. Certain patients are following President Trump’s lead and questioning everything from the pandemic death toll to preventive measures recommended by scientists and medical experts, physicians interviewed by MDedge said.

Patients everywhere share these viewpoints, of course, but research and election results confirm that rural areas are more receptive to conservative viewpoints. In 2018, a Pew Research Center survey reported that rural and urban areas are “becoming more polarized politically,” and “rural areas tend to have a higher concentration of Republicans and Republican-leaning independents.” For example, 40% of rural respondents reported “very warm” or “somewhat warm” feelings toward Donald Trump, compared with just 19% in urban areas.

Dr. Shin has struggled to cope with patients who want to argue about pandemic safety precautions like wearing masks and seem to question whether systemic racism exists.

“We are seeing a lot more people who feel that this pandemic is not real, that it’s a political and not-true infection,” he said in an interview. “We’ve had patients who were angry at us because we made them wear masks, and some were demanding hydroxychloroquine and wanted to have an argument because we’re not going to prescribe it for them.”

In one situation, which he found especially disturbing, Dr. Shin had to leave the exam room because a patient wouldn’t stop challenging him regarding the pandemic. Things have gotten so bad that Dr. Shin has even questioned whether he wants to continue his long career in his small town because of local political attitudes such as opposition to mask-wearing and social distancing.

“Mr. Trump’s misinformation on this pandemic made my job much more difficult. As a minority, I feel less safe in my community than ever,” said Dr. Shin, who described himself as Asian American.

Despite these new stressors, Dr. Shin has experienced some joyful moments while practicing medicine in the pandemic.

Courtesy Dr. Clara Shin

He said a recent home visit to a patient who had been hospitalized for over 3 months and nearly died helped him put political disputes with his patients into perspective.

“He was discharged home but is bedbound. He had gangrene on his toes, and I could not fully examine him using video,” Dr. Shin recalled. “It was tricky to find the house, but a very large Trump sign was very helpful in locating it. It was a good visit: He was happy to see me, and I was happy to see that he was doing okay at home.”

“I need to remind myself that supporting Mr. Trump does not always mean that my patient supports Mr. Trump’s view on the pandemic and the race issues in our country,” Dr. Shin added.

The Washington-based internist said he also tells himself that, even if his patients refuse to follow his strong advice regarding pandemic precautions, it does not mean he has failed as a doctor.

“I need to continue to educate patients about the dangers of COVID infection but cannot be angry if they don’t choose to follow my recommendations,” he noted.

Dr. Fincher says her close connection with patients has allowed her to smooth over politically charged claims about the pandemic in the town of Thomson, Georgia, with a population 6,800.

“I have a sense that, even though we may differ in our understanding of some basic facts, they appreciate what I say since we have a long-term relationship built on trust,” she said. This kind of trust, Dr. Fincher suggested, may be more common than in urban areas where there’s a larger supply of physicians, and patients don’t see the same doctors for long periods of time.

“It’s more meaningful when it comes from me, rather than doctors who are [new to patients] every year when their employer changes their insurance,” she noted.

Rural primary care doctors are facing a new set of obstacles to practicing in the COVID-19 pandemic. These include struggling with seeing patients virtually and treating patients who have politicized the virus. Additionally, the pandemic has exposed rural practices to greater financial difficulties.

Courtesy Dr. Jacqueline W. Fincher

Before the pandemic some rurally based primary care physicians were already working through big challenges, such as having few local medical colleagues to consult and working in small practices with lean budgets. In fact, data gathered by the National Rural Health Association showed that there are only 40 primary care physicians per 100,000 patients in rural regions, compared with 53 in urban areas – and the number of physicians overall is 13 per 10,000 in rural areas, compared with 31 in cities.

In the prepandemic world, for some doctors, the challenges were balanced by the benefits of practicing in these sparsely populated communities with scenic, low-traffic roads. Some perks of practicing in rural areas touted by doctors included having a fast commute, being able to swim in a lake near the office before work, having a low cost of living, and feeling like they are making a difference in their communities as they treat generations of the families they see around town.

But today, new hurdles to practicing medicine in rural America created by the COVID-19 pandemic have caused the hardships to feel heavier than the joys at times for some physicians interviewed by MDedge.

Many independent rural practices in need of assistance were not able to get much from the federal Provider Relief Funds, said John M. Westfall, MD, who is director of the Robert Graham Center for Policy Studies in Family Medicine and Primary Care, in an interview.

“Rural primary care doctors function independently or in smaller critical access hospitals and community health centers,” said Dr. Westfall, who previously practiced family medicine in a small town in Colorado. “Many of these have much less financial reserves so are at risk of cutbacks and closure.”

Jacqueline W. Fincher, MD, an internist based in a tiny Georgia community along the highway between Atlanta and Augusta, said her small practice works on really thin margins and doesn’t have much cushion. At the beginning of the pandemic, all visits were down, and her practice operated at a loss. To help, Dr. Fincher and her colleagues applied for funding from the Small Business Administration’s Paycheck Protection Program (PPP) through the CARES Act.

“COVID-19 has had a tremendous impact especially on primary care practices. We live and die by volume. … Our volume in mid-March to mid-May really dropped dramatically,” explained Dr. Fincher, who is also president of the American College of Physicians. “The PPP sustained us for 2 months, enabling us to pay our staff and to remain open and get us up and running on telehealth.”
 

Starting up telemedicine

Experiencing spotty or no access to broadband Internet is nothing new to rural physicians, but having this problem interfere with their ability to provide care to patients is.

As much of the American health system rapidly embraced telehealth during the pandemic, obtaining access to high-speed Internet has been a major challenge for rural patients, noted Dr. Westfall.

“Some practices were able to quickly adopt some telehealth capacity with phone and video. Changes in payment for telehealth helped. But in some rural communities there was not adequate Internet bandwidth for quality video connections. And some patients did not have the means for high-speed video connections,” Dr. Westfall said.

Indeed, according to a 2019 Pew Research Center survey, 63% of rural Americans say they can access the Internet through a broadband connection at home, compared with 75% and 79% in suburban and urban areas, respectively.

G&P Productions

In the Appalachian town of Zanesville, Ohio, for example, family physician Shelly L. Dunmyer, MD, and her colleagues discovered that many patients don’t have Internet access at home. Dr. Fincher has to go to the office to conduct telehealth visits because her own Internet access at home is unpredictable. As for patients, it may take 15 minutes for them to work out technical glitches and find good Internet reception, said Dr. Fincher. For internist Y. Ki Shin, MD, who practices in the coastal town of Montesano in Washington state, about 25% of his practice’s telehealth visits must be conducted by phone because of limitations on video, such as lack of high-speed access.

But telephone visits are often insufficient replacements for appointments via video, according to several rural physicians interviewed for this piece.

“Telehealth can be frustrating at times due to connectivity issues which can be difficult at times in the rural areas,” said Dr. Fincher. “In order for telehealth to be reasonably helpful to patients and physicians to care for people with chronic problems, the patients must have things like blood pressure monitors, glucometers, and scales to address problems like hypertension, diabetes myelitis, and congestive heart failure.”

“If you have the audio and video and the data from these devices, you’re good. If you don’t have these data, and/or don’t have the video you just can’t provide good care,” she explained.

G&P Productions

Dr. Dunmyer and her colleagues at Medical Home Primary Care Center in Zanesville, Ohio, found a way to get around the problem of patients not being able to access Internet to participate in video visits from their homes. This involved having her patients drive into her practice’s parking lot to participate in modified telehealth visits. Staffers gave iPads to patients in their cars, and Dr. Dunmyer conducted visits from her office, about 50 yards away.

“We were even doing Medicare wellness visits: Instead of asking them to get up and move around the room, we would sit at the window and wave at them, ask them to get out, walk around the car. We were able to check mobility and all kinds of things that we’d normally do in the office,” Dr. Dunmyer explained in an interview.

The family physician noted that her practice is now conducting fewer parking lot visits since her office is allowing in-person appointments, but that they’re still an option for her patients.
 

Treating political adversaries

Some rural physicians have experienced strained relationships with patients for reasons other than technology – stark differences in opinion over the pandemic itself. Certain patients are following President Trump’s lead and questioning everything from the pandemic death toll to preventive measures recommended by scientists and medical experts, physicians interviewed by MDedge said.

Patients everywhere share these viewpoints, of course, but research and election results confirm that rural areas are more receptive to conservative viewpoints. In 2018, a Pew Research Center survey reported that rural and urban areas are “becoming more polarized politically,” and “rural areas tend to have a higher concentration of Republicans and Republican-leaning independents.” For example, 40% of rural respondents reported “very warm” or “somewhat warm” feelings toward Donald Trump, compared with just 19% in urban areas.

Dr. Shin has struggled to cope with patients who want to argue about pandemic safety precautions like wearing masks and seem to question whether systemic racism exists.

“We are seeing a lot more people who feel that this pandemic is not real, that it’s a political and not-true infection,” he said in an interview. “We’ve had patients who were angry at us because we made them wear masks, and some were demanding hydroxychloroquine and wanted to have an argument because we’re not going to prescribe it for them.”

In one situation, which he found especially disturbing, Dr. Shin had to leave the exam room because a patient wouldn’t stop challenging him regarding the pandemic. Things have gotten so bad that Dr. Shin has even questioned whether he wants to continue his long career in his small town because of local political attitudes such as opposition to mask-wearing and social distancing.

“Mr. Trump’s misinformation on this pandemic made my job much more difficult. As a minority, I feel less safe in my community than ever,” said Dr. Shin, who described himself as Asian American.

Despite these new stressors, Dr. Shin has experienced some joyful moments while practicing medicine in the pandemic.

Courtesy Dr. Clara Shin

He said a recent home visit to a patient who had been hospitalized for over 3 months and nearly died helped him put political disputes with his patients into perspective.

“He was discharged home but is bedbound. He had gangrene on his toes, and I could not fully examine him using video,” Dr. Shin recalled. “It was tricky to find the house, but a very large Trump sign was very helpful in locating it. It was a good visit: He was happy to see me, and I was happy to see that he was doing okay at home.”

“I need to remind myself that supporting Mr. Trump does not always mean that my patient supports Mr. Trump’s view on the pandemic and the race issues in our country,” Dr. Shin added.

The Washington-based internist said he also tells himself that, even if his patients refuse to follow his strong advice regarding pandemic precautions, it does not mean he has failed as a doctor.

“I need to continue to educate patients about the dangers of COVID infection but cannot be angry if they don’t choose to follow my recommendations,” he noted.

Dr. Fincher says her close connection with patients has allowed her to smooth over politically charged claims about the pandemic in the town of Thomson, Georgia, with a population 6,800.

“I have a sense that, even though we may differ in our understanding of some basic facts, they appreciate what I say since we have a long-term relationship built on trust,” she said. This kind of trust, Dr. Fincher suggested, may be more common than in urban areas where there’s a larger supply of physicians, and patients don’t see the same doctors for long periods of time.

“It’s more meaningful when it comes from me, rather than doctors who are [new to patients] every year when their employer changes their insurance,” she noted.

Mentoring is often promoted as an organizational practice to promote diversity and inclusion. New or established group members who want to further their careers look for a mentor to guide them toward success within a system by amplifying their strengths and accomplishments and defending and promoting them when necessary. But how can mentoring work if there isn’t a mentor?

For underrepresented groups or marginalized physicians, it too often looks as if there are no mentors who understand the struggles of being a racial or ethnic minority group member or mentors who are even cognizant of those struggles. Mentoring is a practice that occurs within the overarching systems of practice groups, academic departments, hospitals, medicine, and society at large. These systems frequently carry the legacies of bias, discrimination, and exclusion. The mentoring itself that takes place within a biased system risks perpetuating institutional bias, exclusion, or a sense of unworthiness in the mentee. It is stressful for any person with a minority background or even a minority interest to feel that there’s no one to emulate in their immediate working environment. When that is the case, a natural question follows: “Do I even belong here?”

Before departments and psychiatric practices turn to old, surface-level solutions like using mentorship to appear more welcoming to underrepresented groups, leaders must explicitly evaluate their track record of mentorship within their system and determine whether mentorship has been used to protect the status quo or move the culture forward. As mentorship is inherently an imbalanced relationship, there must be department- or group-level reflection about the diversity of mentors and also their examinations of mentors’ own preconceived notions of who will make a “good” mentee.

At the most basic level, leaders can examine whether there are gaps in who is mentored and who is not. Other parts of mentoring relationships should also be examined: a) How can mentoring happen if there is a dearth of underrepresented groups in the department? b) What type of mentoring style is favored? Do departments/groups look for a natural fit between mentor and mentee or are they matched based on interests, ideals, and goals? and c) How is the worthiness for mentorship determined?

One example is the fraught process of evaluating “worthiness” among residents. Prospective mentors frequently divide trainees unofficially into a top-tier candidates, middle-tier performers who may be overlooked, and a bottom tier who are avoided when it comes to mentorship. Because this division is informal and usually based on extremely early perceptions of trainees’ aptitude and openness, the process can be subject to an individual mentor’s conscious and unconscious bias, which then plays a large role in perpetuating systemic racism. When it comes to these informal but often rigid divisions, it can be hard to fall from the top when mentees are buoyed by good will, frequent opportunities to shine, and the mentor’s reputation. Likewise, it can be hard to break out from the middle and bottom groups without a strong advocate or opportunities to demonstrate exceptional proficiency.

Below are three recommendations to consider for improving mentorship within departments:

1) Consider opportunities for senior mentors and potential mentees to interact with one another outside of assigned duties so that some mentorship relationships can be formed organically.

2) Review when mentorship relationships have been ineffective or unsuccessful versus productive and useful for both participants.

3) Increase opportunities for adjunct or former faculty who remain connected to the institution to also be mentors. This approach would open up more possibilities and could increase the diversity of available mentors.

If mentorship is to be part of the armamentarium for promoting equity within academia and workplaces alike, it must be examined and changed to meet the new reality.

Dr. Posada is assistant clinical professor, department of psychiatry and behavioral sciences at George Washington University in Washington. She also serves as staff physician at George Washington Medical Faculty Associates, also in Washington. She disclosed no relevant financial relationships. Dr. Forrester is consultation-liaison psychiatry fellowship training director at the University of Maryland, Baltimore. She disclosed no relevant financial relationships.

Mentoring is often promoted as an organizational practice to promote diversity and inclusion. New or established group members who want to further their careers look for a mentor to guide them toward success within a system by amplifying their strengths and accomplishments and defending and promoting them when necessary. But how can mentoring work if there isn’t a mentor?

For underrepresented groups or marginalized physicians, it too often looks as if there are no mentors who understand the struggles of being a racial or ethnic minority group member or mentors who are even cognizant of those struggles. Mentoring is a practice that occurs within the overarching systems of practice groups, academic departments, hospitals, medicine, and society at large. These systems frequently carry the legacies of bias, discrimination, and exclusion. The mentoring itself that takes place within a biased system risks perpetuating institutional bias, exclusion, or a sense of unworthiness in the mentee. It is stressful for any person with a minority background or even a minority interest to feel that there’s no one to emulate in their immediate working environment. When that is the case, a natural question follows: “Do I even belong here?”

Before departments and psychiatric practices turn to old, surface-level solutions like using mentorship to appear more welcoming to underrepresented groups, leaders must explicitly evaluate their track record of mentorship within their system and determine whether mentorship has been used to protect the status quo or move the culture forward. As mentorship is inherently an imbalanced relationship, there must be department- or group-level reflection about the diversity of mentors and also their examinations of mentors’ own preconceived notions of who will make a “good” mentee.

At the most basic level, leaders can examine whether there are gaps in who is mentored and who is not. Other parts of mentoring relationships should also be examined: a) How can mentoring happen if there is a dearth of underrepresented groups in the department? b) What type of mentoring style is favored? Do departments/groups look for a natural fit between mentor and mentee or are they matched based on interests, ideals, and goals? and c) How is the worthiness for mentorship determined?

One example is the fraught process of evaluating “worthiness” among residents. Prospective mentors frequently divide trainees unofficially into a top-tier candidates, middle-tier performers who may be overlooked, and a bottom tier who are avoided when it comes to mentorship. Because this division is informal and usually based on extremely early perceptions of trainees’ aptitude and openness, the process can be subject to an individual mentor’s conscious and unconscious bias, which then plays a large role in perpetuating systemic racism. When it comes to these informal but often rigid divisions, it can be hard to fall from the top when mentees are buoyed by good will, frequent opportunities to shine, and the mentor’s reputation. Likewise, it can be hard to break out from the middle and bottom groups without a strong advocate or opportunities to demonstrate exceptional proficiency.

Below are three recommendations to consider for improving mentorship within departments:

1) Consider opportunities for senior mentors and potential mentees to interact with one another outside of assigned duties so that some mentorship relationships can be formed organically.

2) Review when mentorship relationships have been ineffective or unsuccessful versus productive and useful for both participants.

3) Increase opportunities for adjunct or former faculty who remain connected to the institution to also be mentors. This approach would open up more possibilities and could increase the diversity of available mentors.

If mentorship is to be part of the armamentarium for promoting equity within academia and workplaces alike, it must be examined and changed to meet the new reality.

Dr. Posada is assistant clinical professor, department of psychiatry and behavioral sciences at George Washington University in Washington. She also serves as staff physician at George Washington Medical Faculty Associates, also in Washington. She disclosed no relevant financial relationships. Dr. Forrester is consultation-liaison psychiatry fellowship training director at the University of Maryland, Baltimore. She disclosed no relevant financial relationships.

Mentoring is often promoted as an organizational practice to promote diversity and inclusion. New or established group members who want to further their careers look for a mentor to guide them toward success within a system by amplifying their strengths and accomplishments and defending and promoting them when necessary. But how can mentoring work if there isn’t a mentor?

For underrepresented groups or marginalized physicians, it too often looks as if there are no mentors who understand the struggles of being a racial or ethnic minority group member or mentors who are even cognizant of those struggles. Mentoring is a practice that occurs within the overarching systems of practice groups, academic departments, hospitals, medicine, and society at large. These systems frequently carry the legacies of bias, discrimination, and exclusion. The mentoring itself that takes place within a biased system risks perpetuating institutional bias, exclusion, or a sense of unworthiness in the mentee. It is stressful for any person with a minority background or even a minority interest to feel that there’s no one to emulate in their immediate working environment. When that is the case, a natural question follows: “Do I even belong here?”

Before departments and psychiatric practices turn to old, surface-level solutions like using mentorship to appear more welcoming to underrepresented groups, leaders must explicitly evaluate their track record of mentorship within their system and determine whether mentorship has been used to protect the status quo or move the culture forward. As mentorship is inherently an imbalanced relationship, there must be department- or group-level reflection about the diversity of mentors and also their examinations of mentors’ own preconceived notions of who will make a “good” mentee.

At the most basic level, leaders can examine whether there are gaps in who is mentored and who is not. Other parts of mentoring relationships should also be examined: a) How can mentoring happen if there is a dearth of underrepresented groups in the department? b) What type of mentoring style is favored? Do departments/groups look for a natural fit between mentor and mentee or are they matched based on interests, ideals, and goals? and c) How is the worthiness for mentorship determined?

One example is the fraught process of evaluating “worthiness” among residents. Prospective mentors frequently divide trainees unofficially into a top-tier candidates, middle-tier performers who may be overlooked, and a bottom tier who are avoided when it comes to mentorship. Because this division is informal and usually based on extremely early perceptions of trainees’ aptitude and openness, the process can be subject to an individual mentor’s conscious and unconscious bias, which then plays a large role in perpetuating systemic racism. When it comes to these informal but often rigid divisions, it can be hard to fall from the top when mentees are buoyed by good will, frequent opportunities to shine, and the mentor’s reputation. Likewise, it can be hard to break out from the middle and bottom groups without a strong advocate or opportunities to demonstrate exceptional proficiency.

Below are three recommendations to consider for improving mentorship within departments:

1) Consider opportunities for senior mentors and potential mentees to interact with one another outside of assigned duties so that some mentorship relationships can be formed organically.

2) Review when mentorship relationships have been ineffective or unsuccessful versus productive and useful for both participants.

3) Increase opportunities for adjunct or former faculty who remain connected to the institution to also be mentors. This approach would open up more possibilities and could increase the diversity of available mentors.

If mentorship is to be part of the armamentarium for promoting equity within academia and workplaces alike, it must be examined and changed to meet the new reality.

Dr. Posada is assistant clinical professor, department of psychiatry and behavioral sciences at George Washington University in Washington. She also serves as staff physician at George Washington Medical Faculty Associates, also in Washington. She disclosed no relevant financial relationships. Dr. Forrester is consultation-liaison psychiatry fellowship training director at the University of Maryland, Baltimore. She disclosed no relevant financial relationships.

Two oral agents with novel mechanisms of action in schizophrenia generated considerable audience interest after acing large phase 2 clinical trials presented at the virtual congress of the European College of Neuropsychopharmacology.

The two successful drugs moving on to definitive phase 3 studies after their performance at ECNP 2020 are KarXT, a proprietary combination of xanomeline and trospium chloride, and an inhibitor of glycine transporter 1 (Gly-T1) known for now as BI 425809.

Pimavanserin, an oral selective serotonin inverse agonist with a high affinity for 5-HT2A receptors and low affinity for 5-HT2C receptors, has taken a more convoluted path through the developmental pipeline for schizophrenia. It recently failed to outperform placebo as adjunctive treatment for schizophrenia on the primary endpoint of improvement in Positive And Negative Syndrome Scale (PANSS) total score in the 6-week, phase 3 ENHANCE (Efficacy and Safety of Adjunctive Pimavanserin for the Treatment of Schizophrenia) study. The drug did, however, show significant benefit on secondary endpoints involving negative symptoms.

And in the 400-patient, 26-week, placebo-controlled, phase 2 ADVANCE trial, adjunctive pimavanserin was positive for the primary endpoint of improvement in the Negative Symptom Assessment-16 (NSA-16) score. A phase 3 program evaluating the drug specifically for negative symptoms is underway.

Another novel therapy, an investigational selective estrogen receptor beta agonist, proved reassuringly safe but completely ineffective in men with schizophrenia in a study presented at ECNP 2020.

“The results, unfortunately, were disappointing. We saw no signal on cognition, no change on brain imaging with fMRI, and no improvement in negative symptoms or PANSS total score,” reported Alan Breier, MD, professor and vice chair of the department of psychiatry at Indiana University in Indianapolis.

KarXT

KarXT combines xanomeline, a selective M1/M4 muscarinic receptor agonist exclusively licensed from Lilly to Karuna Therapeutics, with trospium chloride, a muscarinic antagonist approved for more than a decade in the United States and Europe for treatment of overactive bladder. Xanomeline was synthesized in the 1990s. It showed promising evidence of antipsychotic efficacy in schizophrenia and Alzheimer’s disease in yearlong clinical trials totaling more than 800 patients, but interest in further developing the drug cooled because of limiting GI and other cholinergic adverse events. KarXT, Karuna’s lead product candidate, is designed to maintain the efficacy of xanomeline while trospium, which doesn’t cross the blood-brain barrier, cancels out its side effects, explained Stephen Brannan, MD, a psychiatrist and chief medical officer at the company.

He presented the results of the phase 2 study, a multicenter, randomized, double-blind, placebo-controlled, 5-week trial conducted with 182 schizophrenia inpatients experiencing an acute psychotic exacerbation. All other antipsychotics were washed out before randomization to KarXT at 50 mg xanomeline/20 mg trospium twice daily, titrated to 100/20 twice daily on days 3-7 and 100/20 b.i.d. thereafter, with an optional increase to 125/30 twice daily.

The primary study endpoint was change from baseline to week 5 in PANSS total score. The results were positive at the P < .0001 level, with a mean 17.4-point reduction in the KarXT group, compared with a 5.9-point improvement in placebo-treated controls. The between-group difference was significant by the first assessment at week 2.

Four of five prespecified secondary endpoints were also positive in rapid and sustained fashion: improvement in the PANSS positive subscore, PANSS negative subscore, Marder PANSS negative subscore, and Clinical Global Impressions-Severity. The fifth secondary endpoint – the proportion of patients with a Clinical Global Impressions rating of 1 or 2, meaning normal or only mildly mentally ill – wasn’t significantly different with KarXT, compared with placebo, but Dr. Brannan shrugged that off.

“In hindsight, it was probably a little overly optimistic to think that after 5 weeks [patients with schizophrenia] would be either well or almost well,” he quipped.

An exploratory analysis of participants’ before-and-after scores on a battery of six cognitive tests showed an encouraging trend: Patients on KarXT performed numerically better than did controls on five of the six tests, albeit not significantly so. Moreover, in a further analysis stratified by baseline impairment, patients in the most impaired tertile showed a larger, statistically significant benefit in response to KarXT.

“We’re interested enough that we plan to continue to look at this in our upcoming larger and longer-term trials,” Dr. Brannan said.

As for safety and tolerability, he continued: “We were pleasantly surprised. We certainly see more side effects with KarXT than with placebo, but not by that much, and they’re much, much better than with xanomeline alone.”

The side effects, mostly cholinergic and anticholinergic, occurred 2-4 times more frequently than in controls. Notably, the rates of nausea, vomiting, and dry mouth – three of the five most common treatment-related adverse events in patients on KarXT – decreased over time to levels similar to placebo by week 5. In contrast, rates of constipation and dyspepsia remained stable over time. All side effects were mild to moderate, and none led to study discontinuation.

A key point was that the KarXT-related side effects were not the same ones that are commonly problematic and limiting with current antipsychotics. There was no weight gain or other metabolic changes, sleepiness or sedation, or extrapyramidal symptoms.

“These results show KarXT has the potential to offer patients a novel mechanism-of-action antipsychotic with a different efficacy and/or tolerability profile than current antipsychotic medications,” Dr. Brannan said.

BI 425809

BI 425809 is a once-daily oral inhibitor of glycine transporter 1 (Gly-T1) specifically designed to alleviate cognitive impairment in people with schizophrenia. Underactivity by the NMDA (N-methyl-D-aspartic acid) receptor has been implicated in this cognitive dysfunction. Glycine is an NMDA cotransmitter. By blocking glutamatergic presynaptic and astrocyte reuptake of glycine, BI 425809 results in increased glycine levels in the synaptic cleft, facilitating neurotransmission, explained W. Wolfgang Fleischhacker, MD, president of the Medical University of Innsbruck (Austria), where he is also professor of psychiatry.

He presented the results of a phase 2, randomized, double-blind, 11-country study in which 509 adults with stable schizophrenia on no more than two antipsychotics were placed on add-on BI 425809 at 2, 5, 10, or 25 mg once daily or placebo for 12 weeks.

The primary endpoint was change from baseline to 12 weeks in the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB) score. The results were strongly positive, with patients on the two top doses of BI 425809 – 10 and 25 mg/day – showing roughly a 2-point greater improvement in MCCB overall composite T-score compared with controls. Dr. Fleischhacker drew attention to the high study completion rates in the various study arms, ranging from a low of 91% to 97.6% in the 25 mg/day group.

“That’s a very nice but also an unusual finding for a trial of this length,” he observed.

The high study completion rate was a reflection of the drug’s high-level tolerability. Indeed, the rate of adverse events leading to treatment discontinuation was 0% with BI 425809 at 10 mg/day, 2.4% at 25 mg/day, and identical at 2.4% with placebo. No increase was found in psychiatric adverse events such as suicidal ideation or behavior.

“This is a first very promising result,” Dr. Fleischhacker concluded. “Basically, this is the first study that has really shown in a convincing fashion an effect of any novel compound on cognitive impairment in people suffering from schizophrenia.”

A separate ongoing phase 2 study is evaluating BI 425809 in combination with adjunctive computerized cognitive training in an effort to increase cognitive stimulation. The company is awaiting those study results before designing its phase 3 program.
 

Pimavanserin

It has been a busy year for pimavanserin, with both successes and disappointments in clinical trials addressing a range of psychotic disorders, according to Dragana Bugarski-Kirola, MD, MBA, MSc, vice president for clinical development at Acadia Pharmaceuticals in San Diego.

At present, pimavanserin is Food and Drug Administration–approved as Nuplazid only for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. But in July 2020, on the strength of the positive results of the pivotal phase 3 HARMONY trial, Acadia filed an application with the FDA for marketing approval of the drug for treatment of dementia-related psychosis. In HARMONY, patients on placebo proved to be 2.8-fold more likely to experience a relapse of delusions or hallucinations than with pimavanserin.

A big recent disappointment was that pimavanserin failed to meet its primary endpoint in the phase 3 CLARITY I and CLARITY II trials as adjunctive therapy for major depressive disorder inadequately responsive to a selective serotonin reuptake inhibitor or serotonin norepinephrine reuptake inhibitor. The change in Hamilton Depression Rating Scale–17 scores in patients on the atypical antipsychotic wasn’t significantly better than with placebo. However, pimavanserin did outperform placebo on the secondary endpoint of Clinical Global Impression–Severity. Additional clinical trials of the drug for treatment of major depression are planned, Dr. Bugarski-Kirola said.
 

LY500307

Although schizophrenia is equally common in men and women, the disease has a later onset and more benign course in women. This suggests a possible protective effect of estrogen, and indeed, extensive literature supports the use of exogenous estrogen in schizophrenia, where it reduces relapses and improves cognitive impairment and negative symptoms.

“We have no other agents that do that,” noted Dr. Breier, also chief of the psychotic disorders program and director of the Prevention and Recovery Center at Indiana University.

What he considers the best-executed clinical trial of estradiol in schizophrenia, an 8-week, double-blind, randomized study of a 200-mcg estradiol patch or placebo in 200 women aged 19-46 on antipsychotics, was published last year (JAMA Psychiatry. 2019 Jul 31;76[10]:1-9).

The results were impressive. However, estrogen may not be a viable treatment for men and premenopausal women because of its side effects, including feminization, and increased thrombotic and malignancy risks.

This was the impetus for the placebo-controlled randomized trial of LY500307, a highly selective estrogen receptor beta agonist originally developed by Eli Lilly as a potential treatment for benign prostatic hypertrophy, for which it proved ineffective. In animal models, estrogen receptor beta is responsible for a range of effects, including enhanced cognition, social behavior, and an anxiolytic action, whereas the alpha receptor affects the sex organs, skeletal and metabolic homeostasis, and is responsible for estrogen’s problematic side effects.

All three doses studied in the phase 2 randomized trial, which included 94 men with schizophrenia, proved safe, well-tolerated – and ineffective.

“I think one potential conclusion one could consider from these data is that estrogen receptor alpha engagement may be necessary for the estrogenic therapeutics in schizophrenia,” Dr. Breier said.

He reported having no financial conflicts regarding the trial, funded by Indiana University. Outside the scope of the study, he serves as a consultant to Karuna Therapeutics, BioXcel, and Perception Neuroscience.

Dr. Fleischhacker serves as a consultant to Boehringer Ingelheim, which sponsored the phase 2 study of BI 425809, as well as to Angelini, Richter, and Recordati.
 

[email protected]

SOURCE: ECNP 2020, Session S.12.

Two oral agents with novel mechanisms of action in schizophrenia generated considerable audience interest after acing large phase 2 clinical trials presented at the virtual congress of the European College of Neuropsychopharmacology.

The two successful drugs moving on to definitive phase 3 studies after their performance at ECNP 2020 are KarXT, a proprietary combination of xanomeline and trospium chloride, and an inhibitor of glycine transporter 1 (Gly-T1) known for now as BI 425809.

Pimavanserin, an oral selective serotonin inverse agonist with a high affinity for 5-HT2A receptors and low affinity for 5-HT2C receptors, has taken a more convoluted path through the developmental pipeline for schizophrenia. It recently failed to outperform placebo as adjunctive treatment for schizophrenia on the primary endpoint of improvement in Positive And Negative Syndrome Scale (PANSS) total score in the 6-week, phase 3 ENHANCE (Efficacy and Safety of Adjunctive Pimavanserin for the Treatment of Schizophrenia) study. The drug did, however, show significant benefit on secondary endpoints involving negative symptoms.

And in the 400-patient, 26-week, placebo-controlled, phase 2 ADVANCE trial, adjunctive pimavanserin was positive for the primary endpoint of improvement in the Negative Symptom Assessment-16 (NSA-16) score. A phase 3 program evaluating the drug specifically for negative symptoms is underway.

Another novel therapy, an investigational selective estrogen receptor beta agonist, proved reassuringly safe but completely ineffective in men with schizophrenia in a study presented at ECNP 2020.

“The results, unfortunately, were disappointing. We saw no signal on cognition, no change on brain imaging with fMRI, and no improvement in negative symptoms or PANSS total score,” reported Alan Breier, MD, professor and vice chair of the department of psychiatry at Indiana University in Indianapolis.

KarXT

KarXT combines xanomeline, a selective M1/M4 muscarinic receptor agonist exclusively licensed from Lilly to Karuna Therapeutics, with trospium chloride, a muscarinic antagonist approved for more than a decade in the United States and Europe for treatment of overactive bladder. Xanomeline was synthesized in the 1990s. It showed promising evidence of antipsychotic efficacy in schizophrenia and Alzheimer’s disease in yearlong clinical trials totaling more than 800 patients, but interest in further developing the drug cooled because of limiting GI and other cholinergic adverse events. KarXT, Karuna’s lead product candidate, is designed to maintain the efficacy of xanomeline while trospium, which doesn’t cross the blood-brain barrier, cancels out its side effects, explained Stephen Brannan, MD, a psychiatrist and chief medical officer at the company.

He presented the results of the phase 2 study, a multicenter, randomized, double-blind, placebo-controlled, 5-week trial conducted with 182 schizophrenia inpatients experiencing an acute psychotic exacerbation. All other antipsychotics were washed out before randomization to KarXT at 50 mg xanomeline/20 mg trospium twice daily, titrated to 100/20 twice daily on days 3-7 and 100/20 b.i.d. thereafter, with an optional increase to 125/30 twice daily.

The primary study endpoint was change from baseline to week 5 in PANSS total score. The results were positive at the P < .0001 level, with a mean 17.4-point reduction in the KarXT group, compared with a 5.9-point improvement in placebo-treated controls. The between-group difference was significant by the first assessment at week 2.

Four of five prespecified secondary endpoints were also positive in rapid and sustained fashion: improvement in the PANSS positive subscore, PANSS negative subscore, Marder PANSS negative subscore, and Clinical Global Impressions-Severity. The fifth secondary endpoint – the proportion of patients with a Clinical Global Impressions rating of 1 or 2, meaning normal or only mildly mentally ill – wasn’t significantly different with KarXT, compared with placebo, but Dr. Brannan shrugged that off.

“In hindsight, it was probably a little overly optimistic to think that after 5 weeks [patients with schizophrenia] would be either well or almost well,” he quipped.

An exploratory analysis of participants’ before-and-after scores on a battery of six cognitive tests showed an encouraging trend: Patients on KarXT performed numerically better than did controls on five of the six tests, albeit not significantly so. Moreover, in a further analysis stratified by baseline impairment, patients in the most impaired tertile showed a larger, statistically significant benefit in response to KarXT.

“We’re interested enough that we plan to continue to look at this in our upcoming larger and longer-term trials,” Dr. Brannan said.

As for safety and tolerability, he continued: “We were pleasantly surprised. We certainly see more side effects with KarXT than with placebo, but not by that much, and they’re much, much better than with xanomeline alone.”

The side effects, mostly cholinergic and anticholinergic, occurred 2-4 times more frequently than in controls. Notably, the rates of nausea, vomiting, and dry mouth – three of the five most common treatment-related adverse events in patients on KarXT – decreased over time to levels similar to placebo by week 5. In contrast, rates of constipation and dyspepsia remained stable over time. All side effects were mild to moderate, and none led to study discontinuation.

A key point was that the KarXT-related side effects were not the same ones that are commonly problematic and limiting with current antipsychotics. There was no weight gain or other metabolic changes, sleepiness or sedation, or extrapyramidal symptoms.

“These results show KarXT has the potential to offer patients a novel mechanism-of-action antipsychotic with a different efficacy and/or tolerability profile than current antipsychotic medications,” Dr. Brannan said.

BI 425809

BI 425809 is a once-daily oral inhibitor of glycine transporter 1 (Gly-T1) specifically designed to alleviate cognitive impairment in people with schizophrenia. Underactivity by the NMDA (N-methyl-D-aspartic acid) receptor has been implicated in this cognitive dysfunction. Glycine is an NMDA cotransmitter. By blocking glutamatergic presynaptic and astrocyte reuptake of glycine, BI 425809 results in increased glycine levels in the synaptic cleft, facilitating neurotransmission, explained W. Wolfgang Fleischhacker, MD, president of the Medical University of Innsbruck (Austria), where he is also professor of psychiatry.

He presented the results of a phase 2, randomized, double-blind, 11-country study in which 509 adults with stable schizophrenia on no more than two antipsychotics were placed on add-on BI 425809 at 2, 5, 10, or 25 mg once daily or placebo for 12 weeks.

The primary endpoint was change from baseline to 12 weeks in the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB) score. The results were strongly positive, with patients on the two top doses of BI 425809 – 10 and 25 mg/day – showing roughly a 2-point greater improvement in MCCB overall composite T-score compared with controls. Dr. Fleischhacker drew attention to the high study completion rates in the various study arms, ranging from a low of 91% to 97.6% in the 25 mg/day group.

“That’s a very nice but also an unusual finding for a trial of this length,” he observed.

The high study completion rate was a reflection of the drug’s high-level tolerability. Indeed, the rate of adverse events leading to treatment discontinuation was 0% with BI 425809 at 10 mg/day, 2.4% at 25 mg/day, and identical at 2.4% with placebo. No increase was found in psychiatric adverse events such as suicidal ideation or behavior.

“This is a first very promising result,” Dr. Fleischhacker concluded. “Basically, this is the first study that has really shown in a convincing fashion an effect of any novel compound on cognitive impairment in people suffering from schizophrenia.”

A separate ongoing phase 2 study is evaluating BI 425809 in combination with adjunctive computerized cognitive training in an effort to increase cognitive stimulation. The company is awaiting those study results before designing its phase 3 program.
 

Pimavanserin

It has been a busy year for pimavanserin, with both successes and disappointments in clinical trials addressing a range of psychotic disorders, according to Dragana Bugarski-Kirola, MD, MBA, MSc, vice president for clinical development at Acadia Pharmaceuticals in San Diego.

At present, pimavanserin is Food and Drug Administration–approved as Nuplazid only for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. But in July 2020, on the strength of the positive results of the pivotal phase 3 HARMONY trial, Acadia filed an application with the FDA for marketing approval of the drug for treatment of dementia-related psychosis. In HARMONY, patients on placebo proved to be 2.8-fold more likely to experience a relapse of delusions or hallucinations than with pimavanserin.

A big recent disappointment was that pimavanserin failed to meet its primary endpoint in the phase 3 CLARITY I and CLARITY II trials as adjunctive therapy for major depressive disorder inadequately responsive to a selective serotonin reuptake inhibitor or serotonin norepinephrine reuptake inhibitor. The change in Hamilton Depression Rating Scale–17 scores in patients on the atypical antipsychotic wasn’t significantly better than with placebo. However, pimavanserin did outperform placebo on the secondary endpoint of Clinical Global Impression–Severity. Additional clinical trials of the drug for treatment of major depression are planned, Dr. Bugarski-Kirola said.
 

LY500307

Although schizophrenia is equally common in men and women, the disease has a later onset and more benign course in women. This suggests a possible protective effect of estrogen, and indeed, extensive literature supports the use of exogenous estrogen in schizophrenia, where it reduces relapses and improves cognitive impairment and negative symptoms.

“We have no other agents that do that,” noted Dr. Breier, also chief of the psychotic disorders program and director of the Prevention and Recovery Center at Indiana University.

What he considers the best-executed clinical trial of estradiol in schizophrenia, an 8-week, double-blind, randomized study of a 200-mcg estradiol patch or placebo in 200 women aged 19-46 on antipsychotics, was published last year (JAMA Psychiatry. 2019 Jul 31;76[10]:1-9).

The results were impressive. However, estrogen may not be a viable treatment for men and premenopausal women because of its side effects, including feminization, and increased thrombotic and malignancy risks.

This was the impetus for the placebo-controlled randomized trial of LY500307, a highly selective estrogen receptor beta agonist originally developed by Eli Lilly as a potential treatment for benign prostatic hypertrophy, for which it proved ineffective. In animal models, estrogen receptor beta is responsible for a range of effects, including enhanced cognition, social behavior, and an anxiolytic action, whereas the alpha receptor affects the sex organs, skeletal and metabolic homeostasis, and is responsible for estrogen’s problematic side effects.

All three doses studied in the phase 2 randomized trial, which included 94 men with schizophrenia, proved safe, well-tolerated – and ineffective.

“I think one potential conclusion one could consider from these data is that estrogen receptor alpha engagement may be necessary for the estrogenic therapeutics in schizophrenia,” Dr. Breier said.

He reported having no financial conflicts regarding the trial, funded by Indiana University. Outside the scope of the study, he serves as a consultant to Karuna Therapeutics, BioXcel, and Perception Neuroscience.

Dr. Fleischhacker serves as a consultant to Boehringer Ingelheim, which sponsored the phase 2 study of BI 425809, as well as to Angelini, Richter, and Recordati.
 

[email protected]

SOURCE: ECNP 2020, Session S.12.

Two oral agents with novel mechanisms of action in schizophrenia generated considerable audience interest after acing large phase 2 clinical trials presented at the virtual congress of the European College of Neuropsychopharmacology.

The two successful drugs moving on to definitive phase 3 studies after their performance at ECNP 2020 are KarXT, a proprietary combination of xanomeline and trospium chloride, and an inhibitor of glycine transporter 1 (Gly-T1) known for now as BI 425809.

Pimavanserin, an oral selective serotonin inverse agonist with a high affinity for 5-HT2A receptors and low affinity for 5-HT2C receptors, has taken a more convoluted path through the developmental pipeline for schizophrenia. It recently failed to outperform placebo as adjunctive treatment for schizophrenia on the primary endpoint of improvement in Positive And Negative Syndrome Scale (PANSS) total score in the 6-week, phase 3 ENHANCE (Efficacy and Safety of Adjunctive Pimavanserin for the Treatment of Schizophrenia) study. The drug did, however, show significant benefit on secondary endpoints involving negative symptoms.

And in the 400-patient, 26-week, placebo-controlled, phase 2 ADVANCE trial, adjunctive pimavanserin was positive for the primary endpoint of improvement in the Negative Symptom Assessment-16 (NSA-16) score. A phase 3 program evaluating the drug specifically for negative symptoms is underway.

Another novel therapy, an investigational selective estrogen receptor beta agonist, proved reassuringly safe but completely ineffective in men with schizophrenia in a study presented at ECNP 2020.

“The results, unfortunately, were disappointing. We saw no signal on cognition, no change on brain imaging with fMRI, and no improvement in negative symptoms or PANSS total score,” reported Alan Breier, MD, professor and vice chair of the department of psychiatry at Indiana University in Indianapolis.

KarXT

KarXT combines xanomeline, a selective M1/M4 muscarinic receptor agonist exclusively licensed from Lilly to Karuna Therapeutics, with trospium chloride, a muscarinic antagonist approved for more than a decade in the United States and Europe for treatment of overactive bladder. Xanomeline was synthesized in the 1990s. It showed promising evidence of antipsychotic efficacy in schizophrenia and Alzheimer’s disease in yearlong clinical trials totaling more than 800 patients, but interest in further developing the drug cooled because of limiting GI and other cholinergic adverse events. KarXT, Karuna’s lead product candidate, is designed to maintain the efficacy of xanomeline while trospium, which doesn’t cross the blood-brain barrier, cancels out its side effects, explained Stephen Brannan, MD, a psychiatrist and chief medical officer at the company.

He presented the results of the phase 2 study, a multicenter, randomized, double-blind, placebo-controlled, 5-week trial conducted with 182 schizophrenia inpatients experiencing an acute psychotic exacerbation. All other antipsychotics were washed out before randomization to KarXT at 50 mg xanomeline/20 mg trospium twice daily, titrated to 100/20 twice daily on days 3-7 and 100/20 b.i.d. thereafter, with an optional increase to 125/30 twice daily.

The primary study endpoint was change from baseline to week 5 in PANSS total score. The results were positive at the P < .0001 level, with a mean 17.4-point reduction in the KarXT group, compared with a 5.9-point improvement in placebo-treated controls. The between-group difference was significant by the first assessment at week 2.

Four of five prespecified secondary endpoints were also positive in rapid and sustained fashion: improvement in the PANSS positive subscore, PANSS negative subscore, Marder PANSS negative subscore, and Clinical Global Impressions-Severity. The fifth secondary endpoint – the proportion of patients with a Clinical Global Impressions rating of 1 or 2, meaning normal or only mildly mentally ill – wasn’t significantly different with KarXT, compared with placebo, but Dr. Brannan shrugged that off.

“In hindsight, it was probably a little overly optimistic to think that after 5 weeks [patients with schizophrenia] would be either well or almost well,” he quipped.

An exploratory analysis of participants’ before-and-after scores on a battery of six cognitive tests showed an encouraging trend: Patients on KarXT performed numerically better than did controls on five of the six tests, albeit not significantly so. Moreover, in a further analysis stratified by baseline impairment, patients in the most impaired tertile showed a larger, statistically significant benefit in response to KarXT.

“We’re interested enough that we plan to continue to look at this in our upcoming larger and longer-term trials,” Dr. Brannan said.

As for safety and tolerability, he continued: “We were pleasantly surprised. We certainly see more side effects with KarXT than with placebo, but not by that much, and they’re much, much better than with xanomeline alone.”

The side effects, mostly cholinergic and anticholinergic, occurred 2-4 times more frequently than in controls. Notably, the rates of nausea, vomiting, and dry mouth – three of the five most common treatment-related adverse events in patients on KarXT – decreased over time to levels similar to placebo by week 5. In contrast, rates of constipation and dyspepsia remained stable over time. All side effects were mild to moderate, and none led to study discontinuation.

A key point was that the KarXT-related side effects were not the same ones that are commonly problematic and limiting with current antipsychotics. There was no weight gain or other metabolic changes, sleepiness or sedation, or extrapyramidal symptoms.

“These results show KarXT has the potential to offer patients a novel mechanism-of-action antipsychotic with a different efficacy and/or tolerability profile than current antipsychotic medications,” Dr. Brannan said.

BI 425809

BI 425809 is a once-daily oral inhibitor of glycine transporter 1 (Gly-T1) specifically designed to alleviate cognitive impairment in people with schizophrenia. Underactivity by the NMDA (N-methyl-D-aspartic acid) receptor has been implicated in this cognitive dysfunction. Glycine is an NMDA cotransmitter. By blocking glutamatergic presynaptic and astrocyte reuptake of glycine, BI 425809 results in increased glycine levels in the synaptic cleft, facilitating neurotransmission, explained W. Wolfgang Fleischhacker, MD, president of the Medical University of Innsbruck (Austria), where he is also professor of psychiatry.

He presented the results of a phase 2, randomized, double-blind, 11-country study in which 509 adults with stable schizophrenia on no more than two antipsychotics were placed on add-on BI 425809 at 2, 5, 10, or 25 mg once daily or placebo for 12 weeks.

The primary endpoint was change from baseline to 12 weeks in the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB) score. The results were strongly positive, with patients on the two top doses of BI 425809 – 10 and 25 mg/day – showing roughly a 2-point greater improvement in MCCB overall composite T-score compared with controls. Dr. Fleischhacker drew attention to the high study completion rates in the various study arms, ranging from a low of 91% to 97.6% in the 25 mg/day group.

“That’s a very nice but also an unusual finding for a trial of this length,” he observed.

The high study completion rate was a reflection of the drug’s high-level tolerability. Indeed, the rate of adverse events leading to treatment discontinuation was 0% with BI 425809 at 10 mg/day, 2.4% at 25 mg/day, and identical at 2.4% with placebo. No increase was found in psychiatric adverse events such as suicidal ideation or behavior.

“This is a first very promising result,” Dr. Fleischhacker concluded. “Basically, this is the first study that has really shown in a convincing fashion an effect of any novel compound on cognitive impairment in people suffering from schizophrenia.”

A separate ongoing phase 2 study is evaluating BI 425809 in combination with adjunctive computerized cognitive training in an effort to increase cognitive stimulation. The company is awaiting those study results before designing its phase 3 program.
 

Pimavanserin

It has been a busy year for pimavanserin, with both successes and disappointments in clinical trials addressing a range of psychotic disorders, according to Dragana Bugarski-Kirola, MD, MBA, MSc, vice president for clinical development at Acadia Pharmaceuticals in San Diego.

At present, pimavanserin is Food and Drug Administration–approved as Nuplazid only for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. But in July 2020, on the strength of the positive results of the pivotal phase 3 HARMONY trial, Acadia filed an application with the FDA for marketing approval of the drug for treatment of dementia-related psychosis. In HARMONY, patients on placebo proved to be 2.8-fold more likely to experience a relapse of delusions or hallucinations than with pimavanserin.

A big recent disappointment was that pimavanserin failed to meet its primary endpoint in the phase 3 CLARITY I and CLARITY II trials as adjunctive therapy for major depressive disorder inadequately responsive to a selective serotonin reuptake inhibitor or serotonin norepinephrine reuptake inhibitor. The change in Hamilton Depression Rating Scale–17 scores in patients on the atypical antipsychotic wasn’t significantly better than with placebo. However, pimavanserin did outperform placebo on the secondary endpoint of Clinical Global Impression–Severity. Additional clinical trials of the drug for treatment of major depression are planned, Dr. Bugarski-Kirola said.
 

LY500307

Although schizophrenia is equally common in men and women, the disease has a later onset and more benign course in women. This suggests a possible protective effect of estrogen, and indeed, extensive literature supports the use of exogenous estrogen in schizophrenia, where it reduces relapses and improves cognitive impairment and negative symptoms.

“We have no other agents that do that,” noted Dr. Breier, also chief of the psychotic disorders program and director of the Prevention and Recovery Center at Indiana University.

What he considers the best-executed clinical trial of estradiol in schizophrenia, an 8-week, double-blind, randomized study of a 200-mcg estradiol patch or placebo in 200 women aged 19-46 on antipsychotics, was published last year (JAMA Psychiatry. 2019 Jul 31;76[10]:1-9).

The results were impressive. However, estrogen may not be a viable treatment for men and premenopausal women because of its side effects, including feminization, and increased thrombotic and malignancy risks.

This was the impetus for the placebo-controlled randomized trial of LY500307, a highly selective estrogen receptor beta agonist originally developed by Eli Lilly as a potential treatment for benign prostatic hypertrophy, for which it proved ineffective. In animal models, estrogen receptor beta is responsible for a range of effects, including enhanced cognition, social behavior, and an anxiolytic action, whereas the alpha receptor affects the sex organs, skeletal and metabolic homeostasis, and is responsible for estrogen’s problematic side effects.

All three doses studied in the phase 2 randomized trial, which included 94 men with schizophrenia, proved safe, well-tolerated – and ineffective.

“I think one potential conclusion one could consider from these data is that estrogen receptor alpha engagement may be necessary for the estrogenic therapeutics in schizophrenia,” Dr. Breier said.

He reported having no financial conflicts regarding the trial, funded by Indiana University. Outside the scope of the study, he serves as a consultant to Karuna Therapeutics, BioXcel, and Perception Neuroscience.

Dr. Fleischhacker serves as a consultant to Boehringer Ingelheim, which sponsored the phase 2 study of BI 425809, as well as to Angelini, Richter, and Recordati.
 

[email protected]

SOURCE: ECNP 2020, Session S.12.

The disinhibited binge eating style often seen in individuals with high ADHD symptoms is attributable to a heightened neural reward response to food rather than to the impulsivity that’s a core feature of ADHD, Elizabeth Martin, MSc, reported at the virtual congress of the European College of Neuropsychopharmacology.

She presented a functional MRI brain-imaging study designed to help pin down the mechanism involved in the disordered eating patterns that often accompany ADHD.

“Determining the underlying mechanism between binge eating and ADHD may be helpful in developing novel therapies for both ADHD and binge eating disorder. Our research suggests that further investigation of the role of altered reward processing in ADHD may be an avenue for this,” said Ms. Martin, a doctoral researcher in the department of psychology at the University of Birmingham (England).

She and her coinvestigators recruited 31 university student volunteers with high ADHD symptoms as evidenced by their mean score of 29.3 on the 0-54 Conners’ Adult ADHD Rating Scale, and 27 others with low ADHD symptoms and a mean Conners’ score of 6.8. The two groups didn’t differ in age or BMI. However, not surprisingly, the high-ADHD group exhibited greater impulsivity, with a mean score of 72 on the Barratt Impulsiveness Scale, versus 56.5 in the low ADHD group.

A battery of eating disorder scales was applied to assess participants in terms of binge/disinhibited or restrictive eating patterns. The high- and low–ADHD symptom groups didn’t differ in terms of prevalence of a restrictive eating style, which was low, but the high-ADHD participants scored on average roughly 50% higher on the binge/disinhibited eating style measure, compared with the low-ADHD group.

Each study participant underwent a 1-hour BOLD (blood oxygen level dependent) functional MRI scan while performing two sets of tasks. One task entailed quickly looking at 120 photos of food items and an equal number of nonfood items and rating how appealing the pictures were. The other challenge was what psychologists call a go/no-go task, a computerized cognitive test used to assess inhibitory control based upon reaction times and error rates.

On the go/no-go task, there were no between-group differences in rates of errors of omission or commission or reaction time. Moreover, the MRI results indicated there were no between-group differences in neural circuitry activation during this task. The investigators therefore concluded that the tendency toward binge eating in the high–ADHD symptoms group was not tied to greater impulsivity as reflected in less effective inhibitory processes.

The food picture rating task told a different story. The MRIs demonstrated increased responses to food versus nonfood images in the high-ADHD subjects, compared with the low-ADHD subjects in reward-related brain areas, including the ventromedial prefrontal cortex, caudate nucleus, and ventral tegmental area.

“This is the first evidence that ADHD symptoms in young adults are associated with enhanced neural activation in key reward-related brain areas in response to viewing food pictures,” according to Ms. Martin. “This suggests that enhanced responsiveness to food cues may be a mediating mechanism underlying overeating in ADHD.”

Of note, only one drug – lisdexamfetamine dimesylate (Vyvanse) is Food and Drug Administration-approved for the treatment of both ADHD and binge-eating disorder.

“Until now it’s been unclear how lisdexamfetamine dimesylate reduces binge eating, but our results suggest that one mechanism worthy of further investigation is the potential effect of the drug on food reward processes,” Ms. Martin said.

She reported having no financial conflicts regarding the study, which was supported by university funding.

[email protected]

SOURCE: Martin E. ECNP 2020. Abstr. P.041.

The disinhibited binge eating style often seen in individuals with high ADHD symptoms is attributable to a heightened neural reward response to food rather than to the impulsivity that’s a core feature of ADHD, Elizabeth Martin, MSc, reported at the virtual congress of the European College of Neuropsychopharmacology.

She presented a functional MRI brain-imaging study designed to help pin down the mechanism involved in the disordered eating patterns that often accompany ADHD.

“Determining the underlying mechanism between binge eating and ADHD may be helpful in developing novel therapies for both ADHD and binge eating disorder. Our research suggests that further investigation of the role of altered reward processing in ADHD may be an avenue for this,” said Ms. Martin, a doctoral researcher in the department of psychology at the University of Birmingham (England).

She and her coinvestigators recruited 31 university student volunteers with high ADHD symptoms as evidenced by their mean score of 29.3 on the 0-54 Conners’ Adult ADHD Rating Scale, and 27 others with low ADHD symptoms and a mean Conners’ score of 6.8. The two groups didn’t differ in age or BMI. However, not surprisingly, the high-ADHD group exhibited greater impulsivity, with a mean score of 72 on the Barratt Impulsiveness Scale, versus 56.5 in the low ADHD group.

A battery of eating disorder scales was applied to assess participants in terms of binge/disinhibited or restrictive eating patterns. The high- and low–ADHD symptom groups didn’t differ in terms of prevalence of a restrictive eating style, which was low, but the high-ADHD participants scored on average roughly 50% higher on the binge/disinhibited eating style measure, compared with the low-ADHD group.

Each study participant underwent a 1-hour BOLD (blood oxygen level dependent) functional MRI scan while performing two sets of tasks. One task entailed quickly looking at 120 photos of food items and an equal number of nonfood items and rating how appealing the pictures were. The other challenge was what psychologists call a go/no-go task, a computerized cognitive test used to assess inhibitory control based upon reaction times and error rates.

On the go/no-go task, there were no between-group differences in rates of errors of omission or commission or reaction time. Moreover, the MRI results indicated there were no between-group differences in neural circuitry activation during this task. The investigators therefore concluded that the tendency toward binge eating in the high–ADHD symptoms group was not tied to greater impulsivity as reflected in less effective inhibitory processes.

The food picture rating task told a different story. The MRIs demonstrated increased responses to food versus nonfood images in the high-ADHD subjects, compared with the low-ADHD subjects in reward-related brain areas, including the ventromedial prefrontal cortex, caudate nucleus, and ventral tegmental area.

“This is the first evidence that ADHD symptoms in young adults are associated with enhanced neural activation in key reward-related brain areas in response to viewing food pictures,” according to Ms. Martin. “This suggests that enhanced responsiveness to food cues may be a mediating mechanism underlying overeating in ADHD.”

Of note, only one drug – lisdexamfetamine dimesylate (Vyvanse) is Food and Drug Administration-approved for the treatment of both ADHD and binge-eating disorder.

“Until now it’s been unclear how lisdexamfetamine dimesylate reduces binge eating, but our results suggest that one mechanism worthy of further investigation is the potential effect of the drug on food reward processes,” Ms. Martin said.

She reported having no financial conflicts regarding the study, which was supported by university funding.

[email protected]

SOURCE: Martin E. ECNP 2020. Abstr. P.041.

The disinhibited binge eating style often seen in individuals with high ADHD symptoms is attributable to a heightened neural reward response to food rather than to the impulsivity that’s a core feature of ADHD, Elizabeth Martin, MSc, reported at the virtual congress of the European College of Neuropsychopharmacology.

She presented a functional MRI brain-imaging study designed to help pin down the mechanism involved in the disordered eating patterns that often accompany ADHD.

“Determining the underlying mechanism between binge eating and ADHD may be helpful in developing novel therapies for both ADHD and binge eating disorder. Our research suggests that further investigation of the role of altered reward processing in ADHD may be an avenue for this,” said Ms. Martin, a doctoral researcher in the department of psychology at the University of Birmingham (England).

She and her coinvestigators recruited 31 university student volunteers with high ADHD symptoms as evidenced by their mean score of 29.3 on the 0-54 Conners’ Adult ADHD Rating Scale, and 27 others with low ADHD symptoms and a mean Conners’ score of 6.8. The two groups didn’t differ in age or BMI. However, not surprisingly, the high-ADHD group exhibited greater impulsivity, with a mean score of 72 on the Barratt Impulsiveness Scale, versus 56.5 in the low ADHD group.

A battery of eating disorder scales was applied to assess participants in terms of binge/disinhibited or restrictive eating patterns. The high- and low–ADHD symptom groups didn’t differ in terms of prevalence of a restrictive eating style, which was low, but the high-ADHD participants scored on average roughly 50% higher on the binge/disinhibited eating style measure, compared with the low-ADHD group.

Each study participant underwent a 1-hour BOLD (blood oxygen level dependent) functional MRI scan while performing two sets of tasks. One task entailed quickly looking at 120 photos of food items and an equal number of nonfood items and rating how appealing the pictures were. The other challenge was what psychologists call a go/no-go task, a computerized cognitive test used to assess inhibitory control based upon reaction times and error rates.

On the go/no-go task, there were no between-group differences in rates of errors of omission or commission or reaction time. Moreover, the MRI results indicated there were no between-group differences in neural circuitry activation during this task. The investigators therefore concluded that the tendency toward binge eating in the high–ADHD symptoms group was not tied to greater impulsivity as reflected in less effective inhibitory processes.

The food picture rating task told a different story. The MRIs demonstrated increased responses to food versus nonfood images in the high-ADHD subjects, compared with the low-ADHD subjects in reward-related brain areas, including the ventromedial prefrontal cortex, caudate nucleus, and ventral tegmental area.

“This is the first evidence that ADHD symptoms in young adults are associated with enhanced neural activation in key reward-related brain areas in response to viewing food pictures,” according to Ms. Martin. “This suggests that enhanced responsiveness to food cues may be a mediating mechanism underlying overeating in ADHD.”

Of note, only one drug – lisdexamfetamine dimesylate (Vyvanse) is Food and Drug Administration-approved for the treatment of both ADHD and binge-eating disorder.

“Until now it’s been unclear how lisdexamfetamine dimesylate reduces binge eating, but our results suggest that one mechanism worthy of further investigation is the potential effect of the drug on food reward processes,” Ms. Martin said.

She reported having no financial conflicts regarding the study, which was supported by university funding.

[email protected]

SOURCE: Martin E. ECNP 2020. Abstr. P.041.

The Food and Drug Administration wants updated boxed warnings on benzodiazepines to reflect the “serious” risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions associated with these medications.

“The current prescribing information for benzodiazepines does not provide adequate warnings about these serious risks and harms associated with these medicines so they may be prescribed and used inappropriately,” the FDA said in a safety communication.

The FDA also wants revisions to the patient medication guides for benzodiazepines to help educate patients and caregivers about these risks.

“While benzodiazepines are important therapies for many Americans, they are also commonly abused and misused, often together with opioid pain relievers and other medicines, alcohol, and illicit drugs,” FDA Commissioner Stephen M. Hahn, MD, said in a statement.

“We are taking measures and requiring new labeling information to help health care professionals and patients better understand that, while benzodiazepines have many treatment benefits, they also carry with them an increased risk of abuse, misuse, addiction, and dependence,” said Dr. Hahn.
 

Ninety-two million prescriptions in 2019

Benzodiazepines are widely used to treat anxiety, insomnia, seizures, and other conditions, often for extended periods of time.

According to the FDA, in 2019, an estimated 92 million benzodiazepine prescriptions were dispensed from U.S. outpatient pharmacies, most commonly alprazolam, clonazepam, and lorazepam.

Data from 2018 show that roughly 5.4 million people in the United States 12 years and older abused or misused benzodiazepines in the previous year.

Although the precise risk of benzodiazepine addiction remains unclear, population data “clearly indicate that both primary benzodiazepine use disorders and polysubstance addiction involving benzodiazepines do occur,” the FDA said.

Data from the National Survey on Drug Use and Health from 2015-2016 suggest that half million community-dwelling U.S. adults were estimated to have a benzodiazepine use disorder.
 

Jump in overdose deaths

Overdose deaths involving benzodiazepines jumped from 1,298 in 2010 to 11,537 in 2017 – an increase of more 780%. Most of these deaths involved benzodiazepines taken with prescription opioids.

Before prescribing a benzodiazepine and during treatment, a patient’s risk for abuse, misuse, and addiction should be assessed, the FDA said.

The agency urged particular caution when prescribing benzodiazepines with opioids and other central nervous system depressants, which has resulted in serious adverse events including severe respiratory depression and death.

The FDA also says patients and caregivers should be warned about the risks of abuse, misuse, addiction, dependence, and withdrawal with benzodiazepines and the associated signs and symptoms.

Physicians are encouraged to report adverse events involving benzodiazepines or other medicines to the FDA’s MedWatch program.
 

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

The Food and Drug Administration wants updated boxed warnings on benzodiazepines to reflect the “serious” risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions associated with these medications.

“The current prescribing information for benzodiazepines does not provide adequate warnings about these serious risks and harms associated with these medicines so they may be prescribed and used inappropriately,” the FDA said in a safety communication.

The FDA also wants revisions to the patient medication guides for benzodiazepines to help educate patients and caregivers about these risks.

“While benzodiazepines are important therapies for many Americans, they are also commonly abused and misused, often together with opioid pain relievers and other medicines, alcohol, and illicit drugs,” FDA Commissioner Stephen M. Hahn, MD, said in a statement.

“We are taking measures and requiring new labeling information to help health care professionals and patients better understand that, while benzodiazepines have many treatment benefits, they also carry with them an increased risk of abuse, misuse, addiction, and dependence,” said Dr. Hahn.
 

Ninety-two million prescriptions in 2019

Benzodiazepines are widely used to treat anxiety, insomnia, seizures, and other conditions, often for extended periods of time.

According to the FDA, in 2019, an estimated 92 million benzodiazepine prescriptions were dispensed from U.S. outpatient pharmacies, most commonly alprazolam, clonazepam, and lorazepam.

Data from 2018 show that roughly 5.4 million people in the United States 12 years and older abused or misused benzodiazepines in the previous year.

Although the precise risk of benzodiazepine addiction remains unclear, population data “clearly indicate that both primary benzodiazepine use disorders and polysubstance addiction involving benzodiazepines do occur,” the FDA said.

Data from the National Survey on Drug Use and Health from 2015-2016 suggest that half million community-dwelling U.S. adults were estimated to have a benzodiazepine use disorder.
 

Jump in overdose deaths

Overdose deaths involving benzodiazepines jumped from 1,298 in 2010 to 11,537 in 2017 – an increase of more 780%. Most of these deaths involved benzodiazepines taken with prescription opioids.

Before prescribing a benzodiazepine and during treatment, a patient’s risk for abuse, misuse, and addiction should be assessed, the FDA said.

The agency urged particular caution when prescribing benzodiazepines with opioids and other central nervous system depressants, which has resulted in serious adverse events including severe respiratory depression and death.

The FDA also says patients and caregivers should be warned about the risks of abuse, misuse, addiction, dependence, and withdrawal with benzodiazepines and the associated signs and symptoms.

Physicians are encouraged to report adverse events involving benzodiazepines or other medicines to the FDA’s MedWatch program.
 

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

The Food and Drug Administration wants updated boxed warnings on benzodiazepines to reflect the “serious” risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions associated with these medications.

“The current prescribing information for benzodiazepines does not provide adequate warnings about these serious risks and harms associated with these medicines so they may be prescribed and used inappropriately,” the FDA said in a safety communication.

The FDA also wants revisions to the patient medication guides for benzodiazepines to help educate patients and caregivers about these risks.

“While benzodiazepines are important therapies for many Americans, they are also commonly abused and misused, often together with opioid pain relievers and other medicines, alcohol, and illicit drugs,” FDA Commissioner Stephen M. Hahn, MD, said in a statement.

“We are taking measures and requiring new labeling information to help health care professionals and patients better understand that, while benzodiazepines have many treatment benefits, they also carry with them an increased risk of abuse, misuse, addiction, and dependence,” said Dr. Hahn.
 

Ninety-two million prescriptions in 2019

Benzodiazepines are widely used to treat anxiety, insomnia, seizures, and other conditions, often for extended periods of time.

According to the FDA, in 2019, an estimated 92 million benzodiazepine prescriptions were dispensed from U.S. outpatient pharmacies, most commonly alprazolam, clonazepam, and lorazepam.

Data from 2018 show that roughly 5.4 million people in the United States 12 years and older abused or misused benzodiazepines in the previous year.

Although the precise risk of benzodiazepine addiction remains unclear, population data “clearly indicate that both primary benzodiazepine use disorders and polysubstance addiction involving benzodiazepines do occur,” the FDA said.

Data from the National Survey on Drug Use and Health from 2015-2016 suggest that half million community-dwelling U.S. adults were estimated to have a benzodiazepine use disorder.
 

Jump in overdose deaths

Overdose deaths involving benzodiazepines jumped from 1,298 in 2010 to 11,537 in 2017 – an increase of more 780%. Most of these deaths involved benzodiazepines taken with prescription opioids.

Before prescribing a benzodiazepine and during treatment, a patient’s risk for abuse, misuse, and addiction should be assessed, the FDA said.

The agency urged particular caution when prescribing benzodiazepines with opioids and other central nervous system depressants, which has resulted in serious adverse events including severe respiratory depression and death.

The FDA also says patients and caregivers should be warned about the risks of abuse, misuse, addiction, dependence, and withdrawal with benzodiazepines and the associated signs and symptoms.

Physicians are encouraged to report adverse events involving benzodiazepines or other medicines to the FDA’s MedWatch program.
 

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

Let me tell you about Tim Ferriss. A few years ago, I started reading his best-selling book, The 4-Hour Body. Ferris detailed how he made himself into a one-man experiment – he’d make changes to his diet, checked his weight and his labs, maybe he even had metabolic studies done.

Courtesy Taylor Prinsen

He’d take these measures after soaking in hot baths, then ice baths, and while I admired his discipline, he did lose me during the chapter where he was using steroids. In the end, he advised a dairy-free, low-carbohydrate diet of green vegetables, beans or lentils, and protein for four meals a day, 6 days a week, with free-for-all eating on the 7th day. Then, there was a weight-lifting routine with kettle bells and ice packs to be placed on your shoulders for a set amount of time each day.

I may not remember the program’s details, but something about Ferris fascinated me. He brands himself as being a “human guinea pig,” about “lifestyle design,” and whatever that is, I like it. Perhaps I am attracted to the idea that we might control the trajectories of our generally uncontrollable lives.

Tim Ferriss graduated from Princeton, he’s written five best-selling books and has a popular podcast, he’s been a TED speaker, and he’s been on Fortune’s “40 under 40” list – and there’s so much more. Ferriss is brilliant, innovative, handsome, charismatic, prolific, extraordinarily athletic. I may have forgotten to mention that he was the National Chinese Kickboxing Champion and was a semifinalist in the World Champion Tango competition in Buenos Aires. He’s adventuresome and fearless, and if that isn’t enough, he speaks five languages. In the genetic dice roll, Mr. Ferriss did well, and he’s a driven and energetic hard worker who is open to new experiences.

I subscribe to the Tim Ferriss podcast – as of this writing, there are 466 episodes, with an incredible lineup of interviews with famous and successful guests. I also subscribe to his “5-Bullet Friday” email list where he mentions the interesting things he is reading, watching, learning about, or eating, and the products he is trying – single-ply toilet paper gets a thumbs down – then ends with a thought-provoking quote. This gentleman spends a tremendous amount of time searching and striving, working on himself and his own emotional growth and self-improvement, and yet he still has time for incredible explorations and experiences.

A search for psychic peace

Honestly, were it not for a few little details, I would like to be Tim Ferriss. Who wouldn’t? But what stops me from actually wanting to be Ferriss is that early on while listening to him, I realized that his drive has been fueled by intense psychic pain. He talks openly about being very close to suicide in college, about a tormenting mood disorder, demons to tame, and productivity as an antidote to a fear of failure, not always as a joy for life. There are moments that I have felt so sad for this remarkable stranger. Tim Ferriss is a searcher and what I believe he searches for most is his own psychic peace.

In a forum for psychiatrists, I wish I could write that Ferriss has found solace with our Food and Drug Administration–approved pharmaceuticals and with psychotherapy, but that’s not what he says. What Ferriss has found helpful, however, is psychedelics, and a wide variety of psychological and philosophical teachings ranging from meditation to Stoicism. And most notably, Ferriss has been an advocate for using hallucinogens as a legal medical intervention. Ferriss was one of four philanthropists who donated a total of $17 million to fund the Johns Hopkins Center for Psychedelic & Consciousness Research. He’s helped to move this field forward and to improve its credibility.

On Sept. 14, 2020, Tim Ferriss released a podcast he recorded with his dance partner and close friend, Debbie Millman, and when he recorded it, he was not certain he would release it. None of his usual sponsors endorsed during the podcast. He starts Episode #464 with, “For me, this is the most important podcast episode I’ve ever published. In it, I describe the most life-shaping, certainly the most difficult, and certainly the most transformative journey of my 43 years on this planet. I’ve never shared it before.”

I applaud Mr. Ferriss for going through with posting the podcast, a confessional about how he was repeatedly sexually molested over a 2-year period as a young child by a babysitter’s son. He worried about how this would affect his family, if they would be left feeling guilty or devastated. He says, “Please note that I expect to be completely overwhelmed emotionally and otherwise when this is published and please understand if I’m not able to reply to any outreach.”

Ferriss and Millman had a long discussion about their sexual abuse as children. Millman was abused by her stepfather at the age of 9, and she talks about confronting him many years later. Ferriss has not confronted his perpetrator, though he has contemplated doing so.

Sexual violence and violation at any age leaves people scarred. In a recent letter to the New York Times in response to President Trump’s words of support to Ghislaine Maxwell, the woman who helped Jeffrey Epstein find his victims, Baltimore psychiatrist Robin Weiss wrote, “Thirty-eight years ago, when I was 32, I was raped. I was married, I was a doctor – you might say I was in pretty stable shape. Yet the shame and guilt I felt were overwhelming. Why didn’t I fight harder? How did I let this happen? I knew better, yet it took me years to overcome those irrational feelings.” These feelings of shame, guilt, self-doubt, and self-blame are nearly universal in survivors of sexual trauma. In children, they can be even worse, as children often don’t have an understanding that what is being done to them is wrong. They lack the language and the maturity to process the events, and ongoing abuse may be accompanied by threats to life of the child or their family members if they tell others, as was the case with Millman. She chose to process her abuse and the consequent difficulties she had by seeking psychiatric care. She took antidepressants and has been in psychoanalysis, both of which she has found to be helpful. Her treatment has tamed her demons, it is ongoing decades later and those demons have not vanished.
 

Abuse comes back in ‘a tidal wave’

Not surprisingly, Ferriss struggled with whether to make these events public. While so much of his story feels familiar to those of us who help patients process their trauma, it’s not completely typical. Ferriss remembered these episodes of sexual abuse “in high resolution,” while using ayahuasca, a hallucinogen, about 5 years ago. He describes suppressing and discounting these memories until he attended a 10-day silent retreat where he used psilocybin. I found it interesting that Ferriss fasted for 5 days before attending the retreat “to increase the depth of the experience.” He goes on to say, “Around day 6 of this silent retreat, all of this abuse came back to me like a tidal wave and it was replaying as if I was wearing a virtual reality headset. I was immersed, I wasn’t an observer, it was as though I was being traumatized and retraumatized 24/7.” He describes an excruciating and horrifying experience and he referred to it as a “psychotic break.”

Ferriss goes on to talk about how bringing these memories to light has affected him, how it’s explained many of his behaviors and ways of relating in a way that has helped him organize and understand his life.

“It was at the tail end of the retreat that I realized that these 17 seemingly inexplicable behaviors of mine – these vicious cycles or triggers that I had been treating like separate problems to be solved, were all downstream of this trauma. Oh, now that you click that puzzle piece into place, these really strange behaviors – this self-loathing, this rage that was seemingly so exaggerated and disproportionate – leading to the near-suicide I had in college – all these things fell into places making sense.” It gave him a sense of relief but was simultaneously overwhelming.

Both Ferriss and Millman talk about books and treatments that have been helpful to them. Their knowledge of trauma treatments and resources is impressive and can be found at: Tim Ferriss – My Healing Journey After Childhood Abuse (Includes Extensive Resource List). Their wish is to share their suffering as a way to help others, impart hope, and better connect.
 

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatry Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Let me tell you about Tim Ferriss. A few years ago, I started reading his best-selling book, The 4-Hour Body. Ferris detailed how he made himself into a one-man experiment – he’d make changes to his diet, checked his weight and his labs, maybe he even had metabolic studies done.

Courtesy Taylor Prinsen

He’d take these measures after soaking in hot baths, then ice baths, and while I admired his discipline, he did lose me during the chapter where he was using steroids. In the end, he advised a dairy-free, low-carbohydrate diet of green vegetables, beans or lentils, and protein for four meals a day, 6 days a week, with free-for-all eating on the 7th day. Then, there was a weight-lifting routine with kettle bells and ice packs to be placed on your shoulders for a set amount of time each day.

I may not remember the program’s details, but something about Ferris fascinated me. He brands himself as being a “human guinea pig,” about “lifestyle design,” and whatever that is, I like it. Perhaps I am attracted to the idea that we might control the trajectories of our generally uncontrollable lives.

Tim Ferriss graduated from Princeton, he’s written five best-selling books and has a popular podcast, he’s been a TED speaker, and he’s been on Fortune’s “40 under 40” list – and there’s so much more. Ferriss is brilliant, innovative, handsome, charismatic, prolific, extraordinarily athletic. I may have forgotten to mention that he was the National Chinese Kickboxing Champion and was a semifinalist in the World Champion Tango competition in Buenos Aires. He’s adventuresome and fearless, and if that isn’t enough, he speaks five languages. In the genetic dice roll, Mr. Ferriss did well, and he’s a driven and energetic hard worker who is open to new experiences.

I subscribe to the Tim Ferriss podcast – as of this writing, there are 466 episodes, with an incredible lineup of interviews with famous and successful guests. I also subscribe to his “5-Bullet Friday” email list where he mentions the interesting things he is reading, watching, learning about, or eating, and the products he is trying – single-ply toilet paper gets a thumbs down – then ends with a thought-provoking quote. This gentleman spends a tremendous amount of time searching and striving, working on himself and his own emotional growth and self-improvement, and yet he still has time for incredible explorations and experiences.

A search for psychic peace

Honestly, were it not for a few little details, I would like to be Tim Ferriss. Who wouldn’t? But what stops me from actually wanting to be Ferriss is that early on while listening to him, I realized that his drive has been fueled by intense psychic pain. He talks openly about being very close to suicide in college, about a tormenting mood disorder, demons to tame, and productivity as an antidote to a fear of failure, not always as a joy for life. There are moments that I have felt so sad for this remarkable stranger. Tim Ferriss is a searcher and what I believe he searches for most is his own psychic peace.

In a forum for psychiatrists, I wish I could write that Ferriss has found solace with our Food and Drug Administration–approved pharmaceuticals and with psychotherapy, but that’s not what he says. What Ferriss has found helpful, however, is psychedelics, and a wide variety of psychological and philosophical teachings ranging from meditation to Stoicism. And most notably, Ferriss has been an advocate for using hallucinogens as a legal medical intervention. Ferriss was one of four philanthropists who donated a total of $17 million to fund the Johns Hopkins Center for Psychedelic & Consciousness Research. He’s helped to move this field forward and to improve its credibility.

On Sept. 14, 2020, Tim Ferriss released a podcast he recorded with his dance partner and close friend, Debbie Millman, and when he recorded it, he was not certain he would release it. None of his usual sponsors endorsed during the podcast. He starts Episode #464 with, “For me, this is the most important podcast episode I’ve ever published. In it, I describe the most life-shaping, certainly the most difficult, and certainly the most transformative journey of my 43 years on this planet. I’ve never shared it before.”

I applaud Mr. Ferriss for going through with posting the podcast, a confessional about how he was repeatedly sexually molested over a 2-year period as a young child by a babysitter’s son. He worried about how this would affect his family, if they would be left feeling guilty or devastated. He says, “Please note that I expect to be completely overwhelmed emotionally and otherwise when this is published and please understand if I’m not able to reply to any outreach.”

Ferriss and Millman had a long discussion about their sexual abuse as children. Millman was abused by her stepfather at the age of 9, and she talks about confronting him many years later. Ferriss has not confronted his perpetrator, though he has contemplated doing so.

Sexual violence and violation at any age leaves people scarred. In a recent letter to the New York Times in response to President Trump’s words of support to Ghislaine Maxwell, the woman who helped Jeffrey Epstein find his victims, Baltimore psychiatrist Robin Weiss wrote, “Thirty-eight years ago, when I was 32, I was raped. I was married, I was a doctor – you might say I was in pretty stable shape. Yet the shame and guilt I felt were overwhelming. Why didn’t I fight harder? How did I let this happen? I knew better, yet it took me years to overcome those irrational feelings.” These feelings of shame, guilt, self-doubt, and self-blame are nearly universal in survivors of sexual trauma. In children, they can be even worse, as children often don’t have an understanding that what is being done to them is wrong. They lack the language and the maturity to process the events, and ongoing abuse may be accompanied by threats to life of the child or their family members if they tell others, as was the case with Millman. She chose to process her abuse and the consequent difficulties she had by seeking psychiatric care. She took antidepressants and has been in psychoanalysis, both of which she has found to be helpful. Her treatment has tamed her demons, it is ongoing decades later and those demons have not vanished.
 

Abuse comes back in ‘a tidal wave’

Not surprisingly, Ferriss struggled with whether to make these events public. While so much of his story feels familiar to those of us who help patients process their trauma, it’s not completely typical. Ferriss remembered these episodes of sexual abuse “in high resolution,” while using ayahuasca, a hallucinogen, about 5 years ago. He describes suppressing and discounting these memories until he attended a 10-day silent retreat where he used psilocybin. I found it interesting that Ferriss fasted for 5 days before attending the retreat “to increase the depth of the experience.” He goes on to say, “Around day 6 of this silent retreat, all of this abuse came back to me like a tidal wave and it was replaying as if I was wearing a virtual reality headset. I was immersed, I wasn’t an observer, it was as though I was being traumatized and retraumatized 24/7.” He describes an excruciating and horrifying experience and he referred to it as a “psychotic break.”

Ferriss goes on to talk about how bringing these memories to light has affected him, how it’s explained many of his behaviors and ways of relating in a way that has helped him organize and understand his life.

“It was at the tail end of the retreat that I realized that these 17 seemingly inexplicable behaviors of mine – these vicious cycles or triggers that I had been treating like separate problems to be solved, were all downstream of this trauma. Oh, now that you click that puzzle piece into place, these really strange behaviors – this self-loathing, this rage that was seemingly so exaggerated and disproportionate – leading to the near-suicide I had in college – all these things fell into places making sense.” It gave him a sense of relief but was simultaneously overwhelming.

Both Ferriss and Millman talk about books and treatments that have been helpful to them. Their knowledge of trauma treatments and resources is impressive and can be found at: Tim Ferriss – My Healing Journey After Childhood Abuse (Includes Extensive Resource List). Their wish is to share their suffering as a way to help others, impart hope, and better connect.
 

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatry Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Let me tell you about Tim Ferriss. A few years ago, I started reading his best-selling book, The 4-Hour Body. Ferris detailed how he made himself into a one-man experiment – he’d make changes to his diet, checked his weight and his labs, maybe he even had metabolic studies done.

Courtesy Taylor Prinsen

He’d take these measures after soaking in hot baths, then ice baths, and while I admired his discipline, he did lose me during the chapter where he was using steroids. In the end, he advised a dairy-free, low-carbohydrate diet of green vegetables, beans or lentils, and protein for four meals a day, 6 days a week, with free-for-all eating on the 7th day. Then, there was a weight-lifting routine with kettle bells and ice packs to be placed on your shoulders for a set amount of time each day.

I may not remember the program’s details, but something about Ferris fascinated me. He brands himself as being a “human guinea pig,” about “lifestyle design,” and whatever that is, I like it. Perhaps I am attracted to the idea that we might control the trajectories of our generally uncontrollable lives.

Tim Ferriss graduated from Princeton, he’s written five best-selling books and has a popular podcast, he’s been a TED speaker, and he’s been on Fortune’s “40 under 40” list – and there’s so much more. Ferriss is brilliant, innovative, handsome, charismatic, prolific, extraordinarily athletic. I may have forgotten to mention that he was the National Chinese Kickboxing Champion and was a semifinalist in the World Champion Tango competition in Buenos Aires. He’s adventuresome and fearless, and if that isn’t enough, he speaks five languages. In the genetic dice roll, Mr. Ferriss did well, and he’s a driven and energetic hard worker who is open to new experiences.

I subscribe to the Tim Ferriss podcast – as of this writing, there are 466 episodes, with an incredible lineup of interviews with famous and successful guests. I also subscribe to his “5-Bullet Friday” email list where he mentions the interesting things he is reading, watching, learning about, or eating, and the products he is trying – single-ply toilet paper gets a thumbs down – then ends with a thought-provoking quote. This gentleman spends a tremendous amount of time searching and striving, working on himself and his own emotional growth and self-improvement, and yet he still has time for incredible explorations and experiences.

A search for psychic peace

Honestly, were it not for a few little details, I would like to be Tim Ferriss. Who wouldn’t? But what stops me from actually wanting to be Ferriss is that early on while listening to him, I realized that his drive has been fueled by intense psychic pain. He talks openly about being very close to suicide in college, about a tormenting mood disorder, demons to tame, and productivity as an antidote to a fear of failure, not always as a joy for life. There are moments that I have felt so sad for this remarkable stranger. Tim Ferriss is a searcher and what I believe he searches for most is his own psychic peace.

In a forum for psychiatrists, I wish I could write that Ferriss has found solace with our Food and Drug Administration–approved pharmaceuticals and with psychotherapy, but that’s not what he says. What Ferriss has found helpful, however, is psychedelics, and a wide variety of psychological and philosophical teachings ranging from meditation to Stoicism. And most notably, Ferriss has been an advocate for using hallucinogens as a legal medical intervention. Ferriss was one of four philanthropists who donated a total of $17 million to fund the Johns Hopkins Center for Psychedelic & Consciousness Research. He’s helped to move this field forward and to improve its credibility.

On Sept. 14, 2020, Tim Ferriss released a podcast he recorded with his dance partner and close friend, Debbie Millman, and when he recorded it, he was not certain he would release it. None of his usual sponsors endorsed during the podcast. He starts Episode #464 with, “For me, this is the most important podcast episode I’ve ever published. In it, I describe the most life-shaping, certainly the most difficult, and certainly the most transformative journey of my 43 years on this planet. I’ve never shared it before.”

I applaud Mr. Ferriss for going through with posting the podcast, a confessional about how he was repeatedly sexually molested over a 2-year period as a young child by a babysitter’s son. He worried about how this would affect his family, if they would be left feeling guilty or devastated. He says, “Please note that I expect to be completely overwhelmed emotionally and otherwise when this is published and please understand if I’m not able to reply to any outreach.”

Ferriss and Millman had a long discussion about their sexual abuse as children. Millman was abused by her stepfather at the age of 9, and she talks about confronting him many years later. Ferriss has not confronted his perpetrator, though he has contemplated doing so.

Sexual violence and violation at any age leaves people scarred. In a recent letter to the New York Times in response to President Trump’s words of support to Ghislaine Maxwell, the woman who helped Jeffrey Epstein find his victims, Baltimore psychiatrist Robin Weiss wrote, “Thirty-eight years ago, when I was 32, I was raped. I was married, I was a doctor – you might say I was in pretty stable shape. Yet the shame and guilt I felt were overwhelming. Why didn’t I fight harder? How did I let this happen? I knew better, yet it took me years to overcome those irrational feelings.” These feelings of shame, guilt, self-doubt, and self-blame are nearly universal in survivors of sexual trauma. In children, they can be even worse, as children often don’t have an understanding that what is being done to them is wrong. They lack the language and the maturity to process the events, and ongoing abuse may be accompanied by threats to life of the child or their family members if they tell others, as was the case with Millman. She chose to process her abuse and the consequent difficulties she had by seeking psychiatric care. She took antidepressants and has been in psychoanalysis, both of which she has found to be helpful. Her treatment has tamed her demons, it is ongoing decades later and those demons have not vanished.
 

Abuse comes back in ‘a tidal wave’

Not surprisingly, Ferriss struggled with whether to make these events public. While so much of his story feels familiar to those of us who help patients process their trauma, it’s not completely typical. Ferriss remembered these episodes of sexual abuse “in high resolution,” while using ayahuasca, a hallucinogen, about 5 years ago. He describes suppressing and discounting these memories until he attended a 10-day silent retreat where he used psilocybin. I found it interesting that Ferriss fasted for 5 days before attending the retreat “to increase the depth of the experience.” He goes on to say, “Around day 6 of this silent retreat, all of this abuse came back to me like a tidal wave and it was replaying as if I was wearing a virtual reality headset. I was immersed, I wasn’t an observer, it was as though I was being traumatized and retraumatized 24/7.” He describes an excruciating and horrifying experience and he referred to it as a “psychotic break.”

Ferriss goes on to talk about how bringing these memories to light has affected him, how it’s explained many of his behaviors and ways of relating in a way that has helped him organize and understand his life.

“It was at the tail end of the retreat that I realized that these 17 seemingly inexplicable behaviors of mine – these vicious cycles or triggers that I had been treating like separate problems to be solved, were all downstream of this trauma. Oh, now that you click that puzzle piece into place, these really strange behaviors – this self-loathing, this rage that was seemingly so exaggerated and disproportionate – leading to the near-suicide I had in college – all these things fell into places making sense.” It gave him a sense of relief but was simultaneously overwhelming.

Both Ferriss and Millman talk about books and treatments that have been helpful to them. Their knowledge of trauma treatments and resources is impressive and can be found at: Tim Ferriss – My Healing Journey After Childhood Abuse (Includes Extensive Resource List). Their wish is to share their suffering as a way to help others, impart hope, and better connect.
 

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatry Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Suicidality appears to have increased sharply in Israel during the initial nationwide lockdown implemented in response to the COVID-19 pandemic, Gil Zalsman, MD, MHA, reported at the virtual congress of the European College of Neuropsychopharmacology.

He presented highlights from a soon-to-be-published analysis of the content of online chat sessions fielded by a national crisis hotline (Sahar.org.il) during the first 6 months of 2020, compared with January through June 2019, in the pre-COVID-19 era.

It’s far too early to say whether actual deaths tied to suicide rose significantly during the spring lockdown, since medical examiners often take a long time before ruling suicide as cause of death. But this much is clear: The number of suicide-related chat sessions recorded at the volunteer-staffed national hotline during April 2020 was two-and-a-half times greater than in April 2019, and threefold greater in May 2020 than a year earlier, according to Dr. Zalsman, professor of psychiatry at Tel Aviv University and director of the Geha Mental Health Center in Petach Tikva, Israel, where he also directs an adolescent day unit.

The proportion of chats handled at the crisis hotline, many of them concerned with the standard topics – relationships, stress, fears, anxiety, and other non–suicide-related issues – was 48% greater in the first half of 2020, compared with a year earlier. Indeed, the pandemic is putting an enormous strain on crisis hotlines the world over.

“Everybody who is working hotlines knows that they’re falling apart. There are too many calls, too many chats. They need to multiply their volunteers,” Dr. Zalsman said.

The number of suicide-related online chats jumped the week of March 12, when schools closed across Israel and a partial lockdown began. The peak in suicide-related chats occurred beginning the week of April 17, when the forced total lockdown was declared.

“Everything was closed. You couldn’t go out or the police would arrest you,” Dr. Zalsman recalled.

The suicide-related chat count started to drop off in mid-May, when schools reopened, and continued to decline through the end of June.

Only a small percentage of suicide-related chats were deemed by crisis hotline volunteers and their supervisors to be truly life-threatening situations necessitating a call to the police. But the number of such exchanges was significantly greater in April and May 2020 than in January and February, or in April and May 2019.

Use of the crisis hotline is ordinarily skewed toward tech-savvy young people, or as Dr. Zalsman called them, “kids who live inside their computers.” He note that the psychological impact of the pandemic on children and adolescents is largely unexplored research territory to date.

“For some young kids, the fear that they will contaminate their parents or grandparents is horrifying. You can kill your grandfather by coughing,” Dr. Zalsman said.
 

Older people also seek help

A finding that he and his coinvestigators didn’t anticipate was the significantly increased use of the service by individuals aged 65 and older during the pandemic. This underscores the increased vulnerability of older people, which stems in part from their heightened risk for severe infection and consequent need for prolonged physical isolation, he said.

The conventional thinking among suicidologists is that during times of crisis – wars, natural disasters – suicidality plunges, then rises quickly afterward.

“People withhold themselves. When there’s a big danger from outside they ignore the danger from inside. And once the danger from outside is gone, they’re left with emptiness, unemployment, economic crisis, and they start” taking their own lives, Dr. Zalsman explained. He expects suicidality to increase after the pandemic, or as the Israeli crisis hotline data suggest, perhaps even during it, for multiple reasons. Patients with preexisting psychiatric disorders are often going untreated. The prolonged physical isolation causes emotional difficulties for some people, especially when accompanied by social isolation and loneliness. There is grief over the loss of friends and relatives because of COVID-19. And there is an expectation of looming economic hardship, with mounting unemployment and bankruptcies.

Dr. Zalsman reported having no financial conflicts regarding his study, conducted free of commercial support.

[email protected]

SOURCE: Zalsman G. ECNP 2020, Session TP.06.

Suicidality appears to have increased sharply in Israel during the initial nationwide lockdown implemented in response to the COVID-19 pandemic, Gil Zalsman, MD, MHA, reported at the virtual congress of the European College of Neuropsychopharmacology.

He presented highlights from a soon-to-be-published analysis of the content of online chat sessions fielded by a national crisis hotline (Sahar.org.il) during the first 6 months of 2020, compared with January through June 2019, in the pre-COVID-19 era.

It’s far too early to say whether actual deaths tied to suicide rose significantly during the spring lockdown, since medical examiners often take a long time before ruling suicide as cause of death. But this much is clear: The number of suicide-related chat sessions recorded at the volunteer-staffed national hotline during April 2020 was two-and-a-half times greater than in April 2019, and threefold greater in May 2020 than a year earlier, according to Dr. Zalsman, professor of psychiatry at Tel Aviv University and director of the Geha Mental Health Center in Petach Tikva, Israel, where he also directs an adolescent day unit.

The proportion of chats handled at the crisis hotline, many of them concerned with the standard topics – relationships, stress, fears, anxiety, and other non–suicide-related issues – was 48% greater in the first half of 2020, compared with a year earlier. Indeed, the pandemic is putting an enormous strain on crisis hotlines the world over.

“Everybody who is working hotlines knows that they’re falling apart. There are too many calls, too many chats. They need to multiply their volunteers,” Dr. Zalsman said.

The number of suicide-related online chats jumped the week of March 12, when schools closed across Israel and a partial lockdown began. The peak in suicide-related chats occurred beginning the week of April 17, when the forced total lockdown was declared.

“Everything was closed. You couldn’t go out or the police would arrest you,” Dr. Zalsman recalled.

The suicide-related chat count started to drop off in mid-May, when schools reopened, and continued to decline through the end of June.

Only a small percentage of suicide-related chats were deemed by crisis hotline volunteers and their supervisors to be truly life-threatening situations necessitating a call to the police. But the number of such exchanges was significantly greater in April and May 2020 than in January and February, or in April and May 2019.

Use of the crisis hotline is ordinarily skewed toward tech-savvy young people, or as Dr. Zalsman called them, “kids who live inside their computers.” He note that the psychological impact of the pandemic on children and adolescents is largely unexplored research territory to date.

“For some young kids, the fear that they will contaminate their parents or grandparents is horrifying. You can kill your grandfather by coughing,” Dr. Zalsman said.
 

Older people also seek help

A finding that he and his coinvestigators didn’t anticipate was the significantly increased use of the service by individuals aged 65 and older during the pandemic. This underscores the increased vulnerability of older people, which stems in part from their heightened risk for severe infection and consequent need for prolonged physical isolation, he said.

The conventional thinking among suicidologists is that during times of crisis – wars, natural disasters – suicidality plunges, then rises quickly afterward.

“People withhold themselves. When there’s a big danger from outside they ignore the danger from inside. And once the danger from outside is gone, they’re left with emptiness, unemployment, economic crisis, and they start” taking their own lives, Dr. Zalsman explained. He expects suicidality to increase after the pandemic, or as the Israeli crisis hotline data suggest, perhaps even during it, for multiple reasons. Patients with preexisting psychiatric disorders are often going untreated. The prolonged physical isolation causes emotional difficulties for some people, especially when accompanied by social isolation and loneliness. There is grief over the loss of friends and relatives because of COVID-19. And there is an expectation of looming economic hardship, with mounting unemployment and bankruptcies.

Dr. Zalsman reported having no financial conflicts regarding his study, conducted free of commercial support.

[email protected]

SOURCE: Zalsman G. ECNP 2020, Session TP.06.

Suicidality appears to have increased sharply in Israel during the initial nationwide lockdown implemented in response to the COVID-19 pandemic, Gil Zalsman, MD, MHA, reported at the virtual congress of the European College of Neuropsychopharmacology.

He presented highlights from a soon-to-be-published analysis of the content of online chat sessions fielded by a national crisis hotline (Sahar.org.il) during the first 6 months of 2020, compared with January through June 2019, in the pre-COVID-19 era.

It’s far too early to say whether actual deaths tied to suicide rose significantly during the spring lockdown, since medical examiners often take a long time before ruling suicide as cause of death. But this much is clear: The number of suicide-related chat sessions recorded at the volunteer-staffed national hotline during April 2020 was two-and-a-half times greater than in April 2019, and threefold greater in May 2020 than a year earlier, according to Dr. Zalsman, professor of psychiatry at Tel Aviv University and director of the Geha Mental Health Center in Petach Tikva, Israel, where he also directs an adolescent day unit.

The proportion of chats handled at the crisis hotline, many of them concerned with the standard topics – relationships, stress, fears, anxiety, and other non–suicide-related issues – was 48% greater in the first half of 2020, compared with a year earlier. Indeed, the pandemic is putting an enormous strain on crisis hotlines the world over.

“Everybody who is working hotlines knows that they’re falling apart. There are too many calls, too many chats. They need to multiply their volunteers,” Dr. Zalsman said.

The number of suicide-related online chats jumped the week of March 12, when schools closed across Israel and a partial lockdown began. The peak in suicide-related chats occurred beginning the week of April 17, when the forced total lockdown was declared.

“Everything was closed. You couldn’t go out or the police would arrest you,” Dr. Zalsman recalled.

The suicide-related chat count started to drop off in mid-May, when schools reopened, and continued to decline through the end of June.

Only a small percentage of suicide-related chats were deemed by crisis hotline volunteers and their supervisors to be truly life-threatening situations necessitating a call to the police. But the number of such exchanges was significantly greater in April and May 2020 than in January and February, or in April and May 2019.

Use of the crisis hotline is ordinarily skewed toward tech-savvy young people, or as Dr. Zalsman called them, “kids who live inside their computers.” He note that the psychological impact of the pandemic on children and adolescents is largely unexplored research territory to date.

“For some young kids, the fear that they will contaminate their parents or grandparents is horrifying. You can kill your grandfather by coughing,” Dr. Zalsman said.
 

Older people also seek help

A finding that he and his coinvestigators didn’t anticipate was the significantly increased use of the service by individuals aged 65 and older during the pandemic. This underscores the increased vulnerability of older people, which stems in part from their heightened risk for severe infection and consequent need for prolonged physical isolation, he said.

The conventional thinking among suicidologists is that during times of crisis – wars, natural disasters – suicidality plunges, then rises quickly afterward.

“People withhold themselves. When there’s a big danger from outside they ignore the danger from inside. And once the danger from outside is gone, they’re left with emptiness, unemployment, economic crisis, and they start” taking their own lives, Dr. Zalsman explained. He expects suicidality to increase after the pandemic, or as the Israeli crisis hotline data suggest, perhaps even during it, for multiple reasons. Patients with preexisting psychiatric disorders are often going untreated. The prolonged physical isolation causes emotional difficulties for some people, especially when accompanied by social isolation and loneliness. There is grief over the loss of friends and relatives because of COVID-19. And there is an expectation of looming economic hardship, with mounting unemployment and bankruptcies.

Dr. Zalsman reported having no financial conflicts regarding his study, conducted free of commercial support.

[email protected]

SOURCE: Zalsman G. ECNP 2020, Session TP.06.

Johnson & Johnson (J&J) on Wednesday said it advanced into phase 3 testing of its COVID-19 vaccine candidate, which uses the same technology as an Ebola vaccine already approved by European regulators.

The National Institute of Allergy and Infectious Diseases, which is aiding Johnson & Johnson with development, described this in a news release as the fourth phase 3 clinical trial of evaluating an investigational vaccine for coronavirus disease.

This NIAID tally tracks products likely to be presented soon for Food and Drug Administration approval. (The World Health Organization’s COVID vaccine tracker lists nine candidates as having reached this stage, including products developed in Russia and China.)

As many as 60,000 volunteers will be enrolled in the trial, with about 215 clinical research sites expected to participate, NIAID said. The vaccine will be tested in the United States and abroad.

The start of this test, known as the ENSEMBLE trial, follows positive results from a Phase 1/2a clinical study, which involved a single vaccination. The results of this study have been submitted to medRxiv and are set to be published online imminently.

New Brunswick, N.J–based J&J said it intends to offer the vaccine on “a not-for-profit basis for emergency pandemic use.” If testing proceeds well, J&J might seek an emergency use clearance for the vaccine, which could possibly allow the first batches to be made available in early 2021.

J&J’s vaccine is unusual in that it will be tested based on a single dose, while other advanced candidates have been tested in two-dose regimens.

J&J on Wednesday also released the study protocol for its phase 3 test. The developers of the other late-stage COVID vaccine candidates also have done this, as reported by Medscape Medical News. Because of the great interest in the COVID vaccine, the American Medical Association had last month asked the FDA to keep physicians informed of their COVID-19 vaccine review process.
 

Trials and tribulations

One of these experimental COVID vaccines already has had a setback in phase 3 testing, which is a fairly routine occurrence in drug development. But with a pandemic still causing deaths and disrupting lives around the world, there has been intense interest in each step of the effort to develop a COVID vaccine.

AstraZeneca PLC earlier this month announced a temporary cessation of all their coronavirus vaccine trials to investigate an “unexplained illness” that arose in a participant, as reported by Medscape Medical News.

On September 12, AstraZeneca announced that clinical trials for the AZD1222, which it developed with Oxford University, had resumed in the United Kingdom. On Wednesday, CNBC said Health and Human Services Secretary Alex Azar told the news station that AstraZeneca’s late-stage coronavirus vaccine trial in the United States remains on hold until safety concerns are resolved, a critical issue with all the fast-track COVID vaccines now being tested.

“Look at the AstraZeneca program, phase 3 clinical trial, a lot of hope. [A] single serious adverse event report in the United Kingdom, global shutdown, and [a] hold of the clinical trials,” Mr. Azar told CNBC.

The New York Times has reported on concerns stemming from serious neurologic illnesses in two participants, both women, who received AstraZeneca’s experimental vaccine in Britain.

The Senate Health, Education, Labor and Pensions Committee on Wednesday separately held a hearing with the leaders of the FDA and the Centers of Disease Control and Prevention, allowing an airing of lawmakers’ concerns about a potential rush to approve a COVID vaccine.
 

Details of J&J trial

The J&J trial is designed primarily to determine if the investigational vaccine can prevent moderate to severe COVID-19 after a single dose. It also is designed to examine whether the vaccine can prevent COVID-19 requiring medical intervention and if the vaccine can prevent milder cases of COVID-19 and asymptomatic SARS-CoV-2 infection, NIAID said.

Principal investigators for the phase 3 trial of the J & J vaccine are Paul A. Goepfert, MD, director of the Alabama Vaccine Research Clinic at the University of Alabama in Birmingham; Beatriz Grinsztejn, MD, PhD, director of the Laboratory of Clinical Research on HIV/AIDS at the Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; and Glenda E. Gray, MBBCh, president and chief executive officer of the South African Medical Research Council and coprincipal investigator of the HIV Vaccine Trials Network.

This article first appeared on Medscape.com.

Johnson & Johnson (J&J) on Wednesday said it advanced into phase 3 testing of its COVID-19 vaccine candidate, which uses the same technology as an Ebola vaccine already approved by European regulators.

The National Institute of Allergy and Infectious Diseases, which is aiding Johnson & Johnson with development, described this in a news release as the fourth phase 3 clinical trial of evaluating an investigational vaccine for coronavirus disease.

This NIAID tally tracks products likely to be presented soon for Food and Drug Administration approval. (The World Health Organization’s COVID vaccine tracker lists nine candidates as having reached this stage, including products developed in Russia and China.)

As many as 60,000 volunteers will be enrolled in the trial, with about 215 clinical research sites expected to participate, NIAID said. The vaccine will be tested in the United States and abroad.

The start of this test, known as the ENSEMBLE trial, follows positive results from a Phase 1/2a clinical study, which involved a single vaccination. The results of this study have been submitted to medRxiv and are set to be published online imminently.

New Brunswick, N.J–based J&J said it intends to offer the vaccine on “a not-for-profit basis for emergency pandemic use.” If testing proceeds well, J&J might seek an emergency use clearance for the vaccine, which could possibly allow the first batches to be made available in early 2021.

J&J’s vaccine is unusual in that it will be tested based on a single dose, while other advanced candidates have been tested in two-dose regimens.

J&J on Wednesday also released the study protocol for its phase 3 test. The developers of the other late-stage COVID vaccine candidates also have done this, as reported by Medscape Medical News. Because of the great interest in the COVID vaccine, the American Medical Association had last month asked the FDA to keep physicians informed of their COVID-19 vaccine review process.
 

Trials and tribulations

One of these experimental COVID vaccines already has had a setback in phase 3 testing, which is a fairly routine occurrence in drug development. But with a pandemic still causing deaths and disrupting lives around the world, there has been intense interest in each step of the effort to develop a COVID vaccine.

AstraZeneca PLC earlier this month announced a temporary cessation of all their coronavirus vaccine trials to investigate an “unexplained illness” that arose in a participant, as reported by Medscape Medical News.

On September 12, AstraZeneca announced that clinical trials for the AZD1222, which it developed with Oxford University, had resumed in the United Kingdom. On Wednesday, CNBC said Health and Human Services Secretary Alex Azar told the news station that AstraZeneca’s late-stage coronavirus vaccine trial in the United States remains on hold until safety concerns are resolved, a critical issue with all the fast-track COVID vaccines now being tested.

“Look at the AstraZeneca program, phase 3 clinical trial, a lot of hope. [A] single serious adverse event report in the United Kingdom, global shutdown, and [a] hold of the clinical trials,” Mr. Azar told CNBC.

The New York Times has reported on concerns stemming from serious neurologic illnesses in two participants, both women, who received AstraZeneca’s experimental vaccine in Britain.

The Senate Health, Education, Labor and Pensions Committee on Wednesday separately held a hearing with the leaders of the FDA and the Centers of Disease Control and Prevention, allowing an airing of lawmakers’ concerns about a potential rush to approve a COVID vaccine.
 

Details of J&J trial

The J&J trial is designed primarily to determine if the investigational vaccine can prevent moderate to severe COVID-19 after a single dose. It also is designed to examine whether the vaccine can prevent COVID-19 requiring medical intervention and if the vaccine can prevent milder cases of COVID-19 and asymptomatic SARS-CoV-2 infection, NIAID said.

Principal investigators for the phase 3 trial of the J & J vaccine are Paul A. Goepfert, MD, director of the Alabama Vaccine Research Clinic at the University of Alabama in Birmingham; Beatriz Grinsztejn, MD, PhD, director of the Laboratory of Clinical Research on HIV/AIDS at the Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; and Glenda E. Gray, MBBCh, president and chief executive officer of the South African Medical Research Council and coprincipal investigator of the HIV Vaccine Trials Network.

This article first appeared on Medscape.com.

Johnson & Johnson (J&J) on Wednesday said it advanced into phase 3 testing of its COVID-19 vaccine candidate, which uses the same technology as an Ebola vaccine already approved by European regulators.

The National Institute of Allergy and Infectious Diseases, which is aiding Johnson & Johnson with development, described this in a news release as the fourth phase 3 clinical trial of evaluating an investigational vaccine for coronavirus disease.

This NIAID tally tracks products likely to be presented soon for Food and Drug Administration approval. (The World Health Organization’s COVID vaccine tracker lists nine candidates as having reached this stage, including products developed in Russia and China.)

As many as 60,000 volunteers will be enrolled in the trial, with about 215 clinical research sites expected to participate, NIAID said. The vaccine will be tested in the United States and abroad.

The start of this test, known as the ENSEMBLE trial, follows positive results from a Phase 1/2a clinical study, which involved a single vaccination. The results of this study have been submitted to medRxiv and are set to be published online imminently.

New Brunswick, N.J–based J&J said it intends to offer the vaccine on “a not-for-profit basis for emergency pandemic use.” If testing proceeds well, J&J might seek an emergency use clearance for the vaccine, which could possibly allow the first batches to be made available in early 2021.

J&J’s vaccine is unusual in that it will be tested based on a single dose, while other advanced candidates have been tested in two-dose regimens.

J&J on Wednesday also released the study protocol for its phase 3 test. The developers of the other late-stage COVID vaccine candidates also have done this, as reported by Medscape Medical News. Because of the great interest in the COVID vaccine, the American Medical Association had last month asked the FDA to keep physicians informed of their COVID-19 vaccine review process.
 

Trials and tribulations

One of these experimental COVID vaccines already has had a setback in phase 3 testing, which is a fairly routine occurrence in drug development. But with a pandemic still causing deaths and disrupting lives around the world, there has been intense interest in each step of the effort to develop a COVID vaccine.

AstraZeneca PLC earlier this month announced a temporary cessation of all their coronavirus vaccine trials to investigate an “unexplained illness” that arose in a participant, as reported by Medscape Medical News.

On September 12, AstraZeneca announced that clinical trials for the AZD1222, which it developed with Oxford University, had resumed in the United Kingdom. On Wednesday, CNBC said Health and Human Services Secretary Alex Azar told the news station that AstraZeneca’s late-stage coronavirus vaccine trial in the United States remains on hold until safety concerns are resolved, a critical issue with all the fast-track COVID vaccines now being tested.

“Look at the AstraZeneca program, phase 3 clinical trial, a lot of hope. [A] single serious adverse event report in the United Kingdom, global shutdown, and [a] hold of the clinical trials,” Mr. Azar told CNBC.

The New York Times has reported on concerns stemming from serious neurologic illnesses in two participants, both women, who received AstraZeneca’s experimental vaccine in Britain.

The Senate Health, Education, Labor and Pensions Committee on Wednesday separately held a hearing with the leaders of the FDA and the Centers of Disease Control and Prevention, allowing an airing of lawmakers’ concerns about a potential rush to approve a COVID vaccine.
 

Details of J&J trial

The J&J trial is designed primarily to determine if the investigational vaccine can prevent moderate to severe COVID-19 after a single dose. It also is designed to examine whether the vaccine can prevent COVID-19 requiring medical intervention and if the vaccine can prevent milder cases of COVID-19 and asymptomatic SARS-CoV-2 infection, NIAID said.

Principal investigators for the phase 3 trial of the J & J vaccine are Paul A. Goepfert, MD, director of the Alabama Vaccine Research Clinic at the University of Alabama in Birmingham; Beatriz Grinsztejn, MD, PhD, director of the Laboratory of Clinical Research on HIV/AIDS at the Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; and Glenda E. Gray, MBBCh, president and chief executive officer of the South African Medical Research Council and coprincipal investigator of the HIV Vaccine Trials Network.

This article first appeared on Medscape.com.

Below is a case involving a patient who is not yet ready to quit smoking. We later provide treatment recommendations for this patient based on a new guideline from the American Thoracic Society.

Case

A 58-year-old female comes into the office for a physical exam. She has been smoking two packs a day since she was 23 years of age. You have tried at previous visits to get her to quit, but she hasn’t been interested. The patient says she has a lot of stress, and that it is still not the right time for her to stop smoking. You tell her she needs to quit and, though the patient understands that quitting would be beneficial for her health, she just isn’t ready to try to kick the habit. How do you proceed?

The Guideline in context

Even though this patient stated that she is not ready to stop smoking, she is still a candidate for pharmacological treatment for her tobacco dependence and can be offered varenicline, according to the ATS guideline.¹

It is imperative that tobacco cessation is addressed with patients in the most effective and comprehensive ways possible. In a previously published column, we have discussed the ATS’ recommended approaches for treating patients who are ready to stop smoking cigarettes. The reality is that many patients, if not most, are not ready to quit when we speak to them during any given office visit. The ATS guideline addresses this critical issue by recommending treatment with varenicline in patients who are not ready to stop smoking. It also states that this is a better strategy than waiting to start treatment until patients say they are ready for it.

This recommendation – to prescribe varenicline to smokers even when they are not ready to quit smoking – is based on solid clinical trial evidence. Research has shown that behavior change is dynamic and that the decision to stop smoking is not always a planned one.¹ Patients often make quit attempts between office visits, and are often successful in those attempts. Because the decision to try to stop smoking is influenced by the satisfaction and physical addiction that comes from smoking, a medication such as varenicline that is a partial agonist/antagonist at the alpha4-beta2 nicotinic receptor might increase the likelihood that a patient would decide to try to stop smoking. This is because taking this type of a drug would lead the patient to no longer experience the reinforcing effects of nicotine.² This hypothesis was examined in five randomized trials.¹

In these studies, regular smokers who were not ready to make a quit attempt were randomized to varenicline versus placebo. Twice as many individuals who took varenicline stopped smoking 6 months after starting treatment.¹

Suggested treatment

This patient should be offered varenicline. This individual meets the criteria for this treatment according to the ATS guideline in that the patient is a regular smoker who doesn’t think she is ready to stop smoking but understands she needs to stop and is open to taking medication to assist her with quitting.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. Dr. Sprogell is a third-year resident in the family medicine residency program at Abington Jefferson Health. They have no conflicts related to the content of this piece. For questions or comments, feel free to contact Dr. Skolnik on Twitter @NeilSkolnik.

References

1. Leone F T et al. Initiating pharmacologic treatment in tobacco-dependent adults: An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020 Jul 15;202(2):e5–e31.

2. Ebbert JO et al. Varenicline for smoking cessation: Efficacy, safety, and treatment recommendations. Patient Prefer Adherence. 2010;4:355-62.
 

Below is a case involving a patient who is not yet ready to quit smoking. We later provide treatment recommendations for this patient based on a new guideline from the American Thoracic Society.

Case

A 58-year-old female comes into the office for a physical exam. She has been smoking two packs a day since she was 23 years of age. You have tried at previous visits to get her to quit, but she hasn’t been interested. The patient says she has a lot of stress, and that it is still not the right time for her to stop smoking. You tell her she needs to quit and, though the patient understands that quitting would be beneficial for her health, she just isn’t ready to try to kick the habit. How do you proceed?

The Guideline in context

Even though this patient stated that she is not ready to stop smoking, she is still a candidate for pharmacological treatment for her tobacco dependence and can be offered varenicline, according to the ATS guideline.¹

It is imperative that tobacco cessation is addressed with patients in the most effective and comprehensive ways possible. In a previously published column, we have discussed the ATS’ recommended approaches for treating patients who are ready to stop smoking cigarettes. The reality is that many patients, if not most, are not ready to quit when we speak to them during any given office visit. The ATS guideline addresses this critical issue by recommending treatment with varenicline in patients who are not ready to stop smoking. It also states that this is a better strategy than waiting to start treatment until patients say they are ready for it.

This recommendation – to prescribe varenicline to smokers even when they are not ready to quit smoking – is based on solid clinical trial evidence. Research has shown that behavior change is dynamic and that the decision to stop smoking is not always a planned one.¹ Patients often make quit attempts between office visits, and are often successful in those attempts. Because the decision to try to stop smoking is influenced by the satisfaction and physical addiction that comes from smoking, a medication such as varenicline that is a partial agonist/antagonist at the alpha4-beta2 nicotinic receptor might increase the likelihood that a patient would decide to try to stop smoking. This is because taking this type of a drug would lead the patient to no longer experience the reinforcing effects of nicotine.² This hypothesis was examined in five randomized trials.¹

In these studies, regular smokers who were not ready to make a quit attempt were randomized to varenicline versus placebo. Twice as many individuals who took varenicline stopped smoking 6 months after starting treatment.¹

Suggested treatment

This patient should be offered varenicline. This individual meets the criteria for this treatment according to the ATS guideline in that the patient is a regular smoker who doesn’t think she is ready to stop smoking but understands she needs to stop and is open to taking medication to assist her with quitting.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. Dr. Sprogell is a third-year resident in the family medicine residency program at Abington Jefferson Health. They have no conflicts related to the content of this piece. For questions or comments, feel free to contact Dr. Skolnik on Twitter @NeilSkolnik.

References

1. Leone F T et al. Initiating pharmacologic treatment in tobacco-dependent adults: An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020 Jul 15;202(2):e5–e31.

2. Ebbert JO et al. Varenicline for smoking cessation: Efficacy, safety, and treatment recommendations. Patient Prefer Adherence. 2010;4:355-62.
 

Below is a case involving a patient who is not yet ready to quit smoking. We later provide treatment recommendations for this patient based on a new guideline from the American Thoracic Society.

Case

A 58-year-old female comes into the office for a physical exam. She has been smoking two packs a day since she was 23 years of age. You have tried at previous visits to get her to quit, but she hasn’t been interested. The patient says she has a lot of stress, and that it is still not the right time for her to stop smoking. You tell her she needs to quit and, though the patient understands that quitting would be beneficial for her health, she just isn’t ready to try to kick the habit. How do you proceed?

The Guideline in context

Even though this patient stated that she is not ready to stop smoking, she is still a candidate for pharmacological treatment for her tobacco dependence and can be offered varenicline, according to the ATS guideline.¹

It is imperative that tobacco cessation is addressed with patients in the most effective and comprehensive ways possible. In a previously published column, we have discussed the ATS’ recommended approaches for treating patients who are ready to stop smoking cigarettes. The reality is that many patients, if not most, are not ready to quit when we speak to them during any given office visit. The ATS guideline addresses this critical issue by recommending treatment with varenicline in patients who are not ready to stop smoking. It also states that this is a better strategy than waiting to start treatment until patients say they are ready for it.

This recommendation – to prescribe varenicline to smokers even when they are not ready to quit smoking – is based on solid clinical trial evidence. Research has shown that behavior change is dynamic and that the decision to stop smoking is not always a planned one.¹ Patients often make quit attempts between office visits, and are often successful in those attempts. Because the decision to try to stop smoking is influenced by the satisfaction and physical addiction that comes from smoking, a medication such as varenicline that is a partial agonist/antagonist at the alpha4-beta2 nicotinic receptor might increase the likelihood that a patient would decide to try to stop smoking. This is because taking this type of a drug would lead the patient to no longer experience the reinforcing effects of nicotine.² This hypothesis was examined in five randomized trials.¹

In these studies, regular smokers who were not ready to make a quit attempt were randomized to varenicline versus placebo. Twice as many individuals who took varenicline stopped smoking 6 months after starting treatment.¹

Suggested treatment

This patient should be offered varenicline. This individual meets the criteria for this treatment according to the ATS guideline in that the patient is a regular smoker who doesn’t think she is ready to stop smoking but understands she needs to stop and is open to taking medication to assist her with quitting.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. Dr. Sprogell is a third-year resident in the family medicine residency program at Abington Jefferson Health. They have no conflicts related to the content of this piece. For questions or comments, feel free to contact Dr. Skolnik on Twitter @NeilSkolnik.

References

1. Leone F T et al. Initiating pharmacologic treatment in tobacco-dependent adults: An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020 Jul 15;202(2):e5–e31.

2. Ebbert JO et al. Varenicline for smoking cessation: Efficacy, safety, and treatment recommendations. Patient Prefer Adherence. 2010;4:355-62.