Depression

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

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

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

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

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

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

At-home, noninvasive auricular vagus nerve stimulation (aVNS) therapy is well-tolerated and associated with a significant reduction in postpartum depressive and anxiety symptoms, new research suggests.

In a small proof-of-concept pilot study of 25 women with postpartum depression receiving 6 weeks of daily aVNS treatment, results showed that 74% achieved response and 61% achieved remission, as shown in reduced scores on the Hamilton Rating Scale for Depression (HAM-D17).

Although invasive electrical stimulation of the vagus nerve was approved by the U.S. Food and Drug Administration for treatment-resistant depression in 2005, it involves risk for implantation, infection, and significant side effects, coinvestigator Kristina M. Deligiannidis, MD, director, Women’s Behavioral Health, Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Courtesy The Feinstein Institutes

Potential alternative to meds

“Given that aVNS is a non-invasive treatment which can be administered at home, we wanted to test if this approach was safe, feasible, and could reduce depressive symptoms in women with postpartum depression, as many of these women have barriers to accessing current treatments,” Dr. Deligiannidis said.

Auricular VNS uses surface skin electrodes to stimulate nerve endings of a branch of the vagus nerve, located on the surface of the outer ear. Those nerve endings travel to the brain where they have been shown to modulate brain communication in areas important for mood and anxiety regulation, she said.

Dr. Deligiannidis noted that evidence-based treatments for postpartum depression include psychotherapies and antidepressants. However, some women have difficulty accessing weekly psychotherapy, and, when antidepressants are indicated, many are reluctant to take them if they are breastfeeding because of concerns about the medications getting into their breast milk, she said.

Although most antidepressants are safe in lactation, many women postpone antidepressant treatment until they have finished breastfeeding, which can postpone their postpartum depression treatment, Dr. Deligiannidis added.

“At home treatments reduce many barriers women have to current treatments, and this intervention [of aVNS] does not impact breastfeeding, as it is not a medication approach,” she said.

The researchers enrolled 25 women (mean age, 33.7 years) diagnosed with postpartum depression. Ten of the women (40%) were on a stable dose of antidepressant medication.

The participants self-administered 6 weeks of open-label aVNS for 15 minutes daily at home. They were then observed without intervention for an additional 2 weeks. The women also completed medical, psychiatric, and safety interviews throughout the study period.
 

Promising findings

At baseline, the mean HAM-D17 was 18.4 and was similar for those on (17.8) and off (18.9) antidepressants.

By week 6, the mean HAM-D17 total score decreased by 9.7 points overall, compared with baseline score. For participants on antidepressants, the HAM-D17 decreased by 8.7 points; for women off antidepressants, it decreased by 10.3 points.

In addition, 74% of the women achieved a response to the therapy, and 61% achieved remission of their depressive symptoms.

The most common adverse effects were discomfort (n = 5 patients), headache (n = 3), and dizziness (n = 2). All resolved without intervention.

Commenting on the findings, Anita Clayton, MD, professor and chair, department of psychiatry and neurobehavioral sciences, University of Virginia School of Medicine, Charlottesville, said the study was “quite interesting.”

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

At-home, noninvasive auricular vagus nerve stimulation (aVNS) therapy is well-tolerated and associated with a significant reduction in postpartum depressive and anxiety symptoms, new research suggests.

In a small proof-of-concept pilot study of 25 women with postpartum depression receiving 6 weeks of daily aVNS treatment, results showed that 74% achieved response and 61% achieved remission, as shown in reduced scores on the Hamilton Rating Scale for Depression (HAM-D17).

Although invasive electrical stimulation of the vagus nerve was approved by the U.S. Food and Drug Administration for treatment-resistant depression in 2005, it involves risk for implantation, infection, and significant side effects, coinvestigator Kristina M. Deligiannidis, MD, director, Women’s Behavioral Health, Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Courtesy The Feinstein Institutes

Potential alternative to meds

“Given that aVNS is a non-invasive treatment which can be administered at home, we wanted to test if this approach was safe, feasible, and could reduce depressive symptoms in women with postpartum depression, as many of these women have barriers to accessing current treatments,” Dr. Deligiannidis said.

Auricular VNS uses surface skin electrodes to stimulate nerve endings of a branch of the vagus nerve, located on the surface of the outer ear. Those nerve endings travel to the brain where they have been shown to modulate brain communication in areas important for mood and anxiety regulation, she said.

Dr. Deligiannidis noted that evidence-based treatments for postpartum depression include psychotherapies and antidepressants. However, some women have difficulty accessing weekly psychotherapy, and, when antidepressants are indicated, many are reluctant to take them if they are breastfeeding because of concerns about the medications getting into their breast milk, she said.

Although most antidepressants are safe in lactation, many women postpone antidepressant treatment until they have finished breastfeeding, which can postpone their postpartum depression treatment, Dr. Deligiannidis added.

“At home treatments reduce many barriers women have to current treatments, and this intervention [of aVNS] does not impact breastfeeding, as it is not a medication approach,” she said.

The researchers enrolled 25 women (mean age, 33.7 years) diagnosed with postpartum depression. Ten of the women (40%) were on a stable dose of antidepressant medication.

The participants self-administered 6 weeks of open-label aVNS for 15 minutes daily at home. They were then observed without intervention for an additional 2 weeks. The women also completed medical, psychiatric, and safety interviews throughout the study period.
 

Promising findings

At baseline, the mean HAM-D17 was 18.4 and was similar for those on (17.8) and off (18.9) antidepressants.

By week 6, the mean HAM-D17 total score decreased by 9.7 points overall, compared with baseline score. For participants on antidepressants, the HAM-D17 decreased by 8.7 points; for women off antidepressants, it decreased by 10.3 points.

In addition, 74% of the women achieved a response to the therapy, and 61% achieved remission of their depressive symptoms.

The most common adverse effects were discomfort (n = 5 patients), headache (n = 3), and dizziness (n = 2). All resolved without intervention.

Commenting on the findings, Anita Clayton, MD, professor and chair, department of psychiatry and neurobehavioral sciences, University of Virginia School of Medicine, Charlottesville, said the study was “quite interesting.”

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

At-home, noninvasive auricular vagus nerve stimulation (aVNS) therapy is well-tolerated and associated with a significant reduction in postpartum depressive and anxiety symptoms, new research suggests.

In a small proof-of-concept pilot study of 25 women with postpartum depression receiving 6 weeks of daily aVNS treatment, results showed that 74% achieved response and 61% achieved remission, as shown in reduced scores on the Hamilton Rating Scale for Depression (HAM-D17).

Although invasive electrical stimulation of the vagus nerve was approved by the U.S. Food and Drug Administration for treatment-resistant depression in 2005, it involves risk for implantation, infection, and significant side effects, coinvestigator Kristina M. Deligiannidis, MD, director, Women’s Behavioral Health, Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Courtesy The Feinstein Institutes

Potential alternative to meds

“Given that aVNS is a non-invasive treatment which can be administered at home, we wanted to test if this approach was safe, feasible, and could reduce depressive symptoms in women with postpartum depression, as many of these women have barriers to accessing current treatments,” Dr. Deligiannidis said.

Auricular VNS uses surface skin electrodes to stimulate nerve endings of a branch of the vagus nerve, located on the surface of the outer ear. Those nerve endings travel to the brain where they have been shown to modulate brain communication in areas important for mood and anxiety regulation, she said.

Dr. Deligiannidis noted that evidence-based treatments for postpartum depression include psychotherapies and antidepressants. However, some women have difficulty accessing weekly psychotherapy, and, when antidepressants are indicated, many are reluctant to take them if they are breastfeeding because of concerns about the medications getting into their breast milk, she said.

Although most antidepressants are safe in lactation, many women postpone antidepressant treatment until they have finished breastfeeding, which can postpone their postpartum depression treatment, Dr. Deligiannidis added.

“At home treatments reduce many barriers women have to current treatments, and this intervention [of aVNS] does not impact breastfeeding, as it is not a medication approach,” she said.

The researchers enrolled 25 women (mean age, 33.7 years) diagnosed with postpartum depression. Ten of the women (40%) were on a stable dose of antidepressant medication.

The participants self-administered 6 weeks of open-label aVNS for 15 minutes daily at home. They were then observed without intervention for an additional 2 weeks. The women also completed medical, psychiatric, and safety interviews throughout the study period.
 

Promising findings

At baseline, the mean HAM-D17 was 18.4 and was similar for those on (17.8) and off (18.9) antidepressants.

By week 6, the mean HAM-D17 total score decreased by 9.7 points overall, compared with baseline score. For participants on antidepressants, the HAM-D17 decreased by 8.7 points; for women off antidepressants, it decreased by 10.3 points.

In addition, 74% of the women achieved a response to the therapy, and 61% achieved remission of their depressive symptoms.

The most common adverse effects were discomfort (n = 5 patients), headache (n = 3), and dizziness (n = 2). All resolved without intervention.

Commenting on the findings, Anita Clayton, MD, professor and chair, department of psychiatry and neurobehavioral sciences, University of Virginia School of Medicine, Charlottesville, said the study was “quite interesting.”

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

NEW ORLEANS – Adult patients who completed an intensive outpatient program (IOP) for post-traumatic stress disorder were significantly less likely over the following year to require inpatient or emergency psychiatric treatment, according to a new study released at the annual meeting of the American Psychiatric Association.

In an analysis of 256 individuals, over the 12 months before they joined the IOP, 28.7% and 24.8% had inpatient and emergency department encounters, respectively, according to the researchers. Afterward, those numbers fell to 15.9% (P < .01) and 18.2% (P = .04), respectively.

“Engagement in IOP for patients with PTSD may help avoid the need for higher levels of care such as residential or inpatient treatment,” Nathan Lingafelter, MD, a psychiatrist and researcher at Kaiser Permanente in Oakland, Calif., said in an interview.

Dr. Lingafelter described IOP programs as typically “offering patients a combination of individual therapy, group therapy, and medication management all at an increased frequency of about 3 half-days per week. IOPs are thought to be helpful in helping patients with severe symptoms while they are still in the community – i.e., living in their homes, with their families, occasionally still working at reduced time.”

While other studies have examined the effects of IOP, “the existing literature focuses on how IOP reduces symptoms, rather than looking at how IOP involvement might be associated with patients utilizing different acute care resources,” he said. “Prior studies have also been conducted mostly in veteran populations and in populations with less diversity than our population in Oakland.”

For the new study, researchers tracked 256 IOP participants (83% female; mean age = 39; 44% White, 27% Black, 14% Hispanic, and 7% Asian). The wide majority – 85% – had comorbid depressive disorders.

“Patients are assigned a case manager when they enter the program who they can meet with individually, and they spend time attending group therapy sessions. Patients are also able to meet with a psychiatrist to discuss medications,” Dr. Lingafelter said. “A major component in both the group and individual therapy is helping patients identify which kind of interventions work for them and what we can do now that will help. IOP can really help clarify for patients what their trauma responses are and how to start treatments that actually fit their symptoms.”

The subjects had a mean 0.3 psychiatric encounters in the year before joining the program and 0.2 in the year after (P < .01). Their mean emergency department visits related to mental health fell from 0.5 to 0.3 (P = .03).

The study has limitations. Participants took part in IOP therapy from 2017 to 2018, before the pandemic disrupted mental health treatment. It does not examine whether medication use changed after IOP treatment. It is retrospective and doesn’t confirm that IOP had any positive effect.
 

Multiple benefits of IOP

In an interview, Deborah C. Beidel, PhD, director of UCF RESTORES at the University of Central Florida, Orlando, said IOP has several advantages as a treatment for PTSD. Her clinic, which focuses on PTSD treatment for military veterans, has used the approach to treat hundreds of people.

“First, IOPs can address the stigma that surrounds mental health treatment. If you have a physical injury, you take time off from work to go to physical therapy, which is time-limited. If you have a stress injury, why not do the same? Take a few weeks, get it treated, and get back to work,” she said. “The second reason is that the most effective treatment for PTSD is exposure therapy, which is more effective when treatment sessions occur in a daily as opposed to a weekly or monthly time frame. Third, from a cost and feasibility perspective, an intensive program could reduce overall medical costs and get people back to work sooner.”

The new study is “definitely useful” since it examines the impact of IOP over a longer term, Dr. Beidel said. This kind of data “can influence policy, particularly with insurance companies. If we can build the evidence that short, intensive treatment produces better long-term outcomes, insurance companies will be more likely to pay for the IOP.”

The University of Central Florida program is funded by federal research grants and state funding, she said. “When we calculate the cost, it comes to about $10,000 in therapy time plus an average of about $3,000 in travel related costs – transportation, lodging, meals – for those who travel from out of state for our program.”

What’s next? “Further study is needed to characterize whether these findings are applicable to other practice settings, including virtual treatment programs; the long-term durability of these findings; and whether similar patterns of reduced resource use extend to non–mental health–specific care utilization,” said Dr. Lingafelter, the study’s lead author.

No study funding and no author disclosures were reported. Dr. Beidel disclosed IOP-related research support from the U.S. Army Medical Research and Development Command–Military Operational Medicine Research Program.

NEW ORLEANS – Adult patients who completed an intensive outpatient program (IOP) for post-traumatic stress disorder were significantly less likely over the following year to require inpatient or emergency psychiatric treatment, according to a new study released at the annual meeting of the American Psychiatric Association.

In an analysis of 256 individuals, over the 12 months before they joined the IOP, 28.7% and 24.8% had inpatient and emergency department encounters, respectively, according to the researchers. Afterward, those numbers fell to 15.9% (P < .01) and 18.2% (P = .04), respectively.

“Engagement in IOP for patients with PTSD may help avoid the need for higher levels of care such as residential or inpatient treatment,” Nathan Lingafelter, MD, a psychiatrist and researcher at Kaiser Permanente in Oakland, Calif., said in an interview.

Dr. Lingafelter described IOP programs as typically “offering patients a combination of individual therapy, group therapy, and medication management all at an increased frequency of about 3 half-days per week. IOPs are thought to be helpful in helping patients with severe symptoms while they are still in the community – i.e., living in their homes, with their families, occasionally still working at reduced time.”

While other studies have examined the effects of IOP, “the existing literature focuses on how IOP reduces symptoms, rather than looking at how IOP involvement might be associated with patients utilizing different acute care resources,” he said. “Prior studies have also been conducted mostly in veteran populations and in populations with less diversity than our population in Oakland.”

For the new study, researchers tracked 256 IOP participants (83% female; mean age = 39; 44% White, 27% Black, 14% Hispanic, and 7% Asian). The wide majority – 85% – had comorbid depressive disorders.

“Patients are assigned a case manager when they enter the program who they can meet with individually, and they spend time attending group therapy sessions. Patients are also able to meet with a psychiatrist to discuss medications,” Dr. Lingafelter said. “A major component in both the group and individual therapy is helping patients identify which kind of interventions work for them and what we can do now that will help. IOP can really help clarify for patients what their trauma responses are and how to start treatments that actually fit their symptoms.”

The subjects had a mean 0.3 psychiatric encounters in the year before joining the program and 0.2 in the year after (P < .01). Their mean emergency department visits related to mental health fell from 0.5 to 0.3 (P = .03).

The study has limitations. Participants took part in IOP therapy from 2017 to 2018, before the pandemic disrupted mental health treatment. It does not examine whether medication use changed after IOP treatment. It is retrospective and doesn’t confirm that IOP had any positive effect.
 

Multiple benefits of IOP

In an interview, Deborah C. Beidel, PhD, director of UCF RESTORES at the University of Central Florida, Orlando, said IOP has several advantages as a treatment for PTSD. Her clinic, which focuses on PTSD treatment for military veterans, has used the approach to treat hundreds of people.

“First, IOPs can address the stigma that surrounds mental health treatment. If you have a physical injury, you take time off from work to go to physical therapy, which is time-limited. If you have a stress injury, why not do the same? Take a few weeks, get it treated, and get back to work,” she said. “The second reason is that the most effective treatment for PTSD is exposure therapy, which is more effective when treatment sessions occur in a daily as opposed to a weekly or monthly time frame. Third, from a cost and feasibility perspective, an intensive program could reduce overall medical costs and get people back to work sooner.”

The new study is “definitely useful” since it examines the impact of IOP over a longer term, Dr. Beidel said. This kind of data “can influence policy, particularly with insurance companies. If we can build the evidence that short, intensive treatment produces better long-term outcomes, insurance companies will be more likely to pay for the IOP.”

The University of Central Florida program is funded by federal research grants and state funding, she said. “When we calculate the cost, it comes to about $10,000 in therapy time plus an average of about $3,000 in travel related costs – transportation, lodging, meals – for those who travel from out of state for our program.”

What’s next? “Further study is needed to characterize whether these findings are applicable to other practice settings, including virtual treatment programs; the long-term durability of these findings; and whether similar patterns of reduced resource use extend to non–mental health–specific care utilization,” said Dr. Lingafelter, the study’s lead author.

No study funding and no author disclosures were reported. Dr. Beidel disclosed IOP-related research support from the U.S. Army Medical Research and Development Command–Military Operational Medicine Research Program.

NEW ORLEANS – Adult patients who completed an intensive outpatient program (IOP) for post-traumatic stress disorder were significantly less likely over the following year to require inpatient or emergency psychiatric treatment, according to a new study released at the annual meeting of the American Psychiatric Association.

In an analysis of 256 individuals, over the 12 months before they joined the IOP, 28.7% and 24.8% had inpatient and emergency department encounters, respectively, according to the researchers. Afterward, those numbers fell to 15.9% (P < .01) and 18.2% (P = .04), respectively.

“Engagement in IOP for patients with PTSD may help avoid the need for higher levels of care such as residential or inpatient treatment,” Nathan Lingafelter, MD, a psychiatrist and researcher at Kaiser Permanente in Oakland, Calif., said in an interview.

Dr. Lingafelter described IOP programs as typically “offering patients a combination of individual therapy, group therapy, and medication management all at an increased frequency of about 3 half-days per week. IOPs are thought to be helpful in helping patients with severe symptoms while they are still in the community – i.e., living in their homes, with their families, occasionally still working at reduced time.”

While other studies have examined the effects of IOP, “the existing literature focuses on how IOP reduces symptoms, rather than looking at how IOP involvement might be associated with patients utilizing different acute care resources,” he said. “Prior studies have also been conducted mostly in veteran populations and in populations with less diversity than our population in Oakland.”

For the new study, researchers tracked 256 IOP participants (83% female; mean age = 39; 44% White, 27% Black, 14% Hispanic, and 7% Asian). The wide majority – 85% – had comorbid depressive disorders.

“Patients are assigned a case manager when they enter the program who they can meet with individually, and they spend time attending group therapy sessions. Patients are also able to meet with a psychiatrist to discuss medications,” Dr. Lingafelter said. “A major component in both the group and individual therapy is helping patients identify which kind of interventions work for them and what we can do now that will help. IOP can really help clarify for patients what their trauma responses are and how to start treatments that actually fit their symptoms.”

The subjects had a mean 0.3 psychiatric encounters in the year before joining the program and 0.2 in the year after (P < .01). Their mean emergency department visits related to mental health fell from 0.5 to 0.3 (P = .03).

The study has limitations. Participants took part in IOP therapy from 2017 to 2018, before the pandemic disrupted mental health treatment. It does not examine whether medication use changed after IOP treatment. It is retrospective and doesn’t confirm that IOP had any positive effect.
 

Multiple benefits of IOP

In an interview, Deborah C. Beidel, PhD, director of UCF RESTORES at the University of Central Florida, Orlando, said IOP has several advantages as a treatment for PTSD. Her clinic, which focuses on PTSD treatment for military veterans, has used the approach to treat hundreds of people.

“First, IOPs can address the stigma that surrounds mental health treatment. If you have a physical injury, you take time off from work to go to physical therapy, which is time-limited. If you have a stress injury, why not do the same? Take a few weeks, get it treated, and get back to work,” she said. “The second reason is that the most effective treatment for PTSD is exposure therapy, which is more effective when treatment sessions occur in a daily as opposed to a weekly or monthly time frame. Third, from a cost and feasibility perspective, an intensive program could reduce overall medical costs and get people back to work sooner.”

The new study is “definitely useful” since it examines the impact of IOP over a longer term, Dr. Beidel said. This kind of data “can influence policy, particularly with insurance companies. If we can build the evidence that short, intensive treatment produces better long-term outcomes, insurance companies will be more likely to pay for the IOP.”

The University of Central Florida program is funded by federal research grants and state funding, she said. “When we calculate the cost, it comes to about $10,000 in therapy time plus an average of about $3,000 in travel related costs – transportation, lodging, meals – for those who travel from out of state for our program.”

What’s next? “Further study is needed to characterize whether these findings are applicable to other practice settings, including virtual treatment programs; the long-term durability of these findings; and whether similar patterns of reduced resource use extend to non–mental health–specific care utilization,” said Dr. Lingafelter, the study’s lead author.

No study funding and no author disclosures were reported. Dr. Beidel disclosed IOP-related research support from the U.S. Army Medical Research and Development Command–Military Operational Medicine Research Program.

The study covered in this summary was published in researchsquare.com and has not yet been peer reviewed.

Key takeaways

• The study found a high burden of chronic pain in Syrian adult refugees in Norway that has adverse consequences for their daily functioning.
• Anxiety, , and PTSD are associated with higher levels of chronic pain in the refugee population studied.
• Being a male refugee is associated more strongly with anxiety and depression leading to functional impairment than being a woman. Being a woman is associated with higher odds of chronic pain. Gender acted as an effect modifier between mental illness and functional impairment.
• Future research aimed toward harmonizing and standardizing pain measurement to measure its effect on health burden is needed. Pain should be understood under an ethnocultural construct to enhance transcultural validity.

Why this matters

• The present cross-sectional survey of adult refugees from Syria resettled in Norway is only one of a few studies investigating the burden of chronic pain and how it relates to mental ill health in a general refugee population. Elevated rates of PTSD, depression, and anxiety have been repeatedly found in refugee populations, and high levels of pain have also been documented.
• Attention to the association between chronic pain and mental health should be made by personnel working with refugees. Because of the gender-specific associations between mental illness and functional impairment, initiatives addressing mental health, chronic pain, or functional impairment in refugee populations should consider gender when tailoring their content and outreach.

Study design

• The study involved a cross-sectional, postal survey questionnaire of participants randomly drawn from full population registries in Norway. There was an initial low response. Invitations were sent out in November 2018 and did not close until September 2019. Several efforts were made to boost participation, including one postal or telephone reminder to all nonresponders.
• Participants were refugee adults from Syria aged 18 and older who arrived in Norway between 2015 and 2017. Gender was tested as an effect modifier. 
• Chronic pain was measured with 10 items on the questionnaire and was defined as pain for 3 or more consecutive months in the last year. It included both musculoskeletal pain and pain in five other body regions (stomach, head, genital area, chest, other). 
• Anxiety, depression, and PTSD symptoms were measured with the 25-item Hopkins Symptom Checklist, the Harvard Trauma Questionnaire, and the Refugee Trauma History Checklist. 
• Questionnaires on perceived general health regarding refugee perceptions of their own health, and functional impairment affecting daily activities because of illness, disability, and mental health were adapted from the European Social Survey 2010.

Key results

• A total of 902 participants who responded to the questionnaire were included in the study from roughly 10,000 invitations, giving a participation rate of about 10%, with no differences in gender distribution.
• The overall prevalence of severe chronic pain was 43.1%, and overall perception of poor general health was 39.9%. 
• There was a strong association of chronic pain with all mental illness measured, poor perceived general health, and functional impairment (P < .001).  All mental health variables were associated with increased odds of chronic pain (anxiety odds ratio), 2.42; depression, OR, 2.28; PTSD, OR, 1.97; all OR fully adjusted).
• Chronic pain was associated with poor perceived general health and functional impairment with no difference across gender. Mental health showed weaker association with poor perceived general health than chronic pain.
• Syrian men with mental health had three times higher odds of functional impairment.  For women, there was no evidence of association between any of the mental ill health variables and functional impairment. Being a woman was associated with chronic pain and poor perceived general health but not functional impairment.
• Being a woman was associated with 50% higher odds of chronic pain in both unadjusted and adjusted models.

Limitations

• With a 10% response rate, selection bias in this cross-sectional study may have been present.
• The cross-sectional design of the study limits causality.
• The validity of the survey is questionable because of transcultural construct regarding pain and mental illness.
• Regression models were built with data at hand. Without preregistered plans for data handling, the findings should be viewed as exploratory with a risk for false-positive findings.

Disclosures

• No external funding was received.  The study was funded by the Norwegian Center for Violence and Traumatic Stress Studies.
• None of the authors disclosed relevant financial relationships.

This is a summary of a preprint research study, “Chronic pain, mental health and functional impairment in adult refugees from Syria resettled in Norway: a cross-sectional study,” written by researchers at the Norwegian Centre for Violence and Traumatic Stress Studies in Oslo, the Norwegian Institute of Public Health in Oslo, and the Weill Cornell Medicine in New York City on Research Square.  This study has not yet been peer reviewed. The full text of the study can be found on researchsquare.com. A version of this article first appeared on Medscape.com.

The study covered in this summary was published in researchsquare.com and has not yet been peer reviewed.

Key takeaways

• The study found a high burden of chronic pain in Syrian adult refugees in Norway that has adverse consequences for their daily functioning.
• Anxiety, , and PTSD are associated with higher levels of chronic pain in the refugee population studied.
• Being a male refugee is associated more strongly with anxiety and depression leading to functional impairment than being a woman. Being a woman is associated with higher odds of chronic pain. Gender acted as an effect modifier between mental illness and functional impairment.
• Future research aimed toward harmonizing and standardizing pain measurement to measure its effect on health burden is needed. Pain should be understood under an ethnocultural construct to enhance transcultural validity.

Why this matters

• The present cross-sectional survey of adult refugees from Syria resettled in Norway is only one of a few studies investigating the burden of chronic pain and how it relates to mental ill health in a general refugee population. Elevated rates of PTSD, depression, and anxiety have been repeatedly found in refugee populations, and high levels of pain have also been documented.
• Attention to the association between chronic pain and mental health should be made by personnel working with refugees. Because of the gender-specific associations between mental illness and functional impairment, initiatives addressing mental health, chronic pain, or functional impairment in refugee populations should consider gender when tailoring their content and outreach.

Study design

• The study involved a cross-sectional, postal survey questionnaire of participants randomly drawn from full population registries in Norway. There was an initial low response. Invitations were sent out in November 2018 and did not close until September 2019. Several efforts were made to boost participation, including one postal or telephone reminder to all nonresponders.
• Participants were refugee adults from Syria aged 18 and older who arrived in Norway between 2015 and 2017. Gender was tested as an effect modifier. 
• Chronic pain was measured with 10 items on the questionnaire and was defined as pain for 3 or more consecutive months in the last year. It included both musculoskeletal pain and pain in five other body regions (stomach, head, genital area, chest, other). 
• Anxiety, depression, and PTSD symptoms were measured with the 25-item Hopkins Symptom Checklist, the Harvard Trauma Questionnaire, and the Refugee Trauma History Checklist. 
• Questionnaires on perceived general health regarding refugee perceptions of their own health, and functional impairment affecting daily activities because of illness, disability, and mental health were adapted from the European Social Survey 2010.

Key results

• A total of 902 participants who responded to the questionnaire were included in the study from roughly 10,000 invitations, giving a participation rate of about 10%, with no differences in gender distribution.
• The overall prevalence of severe chronic pain was 43.1%, and overall perception of poor general health was 39.9%. 
• There was a strong association of chronic pain with all mental illness measured, poor perceived general health, and functional impairment (P < .001).  All mental health variables were associated with increased odds of chronic pain (anxiety odds ratio), 2.42; depression, OR, 2.28; PTSD, OR, 1.97; all OR fully adjusted).
• Chronic pain was associated with poor perceived general health and functional impairment with no difference across gender. Mental health showed weaker association with poor perceived general health than chronic pain.
• Syrian men with mental health had three times higher odds of functional impairment.  For women, there was no evidence of association between any of the mental ill health variables and functional impairment. Being a woman was associated with chronic pain and poor perceived general health but not functional impairment.
• Being a woman was associated with 50% higher odds of chronic pain in both unadjusted and adjusted models.

Limitations

• With a 10% response rate, selection bias in this cross-sectional study may have been present.
• The cross-sectional design of the study limits causality.
• The validity of the survey is questionable because of transcultural construct regarding pain and mental illness.
• Regression models were built with data at hand. Without preregistered plans for data handling, the findings should be viewed as exploratory with a risk for false-positive findings.

Disclosures

• No external funding was received.  The study was funded by the Norwegian Center for Violence and Traumatic Stress Studies.
• None of the authors disclosed relevant financial relationships.

This is a summary of a preprint research study, “Chronic pain, mental health and functional impairment in adult refugees from Syria resettled in Norway: a cross-sectional study,” written by researchers at the Norwegian Centre for Violence and Traumatic Stress Studies in Oslo, the Norwegian Institute of Public Health in Oslo, and the Weill Cornell Medicine in New York City on Research Square.  This study has not yet been peer reviewed. The full text of the study can be found on researchsquare.com. A version of this article first appeared on Medscape.com.

The study covered in this summary was published in researchsquare.com and has not yet been peer reviewed.

Key takeaways

• The study found a high burden of chronic pain in Syrian adult refugees in Norway that has adverse consequences for their daily functioning.
• Anxiety, , and PTSD are associated with higher levels of chronic pain in the refugee population studied.
• Being a male refugee is associated more strongly with anxiety and depression leading to functional impairment than being a woman. Being a woman is associated with higher odds of chronic pain. Gender acted as an effect modifier between mental illness and functional impairment.
• Future research aimed toward harmonizing and standardizing pain measurement to measure its effect on health burden is needed. Pain should be understood under an ethnocultural construct to enhance transcultural validity.

Why this matters

• The present cross-sectional survey of adult refugees from Syria resettled in Norway is only one of a few studies investigating the burden of chronic pain and how it relates to mental ill health in a general refugee population. Elevated rates of PTSD, depression, and anxiety have been repeatedly found in refugee populations, and high levels of pain have also been documented.
• Attention to the association between chronic pain and mental health should be made by personnel working with refugees. Because of the gender-specific associations between mental illness and functional impairment, initiatives addressing mental health, chronic pain, or functional impairment in refugee populations should consider gender when tailoring their content and outreach.

Study design

• The study involved a cross-sectional, postal survey questionnaire of participants randomly drawn from full population registries in Norway. There was an initial low response. Invitations were sent out in November 2018 and did not close until September 2019. Several efforts were made to boost participation, including one postal or telephone reminder to all nonresponders.
• Participants were refugee adults from Syria aged 18 and older who arrived in Norway between 2015 and 2017. Gender was tested as an effect modifier. 
• Chronic pain was measured with 10 items on the questionnaire and was defined as pain for 3 or more consecutive months in the last year. It included both musculoskeletal pain and pain in five other body regions (stomach, head, genital area, chest, other). 
• Anxiety, depression, and PTSD symptoms were measured with the 25-item Hopkins Symptom Checklist, the Harvard Trauma Questionnaire, and the Refugee Trauma History Checklist. 
• Questionnaires on perceived general health regarding refugee perceptions of their own health, and functional impairment affecting daily activities because of illness, disability, and mental health were adapted from the European Social Survey 2010.

Key results

• A total of 902 participants who responded to the questionnaire were included in the study from roughly 10,000 invitations, giving a participation rate of about 10%, with no differences in gender distribution.
• The overall prevalence of severe chronic pain was 43.1%, and overall perception of poor general health was 39.9%. 
• There was a strong association of chronic pain with all mental illness measured, poor perceived general health, and functional impairment (P < .001).  All mental health variables were associated with increased odds of chronic pain (anxiety odds ratio), 2.42; depression, OR, 2.28; PTSD, OR, 1.97; all OR fully adjusted).
• Chronic pain was associated with poor perceived general health and functional impairment with no difference across gender. Mental health showed weaker association with poor perceived general health than chronic pain.
• Syrian men with mental health had three times higher odds of functional impairment.  For women, there was no evidence of association between any of the mental ill health variables and functional impairment. Being a woman was associated with chronic pain and poor perceived general health but not functional impairment.
• Being a woman was associated with 50% higher odds of chronic pain in both unadjusted and adjusted models.

Limitations

• With a 10% response rate, selection bias in this cross-sectional study may have been present.
• The cross-sectional design of the study limits causality.
• The validity of the survey is questionable because of transcultural construct regarding pain and mental illness.
• Regression models were built with data at hand. Without preregistered plans for data handling, the findings should be viewed as exploratory with a risk for false-positive findings.

Disclosures

• No external funding was received.  The study was funded by the Norwegian Center for Violence and Traumatic Stress Studies.
• None of the authors disclosed relevant financial relationships.

This is a summary of a preprint research study, “Chronic pain, mental health and functional impairment in adult refugees from Syria resettled in Norway: a cross-sectional study,” written by researchers at the Norwegian Centre for Violence and Traumatic Stress Studies in Oslo, the Norwegian Institute of Public Health in Oslo, and the Weill Cornell Medicine in New York City on Research Square.  This study has not yet been peer reviewed. The full text of the study can be found on researchsquare.com. A version of this article first appeared on Medscape.com.

NEW ORLEANS – A single dose of a synthetic formulation of psilocybin provides rapid improvement in treatment-resistant depression, with benefits sustained for up to 12 weeks, according to results from the largest randomized controlled study of psilocybin to date.

“This is easily the largest study of a psychedelic drug employing modern randomized controlled trial methodology [with] 22 sites and 10 countries, so it’s not your typical phase 2 trial,” the study’s lead author, Guy M. Goodwin, MD, emeritus professor of psychiatry at the University of Oxford, England, said in an interview.

“Importantly, 94% of the patients in the study were psilocybin naive, which is very important for generalizability,” Dr. Goodwin noted.

Long used as psychedelic ‘magic mushrooms,’ psilocybin has gained increased interest in psychiatry in recent years as a potential treatment for severe depression after showing benefits in patients with life-threatening cancers and others with major depressive disorder (MDD).

To put the therapy to test in a more rigorous, randomized trial, Dr. Goodwin and colleagues conducted the phase 2b study of a proprietary synthetic formulation of psilocybin, COMP360 (COMPASS Pathways), recruiting 233 patients with treatment-resistant depression at 22 centers.

The study was presented at the annual meeting of the American Psychiatric Association.

After a 2-week washout period following the discontinuation of antidepressants, the patients were randomized to one of three groups: A single dose of 25 mg (n = 79), 10 mg (n = 75), or a subtherapeutic comparison of 1 mg (n = 79).

The psilocybin was administered in the presence of specially trained therapists who provided psychological support before, during, and after the 6- to 8-hour session.

Patients were then asked to refrain from antidepressant use for at least 3 weeks following the session, and had periodic follow-up for 12 weeks.

For the primary endpoint, those in the 25-mg group, but not the 10-mg dose, showed a significantly greater reduction in depression from baseline versus the 1-mg group on the Montgomery-Åsberg Depression Rating Scale at week 3 (MADRS; -6.6; P < .001).

The benefit was observed at day 2 and week 1 following administration, “confirming the rapid-acting character of the effect,” the investigators reported.

Sustained responses, defined as at least a 50% change from baseline in MADRS total score, were further observed up to week 12 among 20.3% in the 25-mg group and among 5.3% in the 10-mg groups versus 10.1% in the 1-mg group.

On the day of psilocybin treatment, the treatment-emergent side effects that were reported were headache, nausea, and dizziness, with event rates of 83.5% in the 25-mg group, 74.7% in the 10-mg group, and 72.2% in the 1-mg group.

One participant in the 25-mg group experienced acute anxiety and was treated with lorazepam.

The incidence of treatment-emergent serious adverse events from day 2 to week 3 was 6.3% (five patients) in the 25-mg group, 8.0% (six patients) in the 10-mg group, and 1.3% (one patient) in the 1-mg group.

Serious AEs included suicidal ideation and intentional self-injury among two patients each in the 25-mg group, while in the 10-mg group, two had suicidal ideation and one had hospitalization for severe depression.

There were no significant differences between the groups in terms of vital signs or clinical laboratory tests.

Of note, two patients in the 25-mg group had a change from baseline in QTcF >60 msec on day 2. For one patient, the increase was within normal range, and the other had a QTcF interval duration >500 msec on day 2, but levels returned to normal by day 9.
 

Improvements in context

Dr. Goodwin noted that the improvements were swift and impressive when compared with those of the STAR*D trial, which is the largest prospective study of treatment outcomes in patients with MDD.

“In the STAR*D trial, third- and fourth-step treatments showed low response rates of under 15% and high relapse rates,” Dr. Goodwin said. “By comparison, our response rates at 12 weeks were 20%-25%, so almost double that seen for probably equivalent treatment steps in STAR*D, with a single treatment with 25 mg, and no additional antidepressant, so no side effect burden.

“We hope to follow up enough of these patients [in the new study] to get some idea of relapse rates,” Dr. Goodwin added. “These have been low in comparable studies with MDD patients: We will see.”

Commenting on the research, Balwinder Singh, MD, of the department of psychiatry and psychology, Mayo Clinic, Rochester, Minn., said the study represents a valuable addition to needed evidence on psilocybin – with some caveats.

“This study adds to the emerging evidence base of psilocybin for treatment-resistant depression, at least in the short term,” he said in an interview. “I think the challenge in the real world would be to have access to 6-8 hours of therapy with psilocybin when patients struggle to find good therapists who could provide even weekly therapy for an hour.”

In addition, Dr. Singh questioned the durability of a single dose of psilocybin in the long term, noting a recent study (N Engl J Med. 2021 Apr 15. doi: 10.1056/NEJMoa2032994) that evaluated two doses of psilocybin (25 mg) 3 weeks apart, and failed to show any significant difference compared with the serotonergic antidepressant escitalopram at 6 weeks.

He further expressed concern about the emergence of suicidal behaviors in some patients, as well as the prolongation of QTc > 60 msec reported in the two patients.

“This is something to be carefully assessed in future studies, due to the risk of arrhythmias,” Dr. Singh said.

The study was sponsored by COMPASS Pathfinder Limited. Dr. Goodwin is chief medical officer for COMPASS Pathways. Dr. Singh had no disclosures to report.

NEW ORLEANS – A single dose of a synthetic formulation of psilocybin provides rapid improvement in treatment-resistant depression, with benefits sustained for up to 12 weeks, according to results from the largest randomized controlled study of psilocybin to date.

“This is easily the largest study of a psychedelic drug employing modern randomized controlled trial methodology [with] 22 sites and 10 countries, so it’s not your typical phase 2 trial,” the study’s lead author, Guy M. Goodwin, MD, emeritus professor of psychiatry at the University of Oxford, England, said in an interview.

“Importantly, 94% of the patients in the study were psilocybin naive, which is very important for generalizability,” Dr. Goodwin noted.

Long used as psychedelic ‘magic mushrooms,’ psilocybin has gained increased interest in psychiatry in recent years as a potential treatment for severe depression after showing benefits in patients with life-threatening cancers and others with major depressive disorder (MDD).

To put the therapy to test in a more rigorous, randomized trial, Dr. Goodwin and colleagues conducted the phase 2b study of a proprietary synthetic formulation of psilocybin, COMP360 (COMPASS Pathways), recruiting 233 patients with treatment-resistant depression at 22 centers.

The study was presented at the annual meeting of the American Psychiatric Association.

After a 2-week washout period following the discontinuation of antidepressants, the patients were randomized to one of three groups: A single dose of 25 mg (n = 79), 10 mg (n = 75), or a subtherapeutic comparison of 1 mg (n = 79).

The psilocybin was administered in the presence of specially trained therapists who provided psychological support before, during, and after the 6- to 8-hour session.

Patients were then asked to refrain from antidepressant use for at least 3 weeks following the session, and had periodic follow-up for 12 weeks.

For the primary endpoint, those in the 25-mg group, but not the 10-mg dose, showed a significantly greater reduction in depression from baseline versus the 1-mg group on the Montgomery-Åsberg Depression Rating Scale at week 3 (MADRS; -6.6; P < .001).

The benefit was observed at day 2 and week 1 following administration, “confirming the rapid-acting character of the effect,” the investigators reported.

Sustained responses, defined as at least a 50% change from baseline in MADRS total score, were further observed up to week 12 among 20.3% in the 25-mg group and among 5.3% in the 10-mg groups versus 10.1% in the 1-mg group.

On the day of psilocybin treatment, the treatment-emergent side effects that were reported were headache, nausea, and dizziness, with event rates of 83.5% in the 25-mg group, 74.7% in the 10-mg group, and 72.2% in the 1-mg group.

One participant in the 25-mg group experienced acute anxiety and was treated with lorazepam.

The incidence of treatment-emergent serious adverse events from day 2 to week 3 was 6.3% (five patients) in the 25-mg group, 8.0% (six patients) in the 10-mg group, and 1.3% (one patient) in the 1-mg group.

Serious AEs included suicidal ideation and intentional self-injury among two patients each in the 25-mg group, while in the 10-mg group, two had suicidal ideation and one had hospitalization for severe depression.

There were no significant differences between the groups in terms of vital signs or clinical laboratory tests.

Of note, two patients in the 25-mg group had a change from baseline in QTcF >60 msec on day 2. For one patient, the increase was within normal range, and the other had a QTcF interval duration >500 msec on day 2, but levels returned to normal by day 9.
 

Improvements in context

Dr. Goodwin noted that the improvements were swift and impressive when compared with those of the STAR*D trial, which is the largest prospective study of treatment outcomes in patients with MDD.

“In the STAR*D trial, third- and fourth-step treatments showed low response rates of under 15% and high relapse rates,” Dr. Goodwin said. “By comparison, our response rates at 12 weeks were 20%-25%, so almost double that seen for probably equivalent treatment steps in STAR*D, with a single treatment with 25 mg, and no additional antidepressant, so no side effect burden.

“We hope to follow up enough of these patients [in the new study] to get some idea of relapse rates,” Dr. Goodwin added. “These have been low in comparable studies with MDD patients: We will see.”

Commenting on the research, Balwinder Singh, MD, of the department of psychiatry and psychology, Mayo Clinic, Rochester, Minn., said the study represents a valuable addition to needed evidence on psilocybin – with some caveats.

“This study adds to the emerging evidence base of psilocybin for treatment-resistant depression, at least in the short term,” he said in an interview. “I think the challenge in the real world would be to have access to 6-8 hours of therapy with psilocybin when patients struggle to find good therapists who could provide even weekly therapy for an hour.”

In addition, Dr. Singh questioned the durability of a single dose of psilocybin in the long term, noting a recent study (N Engl J Med. 2021 Apr 15. doi: 10.1056/NEJMoa2032994) that evaluated two doses of psilocybin (25 mg) 3 weeks apart, and failed to show any significant difference compared with the serotonergic antidepressant escitalopram at 6 weeks.

He further expressed concern about the emergence of suicidal behaviors in some patients, as well as the prolongation of QTc > 60 msec reported in the two patients.

“This is something to be carefully assessed in future studies, due to the risk of arrhythmias,” Dr. Singh said.

The study was sponsored by COMPASS Pathfinder Limited. Dr. Goodwin is chief medical officer for COMPASS Pathways. Dr. Singh had no disclosures to report.

NEW ORLEANS – A single dose of a synthetic formulation of psilocybin provides rapid improvement in treatment-resistant depression, with benefits sustained for up to 12 weeks, according to results from the largest randomized controlled study of psilocybin to date.

“This is easily the largest study of a psychedelic drug employing modern randomized controlled trial methodology [with] 22 sites and 10 countries, so it’s not your typical phase 2 trial,” the study’s lead author, Guy M. Goodwin, MD, emeritus professor of psychiatry at the University of Oxford, England, said in an interview.

“Importantly, 94% of the patients in the study were psilocybin naive, which is very important for generalizability,” Dr. Goodwin noted.

Long used as psychedelic ‘magic mushrooms,’ psilocybin has gained increased interest in psychiatry in recent years as a potential treatment for severe depression after showing benefits in patients with life-threatening cancers and others with major depressive disorder (MDD).

To put the therapy to test in a more rigorous, randomized trial, Dr. Goodwin and colleagues conducted the phase 2b study of a proprietary synthetic formulation of psilocybin, COMP360 (COMPASS Pathways), recruiting 233 patients with treatment-resistant depression at 22 centers.

The study was presented at the annual meeting of the American Psychiatric Association.

After a 2-week washout period following the discontinuation of antidepressants, the patients were randomized to one of three groups: A single dose of 25 mg (n = 79), 10 mg (n = 75), or a subtherapeutic comparison of 1 mg (n = 79).

The psilocybin was administered in the presence of specially trained therapists who provided psychological support before, during, and after the 6- to 8-hour session.

Patients were then asked to refrain from antidepressant use for at least 3 weeks following the session, and had periodic follow-up for 12 weeks.

For the primary endpoint, those in the 25-mg group, but not the 10-mg dose, showed a significantly greater reduction in depression from baseline versus the 1-mg group on the Montgomery-Åsberg Depression Rating Scale at week 3 (MADRS; -6.6; P < .001).

The benefit was observed at day 2 and week 1 following administration, “confirming the rapid-acting character of the effect,” the investigators reported.

Sustained responses, defined as at least a 50% change from baseline in MADRS total score, were further observed up to week 12 among 20.3% in the 25-mg group and among 5.3% in the 10-mg groups versus 10.1% in the 1-mg group.

On the day of psilocybin treatment, the treatment-emergent side effects that were reported were headache, nausea, and dizziness, with event rates of 83.5% in the 25-mg group, 74.7% in the 10-mg group, and 72.2% in the 1-mg group.

One participant in the 25-mg group experienced acute anxiety and was treated with lorazepam.

The incidence of treatment-emergent serious adverse events from day 2 to week 3 was 6.3% (five patients) in the 25-mg group, 8.0% (six patients) in the 10-mg group, and 1.3% (one patient) in the 1-mg group.

Serious AEs included suicidal ideation and intentional self-injury among two patients each in the 25-mg group, while in the 10-mg group, two had suicidal ideation and one had hospitalization for severe depression.

There were no significant differences between the groups in terms of vital signs or clinical laboratory tests.

Of note, two patients in the 25-mg group had a change from baseline in QTcF >60 msec on day 2. For one patient, the increase was within normal range, and the other had a QTcF interval duration >500 msec on day 2, but levels returned to normal by day 9.
 

Improvements in context

Dr. Goodwin noted that the improvements were swift and impressive when compared with those of the STAR*D trial, which is the largest prospective study of treatment outcomes in patients with MDD.

“In the STAR*D trial, third- and fourth-step treatments showed low response rates of under 15% and high relapse rates,” Dr. Goodwin said. “By comparison, our response rates at 12 weeks were 20%-25%, so almost double that seen for probably equivalent treatment steps in STAR*D, with a single treatment with 25 mg, and no additional antidepressant, so no side effect burden.

“We hope to follow up enough of these patients [in the new study] to get some idea of relapse rates,” Dr. Goodwin added. “These have been low in comparable studies with MDD patients: We will see.”

Commenting on the research, Balwinder Singh, MD, of the department of psychiatry and psychology, Mayo Clinic, Rochester, Minn., said the study represents a valuable addition to needed evidence on psilocybin – with some caveats.

“This study adds to the emerging evidence base of psilocybin for treatment-resistant depression, at least in the short term,” he said in an interview. “I think the challenge in the real world would be to have access to 6-8 hours of therapy with psilocybin when patients struggle to find good therapists who could provide even weekly therapy for an hour.”

In addition, Dr. Singh questioned the durability of a single dose of psilocybin in the long term, noting a recent study (N Engl J Med. 2021 Apr 15. doi: 10.1056/NEJMoa2032994) that evaluated two doses of psilocybin (25 mg) 3 weeks apart, and failed to show any significant difference compared with the serotonergic antidepressant escitalopram at 6 weeks.

He further expressed concern about the emergence of suicidal behaviors in some patients, as well as the prolongation of QTc > 60 msec reported in the two patients.

“This is something to be carefully assessed in future studies, due to the risk of arrhythmias,” Dr. Singh said.

The study was sponsored by COMPASS Pathfinder Limited. Dr. Goodwin is chief medical officer for COMPASS Pathways. Dr. Singh had no disclosures to report.

NEW ORLEANS – Patients experiencing brain fog and other persistent symptoms of long COVID show significant deficits on neuropsychiatric testing that correspond with prior acute COVID-19 infection, adding to mounting evidence of the significant toll the chronic condition can have on mental health.

“Many clinicians have observed the symptoms we describe in this study, however this report is among the first which identify the specific deficits using neuropsychological testing to better characterize the syndrome,” Sean T. Lynch, MD, first author of a study on the issue presented at the annual meeting of the American Psychiatric Association, said in an interview.

Dr. Lynch, of the department of psychiatry, Westchester Medical Center Health System, Valhalla, N.Y., and his colleagues enrolled 60 participants who had experienced acute COVID-19 disease 6-8 months earlier and had undergone neuropsychological, psychiatric, medical, functional, and quality-of-life assessments. Results from the study were published online in the Journal of the Academy of Consultation–Liaison Psychiatry (2022 Jan 25. doi: 10.1016/j.jaclp.2022.01.003).

Among the study participants, 32 were seeking treatment for brain fog in a clinical program for survivors of COVID-19, while the remaining 28 were part of an ongoing longitudinal investigation of neuropsychological, medical, and psychiatric sequelae of COVID-19, but were not seeking care for the persistent symptoms.

Assessments for neurocognitive impairment included a battery of tests used in infectious and other diseases, including the Test of Premorbid Function, the Patient Assessment of Own Function, the Trail Making Test parts A and B, the Stroop Color and Word Test, and others.

Overall, the battery of assessments showed that 37 (62%) of participants had neuropsychological test impairment, with results below the 16th percentile in two tests, while 16 (27%) showed scores indicative of severe impairment (below the second percentile in at least one test and below the 16th percentile in one test).

Those reporting brain fog had scores that were even lower than expected on tests of attention, processing speed, memory, and executive function. And among those reporting brain fog, significantly more had scores reflecting severe impairment compared with the controls (38% vs. 14%; P < .04).

“Based on what we’ve observed in our patients and what others have previously reported, we did expect to find some impairment in this study sample,” Dr. Lynch noted.

“However, we were surprised to find that 27% of the study sample had extremely low neuropsychological test scores, meaning that they scored at least two standard deviations below the expected score on at least one neuropsychological test based on their age and level of education.”

The brain fog group also reported significantly higher levels of depression, fatigue, PTSD, and functional difficulties, and lower quality of life.

Severe impairment on the neuropsychological tests correlated with the extent of acute COVID-19 symptoms, as well as depression scores, number of medical comorbidities, and subjective cognitive complaints.

An analysis of serum levels of the inflammatory markers among 50 of the 60 participants showed that 45% of the patients had an elevated IL-6, 20% had elevated TNF-alpha, and 41% had elevated CRP, compared with reference ranges.

IL-6 levels were found to correlate with acute COVID-19 symptoms, the number of medical comorbidities, fatigue, and measures of executive function, while C-reactive protein (CRP) correlated with current COVID-19 symptoms and depression scores.

In terms of clinical factors that might predict low neuropsychological test scores, Dr. Lynch noted that the “markers that we found to be significant included severity of acute COVID-19 illness, current post-COVID-19 symptoms, measures of depression and anxiety, level of fatigue, and number of medical comorbidities.”

Dr. Lynch noted that the ongoing study will include up to 18-month follow-ups that are currently underway. “The [follow-ups] will examine if symptoms improve over time and evaluate if any intervention that took place was successful,” he said.


 

Survey supports findings

The detrimental effects of mental health symptoms in long COVID were further supported in another study at the APA meeting, an online survey of 787 survivors of acute COVID-19.

In the community survey, presented by Michael Van Ameringen, MD, a professor in the department of psychiatry and behavioral neurosciences at McMaster University, in Hamilton, Ont., all respondents (100%) reported having persistent symptoms of the virus, and as many as 68% indicated that they had not returned to normal functioning, despite only 15% of the respondents having been hospitalized with COVID-19.

A large proportion showed significant depression, anxiety, and posttraumatic stress disorder (PTSD), and the most commonly reported persistent symptoms were fatigue in 75.9% of respondents, brain fog in 67.9%, concentration difficulties in 61.1%, and weakness in 51.2%.

As many as 88.2% of patients said they experienced persistent neurocognitive symptoms, with poor memory and concentration; 56% reported problems with word finding; and 54.1% had slowed thinking.

The respondents showed high rates of anxiety (41.7%) as well as depression (61.4%) as determined by scores above 9 on the Generalized Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaires (PHQ-9).

As many as 40.5% of respondents showed probable PTSD, with scores above 30 on the PTSD checklist (PCL-5). Their mean resilience score on the Brief Resilient Coping Scale was 13.5, suggesting low resilience.

Among the respondents, 43.3% said they had received past treatment for mental health, while 33.5% were currently receiving mental health treatment.

Dr. Van Ameringen noted the important limitation of the study being an online survey with no control group, but said the responses nevertheless raise the question of the role of prior psychiatric disorders in long COVID.

“In our sample, 40% of respondents had a past psychiatric history, so you wonder if that also makes you vulnerable to long COVID,” he said in an interview.

“About a third were getting psychiatric help, but I think the more impaired you are, the more likely you are to seek help.”

Those who were hospitalized with COVID-19 were at a higher risk of PTSD compared with those not hospitalized (P < .001), as were those under the age of 30 (P < .05) or between 31 and 50 vs. over 50 (P < .01).

Dr. Van Ameringen noted that the survey’s high rate of subjects who had not returned to normal functioning was especially striking.

“This is not a minor issue – these are people who are no longer functioning in society,” he said.
 

In pandemics, the brain tends to be ‘overlooked’

Further addressing the neurological effects of COVID-19 at the APA meeting, Avindra Nath, MD, clinical director of the National Institutes of Neurologic Disorders and Stroke in Bethesda, Md., noted that the persisting cognitive and psychiatric symptoms after illness, such as brain fog and depression and anxiety, are not necessarily unique to COVID-19.

“We have seen this before,” he said. “There have been at least seven or eight human coronaviruses, and the interesting thing is each one affects the brain and causes neurological complications.”

The effects are classified differently and have slightly different receptors, “but the consequences are the same.”

Of note, however, research published in The Lancet Psychiatry (2021 May. doi: 10.1016/S2215-0366[21]00084-5) revealed that symptoms such as dementia, mood, and anxiety are significantly higher after COVID-19 compared with other respiratory infections, with the differences increasing at 180 days since the index event.

Dr. Nath noted that, over the decades, he has observed that in pandemics “the brain tends to get overlooked.” He explained that “what can be most important in the end is what happened in the brain, because those are the things that really cause the long-term consequences.”

“These patients are depressed; they have dementia, they have brain fog, and even now that we recognize these issues, we haven’t done a very good job of studying them,” he said. “There’s so much we still don’t know, and a lot of patients are left with these symptoms and nowhere to go.”

Dr. Lynch, Dr. Van Ameringen, and Dr. Nath had no disclosures to report.

NEW ORLEANS – Patients experiencing brain fog and other persistent symptoms of long COVID show significant deficits on neuropsychiatric testing that correspond with prior acute COVID-19 infection, adding to mounting evidence of the significant toll the chronic condition can have on mental health.

“Many clinicians have observed the symptoms we describe in this study, however this report is among the first which identify the specific deficits using neuropsychological testing to better characterize the syndrome,” Sean T. Lynch, MD, first author of a study on the issue presented at the annual meeting of the American Psychiatric Association, said in an interview.

Dr. Lynch, of the department of psychiatry, Westchester Medical Center Health System, Valhalla, N.Y., and his colleagues enrolled 60 participants who had experienced acute COVID-19 disease 6-8 months earlier and had undergone neuropsychological, psychiatric, medical, functional, and quality-of-life assessments. Results from the study were published online in the Journal of the Academy of Consultation–Liaison Psychiatry (2022 Jan 25. doi: 10.1016/j.jaclp.2022.01.003).

Among the study participants, 32 were seeking treatment for brain fog in a clinical program for survivors of COVID-19, while the remaining 28 were part of an ongoing longitudinal investigation of neuropsychological, medical, and psychiatric sequelae of COVID-19, but were not seeking care for the persistent symptoms.

Assessments for neurocognitive impairment included a battery of tests used in infectious and other diseases, including the Test of Premorbid Function, the Patient Assessment of Own Function, the Trail Making Test parts A and B, the Stroop Color and Word Test, and others.

Overall, the battery of assessments showed that 37 (62%) of participants had neuropsychological test impairment, with results below the 16th percentile in two tests, while 16 (27%) showed scores indicative of severe impairment (below the second percentile in at least one test and below the 16th percentile in one test).

Those reporting brain fog had scores that were even lower than expected on tests of attention, processing speed, memory, and executive function. And among those reporting brain fog, significantly more had scores reflecting severe impairment compared with the controls (38% vs. 14%; P < .04).

“Based on what we’ve observed in our patients and what others have previously reported, we did expect to find some impairment in this study sample,” Dr. Lynch noted.

“However, we were surprised to find that 27% of the study sample had extremely low neuropsychological test scores, meaning that they scored at least two standard deviations below the expected score on at least one neuropsychological test based on their age and level of education.”

The brain fog group also reported significantly higher levels of depression, fatigue, PTSD, and functional difficulties, and lower quality of life.

Severe impairment on the neuropsychological tests correlated with the extent of acute COVID-19 symptoms, as well as depression scores, number of medical comorbidities, and subjective cognitive complaints.

An analysis of serum levels of the inflammatory markers among 50 of the 60 participants showed that 45% of the patients had an elevated IL-6, 20% had elevated TNF-alpha, and 41% had elevated CRP, compared with reference ranges.

IL-6 levels were found to correlate with acute COVID-19 symptoms, the number of medical comorbidities, fatigue, and measures of executive function, while C-reactive protein (CRP) correlated with current COVID-19 symptoms and depression scores.

In terms of clinical factors that might predict low neuropsychological test scores, Dr. Lynch noted that the “markers that we found to be significant included severity of acute COVID-19 illness, current post-COVID-19 symptoms, measures of depression and anxiety, level of fatigue, and number of medical comorbidities.”

Dr. Lynch noted that the ongoing study will include up to 18-month follow-ups that are currently underway. “The [follow-ups] will examine if symptoms improve over time and evaluate if any intervention that took place was successful,” he said.


 

Survey supports findings

The detrimental effects of mental health symptoms in long COVID were further supported in another study at the APA meeting, an online survey of 787 survivors of acute COVID-19.

In the community survey, presented by Michael Van Ameringen, MD, a professor in the department of psychiatry and behavioral neurosciences at McMaster University, in Hamilton, Ont., all respondents (100%) reported having persistent symptoms of the virus, and as many as 68% indicated that they had not returned to normal functioning, despite only 15% of the respondents having been hospitalized with COVID-19.

A large proportion showed significant depression, anxiety, and posttraumatic stress disorder (PTSD), and the most commonly reported persistent symptoms were fatigue in 75.9% of respondents, brain fog in 67.9%, concentration difficulties in 61.1%, and weakness in 51.2%.

As many as 88.2% of patients said they experienced persistent neurocognitive symptoms, with poor memory and concentration; 56% reported problems with word finding; and 54.1% had slowed thinking.

The respondents showed high rates of anxiety (41.7%) as well as depression (61.4%) as determined by scores above 9 on the Generalized Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaires (PHQ-9).

As many as 40.5% of respondents showed probable PTSD, with scores above 30 on the PTSD checklist (PCL-5). Their mean resilience score on the Brief Resilient Coping Scale was 13.5, suggesting low resilience.

Among the respondents, 43.3% said they had received past treatment for mental health, while 33.5% were currently receiving mental health treatment.

Dr. Van Ameringen noted the important limitation of the study being an online survey with no control group, but said the responses nevertheless raise the question of the role of prior psychiatric disorders in long COVID.

“In our sample, 40% of respondents had a past psychiatric history, so you wonder if that also makes you vulnerable to long COVID,” he said in an interview.

“About a third were getting psychiatric help, but I think the more impaired you are, the more likely you are to seek help.”

Those who were hospitalized with COVID-19 were at a higher risk of PTSD compared with those not hospitalized (P < .001), as were those under the age of 30 (P < .05) or between 31 and 50 vs. over 50 (P < .01).

Dr. Van Ameringen noted that the survey’s high rate of subjects who had not returned to normal functioning was especially striking.

“This is not a minor issue – these are people who are no longer functioning in society,” he said.
 

In pandemics, the brain tends to be ‘overlooked’

Further addressing the neurological effects of COVID-19 at the APA meeting, Avindra Nath, MD, clinical director of the National Institutes of Neurologic Disorders and Stroke in Bethesda, Md., noted that the persisting cognitive and psychiatric symptoms after illness, such as brain fog and depression and anxiety, are not necessarily unique to COVID-19.

“We have seen this before,” he said. “There have been at least seven or eight human coronaviruses, and the interesting thing is each one affects the brain and causes neurological complications.”

The effects are classified differently and have slightly different receptors, “but the consequences are the same.”

Of note, however, research published in The Lancet Psychiatry (2021 May. doi: 10.1016/S2215-0366[21]00084-5) revealed that symptoms such as dementia, mood, and anxiety are significantly higher after COVID-19 compared with other respiratory infections, with the differences increasing at 180 days since the index event.

Dr. Nath noted that, over the decades, he has observed that in pandemics “the brain tends to get overlooked.” He explained that “what can be most important in the end is what happened in the brain, because those are the things that really cause the long-term consequences.”

“These patients are depressed; they have dementia, they have brain fog, and even now that we recognize these issues, we haven’t done a very good job of studying them,” he said. “There’s so much we still don’t know, and a lot of patients are left with these symptoms and nowhere to go.”

Dr. Lynch, Dr. Van Ameringen, and Dr. Nath had no disclosures to report.

NEW ORLEANS – Patients experiencing brain fog and other persistent symptoms of long COVID show significant deficits on neuropsychiatric testing that correspond with prior acute COVID-19 infection, adding to mounting evidence of the significant toll the chronic condition can have on mental health.

“Many clinicians have observed the symptoms we describe in this study, however this report is among the first which identify the specific deficits using neuropsychological testing to better characterize the syndrome,” Sean T. Lynch, MD, first author of a study on the issue presented at the annual meeting of the American Psychiatric Association, said in an interview.

Dr. Lynch, of the department of psychiatry, Westchester Medical Center Health System, Valhalla, N.Y., and his colleagues enrolled 60 participants who had experienced acute COVID-19 disease 6-8 months earlier and had undergone neuropsychological, psychiatric, medical, functional, and quality-of-life assessments. Results from the study were published online in the Journal of the Academy of Consultation–Liaison Psychiatry (2022 Jan 25. doi: 10.1016/j.jaclp.2022.01.003).

Among the study participants, 32 were seeking treatment for brain fog in a clinical program for survivors of COVID-19, while the remaining 28 were part of an ongoing longitudinal investigation of neuropsychological, medical, and psychiatric sequelae of COVID-19, but were not seeking care for the persistent symptoms.

Assessments for neurocognitive impairment included a battery of tests used in infectious and other diseases, including the Test of Premorbid Function, the Patient Assessment of Own Function, the Trail Making Test parts A and B, the Stroop Color and Word Test, and others.

Overall, the battery of assessments showed that 37 (62%) of participants had neuropsychological test impairment, with results below the 16th percentile in two tests, while 16 (27%) showed scores indicative of severe impairment (below the second percentile in at least one test and below the 16th percentile in one test).

Those reporting brain fog had scores that were even lower than expected on tests of attention, processing speed, memory, and executive function. And among those reporting brain fog, significantly more had scores reflecting severe impairment compared with the controls (38% vs. 14%; P < .04).

“Based on what we’ve observed in our patients and what others have previously reported, we did expect to find some impairment in this study sample,” Dr. Lynch noted.

“However, we were surprised to find that 27% of the study sample had extremely low neuropsychological test scores, meaning that they scored at least two standard deviations below the expected score on at least one neuropsychological test based on their age and level of education.”

The brain fog group also reported significantly higher levels of depression, fatigue, PTSD, and functional difficulties, and lower quality of life.

Severe impairment on the neuropsychological tests correlated with the extent of acute COVID-19 symptoms, as well as depression scores, number of medical comorbidities, and subjective cognitive complaints.

An analysis of serum levels of the inflammatory markers among 50 of the 60 participants showed that 45% of the patients had an elevated IL-6, 20% had elevated TNF-alpha, and 41% had elevated CRP, compared with reference ranges.

IL-6 levels were found to correlate with acute COVID-19 symptoms, the number of medical comorbidities, fatigue, and measures of executive function, while C-reactive protein (CRP) correlated with current COVID-19 symptoms and depression scores.

In terms of clinical factors that might predict low neuropsychological test scores, Dr. Lynch noted that the “markers that we found to be significant included severity of acute COVID-19 illness, current post-COVID-19 symptoms, measures of depression and anxiety, level of fatigue, and number of medical comorbidities.”

Dr. Lynch noted that the ongoing study will include up to 18-month follow-ups that are currently underway. “The [follow-ups] will examine if symptoms improve over time and evaluate if any intervention that took place was successful,” he said.


 

Survey supports findings

The detrimental effects of mental health symptoms in long COVID were further supported in another study at the APA meeting, an online survey of 787 survivors of acute COVID-19.

In the community survey, presented by Michael Van Ameringen, MD, a professor in the department of psychiatry and behavioral neurosciences at McMaster University, in Hamilton, Ont., all respondents (100%) reported having persistent symptoms of the virus, and as many as 68% indicated that they had not returned to normal functioning, despite only 15% of the respondents having been hospitalized with COVID-19.

A large proportion showed significant depression, anxiety, and posttraumatic stress disorder (PTSD), and the most commonly reported persistent symptoms were fatigue in 75.9% of respondents, brain fog in 67.9%, concentration difficulties in 61.1%, and weakness in 51.2%.

As many as 88.2% of patients said they experienced persistent neurocognitive symptoms, with poor memory and concentration; 56% reported problems with word finding; and 54.1% had slowed thinking.

The respondents showed high rates of anxiety (41.7%) as well as depression (61.4%) as determined by scores above 9 on the Generalized Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaires (PHQ-9).

As many as 40.5% of respondents showed probable PTSD, with scores above 30 on the PTSD checklist (PCL-5). Their mean resilience score on the Brief Resilient Coping Scale was 13.5, suggesting low resilience.

Among the respondents, 43.3% said they had received past treatment for mental health, while 33.5% were currently receiving mental health treatment.

Dr. Van Ameringen noted the important limitation of the study being an online survey with no control group, but said the responses nevertheless raise the question of the role of prior psychiatric disorders in long COVID.

“In our sample, 40% of respondents had a past psychiatric history, so you wonder if that also makes you vulnerable to long COVID,” he said in an interview.

“About a third were getting psychiatric help, but I think the more impaired you are, the more likely you are to seek help.”

Those who were hospitalized with COVID-19 were at a higher risk of PTSD compared with those not hospitalized (P < .001), as were those under the age of 30 (P < .05) or between 31 and 50 vs. over 50 (P < .01).

Dr. Van Ameringen noted that the survey’s high rate of subjects who had not returned to normal functioning was especially striking.

“This is not a minor issue – these are people who are no longer functioning in society,” he said.
 

In pandemics, the brain tends to be ‘overlooked’

Further addressing the neurological effects of COVID-19 at the APA meeting, Avindra Nath, MD, clinical director of the National Institutes of Neurologic Disorders and Stroke in Bethesda, Md., noted that the persisting cognitive and psychiatric symptoms after illness, such as brain fog and depression and anxiety, are not necessarily unique to COVID-19.

“We have seen this before,” he said. “There have been at least seven or eight human coronaviruses, and the interesting thing is each one affects the brain and causes neurological complications.”

The effects are classified differently and have slightly different receptors, “but the consequences are the same.”

Of note, however, research published in The Lancet Psychiatry (2021 May. doi: 10.1016/S2215-0366[21]00084-5) revealed that symptoms such as dementia, mood, and anxiety are significantly higher after COVID-19 compared with other respiratory infections, with the differences increasing at 180 days since the index event.

Dr. Nath noted that, over the decades, he has observed that in pandemics “the brain tends to get overlooked.” He explained that “what can be most important in the end is what happened in the brain, because those are the things that really cause the long-term consequences.”

“These patients are depressed; they have dementia, they have brain fog, and even now that we recognize these issues, we haven’t done a very good job of studying them,” he said. “There’s so much we still don’t know, and a lot of patients are left with these symptoms and nowhere to go.”

Dr. Lynch, Dr. Van Ameringen, and Dr. Nath had no disclosures to report.

As the parents of the 19 children shot dead Tuesday in Uvalde, Tex., by a teen gunman grapple with unspeakable grief and funeral preparations, the survivors and their families are dealing with their own angst and likely much more.

While the parents understandably feel lucky that their children made it out, what about the long-term effect on their children of witnessing that carnage, of seeing classmates, friends, and teachers die violently as they stood by helpless and fearful?

The outcome over the next few days, months, and years depends on many factors, but how parents address the trauma both immediately and long-term can make a huge difference, experts say.
 

Posttraumatic growth

Best long-term case scenario? Survivors can experience what experts call posttraumatic growth – reaching out to give back to society, to make the world a better place, and changing who they are and their view of the world.

A prime example of posttraumatic growth: A month after a teen gunman killed 17 students at Marjory Stoneman Douglas High School in Parkland, Fla., on Valentine’s Day 2018, an army of survivors from that day’s bloodbath headed to Washington, D.C., for the now-famous March for Our Lives. The student-led demonstration, with hundreds of thousands of supporters marching, called for gun control legislation and an end to gun violence. It remains a vibrant, nonprofit organization still advocating for universal background checks and increased support of mental health services.
 

No sign of future violence

While most children and teens who witness school violence won’t become high-profile activists, as survivors of Parkland and the numerous other school shootings have, neither will they become the next active shooter, mental health experts say. They can’t point to a study that follows the gun violence victims that shows who does OK and who doesn’t, but they know immediate support and therapy can go a long way to recovery.

“I can’t tell you how any particular child will do,” says Robin Gurwitch, PhD, psychologist and professor at Duke University Medical Center, Durham, N.C. “I can tell you the majority of kids will be OK.”

However, that doesn’t mean a surviving child won’t have behavior and other issues, she says. Research does suggest the next few days, weeks, or months will be rough.

What parents and other caretakers do in the days after the violence will help predict the long-term outcome. Dr. Gurwitch and other experts say it’s important to first focus on what they call “psychological first aid,” then phase in therapy such as trauma-focused cognitive behavioral therapy, if and when it’s needed.
 

First, ‘psychological first aid’

“Psychological first aid is designed to minimize the impact down the road,” Dr. Gurwitch says. “Validate that they are feeling scared or worried.”

Some may be angry, another understandable emotion. In the first few days of witnessing violence – or even just hearing about it – parents should expect clinginess, sleep problems, behavior meltdowns, and irritability, she says.

“Those kinds of changes are likely to last a few weeks,” she says.

If day-to-day functioning is very difficult, “don’t wait for those to pass,” Dr. Gurwitch says. “Reach out for help. Resources will be available. Check with your pediatrician or family physician.”

At home, parents can address specific problems related to the experience, Dr. Gurwitch says. If it’s sleep, she says, parents and kids can work together to figure out how to ease sleep, such as listening to their favorite music before bedtime.

While parents may be inclined to baby the kids after the violence, Dr. Gurwitch says it’s important to maintain routines. So it’s not cruel to insist they do their chores.
 

Expect change

Things won’t be the same.

“Anytime we go through a particular traumatic event, we are changed,” Dr. Gurwitch says. ‘’The question is, what do we do about it? How do we incorporate that change into who we are and have become?”

Also important is figuring out how to make meaning out of what happened.

“I am so impressed by the families at Sandy Hook (the Connecticut elementary school where a gunman killed 26 in 2012),” she says.

They set up foundations and did other advocacy work.

“These types of events are life-changing events,” agrees David Schonfeld, MD, a pediatrician and director of the National Center for Schools Crisis and Bereavement at Children’s Hospital Los Angeles, California. “They will change who children are as people, but it doesn’t mean they are damaged for life. They will remember it as long as they live, and it will also change who they are as a person.”

While people tend to stress the potential negative effects – and there certainly are some – ‘’some individuals actually emerge from these events with a renewed sense of purpose.’’

He tells parents: “Yes, your child has changed, and you can’t go back. But it doesn’t mean they are destined to never be able to cope [with trauma].”
 

Research

The effects of gun violence on children can be serious and dramatic, research shows.

• Exposure to neighborhood gun violence is linked with an increase in children’s mental health issues,  have found. Children living within two or three blocks of gun violence had nearly twice the risk of going to the emergency department with a mental health complaint in the 14 days following the shooting.  
• Exposure to gun violence should be classified, along with maltreatment, household dysfunction, and other issues known to impact children negatively, as an adverse childhood experience, other experts 
• Direct gun violence exposure, witnessing it, and hearing gunshots are all associated with children being victimized in other ways, another  found. And that poly-victimization, as it is called, was strongly associated with having posttraumatic symptoms.

Adverse Childhood Events, as these sorts of experiences are known, can have long-lasting effects on physical and mental health, as well as on even the economic future of a person, says Hansa Bhargava, MD, a pediatrician and chief medical officer of Medscape, WebMD’s sister site for medical professionals.

“Kids who have suffered through violent events can have brain development affected, as well as their immune systems,” she says. “They are more likely to have chronic disease, substance use disorder, sexually transmitted diseases, teen pregnancy, and lifelong depression. A high risk of [posttraumatic stress disorder] is likely for them and their families.”
 

The impact of family support

The gun violence and deaths are likely to remind children of other losses they have experienced, Dr. Schonfeld says, and that can make coping more difficult.

If the trauma from the Tuesday shootings is ‘’layered” on top of trauma from COVID-19 deaths or other trauma such as domestic violence, those children may have a more difficult time, says Allan Chrisman, MD, professor emeritus of psychiatry and behavioral sciences at Duke University Health System. However, protective factors such as the family response and the community response can build resilience in survivors, he says.

“The way in which parents handle it for themselves will have a huge impact on the kids,” Dr. Chrisman says. “The worst outcomes are linked with [parents saying], ‘We don’t want to talk about it.’ ”

The parents are understandably upset, Dr. Gurwitch says. It’s OK to show sadness, anger, and other emotions, but she tells parents: “It’s not OK to completely decompose.” It’s important for the children to see that parents can pull themselves together.
 

Longer-term effects

As time goes on, ‘’a very large percentage will have posttraumatic reactions,” Dr. Schonfeld says. “Those reactions tend to improve over time.”

While people talk about PTSD directly after an incident such as a school shooting, it isn’t officially diagnosed as PTSD until the symptoms describing PTSD have persisted for a month, Dr. Schonfeld says. However, ‘’that doesn’t mean you don’t have a problem” that needs attention from a mental health professional.

“As a country we are already struggling with a mental health crisis,” Dr. Bhargava says. “Events such as this serve to exacerbate even more crisis in a group of innocent children whose only crime was to attend school. We must address the ‘epidemic’ of gun violence and school shootings head on. For the sake of our children and their health. For all of us.”
 

Therapy that works

Cognitive behavioral therapy (CBT) approaches are effective in reducing the trauma, Dr. Gurwitch says.

She often recommends one type of CBT, called trauma-focused cognitive behavioral therapy. This approach involves children and parents and focuses on safety, coping skills, and gradual exposure. It’s a structured and short-term treatment of about eight to 25 sessions.

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

As the parents of the 19 children shot dead Tuesday in Uvalde, Tex., by a teen gunman grapple with unspeakable grief and funeral preparations, the survivors and their families are dealing with their own angst and likely much more.

While the parents understandably feel lucky that their children made it out, what about the long-term effect on their children of witnessing that carnage, of seeing classmates, friends, and teachers die violently as they stood by helpless and fearful?

The outcome over the next few days, months, and years depends on many factors, but how parents address the trauma both immediately and long-term can make a huge difference, experts say.
 

Posttraumatic growth

Best long-term case scenario? Survivors can experience what experts call posttraumatic growth – reaching out to give back to society, to make the world a better place, and changing who they are and their view of the world.

A prime example of posttraumatic growth: A month after a teen gunman killed 17 students at Marjory Stoneman Douglas High School in Parkland, Fla., on Valentine’s Day 2018, an army of survivors from that day’s bloodbath headed to Washington, D.C., for the now-famous March for Our Lives. The student-led demonstration, with hundreds of thousands of supporters marching, called for gun control legislation and an end to gun violence. It remains a vibrant, nonprofit organization still advocating for universal background checks and increased support of mental health services.
 

No sign of future violence

While most children and teens who witness school violence won’t become high-profile activists, as survivors of Parkland and the numerous other school shootings have, neither will they become the next active shooter, mental health experts say. They can’t point to a study that follows the gun violence victims that shows who does OK and who doesn’t, but they know immediate support and therapy can go a long way to recovery.

“I can’t tell you how any particular child will do,” says Robin Gurwitch, PhD, psychologist and professor at Duke University Medical Center, Durham, N.C. “I can tell you the majority of kids will be OK.”

However, that doesn’t mean a surviving child won’t have behavior and other issues, she says. Research does suggest the next few days, weeks, or months will be rough.

What parents and other caretakers do in the days after the violence will help predict the long-term outcome. Dr. Gurwitch and other experts say it’s important to first focus on what they call “psychological first aid,” then phase in therapy such as trauma-focused cognitive behavioral therapy, if and when it’s needed.
 

First, ‘psychological first aid’

“Psychological first aid is designed to minimize the impact down the road,” Dr. Gurwitch says. “Validate that they are feeling scared or worried.”

Some may be angry, another understandable emotion. In the first few days of witnessing violence – or even just hearing about it – parents should expect clinginess, sleep problems, behavior meltdowns, and irritability, she says.

“Those kinds of changes are likely to last a few weeks,” she says.

If day-to-day functioning is very difficult, “don’t wait for those to pass,” Dr. Gurwitch says. “Reach out for help. Resources will be available. Check with your pediatrician or family physician.”

At home, parents can address specific problems related to the experience, Dr. Gurwitch says. If it’s sleep, she says, parents and kids can work together to figure out how to ease sleep, such as listening to their favorite music before bedtime.

While parents may be inclined to baby the kids after the violence, Dr. Gurwitch says it’s important to maintain routines. So it’s not cruel to insist they do their chores.
 

Expect change

Things won’t be the same.

“Anytime we go through a particular traumatic event, we are changed,” Dr. Gurwitch says. ‘’The question is, what do we do about it? How do we incorporate that change into who we are and have become?”

Also important is figuring out how to make meaning out of what happened.

“I am so impressed by the families at Sandy Hook (the Connecticut elementary school where a gunman killed 26 in 2012),” she says.

They set up foundations and did other advocacy work.

“These types of events are life-changing events,” agrees David Schonfeld, MD, a pediatrician and director of the National Center for Schools Crisis and Bereavement at Children’s Hospital Los Angeles, California. “They will change who children are as people, but it doesn’t mean they are damaged for life. They will remember it as long as they live, and it will also change who they are as a person.”

While people tend to stress the potential negative effects – and there certainly are some – ‘’some individuals actually emerge from these events with a renewed sense of purpose.’’

He tells parents: “Yes, your child has changed, and you can’t go back. But it doesn’t mean they are destined to never be able to cope [with trauma].”
 

Research

The effects of gun violence on children can be serious and dramatic, research shows.

• Exposure to neighborhood gun violence is linked with an increase in children’s mental health issues,  have found. Children living within two or three blocks of gun violence had nearly twice the risk of going to the emergency department with a mental health complaint in the 14 days following the shooting.  
• Exposure to gun violence should be classified, along with maltreatment, household dysfunction, and other issues known to impact children negatively, as an adverse childhood experience, other experts 
• Direct gun violence exposure, witnessing it, and hearing gunshots are all associated with children being victimized in other ways, another  found. And that poly-victimization, as it is called, was strongly associated with having posttraumatic symptoms.

Adverse Childhood Events, as these sorts of experiences are known, can have long-lasting effects on physical and mental health, as well as on even the economic future of a person, says Hansa Bhargava, MD, a pediatrician and chief medical officer of Medscape, WebMD’s sister site for medical professionals.

“Kids who have suffered through violent events can have brain development affected, as well as their immune systems,” she says. “They are more likely to have chronic disease, substance use disorder, sexually transmitted diseases, teen pregnancy, and lifelong depression. A high risk of [posttraumatic stress disorder] is likely for them and their families.”
 

The impact of family support

The gun violence and deaths are likely to remind children of other losses they have experienced, Dr. Schonfeld says, and that can make coping more difficult.

If the trauma from the Tuesday shootings is ‘’layered” on top of trauma from COVID-19 deaths or other trauma such as domestic violence, those children may have a more difficult time, says Allan Chrisman, MD, professor emeritus of psychiatry and behavioral sciences at Duke University Health System. However, protective factors such as the family response and the community response can build resilience in survivors, he says.

“The way in which parents handle it for themselves will have a huge impact on the kids,” Dr. Chrisman says. “The worst outcomes are linked with [parents saying], ‘We don’t want to talk about it.’ ”

The parents are understandably upset, Dr. Gurwitch says. It’s OK to show sadness, anger, and other emotions, but she tells parents: “It’s not OK to completely decompose.” It’s important for the children to see that parents can pull themselves together.
 

Longer-term effects

As time goes on, ‘’a very large percentage will have posttraumatic reactions,” Dr. Schonfeld says. “Those reactions tend to improve over time.”

While people talk about PTSD directly after an incident such as a school shooting, it isn’t officially diagnosed as PTSD until the symptoms describing PTSD have persisted for a month, Dr. Schonfeld says. However, ‘’that doesn’t mean you don’t have a problem” that needs attention from a mental health professional.

“As a country we are already struggling with a mental health crisis,” Dr. Bhargava says. “Events such as this serve to exacerbate even more crisis in a group of innocent children whose only crime was to attend school. We must address the ‘epidemic’ of gun violence and school shootings head on. For the sake of our children and their health. For all of us.”
 

Therapy that works

Cognitive behavioral therapy (CBT) approaches are effective in reducing the trauma, Dr. Gurwitch says.

She often recommends one type of CBT, called trauma-focused cognitive behavioral therapy. This approach involves children and parents and focuses on safety, coping skills, and gradual exposure. It’s a structured and short-term treatment of about eight to 25 sessions.

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

As the parents of the 19 children shot dead Tuesday in Uvalde, Tex., by a teen gunman grapple with unspeakable grief and funeral preparations, the survivors and their families are dealing with their own angst and likely much more.

While the parents understandably feel lucky that their children made it out, what about the long-term effect on their children of witnessing that carnage, of seeing classmates, friends, and teachers die violently as they stood by helpless and fearful?

The outcome over the next few days, months, and years depends on many factors, but how parents address the trauma both immediately and long-term can make a huge difference, experts say.
 

Posttraumatic growth

Best long-term case scenario? Survivors can experience what experts call posttraumatic growth – reaching out to give back to society, to make the world a better place, and changing who they are and their view of the world.

A prime example of posttraumatic growth: A month after a teen gunman killed 17 students at Marjory Stoneman Douglas High School in Parkland, Fla., on Valentine’s Day 2018, an army of survivors from that day’s bloodbath headed to Washington, D.C., for the now-famous March for Our Lives. The student-led demonstration, with hundreds of thousands of supporters marching, called for gun control legislation and an end to gun violence. It remains a vibrant, nonprofit organization still advocating for universal background checks and increased support of mental health services.
 

No sign of future violence

While most children and teens who witness school violence won’t become high-profile activists, as survivors of Parkland and the numerous other school shootings have, neither will they become the next active shooter, mental health experts say. They can’t point to a study that follows the gun violence victims that shows who does OK and who doesn’t, but they know immediate support and therapy can go a long way to recovery.

“I can’t tell you how any particular child will do,” says Robin Gurwitch, PhD, psychologist and professor at Duke University Medical Center, Durham, N.C. “I can tell you the majority of kids will be OK.”

However, that doesn’t mean a surviving child won’t have behavior and other issues, she says. Research does suggest the next few days, weeks, or months will be rough.

What parents and other caretakers do in the days after the violence will help predict the long-term outcome. Dr. Gurwitch and other experts say it’s important to first focus on what they call “psychological first aid,” then phase in therapy such as trauma-focused cognitive behavioral therapy, if and when it’s needed.
 

First, ‘psychological first aid’

“Psychological first aid is designed to minimize the impact down the road,” Dr. Gurwitch says. “Validate that they are feeling scared or worried.”

Some may be angry, another understandable emotion. In the first few days of witnessing violence – or even just hearing about it – parents should expect clinginess, sleep problems, behavior meltdowns, and irritability, she says.

“Those kinds of changes are likely to last a few weeks,” she says.

If day-to-day functioning is very difficult, “don’t wait for those to pass,” Dr. Gurwitch says. “Reach out for help. Resources will be available. Check with your pediatrician or family physician.”

At home, parents can address specific problems related to the experience, Dr. Gurwitch says. If it’s sleep, she says, parents and kids can work together to figure out how to ease sleep, such as listening to their favorite music before bedtime.

While parents may be inclined to baby the kids after the violence, Dr. Gurwitch says it’s important to maintain routines. So it’s not cruel to insist they do their chores.
 

Expect change

Things won’t be the same.

“Anytime we go through a particular traumatic event, we are changed,” Dr. Gurwitch says. ‘’The question is, what do we do about it? How do we incorporate that change into who we are and have become?”

Also important is figuring out how to make meaning out of what happened.

“I am so impressed by the families at Sandy Hook (the Connecticut elementary school where a gunman killed 26 in 2012),” she says.

They set up foundations and did other advocacy work.

“These types of events are life-changing events,” agrees David Schonfeld, MD, a pediatrician and director of the National Center for Schools Crisis and Bereavement at Children’s Hospital Los Angeles, California. “They will change who children are as people, but it doesn’t mean they are damaged for life. They will remember it as long as they live, and it will also change who they are as a person.”

While people tend to stress the potential negative effects – and there certainly are some – ‘’some individuals actually emerge from these events with a renewed sense of purpose.’’

He tells parents: “Yes, your child has changed, and you can’t go back. But it doesn’t mean they are destined to never be able to cope [with trauma].”
 

Research

The effects of gun violence on children can be serious and dramatic, research shows.

• Exposure to neighborhood gun violence is linked with an increase in children’s mental health issues,  have found. Children living within two or three blocks of gun violence had nearly twice the risk of going to the emergency department with a mental health complaint in the 14 days following the shooting.  
• Exposure to gun violence should be classified, along with maltreatment, household dysfunction, and other issues known to impact children negatively, as an adverse childhood experience, other experts 
• Direct gun violence exposure, witnessing it, and hearing gunshots are all associated with children being victimized in other ways, another  found. And that poly-victimization, as it is called, was strongly associated with having posttraumatic symptoms.

Adverse Childhood Events, as these sorts of experiences are known, can have long-lasting effects on physical and mental health, as well as on even the economic future of a person, says Hansa Bhargava, MD, a pediatrician and chief medical officer of Medscape, WebMD’s sister site for medical professionals.

“Kids who have suffered through violent events can have brain development affected, as well as their immune systems,” she says. “They are more likely to have chronic disease, substance use disorder, sexually transmitted diseases, teen pregnancy, and lifelong depression. A high risk of [posttraumatic stress disorder] is likely for them and their families.”
 

The impact of family support

The gun violence and deaths are likely to remind children of other losses they have experienced, Dr. Schonfeld says, and that can make coping more difficult.

If the trauma from the Tuesday shootings is ‘’layered” on top of trauma from COVID-19 deaths or other trauma such as domestic violence, those children may have a more difficult time, says Allan Chrisman, MD, professor emeritus of psychiatry and behavioral sciences at Duke University Health System. However, protective factors such as the family response and the community response can build resilience in survivors, he says.

“The way in which parents handle it for themselves will have a huge impact on the kids,” Dr. Chrisman says. “The worst outcomes are linked with [parents saying], ‘We don’t want to talk about it.’ ”

The parents are understandably upset, Dr. Gurwitch says. It’s OK to show sadness, anger, and other emotions, but she tells parents: “It’s not OK to completely decompose.” It’s important for the children to see that parents can pull themselves together.
 

Longer-term effects

As time goes on, ‘’a very large percentage will have posttraumatic reactions,” Dr. Schonfeld says. “Those reactions tend to improve over time.”

While people talk about PTSD directly after an incident such as a school shooting, it isn’t officially diagnosed as PTSD until the symptoms describing PTSD have persisted for a month, Dr. Schonfeld says. However, ‘’that doesn’t mean you don’t have a problem” that needs attention from a mental health professional.

“As a country we are already struggling with a mental health crisis,” Dr. Bhargava says. “Events such as this serve to exacerbate even more crisis in a group of innocent children whose only crime was to attend school. We must address the ‘epidemic’ of gun violence and school shootings head on. For the sake of our children and their health. For all of us.”
 

Therapy that works

Cognitive behavioral therapy (CBT) approaches are effective in reducing the trauma, Dr. Gurwitch says.

She often recommends one type of CBT, called trauma-focused cognitive behavioral therapy. This approach involves children and parents and focuses on safety, coping skills, and gradual exposure. It’s a structured and short-term treatment of about eight to 25 sessions.

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

Cariprazine (Vraylar) is a safe and effective adjunctive treatment for adults with major depressive disorder (MDD) who have an inadequate response to antidepressant monotherapy, new results from a phase 3 study show.

Already approved by the U.S. Food and Drug Administration to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder, cariprazine is under investigation as an add-on therapy for MDD.

“Even patients who appear to be nonresponsive to standard antidepressant drugs have a very good chance of responding” to cariprazine, lead study author Gary Sachs, MD, associate clinical professor of psychiatry at Massachusetts General Hospital, Boston, told this news organization.

He noted that cariprazine, which is a partial agonist at D2 and D3, as well as 5-HT1A, “is an entirely different class” of drugs.

“It’s worth understanding how to use drugs like cariprazine and expanding our nomenclature; instead of referring to these drugs as atypical antipsychotics, perhaps referring to them as atypical antidepressants makes more sense,” Dr. Sachs said.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

More options critical

MDD is among the most common psychiatric disorders in the United States. In 2020, an estimated 21 million adults had at least one major depressive episode.

Previous research has shown almost half of patients with MDD do not experience satisfactory results from their current treatment regimen. Therefore, research on more options for patients is critical, Dr. Sachs said.

Results from a previously published placebo-controlled study showed adjunctive treatment with cariprazine at 2-mg to 4.5-mg per day doses was more effective than placebo in improving depressive symptoms in adults with MDD.

The new analysis included patients with MDD and an inadequate response to antidepressant therapy, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants. They were recruited from 116 centers in the United States and Europe.

Dr. Sachs noted that a nonresponse to an adequate dose of an antidepressant typically means having less than a 50% improvement over 6 weeks or more.

Researchers randomly assigned the patients to oral cariprazine 1.5 mg/day, cariprazine 3 mg/day, or placebo. All continued to take their antidepressant monotherapy.

The analysis included 757 mostly White participants (mean age, 44.8 years; 73.4% women). All had experienced depression for a “huge” part of their life (average, about 14 years), “not to mention their adult life,” said Dr. Sachs.

In addition, at the start of the study, the participants had been depressed for almost 8 months on average.

The primary endpoint was change at week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The mean baseline MADRS total score was 32.5.

Less is sometimes more

Results showed a significantly greater mean reduction in MADRS total score for cariprazine 1.5 mg/day vs. placebo at week 6 (P = .005). Significant differences from placebo were observed as early as week 2 and were maintained at week 4, as well as week 6.

“I can say with great confidence that the 1.5-mg dose met all the standards for efficacy,” Dr. Sachs said.

However, this was not the case for the 3-mg/day dose. Although there was a numerically greater reduction in MADRS total score for this dosage of the drug vs. placebo at week 6, the difference was not statistically significant (P = .07).

At week 6, more patients taking the active drug at 1.5 mg/day than placebo responded to treatment, defined as 50% or greater reduction in MADRS total score (44% vs. 34.9%, respectively; P < .05).

Researchers also assessed scores on the Clinical Global Impressions, finding significantly greater score improvement for both the 1.5-mg/day (P = .0026) and 3-mg/day (P =.0076) groups vs. the placebo group.

Improvement at week 6 in mean total score on the Hamilton Depression Rating Scale (HAM-17) reached nominal significance for cariprazine 1.5 mg/day vs. placebo – but not for 3 mg/day.

The results of this “high-quality” double-blind, randomized, controlled, parallel group study provide “what I regard as proven efficacy,” Dr. Sachs said.

He added that the investigational drug was also relatively safe. “The vast majority of patients tolerated it quite well,” he stressed. In addition, the drop-out rate because of adverse events was “quite low overall.”

The only adverse events (AEs) that occurred with the active treatment at a frequency of 5% or more and double that of placebo were akathisia and nausea. Changes in weight were relatively small, at less than 1 kg, in all treatment groups.

There was one serious AE in each active drug group, one of which was a kidney infection. There were two serious AEs reported in the placebo group, including one patient with multiple sclerosis. There were no deaths.

Dr. Sachs noted an advantage of cariprazine is its long half-life, which makes it more user-friendly because “it forgives you if you miss a dose or two.”

Drug manufacturer AbbVie’s supplemental New Drug Application for cariprazine is currently under review by the FDA for expanded use as adjunctive treatment of MDD. A decision by the agency is expected by the end of this year.

Another potential treatment option

Commenting on the findings, James Murrough, MD, PhD, associate professor of psychiatry and of neuroscience and director of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai, New York, said he welcomes research into additional treatments for MDD.

“Each medicine in a particular class has a unique pharmacology, so a larger number of medication options may help the clinician find a good match for a particular patient,” said Dr. Murrough, who was not involved with the research.

He noted cariprazine is “somewhat unique” among the dopamine modulators in “preferring interactions with the D3 receptor, one of many types of dopamine receptors.”

Although the study results showed cariprazine was effective in MDD, it “does not entirely break new ground” because previous research has already established the drug’s efficacy as adjunctive therapy for patients with depression not responding to a standard antidepressant, said Dr. Murrough.

He also noted that the lower dose, but not the higher dose, of the drug was found to be significantly beneficial for patients, compared with placebo.

“This is a good reminder that higher doses of a medication are not always better,” Dr. Murrough said.

The study was funded by AbbVie. Dr. Sachs is a full-time employee of Signant Health, which conducted the training and quality control for this study. Dr. Murrough has reported no relevant financial relationships.

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

Cariprazine (Vraylar) is a safe and effective adjunctive treatment for adults with major depressive disorder (MDD) who have an inadequate response to antidepressant monotherapy, new results from a phase 3 study show.

Already approved by the U.S. Food and Drug Administration to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder, cariprazine is under investigation as an add-on therapy for MDD.

“Even patients who appear to be nonresponsive to standard antidepressant drugs have a very good chance of responding” to cariprazine, lead study author Gary Sachs, MD, associate clinical professor of psychiatry at Massachusetts General Hospital, Boston, told this news organization.

He noted that cariprazine, which is a partial agonist at D2 and D3, as well as 5-HT1A, “is an entirely different class” of drugs.

“It’s worth understanding how to use drugs like cariprazine and expanding our nomenclature; instead of referring to these drugs as atypical antipsychotics, perhaps referring to them as atypical antidepressants makes more sense,” Dr. Sachs said.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

More options critical

MDD is among the most common psychiatric disorders in the United States. In 2020, an estimated 21 million adults had at least one major depressive episode.

Previous research has shown almost half of patients with MDD do not experience satisfactory results from their current treatment regimen. Therefore, research on more options for patients is critical, Dr. Sachs said.

Results from a previously published placebo-controlled study showed adjunctive treatment with cariprazine at 2-mg to 4.5-mg per day doses was more effective than placebo in improving depressive symptoms in adults with MDD.

The new analysis included patients with MDD and an inadequate response to antidepressant therapy, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants. They were recruited from 116 centers in the United States and Europe.

Dr. Sachs noted that a nonresponse to an adequate dose of an antidepressant typically means having less than a 50% improvement over 6 weeks or more.

Researchers randomly assigned the patients to oral cariprazine 1.5 mg/day, cariprazine 3 mg/day, or placebo. All continued to take their antidepressant monotherapy.

The analysis included 757 mostly White participants (mean age, 44.8 years; 73.4% women). All had experienced depression for a “huge” part of their life (average, about 14 years), “not to mention their adult life,” said Dr. Sachs.

In addition, at the start of the study, the participants had been depressed for almost 8 months on average.

The primary endpoint was change at week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The mean baseline MADRS total score was 32.5.

Less is sometimes more

Results showed a significantly greater mean reduction in MADRS total score for cariprazine 1.5 mg/day vs. placebo at week 6 (P = .005). Significant differences from placebo were observed as early as week 2 and were maintained at week 4, as well as week 6.

“I can say with great confidence that the 1.5-mg dose met all the standards for efficacy,” Dr. Sachs said.

However, this was not the case for the 3-mg/day dose. Although there was a numerically greater reduction in MADRS total score for this dosage of the drug vs. placebo at week 6, the difference was not statistically significant (P = .07).

At week 6, more patients taking the active drug at 1.5 mg/day than placebo responded to treatment, defined as 50% or greater reduction in MADRS total score (44% vs. 34.9%, respectively; P < .05).

Researchers also assessed scores on the Clinical Global Impressions, finding significantly greater score improvement for both the 1.5-mg/day (P = .0026) and 3-mg/day (P =.0076) groups vs. the placebo group.

Improvement at week 6 in mean total score on the Hamilton Depression Rating Scale (HAM-17) reached nominal significance for cariprazine 1.5 mg/day vs. placebo – but not for 3 mg/day.

The results of this “high-quality” double-blind, randomized, controlled, parallel group study provide “what I regard as proven efficacy,” Dr. Sachs said.

He added that the investigational drug was also relatively safe. “The vast majority of patients tolerated it quite well,” he stressed. In addition, the drop-out rate because of adverse events was “quite low overall.”

The only adverse events (AEs) that occurred with the active treatment at a frequency of 5% or more and double that of placebo were akathisia and nausea. Changes in weight were relatively small, at less than 1 kg, in all treatment groups.

There was one serious AE in each active drug group, one of which was a kidney infection. There were two serious AEs reported in the placebo group, including one patient with multiple sclerosis. There were no deaths.

Dr. Sachs noted an advantage of cariprazine is its long half-life, which makes it more user-friendly because “it forgives you if you miss a dose or two.”

Drug manufacturer AbbVie’s supplemental New Drug Application for cariprazine is currently under review by the FDA for expanded use as adjunctive treatment of MDD. A decision by the agency is expected by the end of this year.

Another potential treatment option

Commenting on the findings, James Murrough, MD, PhD, associate professor of psychiatry and of neuroscience and director of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai, New York, said he welcomes research into additional treatments for MDD.

“Each medicine in a particular class has a unique pharmacology, so a larger number of medication options may help the clinician find a good match for a particular patient,” said Dr. Murrough, who was not involved with the research.

He noted cariprazine is “somewhat unique” among the dopamine modulators in “preferring interactions with the D3 receptor, one of many types of dopamine receptors.”

Although the study results showed cariprazine was effective in MDD, it “does not entirely break new ground” because previous research has already established the drug’s efficacy as adjunctive therapy for patients with depression not responding to a standard antidepressant, said Dr. Murrough.

He also noted that the lower dose, but not the higher dose, of the drug was found to be significantly beneficial for patients, compared with placebo.

“This is a good reminder that higher doses of a medication are not always better,” Dr. Murrough said.

The study was funded by AbbVie. Dr. Sachs is a full-time employee of Signant Health, which conducted the training and quality control for this study. Dr. Murrough has reported no relevant financial relationships.

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

Cariprazine (Vraylar) is a safe and effective adjunctive treatment for adults with major depressive disorder (MDD) who have an inadequate response to antidepressant monotherapy, new results from a phase 3 study show.

Already approved by the U.S. Food and Drug Administration to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder, cariprazine is under investigation as an add-on therapy for MDD.

“Even patients who appear to be nonresponsive to standard antidepressant drugs have a very good chance of responding” to cariprazine, lead study author Gary Sachs, MD, associate clinical professor of psychiatry at Massachusetts General Hospital, Boston, told this news organization.

He noted that cariprazine, which is a partial agonist at D2 and D3, as well as 5-HT1A, “is an entirely different class” of drugs.

“It’s worth understanding how to use drugs like cariprazine and expanding our nomenclature; instead of referring to these drugs as atypical antipsychotics, perhaps referring to them as atypical antidepressants makes more sense,” Dr. Sachs said.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

More options critical

MDD is among the most common psychiatric disorders in the United States. In 2020, an estimated 21 million adults had at least one major depressive episode.

Previous research has shown almost half of patients with MDD do not experience satisfactory results from their current treatment regimen. Therefore, research on more options for patients is critical, Dr. Sachs said.

Results from a previously published placebo-controlled study showed adjunctive treatment with cariprazine at 2-mg to 4.5-mg per day doses was more effective than placebo in improving depressive symptoms in adults with MDD.

The new analysis included patients with MDD and an inadequate response to antidepressant therapy, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants. They were recruited from 116 centers in the United States and Europe.

Dr. Sachs noted that a nonresponse to an adequate dose of an antidepressant typically means having less than a 50% improvement over 6 weeks or more.

Researchers randomly assigned the patients to oral cariprazine 1.5 mg/day, cariprazine 3 mg/day, or placebo. All continued to take their antidepressant monotherapy.

The analysis included 757 mostly White participants (mean age, 44.8 years; 73.4% women). All had experienced depression for a “huge” part of their life (average, about 14 years), “not to mention their adult life,” said Dr. Sachs.

In addition, at the start of the study, the participants had been depressed for almost 8 months on average.

The primary endpoint was change at week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. The mean baseline MADRS total score was 32.5.

Less is sometimes more

Results showed a significantly greater mean reduction in MADRS total score for cariprazine 1.5 mg/day vs. placebo at week 6 (P = .005). Significant differences from placebo were observed as early as week 2 and were maintained at week 4, as well as week 6.

“I can say with great confidence that the 1.5-mg dose met all the standards for efficacy,” Dr. Sachs said.

However, this was not the case for the 3-mg/day dose. Although there was a numerically greater reduction in MADRS total score for this dosage of the drug vs. placebo at week 6, the difference was not statistically significant (P = .07).

At week 6, more patients taking the active drug at 1.5 mg/day than placebo responded to treatment, defined as 50% or greater reduction in MADRS total score (44% vs. 34.9%, respectively; P < .05).

Researchers also assessed scores on the Clinical Global Impressions, finding significantly greater score improvement for both the 1.5-mg/day (P = .0026) and 3-mg/day (P =.0076) groups vs. the placebo group.

Improvement at week 6 in mean total score on the Hamilton Depression Rating Scale (HAM-17) reached nominal significance for cariprazine 1.5 mg/day vs. placebo – but not for 3 mg/day.

The results of this “high-quality” double-blind, randomized, controlled, parallel group study provide “what I regard as proven efficacy,” Dr. Sachs said.

He added that the investigational drug was also relatively safe. “The vast majority of patients tolerated it quite well,” he stressed. In addition, the drop-out rate because of adverse events was “quite low overall.”

The only adverse events (AEs) that occurred with the active treatment at a frequency of 5% or more and double that of placebo were akathisia and nausea. Changes in weight were relatively small, at less than 1 kg, in all treatment groups.

There was one serious AE in each active drug group, one of which was a kidney infection. There were two serious AEs reported in the placebo group, including one patient with multiple sclerosis. There were no deaths.

Dr. Sachs noted an advantage of cariprazine is its long half-life, which makes it more user-friendly because “it forgives you if you miss a dose or two.”

Drug manufacturer AbbVie’s supplemental New Drug Application for cariprazine is currently under review by the FDA for expanded use as adjunctive treatment of MDD. A decision by the agency is expected by the end of this year.

Another potential treatment option

Commenting on the findings, James Murrough, MD, PhD, associate professor of psychiatry and of neuroscience and director of the Depression and Anxiety Center for Discovery and Treatment at the Icahn School of Medicine at Mount Sinai, New York, said he welcomes research into additional treatments for MDD.

“Each medicine in a particular class has a unique pharmacology, so a larger number of medication options may help the clinician find a good match for a particular patient,” said Dr. Murrough, who was not involved with the research.

He noted cariprazine is “somewhat unique” among the dopamine modulators in “preferring interactions with the D3 receptor, one of many types of dopamine receptors.”

Although the study results showed cariprazine was effective in MDD, it “does not entirely break new ground” because previous research has already established the drug’s efficacy as adjunctive therapy for patients with depression not responding to a standard antidepressant, said Dr. Murrough.

He also noted that the lower dose, but not the higher dose, of the drug was found to be significantly beneficial for patients, compared with placebo.

“This is a good reminder that higher doses of a medication are not always better,” Dr. Murrough said.

The study was funded by AbbVie. Dr. Sachs is a full-time employee of Signant Health, which conducted the training and quality control for this study. Dr. Murrough has reported no relevant financial relationships.

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

NEW ORLEANS – New research reveals that patients with treatment-resistant depression who were treated with repeated intravenous ketamine show no significant differences in achieving response or remission, compared with those receiving the intranasal formulation of the drug, esketamine – although fewer treatments appear necessary with the intravenous formulation.

“This is one of the first studies to compare the efficacy of IV and intranasal ketamine, and the results give us some indication that, if you treat with IV, you might get a faster response, although at the end, the responses are similar,” said first author Balwinder Singh, MD, of the department of psychiatry and psychology, Mayo Clinic, in Rochester, Minn.

courtesy Balwinder Singh

The findings were presented at the annual meeting of the American Psychiatric Association.

Commenting on the study, Roger S. McIntyre, MD, underscored that “this is an important study that addresses the priority questions that everyone wants to know – not only for clinical reasons, but economic reasons.” Dr. McIntyre, a professor of psychiatry and pharmacology at the University of Toronto, and head of the university’s mood disorders psychopharmacology unit, said that “there are implications not only for clinical outcomes and cost, but also implementation because IV is obviously more demanding and complicated.”

As intravenous ketamine increasingly gained interest as a rapid-acting treatment for patients with severe, treatment-resistant depression, the introduction of a more convenient intranasal formulation was seen as a welcome improvement and received approval from the Food and Drug Administration in 2019. However, while the approval ushered in more coverage by insurance companies, the treatment can still be expensive. Intravenous ketamine does not have FDA approval.

With a lack of studies in the real-world setting comparing efficacy of the two formulations, Dr. Singh and his colleagues conducted the observational study, evaluating the responses of 62 adults with treatment-resistant depression who had received either up to six IV ketamine infusions of 0.5 mg/kg, infused over 40 minutes, or up to eight intranasal esketamine treatments of 56/84 mg, as approved by the FDA, at the Mayo Clinic Depression Center.

Of the patients, who had a mean age of 47 years, 59 had major depression and 3 had bipolar depression. Among them, 76% (47) received intravenous ketamine and 24% (15) received esketamine, which Dr. Singh noted reflected the higher number of patients included before esketamine received FDA approval. The patients had similar comorbidity profiles, with the intravenous ketamine group having a higher body mass index at baseline.

Overall, the patients all had significant improvement in their depression at the end of the acute phase of 4 weeks, with a mean change in on the 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR) scale of –8.6 from baseline (P < .001).

The overall remission rate was 38.7% and overall response rate was 58.1%. Those receiving intravenous ketamine had response and remission rates of 57.4% and 42.6%, versus response and remission rates of 60.0% and 26.7% among the esketamine group, which Dr. Singh said were not significant differences (P > .05).

However, the mean number of treatments necessary to achieve response in the intravenous ketamine group was just 2.3 versus 4.6 with esketamine, and the mean number of treatments to achieve remission were 2.5 versus 6.3, respectively (P = .008).

After a multivariate adjustment, the time to response was determined to be faster with intravenous ketamine versus esketamine (hazard ratio, 2.61; P = .05) and the time to remission was also faster (HR, 5.0; P = .02).

“What this means is you would need fewer treatments to achieve a response or remission with IV ketamine, so there could be an acceleration of patients’ antidepressant response,” Dr. Singh explained.

There were no significant differences between the groups in terms of side effects, and most patients tolerated the treatments well.

Dr. Singh noted the limitation of the study is that it was observational and included a small sample size. Nevertheless, when asked which he would choose if starting treatment when insurance was not an issue, Dr. Singh replied: “I would take patient preference into account, but certainly IV seems to have an advantage.”

Dr. McIntyre noted that, though small, the study’s setting in a real world clinical environment is important.

“Obviously this is observational and not controlled, but the strength is that this involved a real-world cohort of patients and real world applications,” he said. “It’s difficult to have a true comparator head-to-head trial, so that makes this all the more important because it takes into consideration all of the complexities of real world patients.”

Dr. McIntyre emphasized that the study is not “the last word on the story because we need to see a larger sample and replication. But certainly they make an argument that IV ketamine may have an advantage over the speed of onset with intranasal ketamine, which will need to be either replicated or refuted, but it’s a great starting point in the conversation.”
 

Navigating patient preference

Robert Meisner, MD, founding medical director of the McLean Ketamine Service, Division of Psychiatric Neurotherapeutics, McLean Hospital, Harvard Medical School, in Boston, noted that wide-ranging factors may influence patient as well as clinician decisions about which ketamine treatment approach to use.

“When a patient appears to be equally well-suited for both interventions, I continue to be surprised by why one patient will indicate a preference for intranasal esketamine, while another will lean toward IV racemic ketamine,” he said in an interview.

“Some patients find esketamine’s clear and consistent protocol optimal for scheduling and navigating the logistics of daily life; others value the flexibility offered by certain evidence-based, racemic (IV) protocols,” he said. “Predicting who will prefer each treatment, even with the apparent temporal advantage with IV ketamine, is extremely difficult.”

Likewise, in terms of clinician preference, Dr. Meisner notes that key concerns may sway decisions.

“If I’m concerned with labile pressures or hypertension, for example, or if I have a patient with, say, Erlos Danlos Syndrome without a clear subtype, and hence, some risk of undiscovered aneurysmal vascular disease, I may lean toward racemic IV ketamine.”

On the other hand, “some patients find the simplicity and predictability of the maintenance esketamine protocol comforting and psychologically stabilizing,” he added. “Yet others find that their work or family’s erratic demands on their time make one of the evidence-based racemic regimens preferable – inasmuch as it integrates more flexibility and allows them to remain more fully engaged in the basic activities or work and family.”

Dr. Meisner noted the caveat that efforts to decide which method to use are often complicated by substantial misinformation.

“I can’t emphasize how much misinformation continues to abound regarding appropriate (evidence-based) and safe use of ketamine and esketamine,” he said. “Especially on the IV racemic side, there simply is no substantive evidence base for many of the claims that some providers are preaching.”

The confusion, driven in part by social media, “has diffused into sectors of the field and industry that one might assume are relatively immune (i.e., allied physicians, sophisticated payers, etc),” he added.

“In short, two mantra continue to apply,” Dr. Meisner said. “One – if it sounds too good to be true, it probably is; and two – in pharmacology and interventional psychiatry, we see remarkable progress and potential, but there simply is no such thing as a magic bullet.”

Dr. Singh and Dr. Meisner had no disclosures to report. Dr. McIntyre has received research grant support from Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/National Natural Science Foundation of China, and speaker/consultation fees from Lundbeck, Janssen, Alkermes,Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie, and Atai Life Sciences. Dr. McIntyre is a CEO of Braxia Scientific.

NEW ORLEANS – New research reveals that patients with treatment-resistant depression who were treated with repeated intravenous ketamine show no significant differences in achieving response or remission, compared with those receiving the intranasal formulation of the drug, esketamine – although fewer treatments appear necessary with the intravenous formulation.

“This is one of the first studies to compare the efficacy of IV and intranasal ketamine, and the results give us some indication that, if you treat with IV, you might get a faster response, although at the end, the responses are similar,” said first author Balwinder Singh, MD, of the department of psychiatry and psychology, Mayo Clinic, in Rochester, Minn.

courtesy Balwinder Singh

The findings were presented at the annual meeting of the American Psychiatric Association.

Commenting on the study, Roger S. McIntyre, MD, underscored that “this is an important study that addresses the priority questions that everyone wants to know – not only for clinical reasons, but economic reasons.” Dr. McIntyre, a professor of psychiatry and pharmacology at the University of Toronto, and head of the university’s mood disorders psychopharmacology unit, said that “there are implications not only for clinical outcomes and cost, but also implementation because IV is obviously more demanding and complicated.”

As intravenous ketamine increasingly gained interest as a rapid-acting treatment for patients with severe, treatment-resistant depression, the introduction of a more convenient intranasal formulation was seen as a welcome improvement and received approval from the Food and Drug Administration in 2019. However, while the approval ushered in more coverage by insurance companies, the treatment can still be expensive. Intravenous ketamine does not have FDA approval.

With a lack of studies in the real-world setting comparing efficacy of the two formulations, Dr. Singh and his colleagues conducted the observational study, evaluating the responses of 62 adults with treatment-resistant depression who had received either up to six IV ketamine infusions of 0.5 mg/kg, infused over 40 minutes, or up to eight intranasal esketamine treatments of 56/84 mg, as approved by the FDA, at the Mayo Clinic Depression Center.

Of the patients, who had a mean age of 47 years, 59 had major depression and 3 had bipolar depression. Among them, 76% (47) received intravenous ketamine and 24% (15) received esketamine, which Dr. Singh noted reflected the higher number of patients included before esketamine received FDA approval. The patients had similar comorbidity profiles, with the intravenous ketamine group having a higher body mass index at baseline.

Overall, the patients all had significant improvement in their depression at the end of the acute phase of 4 weeks, with a mean change in on the 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR) scale of –8.6 from baseline (P < .001).

The overall remission rate was 38.7% and overall response rate was 58.1%. Those receiving intravenous ketamine had response and remission rates of 57.4% and 42.6%, versus response and remission rates of 60.0% and 26.7% among the esketamine group, which Dr. Singh said were not significant differences (P > .05).

However, the mean number of treatments necessary to achieve response in the intravenous ketamine group was just 2.3 versus 4.6 with esketamine, and the mean number of treatments to achieve remission were 2.5 versus 6.3, respectively (P = .008).

After a multivariate adjustment, the time to response was determined to be faster with intravenous ketamine versus esketamine (hazard ratio, 2.61; P = .05) and the time to remission was also faster (HR, 5.0; P = .02).

“What this means is you would need fewer treatments to achieve a response or remission with IV ketamine, so there could be an acceleration of patients’ antidepressant response,” Dr. Singh explained.

There were no significant differences between the groups in terms of side effects, and most patients tolerated the treatments well.

Dr. Singh noted the limitation of the study is that it was observational and included a small sample size. Nevertheless, when asked which he would choose if starting treatment when insurance was not an issue, Dr. Singh replied: “I would take patient preference into account, but certainly IV seems to have an advantage.”

Dr. McIntyre noted that, though small, the study’s setting in a real world clinical environment is important.

“Obviously this is observational and not controlled, but the strength is that this involved a real-world cohort of patients and real world applications,” he said. “It’s difficult to have a true comparator head-to-head trial, so that makes this all the more important because it takes into consideration all of the complexities of real world patients.”

Dr. McIntyre emphasized that the study is not “the last word on the story because we need to see a larger sample and replication. But certainly they make an argument that IV ketamine may have an advantage over the speed of onset with intranasal ketamine, which will need to be either replicated or refuted, but it’s a great starting point in the conversation.”
 

Navigating patient preference

Robert Meisner, MD, founding medical director of the McLean Ketamine Service, Division of Psychiatric Neurotherapeutics, McLean Hospital, Harvard Medical School, in Boston, noted that wide-ranging factors may influence patient as well as clinician decisions about which ketamine treatment approach to use.

“When a patient appears to be equally well-suited for both interventions, I continue to be surprised by why one patient will indicate a preference for intranasal esketamine, while another will lean toward IV racemic ketamine,” he said in an interview.

“Some patients find esketamine’s clear and consistent protocol optimal for scheduling and navigating the logistics of daily life; others value the flexibility offered by certain evidence-based, racemic (IV) protocols,” he said. “Predicting who will prefer each treatment, even with the apparent temporal advantage with IV ketamine, is extremely difficult.”

Likewise, in terms of clinician preference, Dr. Meisner notes that key concerns may sway decisions.

“If I’m concerned with labile pressures or hypertension, for example, or if I have a patient with, say, Erlos Danlos Syndrome without a clear subtype, and hence, some risk of undiscovered aneurysmal vascular disease, I may lean toward racemic IV ketamine.”

On the other hand, “some patients find the simplicity and predictability of the maintenance esketamine protocol comforting and psychologically stabilizing,” he added. “Yet others find that their work or family’s erratic demands on their time make one of the evidence-based racemic regimens preferable – inasmuch as it integrates more flexibility and allows them to remain more fully engaged in the basic activities or work and family.”

Dr. Meisner noted the caveat that efforts to decide which method to use are often complicated by substantial misinformation.

“I can’t emphasize how much misinformation continues to abound regarding appropriate (evidence-based) and safe use of ketamine and esketamine,” he said. “Especially on the IV racemic side, there simply is no substantive evidence base for many of the claims that some providers are preaching.”

The confusion, driven in part by social media, “has diffused into sectors of the field and industry that one might assume are relatively immune (i.e., allied physicians, sophisticated payers, etc),” he added.

“In short, two mantra continue to apply,” Dr. Meisner said. “One – if it sounds too good to be true, it probably is; and two – in pharmacology and interventional psychiatry, we see remarkable progress and potential, but there simply is no such thing as a magic bullet.”

Dr. Singh and Dr. Meisner had no disclosures to report. Dr. McIntyre has received research grant support from Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/National Natural Science Foundation of China, and speaker/consultation fees from Lundbeck, Janssen, Alkermes,Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie, and Atai Life Sciences. Dr. McIntyre is a CEO of Braxia Scientific.

NEW ORLEANS – New research reveals that patients with treatment-resistant depression who were treated with repeated intravenous ketamine show no significant differences in achieving response or remission, compared with those receiving the intranasal formulation of the drug, esketamine – although fewer treatments appear necessary with the intravenous formulation.

“This is one of the first studies to compare the efficacy of IV and intranasal ketamine, and the results give us some indication that, if you treat with IV, you might get a faster response, although at the end, the responses are similar,” said first author Balwinder Singh, MD, of the department of psychiatry and psychology, Mayo Clinic, in Rochester, Minn.

courtesy Balwinder Singh

The findings were presented at the annual meeting of the American Psychiatric Association.

Commenting on the study, Roger S. McIntyre, MD, underscored that “this is an important study that addresses the priority questions that everyone wants to know – not only for clinical reasons, but economic reasons.” Dr. McIntyre, a professor of psychiatry and pharmacology at the University of Toronto, and head of the university’s mood disorders psychopharmacology unit, said that “there are implications not only for clinical outcomes and cost, but also implementation because IV is obviously more demanding and complicated.”

As intravenous ketamine increasingly gained interest as a rapid-acting treatment for patients with severe, treatment-resistant depression, the introduction of a more convenient intranasal formulation was seen as a welcome improvement and received approval from the Food and Drug Administration in 2019. However, while the approval ushered in more coverage by insurance companies, the treatment can still be expensive. Intravenous ketamine does not have FDA approval.

With a lack of studies in the real-world setting comparing efficacy of the two formulations, Dr. Singh and his colleagues conducted the observational study, evaluating the responses of 62 adults with treatment-resistant depression who had received either up to six IV ketamine infusions of 0.5 mg/kg, infused over 40 minutes, or up to eight intranasal esketamine treatments of 56/84 mg, as approved by the FDA, at the Mayo Clinic Depression Center.

Of the patients, who had a mean age of 47 years, 59 had major depression and 3 had bipolar depression. Among them, 76% (47) received intravenous ketamine and 24% (15) received esketamine, which Dr. Singh noted reflected the higher number of patients included before esketamine received FDA approval. The patients had similar comorbidity profiles, with the intravenous ketamine group having a higher body mass index at baseline.

Overall, the patients all had significant improvement in their depression at the end of the acute phase of 4 weeks, with a mean change in on the 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR) scale of –8.6 from baseline (P < .001).

The overall remission rate was 38.7% and overall response rate was 58.1%. Those receiving intravenous ketamine had response and remission rates of 57.4% and 42.6%, versus response and remission rates of 60.0% and 26.7% among the esketamine group, which Dr. Singh said were not significant differences (P > .05).

However, the mean number of treatments necessary to achieve response in the intravenous ketamine group was just 2.3 versus 4.6 with esketamine, and the mean number of treatments to achieve remission were 2.5 versus 6.3, respectively (P = .008).

After a multivariate adjustment, the time to response was determined to be faster with intravenous ketamine versus esketamine (hazard ratio, 2.61; P = .05) and the time to remission was also faster (HR, 5.0; P = .02).

“What this means is you would need fewer treatments to achieve a response or remission with IV ketamine, so there could be an acceleration of patients’ antidepressant response,” Dr. Singh explained.

There were no significant differences between the groups in terms of side effects, and most patients tolerated the treatments well.

Dr. Singh noted the limitation of the study is that it was observational and included a small sample size. Nevertheless, when asked which he would choose if starting treatment when insurance was not an issue, Dr. Singh replied: “I would take patient preference into account, but certainly IV seems to have an advantage.”

Dr. McIntyre noted that, though small, the study’s setting in a real world clinical environment is important.

“Obviously this is observational and not controlled, but the strength is that this involved a real-world cohort of patients and real world applications,” he said. “It’s difficult to have a true comparator head-to-head trial, so that makes this all the more important because it takes into consideration all of the complexities of real world patients.”

Dr. McIntyre emphasized that the study is not “the last word on the story because we need to see a larger sample and replication. But certainly they make an argument that IV ketamine may have an advantage over the speed of onset with intranasal ketamine, which will need to be either replicated or refuted, but it’s a great starting point in the conversation.”
 

Navigating patient preference

Robert Meisner, MD, founding medical director of the McLean Ketamine Service, Division of Psychiatric Neurotherapeutics, McLean Hospital, Harvard Medical School, in Boston, noted that wide-ranging factors may influence patient as well as clinician decisions about which ketamine treatment approach to use.

“When a patient appears to be equally well-suited for both interventions, I continue to be surprised by why one patient will indicate a preference for intranasal esketamine, while another will lean toward IV racemic ketamine,” he said in an interview.

“Some patients find esketamine’s clear and consistent protocol optimal for scheduling and navigating the logistics of daily life; others value the flexibility offered by certain evidence-based, racemic (IV) protocols,” he said. “Predicting who will prefer each treatment, even with the apparent temporal advantage with IV ketamine, is extremely difficult.”

Likewise, in terms of clinician preference, Dr. Meisner notes that key concerns may sway decisions.

“If I’m concerned with labile pressures or hypertension, for example, or if I have a patient with, say, Erlos Danlos Syndrome without a clear subtype, and hence, some risk of undiscovered aneurysmal vascular disease, I may lean toward racemic IV ketamine.”

On the other hand, “some patients find the simplicity and predictability of the maintenance esketamine protocol comforting and psychologically stabilizing,” he added. “Yet others find that their work or family’s erratic demands on their time make one of the evidence-based racemic regimens preferable – inasmuch as it integrates more flexibility and allows them to remain more fully engaged in the basic activities or work and family.”

Dr. Meisner noted the caveat that efforts to decide which method to use are often complicated by substantial misinformation.

“I can’t emphasize how much misinformation continues to abound regarding appropriate (evidence-based) and safe use of ketamine and esketamine,” he said. “Especially on the IV racemic side, there simply is no substantive evidence base for many of the claims that some providers are preaching.”

The confusion, driven in part by social media, “has diffused into sectors of the field and industry that one might assume are relatively immune (i.e., allied physicians, sophisticated payers, etc),” he added.

“In short, two mantra continue to apply,” Dr. Meisner said. “One – if it sounds too good to be true, it probably is; and two – in pharmacology and interventional psychiatry, we see remarkable progress and potential, but there simply is no such thing as a magic bullet.”

Dr. Singh and Dr. Meisner had no disclosures to report. Dr. McIntyre has received research grant support from Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/National Natural Science Foundation of China, and speaker/consultation fees from Lundbeck, Janssen, Alkermes,Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie, and Atai Life Sciences. Dr. McIntyre is a CEO of Braxia Scientific.

The 2020 explosion that rocked Beirut, killing more than 200, injuring more than 7,000 and causing millions of dollars in damage had a significant impact on the mental health of Lebanese expatriates, leaving many grappling with anxiety, depression, and posttraumatic stress disorder, results of a new survey show.

The findings highlight the importance of considering the well-being of expatriates dealing with adverse events in their home countries, the investigators say.

Dr. Gaëlle Rached

“Everyone, including doctors, should be more sensitive to expatriates around them; we should look out for them especially when their home country is going through a traumatic event,” study investigator Gaëlle Rached, MD, MSc, research postdoctoral fellow, Northwestern University, Chicago, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

A historic explosion

It is estimated that approximately 14 million Lebanese citizens live outside their home country, which is more than double the population of Lebanon. However, the trauma-related mental health of these and other expatriate communities is understudied, said Dr. Rached.

“If you look at the literature, next to no one has examined expatriates’ mental health, and more so in the context of trauma.”

Dr. Rached has personal experience with the event. She was in Beirut on Aug. 4, 2020, when the Lebanese capital was rocked by an explosion attributed to ammonium nitrate stored at the city’s port. It was one of the biggest nonnuclear explosions in history and left hundreds homeless, killed, or injured. Dr. Rached watched as her father was injured and her house destroyed.

She heard anecdotes of Lebanese expatriates, experiencing trauma as a result of the blast. Many were unable to contact friends and loved ones in the wake of the tragedy.

“That prompted us to look at expatriate mental health following this traumatic incident,” she said.

She and her colleagues used various social media platforms to advertise the survey. They also reached out to the International Lebanese Medical Association, which has “a strong base” in the United States, said Dr. Rached.

She was “shocked” at how many expatriates responded. “People really wanted to speak up and express themselves” – whether because of survivor’s guilt or for some other reason, she said.

The survey included 670 adults with Lebanese nationality or who were first generation Lebanese living abroad. The study population had a median age 31 years and 62.2% female, most living in North America or Europe. Over one-third of respondents (270) had been living abroad from 1-5 years but many had been away for more than 20 years.

Study participants completed the Hopkins Symptoms Checklist (HSCL), which screens for anxiety and depression. On this checklist, a score of 1.75 is a typical cutoff value for symptomatic cases.

The investigators found 41.2% of participants scored higher than this threshold. Being younger, female and visiting Lebanon at the time of the blast, were factors associated with higher HSCL scores.
 

No tincture of time

Interestingly, the amount of time since emigrating from Lebanon was unrelated to the score. “Our results show that, no matter how long you’ve been away, you’re prone to the same negative outcome,” said Dr. Rached.

Of the total study population, 268 personally experienced the explosion and/or had close friends or family physically affected by it. These expatriates completed the Post-traumatic Checklist for DSM-5 (PCL-5).

Here, the analysis showed that many of these respondents (57.5%) scored above 33, which is higher than the threshold for probable PTSD. Being female was linked to higher PCL-5 scores.

These findings suggest the mental health of expatriates may be negatively affected by traumatic incidents in their home countries, even if they didn’t witness the event firsthand and have been away from their home country for a long time.

The results may be especially timely as many countries are taking in a flood of refugees fleeing war in Ukraine. However, Dr. Rached said, the findings from her research may not apply to Ukrainians.

“I don’t think the results can be extrapolated, given that the nature of the trauma is a little bit different,” she said, adding that the Beirut blast was “monumental” but it was over quickly. In contrast, there’s no end in sight for the Russian invasion of Ukraine.

Dr. Rached noted the study data are preliminary and limited because there’s no way to determine whether respondents had mental health issues before the blast.
 

Global psychiatrist shortage

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry in Omaha, and incoming chair of the APA’s Council on Communications, said he found the presentation “fascinating on several levels.”

It’s increasingly important for psychiatrists to be “trauma informed,” Dr. Liu told a press briefing highlighting the study. “It’s not just about looking at the biological correlates of illness,” meaning looking at genetic markers etc, “but also looking at the environment in which people live, work, and/or are in therapy or in treatment.”

In a later interview, Dr. Liu said he was impressed by the fact that Dr. Rached, who has “a very deep personal connection to this community,” is using her own personal trauma to help identify others are at risk who may need future care.

Dr. Liu, whose own family sponsors Afghan refugees, said the research underlines the need to ensure training for psychiatrists everywhere to help manage the expatriate population. As it stands, there’s “a huge shortage of psychiatrists around the world,” particularly in countries that have been affected by trauma, said Dr. Liu.

The researchers and Dr. Liu reported no relevant financial relationships.

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

The 2020 explosion that rocked Beirut, killing more than 200, injuring more than 7,000 and causing millions of dollars in damage had a significant impact on the mental health of Lebanese expatriates, leaving many grappling with anxiety, depression, and posttraumatic stress disorder, results of a new survey show.

The findings highlight the importance of considering the well-being of expatriates dealing with adverse events in their home countries, the investigators say.

Dr. Gaëlle Rached

“Everyone, including doctors, should be more sensitive to expatriates around them; we should look out for them especially when their home country is going through a traumatic event,” study investigator Gaëlle Rached, MD, MSc, research postdoctoral fellow, Northwestern University, Chicago, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

A historic explosion

It is estimated that approximately 14 million Lebanese citizens live outside their home country, which is more than double the population of Lebanon. However, the trauma-related mental health of these and other expatriate communities is understudied, said Dr. Rached.

“If you look at the literature, next to no one has examined expatriates’ mental health, and more so in the context of trauma.”

Dr. Rached has personal experience with the event. She was in Beirut on Aug. 4, 2020, when the Lebanese capital was rocked by an explosion attributed to ammonium nitrate stored at the city’s port. It was one of the biggest nonnuclear explosions in history and left hundreds homeless, killed, or injured. Dr. Rached watched as her father was injured and her house destroyed.

She heard anecdotes of Lebanese expatriates, experiencing trauma as a result of the blast. Many were unable to contact friends and loved ones in the wake of the tragedy.

“That prompted us to look at expatriate mental health following this traumatic incident,” she said.

She and her colleagues used various social media platforms to advertise the survey. They also reached out to the International Lebanese Medical Association, which has “a strong base” in the United States, said Dr. Rached.

She was “shocked” at how many expatriates responded. “People really wanted to speak up and express themselves” – whether because of survivor’s guilt or for some other reason, she said.

The survey included 670 adults with Lebanese nationality or who were first generation Lebanese living abroad. The study population had a median age 31 years and 62.2% female, most living in North America or Europe. Over one-third of respondents (270) had been living abroad from 1-5 years but many had been away for more than 20 years.

Study participants completed the Hopkins Symptoms Checklist (HSCL), which screens for anxiety and depression. On this checklist, a score of 1.75 is a typical cutoff value for symptomatic cases.

The investigators found 41.2% of participants scored higher than this threshold. Being younger, female and visiting Lebanon at the time of the blast, were factors associated with higher HSCL scores.
 

No tincture of time

Interestingly, the amount of time since emigrating from Lebanon was unrelated to the score. “Our results show that, no matter how long you’ve been away, you’re prone to the same negative outcome,” said Dr. Rached.

Of the total study population, 268 personally experienced the explosion and/or had close friends or family physically affected by it. These expatriates completed the Post-traumatic Checklist for DSM-5 (PCL-5).

Here, the analysis showed that many of these respondents (57.5%) scored above 33, which is higher than the threshold for probable PTSD. Being female was linked to higher PCL-5 scores.

These findings suggest the mental health of expatriates may be negatively affected by traumatic incidents in their home countries, even if they didn’t witness the event firsthand and have been away from their home country for a long time.

The results may be especially timely as many countries are taking in a flood of refugees fleeing war in Ukraine. However, Dr. Rached said, the findings from her research may not apply to Ukrainians.

“I don’t think the results can be extrapolated, given that the nature of the trauma is a little bit different,” she said, adding that the Beirut blast was “monumental” but it was over quickly. In contrast, there’s no end in sight for the Russian invasion of Ukraine.

Dr. Rached noted the study data are preliminary and limited because there’s no way to determine whether respondents had mental health issues before the blast.
 

Global psychiatrist shortage

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry in Omaha, and incoming chair of the APA’s Council on Communications, said he found the presentation “fascinating on several levels.”

It’s increasingly important for psychiatrists to be “trauma informed,” Dr. Liu told a press briefing highlighting the study. “It’s not just about looking at the biological correlates of illness,” meaning looking at genetic markers etc, “but also looking at the environment in which people live, work, and/or are in therapy or in treatment.”

In a later interview, Dr. Liu said he was impressed by the fact that Dr. Rached, who has “a very deep personal connection to this community,” is using her own personal trauma to help identify others are at risk who may need future care.

Dr. Liu, whose own family sponsors Afghan refugees, said the research underlines the need to ensure training for psychiatrists everywhere to help manage the expatriate population. As it stands, there’s “a huge shortage of psychiatrists around the world,” particularly in countries that have been affected by trauma, said Dr. Liu.

The researchers and Dr. Liu reported no relevant financial relationships.

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

The 2020 explosion that rocked Beirut, killing more than 200, injuring more than 7,000 and causing millions of dollars in damage had a significant impact on the mental health of Lebanese expatriates, leaving many grappling with anxiety, depression, and posttraumatic stress disorder, results of a new survey show.

The findings highlight the importance of considering the well-being of expatriates dealing with adverse events in their home countries, the investigators say.

Dr. Gaëlle Rached

“Everyone, including doctors, should be more sensitive to expatriates around them; we should look out for them especially when their home country is going through a traumatic event,” study investigator Gaëlle Rached, MD, MSc, research postdoctoral fellow, Northwestern University, Chicago, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

A historic explosion

It is estimated that approximately 14 million Lebanese citizens live outside their home country, which is more than double the population of Lebanon. However, the trauma-related mental health of these and other expatriate communities is understudied, said Dr. Rached.

“If you look at the literature, next to no one has examined expatriates’ mental health, and more so in the context of trauma.”

Dr. Rached has personal experience with the event. She was in Beirut on Aug. 4, 2020, when the Lebanese capital was rocked by an explosion attributed to ammonium nitrate stored at the city’s port. It was one of the biggest nonnuclear explosions in history and left hundreds homeless, killed, or injured. Dr. Rached watched as her father was injured and her house destroyed.

She heard anecdotes of Lebanese expatriates, experiencing trauma as a result of the blast. Many were unable to contact friends and loved ones in the wake of the tragedy.

“That prompted us to look at expatriate mental health following this traumatic incident,” she said.

She and her colleagues used various social media platforms to advertise the survey. They also reached out to the International Lebanese Medical Association, which has “a strong base” in the United States, said Dr. Rached.

She was “shocked” at how many expatriates responded. “People really wanted to speak up and express themselves” – whether because of survivor’s guilt or for some other reason, she said.

The survey included 670 adults with Lebanese nationality or who were first generation Lebanese living abroad. The study population had a median age 31 years and 62.2% female, most living in North America or Europe. Over one-third of respondents (270) had been living abroad from 1-5 years but many had been away for more than 20 years.

Study participants completed the Hopkins Symptoms Checklist (HSCL), which screens for anxiety and depression. On this checklist, a score of 1.75 is a typical cutoff value for symptomatic cases.

The investigators found 41.2% of participants scored higher than this threshold. Being younger, female and visiting Lebanon at the time of the blast, were factors associated with higher HSCL scores.
 

No tincture of time

Interestingly, the amount of time since emigrating from Lebanon was unrelated to the score. “Our results show that, no matter how long you’ve been away, you’re prone to the same negative outcome,” said Dr. Rached.

Of the total study population, 268 personally experienced the explosion and/or had close friends or family physically affected by it. These expatriates completed the Post-traumatic Checklist for DSM-5 (PCL-5).

Here, the analysis showed that many of these respondents (57.5%) scored above 33, which is higher than the threshold for probable PTSD. Being female was linked to higher PCL-5 scores.

These findings suggest the mental health of expatriates may be negatively affected by traumatic incidents in their home countries, even if they didn’t witness the event firsthand and have been away from their home country for a long time.

The results may be especially timely as many countries are taking in a flood of refugees fleeing war in Ukraine. However, Dr. Rached said, the findings from her research may not apply to Ukrainians.

“I don’t think the results can be extrapolated, given that the nature of the trauma is a little bit different,” she said, adding that the Beirut blast was “monumental” but it was over quickly. In contrast, there’s no end in sight for the Russian invasion of Ukraine.

Dr. Rached noted the study data are preliminary and limited because there’s no way to determine whether respondents had mental health issues before the blast.
 

Global psychiatrist shortage

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry in Omaha, and incoming chair of the APA’s Council on Communications, said he found the presentation “fascinating on several levels.”

It’s increasingly important for psychiatrists to be “trauma informed,” Dr. Liu told a press briefing highlighting the study. “It’s not just about looking at the biological correlates of illness,” meaning looking at genetic markers etc, “but also looking at the environment in which people live, work, and/or are in therapy or in treatment.”

In a later interview, Dr. Liu said he was impressed by the fact that Dr. Rached, who has “a very deep personal connection to this community,” is using her own personal trauma to help identify others are at risk who may need future care.

Dr. Liu, whose own family sponsors Afghan refugees, said the research underlines the need to ensure training for psychiatrists everywhere to help manage the expatriate population. As it stands, there’s “a huge shortage of psychiatrists around the world,” particularly in countries that have been affected by trauma, said Dr. Liu.

The researchers and Dr. Liu reported no relevant financial relationships.

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