MDedge Psychiatry

Lack of time for self-care and rest are particularly harmful to women’s health. Various speakers at the VII National Conference of the Onda Foundation, Italy’s National Observatory for Women and Gender’s Health, focused on this topic. The conference was dedicated to the social factors that determine health within the context of gender medicine.

In our society, housework and raising a family are responsibilities placed predominantly on the shoulders of women. These responsibilities contribute significantly to women’s daily workload. The most overburdened women are working mothers (according to ISTAT, Italy’s Office for National Statistics, 2019), who are forced to combine their professional responsibilities with family life, dedicating 8 hours and 20 minutes per day to paid and unpaid work overall, compared with the 7 hours and 29 minutes spent by working fathers. Working mothers between ages 25 and 44 years have on average 2 hours and 35 minutes of free time per day.
 

Stress and sleep deprivation

“Under these conditions, the risk of chronic stress is raised, and stress leads to depression. The rate of depression in the female population is double that of the male population,” said Claudio Mencacci, MD, chair of the Italian Society of Neuropsychopharmacology and the Onda Foundation. “What’s more, stress increases the risk of cardiovascular and metabolic diseases, asthma, arthritis, and autoimmune diseases.”

The one thing that is especially damaging to physical and mental health is sleep deprivation, and working mothers get less sleep than do working fathers. “This is partially due to biological factors: hormonal changes that take place toward the end of adolescence in women during the premenstrual period are responsible for an increased rate of sleep disturbance and insomnia,” said Dr. Mencacci. “During pregnancy and the postpartum period, female sex hormones make sleep lighter, reducing time spent in the REM sleep stage. Then there’s the social aspect that plays a decisive role: by and large, it’s mothers who take care of the youngest children at night.”

According to a 2019 German study, during the first 6 years of life of the first child, a mother loses on average 44 minutes sleep per night, compared with the average time spent sleeping before pregnancy; a father loses 14 minutes.

“Another aspect to bear in mind is that, for cultural reasons, women tend to overlook the issue and not seek help, deeming sleep deprivation normal,” said Dr. Mencacci.
 

Caregivers at greatest risk

The negative effects of stress are evident in people continuously caring for a dependent older or disabled family member, so-called caregivers. This is, “A group predominantly made up of women aged between 45 and 55 years,” said Marina Petrini, PhD, of the Italian Health Institute’s Gender Medicine Center of Excellence. Dr. Petrini coordinated a study on stress and health in family caregivers.

“The results obtained reveal a high level of stress, especially among female caregivers, who are more exposed to the risk of severe symptoms of depression, physical disorders, especially those affecting the nervous and immune systems, and who tend to adopt irregular eating patterns and sedentary habits,” said Dr. Petrini.
 

Limited treatment access

Another study presented at the Onda Foundation’s conference, which shows just how much a lack of “me time” can damage your health, is the Access to Diagnostic Medicine and Treatment by Region: the Patient’s Perspective Survey, conducted by market research agency Elma Research on a sample of cancer patients requiring specialist treatment.

“Forty percent of them had to move to a different region from the one they live in to get the care they needed,” said Massimo Massagrande, CEO of Elma Research. “Of that group, 40% had to move to an area not neighboring their own. The impact of area of residence is heavy, in terms of money and logistics – so much so that a large proportion of patients interviewed were forced to turn their back on the best available treatments. For women responding to our survey, the biggest obstacle is the impossibility of reconciling the effects of a move or the prospective of a temporary transfer to another region with their responsibilities for looking after their family.”

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Lack of time for self-care and rest are particularly harmful to women’s health. Various speakers at the VII National Conference of the Onda Foundation, Italy’s National Observatory for Women and Gender’s Health, focused on this topic. The conference was dedicated to the social factors that determine health within the context of gender medicine.

In our society, housework and raising a family are responsibilities placed predominantly on the shoulders of women. These responsibilities contribute significantly to women’s daily workload. The most overburdened women are working mothers (according to ISTAT, Italy’s Office for National Statistics, 2019), who are forced to combine their professional responsibilities with family life, dedicating 8 hours and 20 minutes per day to paid and unpaid work overall, compared with the 7 hours and 29 minutes spent by working fathers. Working mothers between ages 25 and 44 years have on average 2 hours and 35 minutes of free time per day.
 

Stress and sleep deprivation

“Under these conditions, the risk of chronic stress is raised, and stress leads to depression. The rate of depression in the female population is double that of the male population,” said Claudio Mencacci, MD, chair of the Italian Society of Neuropsychopharmacology and the Onda Foundation. “What’s more, stress increases the risk of cardiovascular and metabolic diseases, asthma, arthritis, and autoimmune diseases.”

The one thing that is especially damaging to physical and mental health is sleep deprivation, and working mothers get less sleep than do working fathers. “This is partially due to biological factors: hormonal changes that take place toward the end of adolescence in women during the premenstrual period are responsible for an increased rate of sleep disturbance and insomnia,” said Dr. Mencacci. “During pregnancy and the postpartum period, female sex hormones make sleep lighter, reducing time spent in the REM sleep stage. Then there’s the social aspect that plays a decisive role: by and large, it’s mothers who take care of the youngest children at night.”

According to a 2019 German study, during the first 6 years of life of the first child, a mother loses on average 44 minutes sleep per night, compared with the average time spent sleeping before pregnancy; a father loses 14 minutes.

“Another aspect to bear in mind is that, for cultural reasons, women tend to overlook the issue and not seek help, deeming sleep deprivation normal,” said Dr. Mencacci.
 

Caregivers at greatest risk

The negative effects of stress are evident in people continuously caring for a dependent older or disabled family member, so-called caregivers. This is, “A group predominantly made up of women aged between 45 and 55 years,” said Marina Petrini, PhD, of the Italian Health Institute’s Gender Medicine Center of Excellence. Dr. Petrini coordinated a study on stress and health in family caregivers.

“The results obtained reveal a high level of stress, especially among female caregivers, who are more exposed to the risk of severe symptoms of depression, physical disorders, especially those affecting the nervous and immune systems, and who tend to adopt irregular eating patterns and sedentary habits,” said Dr. Petrini.
 

Limited treatment access

Another study presented at the Onda Foundation’s conference, which shows just how much a lack of “me time” can damage your health, is the Access to Diagnostic Medicine and Treatment by Region: the Patient’s Perspective Survey, conducted by market research agency Elma Research on a sample of cancer patients requiring specialist treatment.

“Forty percent of them had to move to a different region from the one they live in to get the care they needed,” said Massimo Massagrande, CEO of Elma Research. “Of that group, 40% had to move to an area not neighboring their own. The impact of area of residence is heavy, in terms of money and logistics – so much so that a large proportion of patients interviewed were forced to turn their back on the best available treatments. For women responding to our survey, the biggest obstacle is the impossibility of reconciling the effects of a move or the prospective of a temporary transfer to another region with their responsibilities for looking after their family.”

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Lack of time for self-care and rest are particularly harmful to women’s health. Various speakers at the VII National Conference of the Onda Foundation, Italy’s National Observatory for Women and Gender’s Health, focused on this topic. The conference was dedicated to the social factors that determine health within the context of gender medicine.

In our society, housework and raising a family are responsibilities placed predominantly on the shoulders of women. These responsibilities contribute significantly to women’s daily workload. The most overburdened women are working mothers (according to ISTAT, Italy’s Office for National Statistics, 2019), who are forced to combine their professional responsibilities with family life, dedicating 8 hours and 20 minutes per day to paid and unpaid work overall, compared with the 7 hours and 29 minutes spent by working fathers. Working mothers between ages 25 and 44 years have on average 2 hours and 35 minutes of free time per day.
 

Stress and sleep deprivation

“Under these conditions, the risk of chronic stress is raised, and stress leads to depression. The rate of depression in the female population is double that of the male population,” said Claudio Mencacci, MD, chair of the Italian Society of Neuropsychopharmacology and the Onda Foundation. “What’s more, stress increases the risk of cardiovascular and metabolic diseases, asthma, arthritis, and autoimmune diseases.”

The one thing that is especially damaging to physical and mental health is sleep deprivation, and working mothers get less sleep than do working fathers. “This is partially due to biological factors: hormonal changes that take place toward the end of adolescence in women during the premenstrual period are responsible for an increased rate of sleep disturbance and insomnia,” said Dr. Mencacci. “During pregnancy and the postpartum period, female sex hormones make sleep lighter, reducing time spent in the REM sleep stage. Then there’s the social aspect that plays a decisive role: by and large, it’s mothers who take care of the youngest children at night.”

According to a 2019 German study, during the first 6 years of life of the first child, a mother loses on average 44 minutes sleep per night, compared with the average time spent sleeping before pregnancy; a father loses 14 minutes.

“Another aspect to bear in mind is that, for cultural reasons, women tend to overlook the issue and not seek help, deeming sleep deprivation normal,” said Dr. Mencacci.
 

Caregivers at greatest risk

The negative effects of stress are evident in people continuously caring for a dependent older or disabled family member, so-called caregivers. This is, “A group predominantly made up of women aged between 45 and 55 years,” said Marina Petrini, PhD, of the Italian Health Institute’s Gender Medicine Center of Excellence. Dr. Petrini coordinated a study on stress and health in family caregivers.

“The results obtained reveal a high level of stress, especially among female caregivers, who are more exposed to the risk of severe symptoms of depression, physical disorders, especially those affecting the nervous and immune systems, and who tend to adopt irregular eating patterns and sedentary habits,” said Dr. Petrini.
 

Limited treatment access

Another study presented at the Onda Foundation’s conference, which shows just how much a lack of “me time” can damage your health, is the Access to Diagnostic Medicine and Treatment by Region: the Patient’s Perspective Survey, conducted by market research agency Elma Research on a sample of cancer patients requiring specialist treatment.

“Forty percent of them had to move to a different region from the one they live in to get the care they needed,” said Massimo Massagrande, CEO of Elma Research. “Of that group, 40% had to move to an area not neighboring their own. The impact of area of residence is heavy, in terms of money and logistics – so much so that a large proportion of patients interviewed were forced to turn their back on the best available treatments. For women responding to our survey, the biggest obstacle is the impossibility of reconciling the effects of a move or the prospective of a temporary transfer to another region with their responsibilities for looking after their family.”

This article was translated from Univadis Italy. A version appeared on Medscape.com.

PHILADELPHIA – About two in five perimenopausal or postmenopausal women have ever used cannabis in any form, but 10% have used it in the past month, according to cross-sectional survey results presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

Though most women reported using cannabis for recreational reasons, 13% used it only for medical reasons, most often for chronic pain, anxiety, sleep, and stress.

“These findings highlight the importance of recognizing and discussing cannabis use in the health care setting, and the need for additional research to evaluate the potential harms and/or benefits of use in this vulnerable population,” Carolyn J. Gibson, PhD, MPH, a staff psychologist in women’s health at the San Francisco VA Health Care System and an assistant professor of psychiatry and behavioral sciences at the University of California, San Francisco, told attendees.

As cannabis has become more accessible, with its use legalized in 38 states and Washington, D.C., the proportion of U.S. adults using it has doubled over about a decade, from 6% in 2007 to 12% in 2019, Dr. Gibson said. Further, women aged 50 and older are among the fastest-growing groups of users of cannabis, and it’s being increasingly used – and marketed – for treating menopause-related and aging-related symptoms, including insomnia, anxiety, and chronic pain, she said.

“With these decisions to use cannabis, medically or for these other purposes, there’s this perception that it’s harmless,” Dr. Gibson said. Yet potential health risks associated with cannabis include the usual health effects associated with any kind of smoking as well as dependence in those who use it more frequently and/or develop a tolerance for it. She noted that average THC potency has increased over time, and acute risks for using cannabis with high levels of THC – at least 15% or at least 10 mg – can include anxiety/panic, confusion, disturbing/intrusive thoughts, psychosis, and effects on coordination and cognition. She also acknowledged, however, that most of the data available on risks come from studies of men and younger adults rather than older women.

Given the growing normalization of cannabis use, Dr. Gibson’s team sought to better understand prevalence of use as well as types of use and reasons for use in perimenopasual and postmenopausal women. They analyzed data from a cross-sectional survey of women and gender-diverse members, aged 45-64, of Ipsos KnowledgePanel, an online panel with more than 60,000 participating members in the United States.

All the respondents identified themselves as female at birth and had not used gender-affirming therapy or undergone gender-affirming surgery. The survey included questions on sociodemographics, menopause status, frequency of cannabis use, types of cannabis used, reasons for using cannabis, and use of cannabis in the previous 30 days. The 5,174 respondents were an average 55 years old and predominantly non-Hispanic white (63%), with 13% non-Hispanic Black and 16% Hispanic. Two-thirds of the women reported working full- or part-time (67%) and two-thirds were postmenopausal (68%), with 64% reporting experiencing menopause symptoms.

About two in five respondents (42%) had ever used cannabis in any form, most often smoking it (83%) or consuming edibles (51%). Among those who had ever used it, 30% reported having smoked it daily or nearly daily for at least a year at some point.

Ten percent of respondents had used cannabis in the past month, again primarily smoking (56%) or edibles (52%), though 39% said they used it in more than one form, including vaping, dabbing, or topical use. Nearly half (46%) of the respondents who smoked cannabis recently did not know the THC potency of what they consumed, and just over 20% of those consuming edibles didn’t know the THC potency of what they used. However, about a third of those taking edibles used cannabis with less than 10 mg of THC, and a little over a quarter used edibles with 10 mg of THC.

Within the 10% who had used cannabis in the past month, nearly a third (31%) of respondents – or around 3.1% of the total sample – reported smoking cannabis daily or almost daily, and 19% (or 1.9% of the overall sample) consumed cannabis edibles daily or almost daily.

Most of the respondents who used cannabis said it was for recreational use (62%), but a quarter (25%) reported using it for both recreational and medical reasons, and 13% used it only for medical reasons. The most common reason women used cannabis was to treat chronic pain (28%), followed by nearly as many women reporting cannabis use for anxiety (24%), sleep (22%), and stress (22%). Six percent of women used cannabis specifically for menopause-related sleep and mood problems.

Given the growing use of cannabis in this population and the dearth of data on its effects in older women, Dr. Gibson highlighted the need for research examining the potential benefits and harms of cannabis for menopausal women.
 

Not risk-free

Susan D. Reed, MD, MPH, MSCP, a professor emeritus of ob.gyn. at the University of Washington, Seattle, and president of the Menopause Society, found the study well-executed and was not surprised by how many respondents had ever used cannabis.

“What did surprise me was that nearly a third reported daily use for at least 1 year and that 38% were medical marijuana users, not just recreational,” Dr. Reed said in an interview. The proportions of women using cannabis for menopausal symptoms or using it daily are concerning, she added.

“These individuals are at risk for dependence and health risks related to marijuana use,” Dr. Reed said. “Providers should always ask patients about OTC products, herbals, supplements, cannabis use, and alternative management of menopausal symptoms to better understand patient preferences for menopausal symptom therapies, so that treatment plans can be discussed with individual patient preferences in mind. We need to start with where the patient is coming from.”

Data presented throughout the conference has shown how people are “disillusioned with the care they are receiving for menopause,” Dr. Reed added. “It is so difficult to distinguish truth from myths based on information gained through social media, family, and friends, and that often is where most people are getting their information.”

Physicians often have not received adequate training on how to provide people with accurate information about menopause and managing menopausal symptoms, so she advises patients and physicians to visit reliable sites such as the Menopause Society, the Swan Study, and My Menoplan.

The research was funded by the Tobacco-Related Disease Research Program and the Veterans Administration. Dr. Gibson has provided unpaid consultation to Astellas Pharmaceuticals. Dr. Reed has received research support from Bayer and receives royalties from UpToDate.

PHILADELPHIA – About two in five perimenopausal or postmenopausal women have ever used cannabis in any form, but 10% have used it in the past month, according to cross-sectional survey results presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

Though most women reported using cannabis for recreational reasons, 13% used it only for medical reasons, most often for chronic pain, anxiety, sleep, and stress.

“These findings highlight the importance of recognizing and discussing cannabis use in the health care setting, and the need for additional research to evaluate the potential harms and/or benefits of use in this vulnerable population,” Carolyn J. Gibson, PhD, MPH, a staff psychologist in women’s health at the San Francisco VA Health Care System and an assistant professor of psychiatry and behavioral sciences at the University of California, San Francisco, told attendees.

As cannabis has become more accessible, with its use legalized in 38 states and Washington, D.C., the proportion of U.S. adults using it has doubled over about a decade, from 6% in 2007 to 12% in 2019, Dr. Gibson said. Further, women aged 50 and older are among the fastest-growing groups of users of cannabis, and it’s being increasingly used – and marketed – for treating menopause-related and aging-related symptoms, including insomnia, anxiety, and chronic pain, she said.

“With these decisions to use cannabis, medically or for these other purposes, there’s this perception that it’s harmless,” Dr. Gibson said. Yet potential health risks associated with cannabis include the usual health effects associated with any kind of smoking as well as dependence in those who use it more frequently and/or develop a tolerance for it. She noted that average THC potency has increased over time, and acute risks for using cannabis with high levels of THC – at least 15% or at least 10 mg – can include anxiety/panic, confusion, disturbing/intrusive thoughts, psychosis, and effects on coordination and cognition. She also acknowledged, however, that most of the data available on risks come from studies of men and younger adults rather than older women.

Given the growing normalization of cannabis use, Dr. Gibson’s team sought to better understand prevalence of use as well as types of use and reasons for use in perimenopasual and postmenopausal women. They analyzed data from a cross-sectional survey of women and gender-diverse members, aged 45-64, of Ipsos KnowledgePanel, an online panel with more than 60,000 participating members in the United States.

All the respondents identified themselves as female at birth and had not used gender-affirming therapy or undergone gender-affirming surgery. The survey included questions on sociodemographics, menopause status, frequency of cannabis use, types of cannabis used, reasons for using cannabis, and use of cannabis in the previous 30 days. The 5,174 respondents were an average 55 years old and predominantly non-Hispanic white (63%), with 13% non-Hispanic Black and 16% Hispanic. Two-thirds of the women reported working full- or part-time (67%) and two-thirds were postmenopausal (68%), with 64% reporting experiencing menopause symptoms.

About two in five respondents (42%) had ever used cannabis in any form, most often smoking it (83%) or consuming edibles (51%). Among those who had ever used it, 30% reported having smoked it daily or nearly daily for at least a year at some point.

Ten percent of respondents had used cannabis in the past month, again primarily smoking (56%) or edibles (52%), though 39% said they used it in more than one form, including vaping, dabbing, or topical use. Nearly half (46%) of the respondents who smoked cannabis recently did not know the THC potency of what they consumed, and just over 20% of those consuming edibles didn’t know the THC potency of what they used. However, about a third of those taking edibles used cannabis with less than 10 mg of THC, and a little over a quarter used edibles with 10 mg of THC.

Within the 10% who had used cannabis in the past month, nearly a third (31%) of respondents – or around 3.1% of the total sample – reported smoking cannabis daily or almost daily, and 19% (or 1.9% of the overall sample) consumed cannabis edibles daily or almost daily.

Most of the respondents who used cannabis said it was for recreational use (62%), but a quarter (25%) reported using it for both recreational and medical reasons, and 13% used it only for medical reasons. The most common reason women used cannabis was to treat chronic pain (28%), followed by nearly as many women reporting cannabis use for anxiety (24%), sleep (22%), and stress (22%). Six percent of women used cannabis specifically for menopause-related sleep and mood problems.

Given the growing use of cannabis in this population and the dearth of data on its effects in older women, Dr. Gibson highlighted the need for research examining the potential benefits and harms of cannabis for menopausal women.
 

Not risk-free

Susan D. Reed, MD, MPH, MSCP, a professor emeritus of ob.gyn. at the University of Washington, Seattle, and president of the Menopause Society, found the study well-executed and was not surprised by how many respondents had ever used cannabis.

“What did surprise me was that nearly a third reported daily use for at least 1 year and that 38% were medical marijuana users, not just recreational,” Dr. Reed said in an interview. The proportions of women using cannabis for menopausal symptoms or using it daily are concerning, she added.

“These individuals are at risk for dependence and health risks related to marijuana use,” Dr. Reed said. “Providers should always ask patients about OTC products, herbals, supplements, cannabis use, and alternative management of menopausal symptoms to better understand patient preferences for menopausal symptom therapies, so that treatment plans can be discussed with individual patient preferences in mind. We need to start with where the patient is coming from.”

Data presented throughout the conference has shown how people are “disillusioned with the care they are receiving for menopause,” Dr. Reed added. “It is so difficult to distinguish truth from myths based on information gained through social media, family, and friends, and that often is where most people are getting their information.”

Physicians often have not received adequate training on how to provide people with accurate information about menopause and managing menopausal symptoms, so she advises patients and physicians to visit reliable sites such as the Menopause Society, the Swan Study, and My Menoplan.

The research was funded by the Tobacco-Related Disease Research Program and the Veterans Administration. Dr. Gibson has provided unpaid consultation to Astellas Pharmaceuticals. Dr. Reed has received research support from Bayer and receives royalties from UpToDate.

PHILADELPHIA – About two in five perimenopausal or postmenopausal women have ever used cannabis in any form, but 10% have used it in the past month, according to cross-sectional survey results presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

Though most women reported using cannabis for recreational reasons, 13% used it only for medical reasons, most often for chronic pain, anxiety, sleep, and stress.

“These findings highlight the importance of recognizing and discussing cannabis use in the health care setting, and the need for additional research to evaluate the potential harms and/or benefits of use in this vulnerable population,” Carolyn J. Gibson, PhD, MPH, a staff psychologist in women’s health at the San Francisco VA Health Care System and an assistant professor of psychiatry and behavioral sciences at the University of California, San Francisco, told attendees.

As cannabis has become more accessible, with its use legalized in 38 states and Washington, D.C., the proportion of U.S. adults using it has doubled over about a decade, from 6% in 2007 to 12% in 2019, Dr. Gibson said. Further, women aged 50 and older are among the fastest-growing groups of users of cannabis, and it’s being increasingly used – and marketed – for treating menopause-related and aging-related symptoms, including insomnia, anxiety, and chronic pain, she said.

“With these decisions to use cannabis, medically or for these other purposes, there’s this perception that it’s harmless,” Dr. Gibson said. Yet potential health risks associated with cannabis include the usual health effects associated with any kind of smoking as well as dependence in those who use it more frequently and/or develop a tolerance for it. She noted that average THC potency has increased over time, and acute risks for using cannabis with high levels of THC – at least 15% or at least 10 mg – can include anxiety/panic, confusion, disturbing/intrusive thoughts, psychosis, and effects on coordination and cognition. She also acknowledged, however, that most of the data available on risks come from studies of men and younger adults rather than older women.

Given the growing normalization of cannabis use, Dr. Gibson’s team sought to better understand prevalence of use as well as types of use and reasons for use in perimenopasual and postmenopausal women. They analyzed data from a cross-sectional survey of women and gender-diverse members, aged 45-64, of Ipsos KnowledgePanel, an online panel with more than 60,000 participating members in the United States.

All the respondents identified themselves as female at birth and had not used gender-affirming therapy or undergone gender-affirming surgery. The survey included questions on sociodemographics, menopause status, frequency of cannabis use, types of cannabis used, reasons for using cannabis, and use of cannabis in the previous 30 days. The 5,174 respondents were an average 55 years old and predominantly non-Hispanic white (63%), with 13% non-Hispanic Black and 16% Hispanic. Two-thirds of the women reported working full- or part-time (67%) and two-thirds were postmenopausal (68%), with 64% reporting experiencing menopause symptoms.

About two in five respondents (42%) had ever used cannabis in any form, most often smoking it (83%) or consuming edibles (51%). Among those who had ever used it, 30% reported having smoked it daily or nearly daily for at least a year at some point.

Ten percent of respondents had used cannabis in the past month, again primarily smoking (56%) or edibles (52%), though 39% said they used it in more than one form, including vaping, dabbing, or topical use. Nearly half (46%) of the respondents who smoked cannabis recently did not know the THC potency of what they consumed, and just over 20% of those consuming edibles didn’t know the THC potency of what they used. However, about a third of those taking edibles used cannabis with less than 10 mg of THC, and a little over a quarter used edibles with 10 mg of THC.

Within the 10% who had used cannabis in the past month, nearly a third (31%) of respondents – or around 3.1% of the total sample – reported smoking cannabis daily or almost daily, and 19% (or 1.9% of the overall sample) consumed cannabis edibles daily or almost daily.

Most of the respondents who used cannabis said it was for recreational use (62%), but a quarter (25%) reported using it for both recreational and medical reasons, and 13% used it only for medical reasons. The most common reason women used cannabis was to treat chronic pain (28%), followed by nearly as many women reporting cannabis use for anxiety (24%), sleep (22%), and stress (22%). Six percent of women used cannabis specifically for menopause-related sleep and mood problems.

Given the growing use of cannabis in this population and the dearth of data on its effects in older women, Dr. Gibson highlighted the need for research examining the potential benefits and harms of cannabis for menopausal women.
 

Not risk-free

Susan D. Reed, MD, MPH, MSCP, a professor emeritus of ob.gyn. at the University of Washington, Seattle, and president of the Menopause Society, found the study well-executed and was not surprised by how many respondents had ever used cannabis.

“What did surprise me was that nearly a third reported daily use for at least 1 year and that 38% were medical marijuana users, not just recreational,” Dr. Reed said in an interview. The proportions of women using cannabis for menopausal symptoms or using it daily are concerning, she added.

“These individuals are at risk for dependence and health risks related to marijuana use,” Dr. Reed said. “Providers should always ask patients about OTC products, herbals, supplements, cannabis use, and alternative management of menopausal symptoms to better understand patient preferences for menopausal symptom therapies, so that treatment plans can be discussed with individual patient preferences in mind. We need to start with where the patient is coming from.”

Data presented throughout the conference has shown how people are “disillusioned with the care they are receiving for menopause,” Dr. Reed added. “It is so difficult to distinguish truth from myths based on information gained through social media, family, and friends, and that often is where most people are getting their information.”

Physicians often have not received adequate training on how to provide people with accurate information about menopause and managing menopausal symptoms, so she advises patients and physicians to visit reliable sites such as the Menopause Society, the Swan Study, and My Menoplan.

The research was funded by the Tobacco-Related Disease Research Program and the Veterans Administration. Dr. Gibson has provided unpaid consultation to Astellas Pharmaceuticals. Dr. Reed has received research support from Bayer and receives royalties from UpToDate.

Routine screening for depression and anxiety at each primary care clinical encounter in order to meet performance metrics could compromise accuracy and clinical care, based on data from more than 380,000 individuals in primary care.

“Prioritizing repetition of intake screening questionnaires at primary care visits may have unintended consequences such as administrative burden, provision of low-value care, and reduced clinical capacity to deliver other, high-value services,” but the accuracy of workflow-based intake screening on subsequent diagnosis has not been explored, wrote Jodi Simon, DrPH, of AllianceChicago, Ill., and colleagues.

In a study published in the Annals of Family Medicine, the researchers reviewed data from screenings performed on 380,057 patients in primary care settings. They examined the accuracy and utility of the Patient Health Questionnaire (PHQ-2) for depression and the Generalized Anxiety Disorder 2 (GAD-2) for anxiety.

The data included 1,883,317 screenings with PHQ-2s and 1,573,107 with GAD-2s. Of these, 92.3% of PHQ-2 screenings and 91.4% of GAD-2 screenings indicated low likelihood of depression or anxiety (defined as cumulative scores of 0 or 1). Mean scores for the PHQ-2 and GAD-2 in the study population were 0.29 and 0.35, respectively.

In the current study, 11% of patients had positive PHQ-2 scores (defined as 2 or higher) vs. 47%-53% seen in previous studies and census data.

In an analysis of new diagnoses of depression and anxiety, the researchers found that 42.3% of patients with a new depression diagnosis were not identified on intake screening; they had scores of 0 or 1 on the PHQ-2 in the past 30 days. Similarly, 42.7% of patients with a new anxiety diagnosis had scores of 0 or 1 on the GAD-2 in the past 30 days.

In other words, “Screening only detected risk in 57.7% of patients subsequently diagnosed with depression and 57.3% of patients subsequently diagnosed with anxiety,” the researchers said. This low positivity rate in patients diagnosed within 30 days merits further research, they added.

More studies are needed, but preliminary interviews with patients, clinicians, and staff indicate that time constraints and variation in the administration of questionnaires are among the factors contributing to inaccurate screening, the researchers noted.

The current study results suggest that screenings for anxiety and depression may occur in a perfunctory or inconsistent manner that might compromise accuracy when they are part of the workflow for each clinical visit in order to meet performance metrics, they said. “Ineffective screening may unintentionally detract from clinical care because care teams and patients have less time and cognitive energy to focus on other priorities during busy clinical encounters,” they added.

Alternatively, screening for anxiety and depression at regular intervals rather than each clinical encounter could improve reliability, the researchers concluded.

The study was funded by the American Medical Association Transformation Initiative. The researchers had no financial conflicts to disclose.

Routine screening for depression and anxiety at each primary care clinical encounter in order to meet performance metrics could compromise accuracy and clinical care, based on data from more than 380,000 individuals in primary care.

“Prioritizing repetition of intake screening questionnaires at primary care visits may have unintended consequences such as administrative burden, provision of low-value care, and reduced clinical capacity to deliver other, high-value services,” but the accuracy of workflow-based intake screening on subsequent diagnosis has not been explored, wrote Jodi Simon, DrPH, of AllianceChicago, Ill., and colleagues.

In a study published in the Annals of Family Medicine, the researchers reviewed data from screenings performed on 380,057 patients in primary care settings. They examined the accuracy and utility of the Patient Health Questionnaire (PHQ-2) for depression and the Generalized Anxiety Disorder 2 (GAD-2) for anxiety.

The data included 1,883,317 screenings with PHQ-2s and 1,573,107 with GAD-2s. Of these, 92.3% of PHQ-2 screenings and 91.4% of GAD-2 screenings indicated low likelihood of depression or anxiety (defined as cumulative scores of 0 or 1). Mean scores for the PHQ-2 and GAD-2 in the study population were 0.29 and 0.35, respectively.

In the current study, 11% of patients had positive PHQ-2 scores (defined as 2 or higher) vs. 47%-53% seen in previous studies and census data.

In an analysis of new diagnoses of depression and anxiety, the researchers found that 42.3% of patients with a new depression diagnosis were not identified on intake screening; they had scores of 0 or 1 on the PHQ-2 in the past 30 days. Similarly, 42.7% of patients with a new anxiety diagnosis had scores of 0 or 1 on the GAD-2 in the past 30 days.

In other words, “Screening only detected risk in 57.7% of patients subsequently diagnosed with depression and 57.3% of patients subsequently diagnosed with anxiety,” the researchers said. This low positivity rate in patients diagnosed within 30 days merits further research, they added.

More studies are needed, but preliminary interviews with patients, clinicians, and staff indicate that time constraints and variation in the administration of questionnaires are among the factors contributing to inaccurate screening, the researchers noted.

The current study results suggest that screenings for anxiety and depression may occur in a perfunctory or inconsistent manner that might compromise accuracy when they are part of the workflow for each clinical visit in order to meet performance metrics, they said. “Ineffective screening may unintentionally detract from clinical care because care teams and patients have less time and cognitive energy to focus on other priorities during busy clinical encounters,” they added.

Alternatively, screening for anxiety and depression at regular intervals rather than each clinical encounter could improve reliability, the researchers concluded.

The study was funded by the American Medical Association Transformation Initiative. The researchers had no financial conflicts to disclose.

Routine screening for depression and anxiety at each primary care clinical encounter in order to meet performance metrics could compromise accuracy and clinical care, based on data from more than 380,000 individuals in primary care.

“Prioritizing repetition of intake screening questionnaires at primary care visits may have unintended consequences such as administrative burden, provision of low-value care, and reduced clinical capacity to deliver other, high-value services,” but the accuracy of workflow-based intake screening on subsequent diagnosis has not been explored, wrote Jodi Simon, DrPH, of AllianceChicago, Ill., and colleagues.

In a study published in the Annals of Family Medicine, the researchers reviewed data from screenings performed on 380,057 patients in primary care settings. They examined the accuracy and utility of the Patient Health Questionnaire (PHQ-2) for depression and the Generalized Anxiety Disorder 2 (GAD-2) for anxiety.

The data included 1,883,317 screenings with PHQ-2s and 1,573,107 with GAD-2s. Of these, 92.3% of PHQ-2 screenings and 91.4% of GAD-2 screenings indicated low likelihood of depression or anxiety (defined as cumulative scores of 0 or 1). Mean scores for the PHQ-2 and GAD-2 in the study population were 0.29 and 0.35, respectively.

In the current study, 11% of patients had positive PHQ-2 scores (defined as 2 or higher) vs. 47%-53% seen in previous studies and census data.

In an analysis of new diagnoses of depression and anxiety, the researchers found that 42.3% of patients with a new depression diagnosis were not identified on intake screening; they had scores of 0 or 1 on the PHQ-2 in the past 30 days. Similarly, 42.7% of patients with a new anxiety diagnosis had scores of 0 or 1 on the GAD-2 in the past 30 days.

In other words, “Screening only detected risk in 57.7% of patients subsequently diagnosed with depression and 57.3% of patients subsequently diagnosed with anxiety,” the researchers said. This low positivity rate in patients diagnosed within 30 days merits further research, they added.

More studies are needed, but preliminary interviews with patients, clinicians, and staff indicate that time constraints and variation in the administration of questionnaires are among the factors contributing to inaccurate screening, the researchers noted.

The current study results suggest that screenings for anxiety and depression may occur in a perfunctory or inconsistent manner that might compromise accuracy when they are part of the workflow for each clinical visit in order to meet performance metrics, they said. “Ineffective screening may unintentionally detract from clinical care because care teams and patients have less time and cognitive energy to focus on other priorities during busy clinical encounters,” they added.

Alternatively, screening for anxiety and depression at regular intervals rather than each clinical encounter could improve reliability, the researchers concluded.

The study was funded by the American Medical Association Transformation Initiative. The researchers had no financial conflicts to disclose.

A 16-year-old female presents for a self-identified concern around the possibility that she is experiencing an autism spectrum disorder. She relays to the developmental pediatrician that she has been learning a lot about autism on TikTok and through other social media sites, and has become strongly convinced that she meets medical criteria for this disorder.

Oregon Health & Science University (OHSU)

A careful developmental history via a detailed interview with the mother reveals normal acquisition of early developmental milestones in addition to long-standing well-modulated eye contact felt to be paired fluidly with directed affect and gestures. The teen is described as having been an engaging toddler and preschooler, without restricted interests or repetitive behaviors, and having had no major challenges in grade school with behaviors, friendships, or academics.

During the pandemic, however, the teen became quite isolated. She developed anxiety with depression, and then started having some new repetitive arm movements within the last 12-18 months. In clinic, the teen makes robustly effortful arm-waving movements, which are noted to wane when she becomes more animated and excited during conversation, and to increase when she is less distracted by conversation and more focused on the movements.

She directs affect nicely toward her mother, while avoiding looking in the direction of the examiner until later in the evaluation when she becomes more relaxed. Prosody of speech and intonation are typical, and she describes having a close group of friends with whom she spends quite a bit of time.

The Autism Diagnostic Observation Schedule (ADOS-2 module 3) is used to gather structured observations, and these social presses yield flowing social engagement with the examiner, good understanding of humor, and overall excellent verbal and nonverbal communication skills. The teen describes hypervigilance around the emotions of others, a natural ease in understanding the perspectives of others, and a quick ability to read the energy of a room. She does have some interest in some more obscure online game forums, but her friends do as well, and she otherwise does not have a history of intrusive fixations. A social history reveals past significant verbal abuse in the home by means of her father during her first 11 years of life, which is described as quite traumatic.

After careful and thoughtful consideration (recognizing the known statistics around girls assigned female at birth, as well as nonbinary individuals and minoritized groups being underdiagnosed with autism), the history and observations are not felt to be consistent with autism, but with anxiety within the context of a trauma and stressor-related disorder. Even when accounting for the possibility of “masking,” the teen still does not meet criteria for autism based on history and presentation. The habit movements are not typical of usual stereotypies or of tics (which tend to increase with excitement and tend to have a more effortless quality), and are felt to possibly be functional in origin. Upon gently sharing these conclusions with the teen, she bursts into tears, stating her friends may now accuse her of lying, as she has already been claiming to have autism online and in person at school.
 

Countering social media diagnoses

This type of scenario is becoming increasingly common, with teens turning online primarily to social media accounts to gain knowledge around various neurologic and mental health conditions. Greater normalization of neurodiversity and greater access to high-quality information about neurodevelopmental differences is certainly progress, though unfortunately some online depictions of these conditions are simply not accurate. Many adolescents are keenly searching for both their personal identity and also a community through which they might feel wholly accepted, after experiencing some level of isolation during the pandemic followed by increased social discomfort in attempting to reintegrate into school life and society. It is important to take time to understand the drive behind an adolescent’s apparent desire for a specific diagnosis, particularly if that diagnosis is not felt to be an accurate conceptualization of the teen’s presentation by a skilled professional. Connecting the teen with a good-fit therapist and working to replace excessive screen time with exercise, outdoor activities, and in-person engagement with friends and family are also crucial interventions, though they can be incredibly difficult for families to achieve given various patient-specific and societal barriers. The overlap in symptomatology among anxiety, attention-deficit/hyperactivity disorder, and autism spectrum disorders is expansive, making it understandable that young people might misjudge their personal experience of life for a neurodevelopmental disorder for which they do not truly meet criteria. Increasing access to therapists well versed in trauma-informed care is a frequently referenced need, highlighted in this case.

Another case

In contrast to the case scenario above is that of a 19-year-old female presenting for a formal autism evaluation at the urging of her father, who has had concerns around her severe “shyness” throughout her life. He is concerned that she was not able to obtain a high school diploma despite appearing to have adequate cognitive skills, is currently quite isolated, and does not appear equipped to hold a job at this time. He describes her as having been a very quiet and self-directed young child who greatly benefited from the communication and social scaffolding provided by her slightly older and neurotypical sister. She has generally not had true friends, though she had no behavioral or academic difficulties in school other than seeming aloof and unusually quiet. Atypical social approaches have become more apparent over time, as relationship navigation has become more complex with age. She is noted to have frequent stereotyped hand-to-face movements throughout the evaluation, as well as a flat affect and unusual voice quality. She speaks slowly and softly, and while she does make eye contact, it is less well modulated than would be expected. She is very focused on her cat and online interests during conversation, and tends to give stilted answers to open-ended questions. During the interview portion of the ADOS, she demonstrates little insight into friendships and reports feeling very content on her own, though is open to the idea of relationships in the future and would like to learn how to achieve connections with others. Her father reports she tends to be generally quite blunt and has difficulty understanding humor and others’ perspectives. An autism diagnosis is made with the recommendation of application to Developmental Disability Services, given impaired adaptive skills, as a means of utilizing community-based supports to facilitate eventually obtaining a high school equivalency credential, a job, healthier living habits, and comfortable social outlets.

Discussion

It is crucial for providers to be aware of nuanced presentations of autism spectrum disorders that may have been missed in early childhood when social demands are less complicated, particularly in persons identified as female at birth, nonbinary individuals, and those belonging to minority groups. It is also important to address the widely acknowledged trend of adolescents turning to social media influencers for information around neurodevelopmental conditions, at a time in their lives when social anxiety and self-awareness are generally heightened. For an adolescent, a young social media influencer may feel like a more salient and reliable source of information than an adult with various letters after their name. A respectful relationship between a teen and a thoughtful primary care provider can help gain trust to foster open conversations around their concerns, which can further help determine if a referral to a psychologist or developmental pediatrician for a formal autism assessment is truly warranted, highlighting the need for increased diagnostic capacity for such. While it is certainly important for providers to keep an open mind and to have continued awareness around the concept of late autism diagnoses, it is wise to also be aware of this recent trend among adolescents as providers seek to guide youth toward appropriate therapies and services.

Dr. Roth is a developmental and behavioral pediatrician in Eugene, Ore. She has no conflicts of interest.

A 16-year-old female presents for a self-identified concern around the possibility that she is experiencing an autism spectrum disorder. She relays to the developmental pediatrician that she has been learning a lot about autism on TikTok and through other social media sites, and has become strongly convinced that she meets medical criteria for this disorder.

Oregon Health & Science University (OHSU)

A careful developmental history via a detailed interview with the mother reveals normal acquisition of early developmental milestones in addition to long-standing well-modulated eye contact felt to be paired fluidly with directed affect and gestures. The teen is described as having been an engaging toddler and preschooler, without restricted interests or repetitive behaviors, and having had no major challenges in grade school with behaviors, friendships, or academics.

During the pandemic, however, the teen became quite isolated. She developed anxiety with depression, and then started having some new repetitive arm movements within the last 12-18 months. In clinic, the teen makes robustly effortful arm-waving movements, which are noted to wane when she becomes more animated and excited during conversation, and to increase when she is less distracted by conversation and more focused on the movements.

She directs affect nicely toward her mother, while avoiding looking in the direction of the examiner until later in the evaluation when she becomes more relaxed. Prosody of speech and intonation are typical, and she describes having a close group of friends with whom she spends quite a bit of time.

The Autism Diagnostic Observation Schedule (ADOS-2 module 3) is used to gather structured observations, and these social presses yield flowing social engagement with the examiner, good understanding of humor, and overall excellent verbal and nonverbal communication skills. The teen describes hypervigilance around the emotions of others, a natural ease in understanding the perspectives of others, and a quick ability to read the energy of a room. She does have some interest in some more obscure online game forums, but her friends do as well, and she otherwise does not have a history of intrusive fixations. A social history reveals past significant verbal abuse in the home by means of her father during her first 11 years of life, which is described as quite traumatic.

After careful and thoughtful consideration (recognizing the known statistics around girls assigned female at birth, as well as nonbinary individuals and minoritized groups being underdiagnosed with autism), the history and observations are not felt to be consistent with autism, but with anxiety within the context of a trauma and stressor-related disorder. Even when accounting for the possibility of “masking,” the teen still does not meet criteria for autism based on history and presentation. The habit movements are not typical of usual stereotypies or of tics (which tend to increase with excitement and tend to have a more effortless quality), and are felt to possibly be functional in origin. Upon gently sharing these conclusions with the teen, she bursts into tears, stating her friends may now accuse her of lying, as she has already been claiming to have autism online and in person at school.
 

Countering social media diagnoses

This type of scenario is becoming increasingly common, with teens turning online primarily to social media accounts to gain knowledge around various neurologic and mental health conditions. Greater normalization of neurodiversity and greater access to high-quality information about neurodevelopmental differences is certainly progress, though unfortunately some online depictions of these conditions are simply not accurate. Many adolescents are keenly searching for both their personal identity and also a community through which they might feel wholly accepted, after experiencing some level of isolation during the pandemic followed by increased social discomfort in attempting to reintegrate into school life and society. It is important to take time to understand the drive behind an adolescent’s apparent desire for a specific diagnosis, particularly if that diagnosis is not felt to be an accurate conceptualization of the teen’s presentation by a skilled professional. Connecting the teen with a good-fit therapist and working to replace excessive screen time with exercise, outdoor activities, and in-person engagement with friends and family are also crucial interventions, though they can be incredibly difficult for families to achieve given various patient-specific and societal barriers. The overlap in symptomatology among anxiety, attention-deficit/hyperactivity disorder, and autism spectrum disorders is expansive, making it understandable that young people might misjudge their personal experience of life for a neurodevelopmental disorder for which they do not truly meet criteria. Increasing access to therapists well versed in trauma-informed care is a frequently referenced need, highlighted in this case.

Another case

In contrast to the case scenario above is that of a 19-year-old female presenting for a formal autism evaluation at the urging of her father, who has had concerns around her severe “shyness” throughout her life. He is concerned that she was not able to obtain a high school diploma despite appearing to have adequate cognitive skills, is currently quite isolated, and does not appear equipped to hold a job at this time. He describes her as having been a very quiet and self-directed young child who greatly benefited from the communication and social scaffolding provided by her slightly older and neurotypical sister. She has generally not had true friends, though she had no behavioral or academic difficulties in school other than seeming aloof and unusually quiet. Atypical social approaches have become more apparent over time, as relationship navigation has become more complex with age. She is noted to have frequent stereotyped hand-to-face movements throughout the evaluation, as well as a flat affect and unusual voice quality. She speaks slowly and softly, and while she does make eye contact, it is less well modulated than would be expected. She is very focused on her cat and online interests during conversation, and tends to give stilted answers to open-ended questions. During the interview portion of the ADOS, she demonstrates little insight into friendships and reports feeling very content on her own, though is open to the idea of relationships in the future and would like to learn how to achieve connections with others. Her father reports she tends to be generally quite blunt and has difficulty understanding humor and others’ perspectives. An autism diagnosis is made with the recommendation of application to Developmental Disability Services, given impaired adaptive skills, as a means of utilizing community-based supports to facilitate eventually obtaining a high school equivalency credential, a job, healthier living habits, and comfortable social outlets.

Discussion

It is crucial for providers to be aware of nuanced presentations of autism spectrum disorders that may have been missed in early childhood when social demands are less complicated, particularly in persons identified as female at birth, nonbinary individuals, and those belonging to minority groups. It is also important to address the widely acknowledged trend of adolescents turning to social media influencers for information around neurodevelopmental conditions, at a time in their lives when social anxiety and self-awareness are generally heightened. For an adolescent, a young social media influencer may feel like a more salient and reliable source of information than an adult with various letters after their name. A respectful relationship between a teen and a thoughtful primary care provider can help gain trust to foster open conversations around their concerns, which can further help determine if a referral to a psychologist or developmental pediatrician for a formal autism assessment is truly warranted, highlighting the need for increased diagnostic capacity for such. While it is certainly important for providers to keep an open mind and to have continued awareness around the concept of late autism diagnoses, it is wise to also be aware of this recent trend among adolescents as providers seek to guide youth toward appropriate therapies and services.

Dr. Roth is a developmental and behavioral pediatrician in Eugene, Ore. She has no conflicts of interest.

A 16-year-old female presents for a self-identified concern around the possibility that she is experiencing an autism spectrum disorder. She relays to the developmental pediatrician that she has been learning a lot about autism on TikTok and through other social media sites, and has become strongly convinced that she meets medical criteria for this disorder.

Oregon Health & Science University (OHSU)

A careful developmental history via a detailed interview with the mother reveals normal acquisition of early developmental milestones in addition to long-standing well-modulated eye contact felt to be paired fluidly with directed affect and gestures. The teen is described as having been an engaging toddler and preschooler, without restricted interests or repetitive behaviors, and having had no major challenges in grade school with behaviors, friendships, or academics.

During the pandemic, however, the teen became quite isolated. She developed anxiety with depression, and then started having some new repetitive arm movements within the last 12-18 months. In clinic, the teen makes robustly effortful arm-waving movements, which are noted to wane when she becomes more animated and excited during conversation, and to increase when she is less distracted by conversation and more focused on the movements.

She directs affect nicely toward her mother, while avoiding looking in the direction of the examiner until later in the evaluation when she becomes more relaxed. Prosody of speech and intonation are typical, and she describes having a close group of friends with whom she spends quite a bit of time.

The Autism Diagnostic Observation Schedule (ADOS-2 module 3) is used to gather structured observations, and these social presses yield flowing social engagement with the examiner, good understanding of humor, and overall excellent verbal and nonverbal communication skills. The teen describes hypervigilance around the emotions of others, a natural ease in understanding the perspectives of others, and a quick ability to read the energy of a room. She does have some interest in some more obscure online game forums, but her friends do as well, and she otherwise does not have a history of intrusive fixations. A social history reveals past significant verbal abuse in the home by means of her father during her first 11 years of life, which is described as quite traumatic.

After careful and thoughtful consideration (recognizing the known statistics around girls assigned female at birth, as well as nonbinary individuals and minoritized groups being underdiagnosed with autism), the history and observations are not felt to be consistent with autism, but with anxiety within the context of a trauma and stressor-related disorder. Even when accounting for the possibility of “masking,” the teen still does not meet criteria for autism based on history and presentation. The habit movements are not typical of usual stereotypies or of tics (which tend to increase with excitement and tend to have a more effortless quality), and are felt to possibly be functional in origin. Upon gently sharing these conclusions with the teen, she bursts into tears, stating her friends may now accuse her of lying, as she has already been claiming to have autism online and in person at school.
 

Countering social media diagnoses

This type of scenario is becoming increasingly common, with teens turning online primarily to social media accounts to gain knowledge around various neurologic and mental health conditions. Greater normalization of neurodiversity and greater access to high-quality information about neurodevelopmental differences is certainly progress, though unfortunately some online depictions of these conditions are simply not accurate. Many adolescents are keenly searching for both their personal identity and also a community through which they might feel wholly accepted, after experiencing some level of isolation during the pandemic followed by increased social discomfort in attempting to reintegrate into school life and society. It is important to take time to understand the drive behind an adolescent’s apparent desire for a specific diagnosis, particularly if that diagnosis is not felt to be an accurate conceptualization of the teen’s presentation by a skilled professional. Connecting the teen with a good-fit therapist and working to replace excessive screen time with exercise, outdoor activities, and in-person engagement with friends and family are also crucial interventions, though they can be incredibly difficult for families to achieve given various patient-specific and societal barriers. The overlap in symptomatology among anxiety, attention-deficit/hyperactivity disorder, and autism spectrum disorders is expansive, making it understandable that young people might misjudge their personal experience of life for a neurodevelopmental disorder for which they do not truly meet criteria. Increasing access to therapists well versed in trauma-informed care is a frequently referenced need, highlighted in this case.

Another case

In contrast to the case scenario above is that of a 19-year-old female presenting for a formal autism evaluation at the urging of her father, who has had concerns around her severe “shyness” throughout her life. He is concerned that she was not able to obtain a high school diploma despite appearing to have adequate cognitive skills, is currently quite isolated, and does not appear equipped to hold a job at this time. He describes her as having been a very quiet and self-directed young child who greatly benefited from the communication and social scaffolding provided by her slightly older and neurotypical sister. She has generally not had true friends, though she had no behavioral or academic difficulties in school other than seeming aloof and unusually quiet. Atypical social approaches have become more apparent over time, as relationship navigation has become more complex with age. She is noted to have frequent stereotyped hand-to-face movements throughout the evaluation, as well as a flat affect and unusual voice quality. She speaks slowly and softly, and while she does make eye contact, it is less well modulated than would be expected. She is very focused on her cat and online interests during conversation, and tends to give stilted answers to open-ended questions. During the interview portion of the ADOS, she demonstrates little insight into friendships and reports feeling very content on her own, though is open to the idea of relationships in the future and would like to learn how to achieve connections with others. Her father reports she tends to be generally quite blunt and has difficulty understanding humor and others’ perspectives. An autism diagnosis is made with the recommendation of application to Developmental Disability Services, given impaired adaptive skills, as a means of utilizing community-based supports to facilitate eventually obtaining a high school equivalency credential, a job, healthier living habits, and comfortable social outlets.

Discussion

It is crucial for providers to be aware of nuanced presentations of autism spectrum disorders that may have been missed in early childhood when social demands are less complicated, particularly in persons identified as female at birth, nonbinary individuals, and those belonging to minority groups. It is also important to address the widely acknowledged trend of adolescents turning to social media influencers for information around neurodevelopmental conditions, at a time in their lives when social anxiety and self-awareness are generally heightened. For an adolescent, a young social media influencer may feel like a more salient and reliable source of information than an adult with various letters after their name. A respectful relationship between a teen and a thoughtful primary care provider can help gain trust to foster open conversations around their concerns, which can further help determine if a referral to a psychologist or developmental pediatrician for a formal autism assessment is truly warranted, highlighting the need for increased diagnostic capacity for such. While it is certainly important for providers to keep an open mind and to have continued awareness around the concept of late autism diagnoses, it is wise to also be aware of this recent trend among adolescents as providers seek to guide youth toward appropriate therapies and services.

Dr. Roth is a developmental and behavioral pediatrician in Eugene, Ore. She has no conflicts of interest.

BARCELONA – Intermittent benzodiazepine use significantly reduces the risk for falls, fractures, and mortality in older adults compared with chronic use of these medications, results of a large-scale study show.

Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.

Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.

Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.

However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.

The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
 

Wide range of adverse outcomes

The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.

“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.

Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.

Moreover, chronic use is more common in older versus younger patients.

Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.

“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”

To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.

They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.

Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.

Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.

The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.

As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.

Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.

Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.

After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
 

Sex differences

In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).

There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).

A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).

Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).

The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”

He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.

“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.

If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.

“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
 

Confirmatory research

In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.

“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.

Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”

In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”

Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”

“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.

The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.

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

BARCELONA – Intermittent benzodiazepine use significantly reduces the risk for falls, fractures, and mortality in older adults compared with chronic use of these medications, results of a large-scale study show.

Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.

Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.

Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.

However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.

The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
 

Wide range of adverse outcomes

The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.

“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.

Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.

Moreover, chronic use is more common in older versus younger patients.

Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.

“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”

To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.

They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.

Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.

Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.

The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.

As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.

Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.

Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.

After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
 

Sex differences

In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).

There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).

A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).

Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).

The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”

He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.

“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.

If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.

“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
 

Confirmatory research

In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.

“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.

Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”

In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”

Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”

“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.

The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.

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

BARCELONA – Intermittent benzodiazepine use significantly reduces the risk for falls, fractures, and mortality in older adults compared with chronic use of these medications, results of a large-scale study show.

Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.

Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.

Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.

However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.

The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
 

Wide range of adverse outcomes

The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.

“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.

Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.

Moreover, chronic use is more common in older versus younger patients.

Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.

“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”

To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.

They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.

Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.

Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.

The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.

As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.

Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.

Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.

After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
 

Sex differences

In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).

There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).

A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).

Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).

The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”

He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.

“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.

If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.

“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
 

Confirmatory research

In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.

“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.

Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”

In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”

Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”

“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.

The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.

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

BARCELONA – Intranasal esketamine (Spravato, Janssen) is superior to extended-release quetiapine (Seroquel, AstraZeneca), an atypical antipsychotic, for treatment-resistant depression (TRD), results of a large, multicenter, head-to-head phase 3 trial show.

Results from the ESCAPE-TRD study, which included 675 participants with TRD, show that esketamine was associated with significantly increased rates of both depression and functional remission, compared with quetiapine.

More than 675 patients were randomly assigned to receive one of the two drugs along with ongoing treatment with an SSRI or a serotonin-norepinephrine reuptake inhibitor (SNRI).

Esketamine increased remission rates at 2 and 8 months over quetiapine by 72% and raised functional remission rates at 8 months by 88% while decreasing adverse event rates.

The findings were presented at the annual meeting of the European College of Neuropsychopharmacology and were published online in the New England Journal of Medicine.
 

New hope

The results provide “some hope for our patients suffering from TRD, which, given the data, is somewhat of a misnomer,” said study investigator Andreas Reif, MD, professor of psychiatry, psychosomatic medicine, and psychotherapy, University Hospital Frankfurt–Goethe University, Frankfurt am Main, Germany, and president-elect of the ECNP.

“These patients are not resistant, they just have resistance to monoaminergic drugs,” he added. Esketamine, he said, is a “new weapon in our armamentarium.”

Dr. Reif said TRD is a serious condition that affects approximately 20%-30% of those with major depressive disorder and has “substantial impact” on patients’ lives, including quality of life and level of functioning.

“We know that esketamine nasal spray is effective in TRD. However, up to now, there were only placebo-controlled trials in addition to ongoing antidepressant treatment,” Dr. Reif noted. Consequently, he added, a head-to-head comparison with an active agent with proven efficacy was “urgently needed.”

For the trial, patients from 171 sites in 24 countries with TRD, defined as a less than 25% improvement in symptoms with two or more consecutive treatments of adequate dosage and duration, were randomly assigned to receive esketamine nasal spray (n = 336) or quetiapine (n = 340) extended release together with ongoing SSRI or SNRI therapy.

Both esketamine and quetiapine were flexibly dosed. The primary endpoint was rates of remission at week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS). After week 8, patients entered a maintenance phase that lasted to week 32.

Dr. Reif said the study population was representative of a typical TRD population.

The average duration of the current depression episode was more than 5 years, and the average MADRS score was above 30.
 

Key findings

Results showed that those who received esketamine in combination with an SSRI or SNRI experienced a significantly higher rate of remission at week 8, compared with those treated with quetiapine (27.1% vs. 17.6%; P = .003). This equated to an adjusted odds ratio for remission of 1.74 (P = .003).

Use of esketamine was also associated with a higher rate of remission at week 8, and patients remained relapse free at week 32 (21.7% vs. 14.1% with quetiapine; odds ratio, 1.72; P = .008).

At every time point through the study, the proportion of patients experiencing remission was significantly greater with esketamine than with quetiapine. The absolute rate of remission at week 32 was 55.0%, versus 37.0% (P < .001).

Dr. Reif noted that the definition of remission used in the study was a MADRS score of less than or equal to 10, but if the “more lenient” definition of less than or equal to 12, which has been used previously, were to be applied, the absolute remission rates would rise to 65.1%, versus 46.7%.

Dr. Reif also presented results on functional remission rates beyond 32 weeks – data that were not included in the study as published in NEJM.

While remission rates increased over time in both study arms, the functional remission rate at week 32 was, again, significantly higher with esketamine than with quetiapine (38.1% vs. 25.0%; OR, 1.88; P < .001).

The safety data revealed no new signals, Dr. Reif said. Use of esketamine was associated with a lower rate of treatment-emergent adverse events that led to treatment discontinuation, at 4.2% vs. 11.0% with quetiapine.

Among patients given the ketamine-derived drug, there were lower rates of nervous system disorders, and there were no incidences of weight gain, fatigue, or hangover.

Dr. Reif said the results show that esketamine nasal spray was superior to quetiapine in achieving remission over time and that it “greatly improves patients’ functional impairment” while achieving “generally lower” adverse event rates.

He added that they are currently running a significant number of secondary analyses “to give us a better grasp of which patient benefits most” from esketamine therapy over quetiapine. The results may potentially be used to guide patient selection.
 

‘Tremendous advance’

Session co-chair Mark Weiser, MD, chairman at the department of psychiatry, Tel Aviv (Israel) University, said in an interview that the results are “very exciting” and offer “further proof of a tremendous advance in our field.”

Dr. Weiser, who was not involved in the study, added that demonstrating functional improvement with esketamine was key.

“It’s great to improve symptoms,” he said, “but to have patients show an improvement in their functionality is really the bottom line of this. Not only do you feel better, but you function better, and that’s of extreme importance and makes us feel very optimistic about the future.”

Josep Antoni Ramos-Quiroga, MD, PhD, head of psychiatry, Vall Hebron University Hospital and Autonomous University of Barcelona, welcomed the findings.

“The results of this study show the superior response and safety of esketamine nasal spray when compared with quetiapine,” he said in a release. “This gives people with treatment-resistant depression more safe treatment options.”

The study was funded by Janssen EMEA. Dr. Reif has relationships with Boehringer Ingelheim, COMPASS, Janssen Pharmaceuticals, LivaNova USA, Medice, Saga Therapeutics, and Shire. Other authors have disclosed numerous relationships with industry.

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

BARCELONA – Intranasal esketamine (Spravato, Janssen) is superior to extended-release quetiapine (Seroquel, AstraZeneca), an atypical antipsychotic, for treatment-resistant depression (TRD), results of a large, multicenter, head-to-head phase 3 trial show.

Results from the ESCAPE-TRD study, which included 675 participants with TRD, show that esketamine was associated with significantly increased rates of both depression and functional remission, compared with quetiapine.

More than 675 patients were randomly assigned to receive one of the two drugs along with ongoing treatment with an SSRI or a serotonin-norepinephrine reuptake inhibitor (SNRI).

Esketamine increased remission rates at 2 and 8 months over quetiapine by 72% and raised functional remission rates at 8 months by 88% while decreasing adverse event rates.

The findings were presented at the annual meeting of the European College of Neuropsychopharmacology and were published online in the New England Journal of Medicine.
 

New hope

The results provide “some hope for our patients suffering from TRD, which, given the data, is somewhat of a misnomer,” said study investigator Andreas Reif, MD, professor of psychiatry, psychosomatic medicine, and psychotherapy, University Hospital Frankfurt–Goethe University, Frankfurt am Main, Germany, and president-elect of the ECNP.

“These patients are not resistant, they just have resistance to monoaminergic drugs,” he added. Esketamine, he said, is a “new weapon in our armamentarium.”

Dr. Reif said TRD is a serious condition that affects approximately 20%-30% of those with major depressive disorder and has “substantial impact” on patients’ lives, including quality of life and level of functioning.

“We know that esketamine nasal spray is effective in TRD. However, up to now, there were only placebo-controlled trials in addition to ongoing antidepressant treatment,” Dr. Reif noted. Consequently, he added, a head-to-head comparison with an active agent with proven efficacy was “urgently needed.”

For the trial, patients from 171 sites in 24 countries with TRD, defined as a less than 25% improvement in symptoms with two or more consecutive treatments of adequate dosage and duration, were randomly assigned to receive esketamine nasal spray (n = 336) or quetiapine (n = 340) extended release together with ongoing SSRI or SNRI therapy.

Both esketamine and quetiapine were flexibly dosed. The primary endpoint was rates of remission at week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS). After week 8, patients entered a maintenance phase that lasted to week 32.

Dr. Reif said the study population was representative of a typical TRD population.

The average duration of the current depression episode was more than 5 years, and the average MADRS score was above 30.
 

Key findings

Results showed that those who received esketamine in combination with an SSRI or SNRI experienced a significantly higher rate of remission at week 8, compared with those treated with quetiapine (27.1% vs. 17.6%; P = .003). This equated to an adjusted odds ratio for remission of 1.74 (P = .003).

Use of esketamine was also associated with a higher rate of remission at week 8, and patients remained relapse free at week 32 (21.7% vs. 14.1% with quetiapine; odds ratio, 1.72; P = .008).

At every time point through the study, the proportion of patients experiencing remission was significantly greater with esketamine than with quetiapine. The absolute rate of remission at week 32 was 55.0%, versus 37.0% (P < .001).

Dr. Reif noted that the definition of remission used in the study was a MADRS score of less than or equal to 10, but if the “more lenient” definition of less than or equal to 12, which has been used previously, were to be applied, the absolute remission rates would rise to 65.1%, versus 46.7%.

Dr. Reif also presented results on functional remission rates beyond 32 weeks – data that were not included in the study as published in NEJM.

While remission rates increased over time in both study arms, the functional remission rate at week 32 was, again, significantly higher with esketamine than with quetiapine (38.1% vs. 25.0%; OR, 1.88; P < .001).

The safety data revealed no new signals, Dr. Reif said. Use of esketamine was associated with a lower rate of treatment-emergent adverse events that led to treatment discontinuation, at 4.2% vs. 11.0% with quetiapine.

Among patients given the ketamine-derived drug, there were lower rates of nervous system disorders, and there were no incidences of weight gain, fatigue, or hangover.

Dr. Reif said the results show that esketamine nasal spray was superior to quetiapine in achieving remission over time and that it “greatly improves patients’ functional impairment” while achieving “generally lower” adverse event rates.

He added that they are currently running a significant number of secondary analyses “to give us a better grasp of which patient benefits most” from esketamine therapy over quetiapine. The results may potentially be used to guide patient selection.
 

‘Tremendous advance’

Session co-chair Mark Weiser, MD, chairman at the department of psychiatry, Tel Aviv (Israel) University, said in an interview that the results are “very exciting” and offer “further proof of a tremendous advance in our field.”

Dr. Weiser, who was not involved in the study, added that demonstrating functional improvement with esketamine was key.

“It’s great to improve symptoms,” he said, “but to have patients show an improvement in their functionality is really the bottom line of this. Not only do you feel better, but you function better, and that’s of extreme importance and makes us feel very optimistic about the future.”

Josep Antoni Ramos-Quiroga, MD, PhD, head of psychiatry, Vall Hebron University Hospital and Autonomous University of Barcelona, welcomed the findings.

“The results of this study show the superior response and safety of esketamine nasal spray when compared with quetiapine,” he said in a release. “This gives people with treatment-resistant depression more safe treatment options.”

The study was funded by Janssen EMEA. Dr. Reif has relationships with Boehringer Ingelheim, COMPASS, Janssen Pharmaceuticals, LivaNova USA, Medice, Saga Therapeutics, and Shire. Other authors have disclosed numerous relationships with industry.

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

BARCELONA – Intranasal esketamine (Spravato, Janssen) is superior to extended-release quetiapine (Seroquel, AstraZeneca), an atypical antipsychotic, for treatment-resistant depression (TRD), results of a large, multicenter, head-to-head phase 3 trial show.

Results from the ESCAPE-TRD study, which included 675 participants with TRD, show that esketamine was associated with significantly increased rates of both depression and functional remission, compared with quetiapine.

More than 675 patients were randomly assigned to receive one of the two drugs along with ongoing treatment with an SSRI or a serotonin-norepinephrine reuptake inhibitor (SNRI).

Esketamine increased remission rates at 2 and 8 months over quetiapine by 72% and raised functional remission rates at 8 months by 88% while decreasing adverse event rates.

The findings were presented at the annual meeting of the European College of Neuropsychopharmacology and were published online in the New England Journal of Medicine.
 

New hope

The results provide “some hope for our patients suffering from TRD, which, given the data, is somewhat of a misnomer,” said study investigator Andreas Reif, MD, professor of psychiatry, psychosomatic medicine, and psychotherapy, University Hospital Frankfurt–Goethe University, Frankfurt am Main, Germany, and president-elect of the ECNP.

“These patients are not resistant, they just have resistance to monoaminergic drugs,” he added. Esketamine, he said, is a “new weapon in our armamentarium.”

Dr. Reif said TRD is a serious condition that affects approximately 20%-30% of those with major depressive disorder and has “substantial impact” on patients’ lives, including quality of life and level of functioning.

“We know that esketamine nasal spray is effective in TRD. However, up to now, there were only placebo-controlled trials in addition to ongoing antidepressant treatment,” Dr. Reif noted. Consequently, he added, a head-to-head comparison with an active agent with proven efficacy was “urgently needed.”

For the trial, patients from 171 sites in 24 countries with TRD, defined as a less than 25% improvement in symptoms with two or more consecutive treatments of adequate dosage and duration, were randomly assigned to receive esketamine nasal spray (n = 336) or quetiapine (n = 340) extended release together with ongoing SSRI or SNRI therapy.

Both esketamine and quetiapine were flexibly dosed. The primary endpoint was rates of remission at week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS). After week 8, patients entered a maintenance phase that lasted to week 32.

Dr. Reif said the study population was representative of a typical TRD population.

The average duration of the current depression episode was more than 5 years, and the average MADRS score was above 30.
 

Key findings

Results showed that those who received esketamine in combination with an SSRI or SNRI experienced a significantly higher rate of remission at week 8, compared with those treated with quetiapine (27.1% vs. 17.6%; P = .003). This equated to an adjusted odds ratio for remission of 1.74 (P = .003).

Use of esketamine was also associated with a higher rate of remission at week 8, and patients remained relapse free at week 32 (21.7% vs. 14.1% with quetiapine; odds ratio, 1.72; P = .008).

At every time point through the study, the proportion of patients experiencing remission was significantly greater with esketamine than with quetiapine. The absolute rate of remission at week 32 was 55.0%, versus 37.0% (P < .001).

Dr. Reif noted that the definition of remission used in the study was a MADRS score of less than or equal to 10, but if the “more lenient” definition of less than or equal to 12, which has been used previously, were to be applied, the absolute remission rates would rise to 65.1%, versus 46.7%.

Dr. Reif also presented results on functional remission rates beyond 32 weeks – data that were not included in the study as published in NEJM.

While remission rates increased over time in both study arms, the functional remission rate at week 32 was, again, significantly higher with esketamine than with quetiapine (38.1% vs. 25.0%; OR, 1.88; P < .001).

The safety data revealed no new signals, Dr. Reif said. Use of esketamine was associated with a lower rate of treatment-emergent adverse events that led to treatment discontinuation, at 4.2% vs. 11.0% with quetiapine.

Among patients given the ketamine-derived drug, there were lower rates of nervous system disorders, and there were no incidences of weight gain, fatigue, or hangover.

Dr. Reif said the results show that esketamine nasal spray was superior to quetiapine in achieving remission over time and that it “greatly improves patients’ functional impairment” while achieving “generally lower” adverse event rates.

He added that they are currently running a significant number of secondary analyses “to give us a better grasp of which patient benefits most” from esketamine therapy over quetiapine. The results may potentially be used to guide patient selection.
 

‘Tremendous advance’

Session co-chair Mark Weiser, MD, chairman at the department of psychiatry, Tel Aviv (Israel) University, said in an interview that the results are “very exciting” and offer “further proof of a tremendous advance in our field.”

Dr. Weiser, who was not involved in the study, added that demonstrating functional improvement with esketamine was key.

“It’s great to improve symptoms,” he said, “but to have patients show an improvement in their functionality is really the bottom line of this. Not only do you feel better, but you function better, and that’s of extreme importance and makes us feel very optimistic about the future.”

Josep Antoni Ramos-Quiroga, MD, PhD, head of psychiatry, Vall Hebron University Hospital and Autonomous University of Barcelona, welcomed the findings.

“The results of this study show the superior response and safety of esketamine nasal spray when compared with quetiapine,” he said in a release. “This gives people with treatment-resistant depression more safe treatment options.”

The study was funded by Janssen EMEA. Dr. Reif has relationships with Boehringer Ingelheim, COMPASS, Janssen Pharmaceuticals, LivaNova USA, Medice, Saga Therapeutics, and Shire. Other authors have disclosed numerous relationships with industry.

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

The Food and Drug Administration approval of zuranolone for postpartum depression in August 2023 has raised many important questions (and opinions) about its future use in clinical practice.

At the UNC-Chapel Hill Center for Women’s Mood Disorders, we treat women and pregnant people throughout hormonal transitions, including pregnancy and the postpartum, and have been part of development, research, and now delivery of both brexanolone and zuranolone. While we are excited about new tools in the arsenal for alleviating maternal mental health, we also want to be clear that our work is far from complete and continued efforts to care for pregnant people and their families are imperative.

courtesy UNC-Chapel Hill

What is zuranolone?

Zuranolone (brand name Zurzuvae) is an oral medication developed by Sage Therapeutics and Biogen. It is a positive allosteric modulator of the GABA_A receptor, the brain’s major inhibitory system. As a positive allosteric modulator, it increases the sensitivity of the GABA_A receptor to GABA.

Zuranolone is very similar to brexanolone, a synthetic form of allopregnanolone, a neurosteroid byproduct of progesterone (see below). However, zuranolone is not an oral form of brexanolone – it was slightly modified to ensure good oral stability and bioavailability. It is metabolized by the hepatic enzyme CYP3A4 and has a half-life of 16-23 hours. Zurzuvae is currently produced in capsule form.
 

What does zuranolone treat?

Zuranolone is the first FDA-approved oral drug for postpartum depression (PPD). It follows brexanolone, an intravenous drug, which was the first FDA-approved medication for PPD. Though these are the first medications with specific approval for PDD, many other treatment options are currently available including therapy, SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs), and other treatments used in major depression.

How does zuranolone work?

courtesy UNC-Chapel Hill

Zuranolone is a neuroactive steroid, which means that it is a steroid that goes into and acts on the brain. Zuranolone binds to different GABA receptor subunits from those bound by other positive modulators, such as benzodiazepines (for example, lorazepam). As a synthetic form of allopregnanolone, a metabolite of progesterone which rises dramatically in pregnancy then drops during labor and delivery, zuranolone was originally thought to mitigate the response to this drop in patients that are vulnerable to it during the postpartum. An alternative proposed mechanism is that the increased GABAergic, inhibitory signaling with zuranolone may act directly to decrease depression irrespective of the exact mechanism by which the depression occurred.

How was it studied?

Zuranolone was studied in women with severe postpartum depression and had to meet criteria for major depressive disorder (MDD) no earlier than the third trimester of pregnancy (about 28 weeks’ gestation) and no later than 4 weeks post partum. Patients were excluded from these studies if they had a history of bipolar disorder, psychotic disorders, attempted suicide, or if they were at risk for suicide.

The two phase 3 clinical trials that led to FDA approval are ROBIN and SKYLARK. These studies measured the efficacy and safety of zuranolone at 30 mg and 50 mg, respectively, and met their end points of rapid improvement in depressive and anxiety symptoms in postpartum depression.
 

When will we be able to start using it?

It is anticipated that zuranolone will become commercially available in early 2024.

Who can prescribe it?

courtesy UNC-Chapel Hill

Those with medical licenses. Most people will likely receive treatment from their obstetric, family medicine, or psychiatric clinicians.

How much will it cost?

The manufacturers have not released this information as of August 2023.

What sort of doses and duration is recommended?

The current FDA recommended dose is 50 mg for 14 days, taken once per evening with a fatty meal. The dose can be reduced to 40 mg if there are central nervous system (CNS) depressant effects, and to 30 mg if the patient has severe hepatic or moderate-severe renal impairment. There are currently no studies on longer courses of treatment.

What happens if the patient relapses after a 14-day trial?

While there is no clear guidance, an open-label trial (The SHORELINE Study) demonstrated that a repeated 14-day administration can restore clinical response.

What are the side effects?

courtesy UNC-Chapel Hill

Common side effects include drowsiness, dizziness, lower energy, diarrhea, and symptoms similar to the common cold. Zuranolone can act like a CNS depressant and can lead to sedation and somnolence.

Are there any boxed warnings?

Because of the CNS depressant effects, zuranolone was given a boxed warning that patients should not drive or operate heavy machinery within 12 hours of taking the medication as it may lead to impairment. Similar to other antidepressants, there is also a warning that zuranolone may increase risk for suicidal thoughts in patients under 24 years old.

Can it be used with other medications?

Yes. In the original trials, women were allowed to remain on medications treating their depressive symptoms (such as SSRIs and SNRIs). According to the FDA, zuranolone can be used alone or with other antidepressants.

Are there any medicines to avoid?

We recommend caution with other medications which may increase sedation, such as benzodiazepines.

Can it be used with birth control?

Yes. In fact, because the outcomes on a fetus are not yet studied, it is recommended that patients be on concurrent birth control during treatment and for a week after cessation. This does not mean that zuranolone is known to cause issues with fetal development, but rather that we do not know at this time.

Can it be used in pregnancy?

As above, the outcomes on fetal development are not known at this time, nor are the effects of zuranolone on labor and delivery. More research will need to be done to understand if there is risk with taking zuranolone during pregnancy. It should be noted that allopregnanolone levels ordinarily reach quite high levels during pregnancy.
 

Long-term side effects?

Long-term side effects are unknown. The study duration of ROBIN and SKYLARK was 45 days.

Breastfeeding?

Use in lactation has not yet been studied. Continued research is needed.

Can it be used in mood changes related to other reproductive changes or diagnoses like premenstrual dysphoric disorder and perimenopause?

The mechanism by which zuranolone is thought to work – that is, during changes in reproductive hormones – is implicated in other reproductive transitions such as premenstrual dysphoric disorder and perimenopause when reproductive hormones are fluctuating, though at lower levels than in pregnancy. Research will be required to assess efficacy and safety; however, the mechanistic reasons is worth pursuing. Additionally, zuranolone has not been studied in postpartum psychosis.

Can zuranolone be used to treat other affective conditions besides postpartum depression? Bipolar disorder?

Zuranolone is currently only approved for the treatment of postpartum depression. It has not received FDA approval for major depression outside of the perinatal period at this time. Whether it may be beneficial for patients with a depressive episode that is part of an underlying bipolar disorder or other psychiatric illness is not yet known.

Anxiety?

Along with depressive symptoms, women who received zuranolone in the clinical trials also had improvements in anxiety symptoms. These findings provide some hope that zuranolone may eventually be beneficial in patients with anxiety.

However, to date zuranolone has not been directly studied as a treatment for anxiety disorders (such as generalized anxiety disorder, panic disorder, etc.), so its efficacy for these illnesses is currently unknown.
 

Insomnia?

In a study of 153 postpartum women, randomized to placebo or zuranolone, scale questions for insomnia were improved in the group receiving zuranolone. This provides some hope that, if zuranolone is appropriate, concurrent polypharmacy with a sleep aid can be avoided. Additionally, future evaluation of use in insomnia outside of PPD may be warranted.

How is it different from brexanolone?

The two are slightly different molecules. Brexanolone is synthetically identical to allopregnanolone and zuranolone has been altered to be active and orally bioavailable.

Brexanolone is a 60-hour infusion that requires hospital admission at an approved health care site. Zuranolone is an oral at-home once-daily dosing treatment for 14 days. Zuranolone does not require enrollment in a risk evaluation and mitigation strategy for risk of excessive sedation and sudden loss of consciousness.
 

When would you consider zuranolone vs. brexanolone vs. other antidepressants?

Zuranolone and brexanolone are rapid-acting antidepressants with a response within 14 days or 60 hours, respectively. Antidepressants such as SSRIs/SNRIs are still available, well studied, and work, although take longer to reach clinical efficacy and are accompanied by potentially troubling side effects (for example, weight gain, sexual dysfunction).

Time to treatment effect should be considered when assessing severity of symptoms and functional impairment of the mother and the overall family unit. Brexanolone requires continuous monitoring which may be beneficial for women who are severely impaired and may benefit from frequent clinical monitoring. Brexanolone does not require a dose reduction with hepatic impairment, however, should be avoided in end-stage renal disease because of the potential accumulation of the solubilizing agent.
 

Where can I find more information?

Many states have maternal mental health consultation lines (examples include NCMATTERS here in North Carolina and MCPAP for Moms in Massachusetts) for clinicians (mental health, primary care, and obstetricians) that can be utilized for questions about prescribing. Postpartum Support International also has a clinician line for those without state services.

We plan to update this entry upon market release and access to new information.

Dr. Riddle and Dr. Nathan are assistant professors in the department of psychiatry at the University of North Carolina at Chapel Hill. Dr. Richardson is a perinatal psychiatry fellow, department of psychiatry, UNC-Chapel Hill. Dr. Rubinow is Distinguished Professor in the department of psychiatry, UNC-Chapel Hill. Dr. Meltzer-Brody is Assad Meymandi Distinguished Professor and Chair, department of psychiatry, UNC-Chapel Hill.

References

Deligiannidis KM et al. J Clin Psychiatry. 2023 Jan 30;84(1):22m14475. doi: 10.4088/JCP.22m14475.

Deligiannidis KM et al. . Obstetrics & Gynecology. 2023 May;141(5S):64S-65S. doi: 10.1097/01.AOG.0000930588.16136.3f.

Deligiannidis KM et al. Am J Psychiatry. 2023 Sep 1;180(9):668-75. doi: 10.1176/appi.ajp.20220785.

Deligiannidis KM et al. JAMA Psychiatry. 2021 Sep 1;78(9):951-59. doi: 10.1001/jamapsychiatry.2021.1559.

FDA Approves First Oral Treatment for Postpartum Depression. 2023 Aug 4. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression

ZURZUVAE – HIGHLIGHTS OF PRESCRIBING INFORMATION. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217369s000lbl.pdf

The Food and Drug Administration approval of zuranolone for postpartum depression in August 2023 has raised many important questions (and opinions) about its future use in clinical practice.

At the UNC-Chapel Hill Center for Women’s Mood Disorders, we treat women and pregnant people throughout hormonal transitions, including pregnancy and the postpartum, and have been part of development, research, and now delivery of both brexanolone and zuranolone. While we are excited about new tools in the arsenal for alleviating maternal mental health, we also want to be clear that our work is far from complete and continued efforts to care for pregnant people and their families are imperative.

courtesy UNC-Chapel Hill

What is zuranolone?

Zuranolone (brand name Zurzuvae) is an oral medication developed by Sage Therapeutics and Biogen. It is a positive allosteric modulator of the GABA_A receptor, the brain’s major inhibitory system. As a positive allosteric modulator, it increases the sensitivity of the GABA_A receptor to GABA.

Zuranolone is very similar to brexanolone, a synthetic form of allopregnanolone, a neurosteroid byproduct of progesterone (see below). However, zuranolone is not an oral form of brexanolone – it was slightly modified to ensure good oral stability and bioavailability. It is metabolized by the hepatic enzyme CYP3A4 and has a half-life of 16-23 hours. Zurzuvae is currently produced in capsule form.
 

What does zuranolone treat?

Zuranolone is the first FDA-approved oral drug for postpartum depression (PPD). It follows brexanolone, an intravenous drug, which was the first FDA-approved medication for PPD. Though these are the first medications with specific approval for PDD, many other treatment options are currently available including therapy, SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs), and other treatments used in major depression.

How does zuranolone work?

courtesy UNC-Chapel Hill

Zuranolone is a neuroactive steroid, which means that it is a steroid that goes into and acts on the brain. Zuranolone binds to different GABA receptor subunits from those bound by other positive modulators, such as benzodiazepines (for example, lorazepam). As a synthetic form of allopregnanolone, a metabolite of progesterone which rises dramatically in pregnancy then drops during labor and delivery, zuranolone was originally thought to mitigate the response to this drop in patients that are vulnerable to it during the postpartum. An alternative proposed mechanism is that the increased GABAergic, inhibitory signaling with zuranolone may act directly to decrease depression irrespective of the exact mechanism by which the depression occurred.

How was it studied?

Zuranolone was studied in women with severe postpartum depression and had to meet criteria for major depressive disorder (MDD) no earlier than the third trimester of pregnancy (about 28 weeks’ gestation) and no later than 4 weeks post partum. Patients were excluded from these studies if they had a history of bipolar disorder, psychotic disorders, attempted suicide, or if they were at risk for suicide.

The two phase 3 clinical trials that led to FDA approval are ROBIN and SKYLARK. These studies measured the efficacy and safety of zuranolone at 30 mg and 50 mg, respectively, and met their end points of rapid improvement in depressive and anxiety symptoms in postpartum depression.
 

When will we be able to start using it?

It is anticipated that zuranolone will become commercially available in early 2024.

Who can prescribe it?

courtesy UNC-Chapel Hill

Those with medical licenses. Most people will likely receive treatment from their obstetric, family medicine, or psychiatric clinicians.

How much will it cost?

The manufacturers have not released this information as of August 2023.

What sort of doses and duration is recommended?

The current FDA recommended dose is 50 mg for 14 days, taken once per evening with a fatty meal. The dose can be reduced to 40 mg if there are central nervous system (CNS) depressant effects, and to 30 mg if the patient has severe hepatic or moderate-severe renal impairment. There are currently no studies on longer courses of treatment.

What happens if the patient relapses after a 14-day trial?

While there is no clear guidance, an open-label trial (The SHORELINE Study) demonstrated that a repeated 14-day administration can restore clinical response.

What are the side effects?

courtesy UNC-Chapel Hill

Common side effects include drowsiness, dizziness, lower energy, diarrhea, and symptoms similar to the common cold. Zuranolone can act like a CNS depressant and can lead to sedation and somnolence.

Are there any boxed warnings?

Because of the CNS depressant effects, zuranolone was given a boxed warning that patients should not drive or operate heavy machinery within 12 hours of taking the medication as it may lead to impairment. Similar to other antidepressants, there is also a warning that zuranolone may increase risk for suicidal thoughts in patients under 24 years old.

Can it be used with other medications?

Yes. In the original trials, women were allowed to remain on medications treating their depressive symptoms (such as SSRIs and SNRIs). According to the FDA, zuranolone can be used alone or with other antidepressants.

Are there any medicines to avoid?

We recommend caution with other medications which may increase sedation, such as benzodiazepines.

Can it be used with birth control?

Yes. In fact, because the outcomes on a fetus are not yet studied, it is recommended that patients be on concurrent birth control during treatment and for a week after cessation. This does not mean that zuranolone is known to cause issues with fetal development, but rather that we do not know at this time.

Can it be used in pregnancy?

As above, the outcomes on fetal development are not known at this time, nor are the effects of zuranolone on labor and delivery. More research will need to be done to understand if there is risk with taking zuranolone during pregnancy. It should be noted that allopregnanolone levels ordinarily reach quite high levels during pregnancy.
 

Long-term side effects?

Long-term side effects are unknown. The study duration of ROBIN and SKYLARK was 45 days.

Breastfeeding?

Use in lactation has not yet been studied. Continued research is needed.

Can it be used in mood changes related to other reproductive changes or diagnoses like premenstrual dysphoric disorder and perimenopause?

The mechanism by which zuranolone is thought to work – that is, during changes in reproductive hormones – is implicated in other reproductive transitions such as premenstrual dysphoric disorder and perimenopause when reproductive hormones are fluctuating, though at lower levels than in pregnancy. Research will be required to assess efficacy and safety; however, the mechanistic reasons is worth pursuing. Additionally, zuranolone has not been studied in postpartum psychosis.

Can zuranolone be used to treat other affective conditions besides postpartum depression? Bipolar disorder?

Zuranolone is currently only approved for the treatment of postpartum depression. It has not received FDA approval for major depression outside of the perinatal period at this time. Whether it may be beneficial for patients with a depressive episode that is part of an underlying bipolar disorder or other psychiatric illness is not yet known.

Anxiety?

Along with depressive symptoms, women who received zuranolone in the clinical trials also had improvements in anxiety symptoms. These findings provide some hope that zuranolone may eventually be beneficial in patients with anxiety.

However, to date zuranolone has not been directly studied as a treatment for anxiety disorders (such as generalized anxiety disorder, panic disorder, etc.), so its efficacy for these illnesses is currently unknown.
 

Insomnia?

In a study of 153 postpartum women, randomized to placebo or zuranolone, scale questions for insomnia were improved in the group receiving zuranolone. This provides some hope that, if zuranolone is appropriate, concurrent polypharmacy with a sleep aid can be avoided. Additionally, future evaluation of use in insomnia outside of PPD may be warranted.

How is it different from brexanolone?

The two are slightly different molecules. Brexanolone is synthetically identical to allopregnanolone and zuranolone has been altered to be active and orally bioavailable.

Brexanolone is a 60-hour infusion that requires hospital admission at an approved health care site. Zuranolone is an oral at-home once-daily dosing treatment for 14 days. Zuranolone does not require enrollment in a risk evaluation and mitigation strategy for risk of excessive sedation and sudden loss of consciousness.
 

When would you consider zuranolone vs. brexanolone vs. other antidepressants?

Zuranolone and brexanolone are rapid-acting antidepressants with a response within 14 days or 60 hours, respectively. Antidepressants such as SSRIs/SNRIs are still available, well studied, and work, although take longer to reach clinical efficacy and are accompanied by potentially troubling side effects (for example, weight gain, sexual dysfunction).

Time to treatment effect should be considered when assessing severity of symptoms and functional impairment of the mother and the overall family unit. Brexanolone requires continuous monitoring which may be beneficial for women who are severely impaired and may benefit from frequent clinical monitoring. Brexanolone does not require a dose reduction with hepatic impairment, however, should be avoided in end-stage renal disease because of the potential accumulation of the solubilizing agent.
 

Where can I find more information?

Many states have maternal mental health consultation lines (examples include NCMATTERS here in North Carolina and MCPAP for Moms in Massachusetts) for clinicians (mental health, primary care, and obstetricians) that can be utilized for questions about prescribing. Postpartum Support International also has a clinician line for those without state services.

We plan to update this entry upon market release and access to new information.

Dr. Riddle and Dr. Nathan are assistant professors in the department of psychiatry at the University of North Carolina at Chapel Hill. Dr. Richardson is a perinatal psychiatry fellow, department of psychiatry, UNC-Chapel Hill. Dr. Rubinow is Distinguished Professor in the department of psychiatry, UNC-Chapel Hill. Dr. Meltzer-Brody is Assad Meymandi Distinguished Professor and Chair, department of psychiatry, UNC-Chapel Hill.

References

Deligiannidis KM et al. J Clin Psychiatry. 2023 Jan 30;84(1):22m14475. doi: 10.4088/JCP.22m14475.

Deligiannidis KM et al. . Obstetrics & Gynecology. 2023 May;141(5S):64S-65S. doi: 10.1097/01.AOG.0000930588.16136.3f.

Deligiannidis KM et al. Am J Psychiatry. 2023 Sep 1;180(9):668-75. doi: 10.1176/appi.ajp.20220785.

Deligiannidis KM et al. JAMA Psychiatry. 2021 Sep 1;78(9):951-59. doi: 10.1001/jamapsychiatry.2021.1559.

FDA Approves First Oral Treatment for Postpartum Depression. 2023 Aug 4. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression

ZURZUVAE – HIGHLIGHTS OF PRESCRIBING INFORMATION. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217369s000lbl.pdf

The Food and Drug Administration approval of zuranolone for postpartum depression in August 2023 has raised many important questions (and opinions) about its future use in clinical practice.

At the UNC-Chapel Hill Center for Women’s Mood Disorders, we treat women and pregnant people throughout hormonal transitions, including pregnancy and the postpartum, and have been part of development, research, and now delivery of both brexanolone and zuranolone. While we are excited about new tools in the arsenal for alleviating maternal mental health, we also want to be clear that our work is far from complete and continued efforts to care for pregnant people and their families are imperative.

courtesy UNC-Chapel Hill

What is zuranolone?

Zuranolone (brand name Zurzuvae) is an oral medication developed by Sage Therapeutics and Biogen. It is a positive allosteric modulator of the GABA_A receptor, the brain’s major inhibitory system. As a positive allosteric modulator, it increases the sensitivity of the GABA_A receptor to GABA.

Zuranolone is very similar to brexanolone, a synthetic form of allopregnanolone, a neurosteroid byproduct of progesterone (see below). However, zuranolone is not an oral form of brexanolone – it was slightly modified to ensure good oral stability and bioavailability. It is metabolized by the hepatic enzyme CYP3A4 and has a half-life of 16-23 hours. Zurzuvae is currently produced in capsule form.
 

What does zuranolone treat?

Zuranolone is the first FDA-approved oral drug for postpartum depression (PPD). It follows brexanolone, an intravenous drug, which was the first FDA-approved medication for PPD. Though these are the first medications with specific approval for PDD, many other treatment options are currently available including therapy, SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs), and other treatments used in major depression.

How does zuranolone work?

courtesy UNC-Chapel Hill

Zuranolone is a neuroactive steroid, which means that it is a steroid that goes into and acts on the brain. Zuranolone binds to different GABA receptor subunits from those bound by other positive modulators, such as benzodiazepines (for example, lorazepam). As a synthetic form of allopregnanolone, a metabolite of progesterone which rises dramatically in pregnancy then drops during labor and delivery, zuranolone was originally thought to mitigate the response to this drop in patients that are vulnerable to it during the postpartum. An alternative proposed mechanism is that the increased GABAergic, inhibitory signaling with zuranolone may act directly to decrease depression irrespective of the exact mechanism by which the depression occurred.

How was it studied?

Zuranolone was studied in women with severe postpartum depression and had to meet criteria for major depressive disorder (MDD) no earlier than the third trimester of pregnancy (about 28 weeks’ gestation) and no later than 4 weeks post partum. Patients were excluded from these studies if they had a history of bipolar disorder, psychotic disorders, attempted suicide, or if they were at risk for suicide.

The two phase 3 clinical trials that led to FDA approval are ROBIN and SKYLARK. These studies measured the efficacy and safety of zuranolone at 30 mg and 50 mg, respectively, and met their end points of rapid improvement in depressive and anxiety symptoms in postpartum depression.
 

When will we be able to start using it?

It is anticipated that zuranolone will become commercially available in early 2024.

Who can prescribe it?

courtesy UNC-Chapel Hill

Those with medical licenses. Most people will likely receive treatment from their obstetric, family medicine, or psychiatric clinicians.

How much will it cost?

The manufacturers have not released this information as of August 2023.

What sort of doses and duration is recommended?

The current FDA recommended dose is 50 mg for 14 days, taken once per evening with a fatty meal. The dose can be reduced to 40 mg if there are central nervous system (CNS) depressant effects, and to 30 mg if the patient has severe hepatic or moderate-severe renal impairment. There are currently no studies on longer courses of treatment.

What happens if the patient relapses after a 14-day trial?

While there is no clear guidance, an open-label trial (The SHORELINE Study) demonstrated that a repeated 14-day administration can restore clinical response.

What are the side effects?

courtesy UNC-Chapel Hill

Common side effects include drowsiness, dizziness, lower energy, diarrhea, and symptoms similar to the common cold. Zuranolone can act like a CNS depressant and can lead to sedation and somnolence.

Are there any boxed warnings?

Because of the CNS depressant effects, zuranolone was given a boxed warning that patients should not drive or operate heavy machinery within 12 hours of taking the medication as it may lead to impairment. Similar to other antidepressants, there is also a warning that zuranolone may increase risk for suicidal thoughts in patients under 24 years old.

Can it be used with other medications?

Yes. In the original trials, women were allowed to remain on medications treating their depressive symptoms (such as SSRIs and SNRIs). According to the FDA, zuranolone can be used alone or with other antidepressants.

Are there any medicines to avoid?

We recommend caution with other medications which may increase sedation, such as benzodiazepines.

Can it be used with birth control?

Yes. In fact, because the outcomes on a fetus are not yet studied, it is recommended that patients be on concurrent birth control during treatment and for a week after cessation. This does not mean that zuranolone is known to cause issues with fetal development, but rather that we do not know at this time.

Can it be used in pregnancy?

As above, the outcomes on fetal development are not known at this time, nor are the effects of zuranolone on labor and delivery. More research will need to be done to understand if there is risk with taking zuranolone during pregnancy. It should be noted that allopregnanolone levels ordinarily reach quite high levels during pregnancy.
 

Long-term side effects?

Long-term side effects are unknown. The study duration of ROBIN and SKYLARK was 45 days.

Breastfeeding?

Use in lactation has not yet been studied. Continued research is needed.

Can it be used in mood changes related to other reproductive changes or diagnoses like premenstrual dysphoric disorder and perimenopause?

The mechanism by which zuranolone is thought to work – that is, during changes in reproductive hormones – is implicated in other reproductive transitions such as premenstrual dysphoric disorder and perimenopause when reproductive hormones are fluctuating, though at lower levels than in pregnancy. Research will be required to assess efficacy and safety; however, the mechanistic reasons is worth pursuing. Additionally, zuranolone has not been studied in postpartum psychosis.

Can zuranolone be used to treat other affective conditions besides postpartum depression? Bipolar disorder?

Zuranolone is currently only approved for the treatment of postpartum depression. It has not received FDA approval for major depression outside of the perinatal period at this time. Whether it may be beneficial for patients with a depressive episode that is part of an underlying bipolar disorder or other psychiatric illness is not yet known.

Anxiety?

Along with depressive symptoms, women who received zuranolone in the clinical trials also had improvements in anxiety symptoms. These findings provide some hope that zuranolone may eventually be beneficial in patients with anxiety.

However, to date zuranolone has not been directly studied as a treatment for anxiety disorders (such as generalized anxiety disorder, panic disorder, etc.), so its efficacy for these illnesses is currently unknown.
 

Insomnia?

In a study of 153 postpartum women, randomized to placebo or zuranolone, scale questions for insomnia were improved in the group receiving zuranolone. This provides some hope that, if zuranolone is appropriate, concurrent polypharmacy with a sleep aid can be avoided. Additionally, future evaluation of use in insomnia outside of PPD may be warranted.

How is it different from brexanolone?

The two are slightly different molecules. Brexanolone is synthetically identical to allopregnanolone and zuranolone has been altered to be active and orally bioavailable.

Brexanolone is a 60-hour infusion that requires hospital admission at an approved health care site. Zuranolone is an oral at-home once-daily dosing treatment for 14 days. Zuranolone does not require enrollment in a risk evaluation and mitigation strategy for risk of excessive sedation and sudden loss of consciousness.
 

When would you consider zuranolone vs. brexanolone vs. other antidepressants?

Zuranolone and brexanolone are rapid-acting antidepressants with a response within 14 days or 60 hours, respectively. Antidepressants such as SSRIs/SNRIs are still available, well studied, and work, although take longer to reach clinical efficacy and are accompanied by potentially troubling side effects (for example, weight gain, sexual dysfunction).

Time to treatment effect should be considered when assessing severity of symptoms and functional impairment of the mother and the overall family unit. Brexanolone requires continuous monitoring which may be beneficial for women who are severely impaired and may benefit from frequent clinical monitoring. Brexanolone does not require a dose reduction with hepatic impairment, however, should be avoided in end-stage renal disease because of the potential accumulation of the solubilizing agent.
 

Where can I find more information?

Many states have maternal mental health consultation lines (examples include NCMATTERS here in North Carolina and MCPAP for Moms in Massachusetts) for clinicians (mental health, primary care, and obstetricians) that can be utilized for questions about prescribing. Postpartum Support International also has a clinician line for those without state services.

We plan to update this entry upon market release and access to new information.

Dr. Riddle and Dr. Nathan are assistant professors in the department of psychiatry at the University of North Carolina at Chapel Hill. Dr. Richardson is a perinatal psychiatry fellow, department of psychiatry, UNC-Chapel Hill. Dr. Rubinow is Distinguished Professor in the department of psychiatry, UNC-Chapel Hill. Dr. Meltzer-Brody is Assad Meymandi Distinguished Professor and Chair, department of psychiatry, UNC-Chapel Hill.

References

Deligiannidis KM et al. J Clin Psychiatry. 2023 Jan 30;84(1):22m14475. doi: 10.4088/JCP.22m14475.

Deligiannidis KM et al. . Obstetrics & Gynecology. 2023 May;141(5S):64S-65S. doi: 10.1097/01.AOG.0000930588.16136.3f.

Deligiannidis KM et al. Am J Psychiatry. 2023 Sep 1;180(9):668-75. doi: 10.1176/appi.ajp.20220785.

Deligiannidis KM et al. JAMA Psychiatry. 2021 Sep 1;78(9):951-59. doi: 10.1001/jamapsychiatry.2021.1559.

FDA Approves First Oral Treatment for Postpartum Depression. 2023 Aug 4. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression

ZURZUVAE – HIGHLIGHTS OF PRESCRIBING INFORMATION. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217369s000lbl.pdf

BARCELONA – Running therapy rivals antidepressant medication for the treatment of depression and anxiety, results of a new study show. However, running provides greater physical health benefits while adherence is greater with drug treatment.

“Both interventions helped with the depression to around the same extent,” study presenter Brenda W.J.H. Penninx, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam said in a release.

However, medication “generally had worse impact on body weight, heart rate variability, and blood pressure, whereas running therapy led to improved effect on general fitness and heart rate,” Dr. Penninx added.

The findings were presented at the annual congress of the European College of Neuropsychopharmacology and recently published in the Journal of Affective Disorders.
 

Research gap

Previous research suggests exercise interventions can have a therapeutic effect equivalent to antidepressants, but their impact on physical health has been “poorly examined in a psychiatric population, the investigators note.

The authors note that depressive and anxiety disorders “cause immense suffering by compromising both mental and physical health,” and the need for effective treatments is “pressing.”

Although antidepressant medication is considered a “standard first-line treatment” alongside psychotherapy, the drugs are “not effective for all and [are] often associated with side effects.”

The Mood Treatment with Antidepressant or Running (MOTAR) study was a partially randomized pragmatic trial in adults with depression and/or anxiety disorder, as determined using the DSM-IV algorithms with the Composite International Diagnostic Interview (CIDI).

The 16-week intervention study included 141 patients with depression and/or anxiety. The mean age was 38.2 years and 58% were women. Participants were offered a choice of treatment: 16 weeks of treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram (Lexapro) or a 16-week group-based running therapy.

Patients without a strong preference for treatment allocation were randomly assigned to either antidepressant medication or running therapy, while those unwilling to be randomized were allocated to their preferred intervention.

A total of 22 patients were randomly assigned to receive antidepressant treatment and 13 to running therapy. A total of 36 participants chose antidepressant treatment, while 83 chose the running therapy.

Running therapy involved 16 weeks of supervised 45-minute outdoor running sessions to a target of two to three sessions per week, in line with U.S. Centers for Disease Control and Prevention/American College of Sports Medicine recommendations.
 

Physical health benefits

Treatment adherence in the antidepressant group, defined as still using treatment at the posttreatment assessment, was 82.2% vs. 52.1% among running therapy participants, where adherence was specified as completing more than 22 sessions.

Remission was defined as no longer meeting the criteria of a current depressive or anxiety disorder via CIDI at week 16.

On intention-to-treat analysis, this requirement was met by 44.8% of patients taking antidepressants and 43.3% of those in the running therapy group (P = .88).

However, running therapy patients showed significant improvements in weight (P = .001), waist circumference (P = .011), systolic and diastolic blood pressure (P = .011 and P = .002, respectively), heart rate (P = .033), and heart rate variability (P = .006).

The investigators note the more favorable physical health changes in the running therapy group were attributable to “larger improvements in the running therapy group but also due to larger deterioration in the antidepressant group.”

Antidepressants are generally safe and effective and work for most people, said Dr. Penninx. She also noted that untreated depression leads to worse outcomes, so “antidepressants are generally a good choice.”

Nevertheless, she said, “we need to extend our treatment arsenal as not all patients respond to antidepressants or are willing to take them.”

The study’s results, she added, suggest that “implementing exercise therapy is something we should take much more seriously, as it could be a good, and maybe even better, choice for some of our patients.”

Francesca Cirulli, PhD, senior researcher and group leader at the National Institute of Health, Rome, said in an interview that the study is notable because it is one of the first to prospectively measure the effects of antidepressants and running on physical health.

Dr. Cirulli suggested that running therapy could be tried ahead of treatment with antidepressants if patients prefer physical exercise and can adhere to it. However, she said, the findings also suggest that an increase in physical activity should accompany treatment with antidepressant medications.

Overall, Dr. Cirulli said “the message should not be that everyone can be helped by running and antidepressants are bad,” but rather “these are both helpful, but not excellent, interventions against depression.”
 

‘Important limitations’

In a comment, Eduard Vieta, MD, PhD, chair of the department of psychiatry and psychology at the University of Barcelona Hospital Clinic, noted the study has “very important limitations.”

Among the limitations: the inclusion of nonrandomized patients who received the treatment of their choice, causing obvious bias and the “lack of binding and power issues” over the number of patients enrolled. 

Dr. Vieta also said that the results “seem obvious, because it is known that exercise improves physical health.”

The trial therefore shows, “if you can find people who are able to do exercise while depressed and adhere to it, those would benefit from that practice,” he noted.

Also commenting on the research, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said the results are confirmatory and “again show physical health can influence mental health.”

However, Dr. Ruhe underlined, while it is “common practice” to allow patients to follow their treatment preference and is “understandable from a pragmatic point of view,” the group comparison may be “biased,” compared with a “truly randomized study.”

“For example, patients in the antidepressant group were more depressed, which might be associated with less chance of persisting engagement in the exercises,” he said. “So, we have to be careful not to overinterpret the comparisons between groups, which the authors acknowledge properly.”

Turning to the difference in adherence between the two interventions, Dr. Ruhe said the results show adopting, and adhering to, a lifestyle habit is more difficult than taking a pill.

“This is not exclusively found in psychiatry, indicating that we also have to focus on how to improve compliance to healthy behavior. This could have tremendous impact on health care more generally, but also on psychiatric diseases,” Dr. Ruhe said.

The MOTAR study was funded by a NWO-VICI grant. Funding for the inflammatory markers was provided by ZonMw: The Netherlands Organization for Health Research and Development. The study authors and clinicians interviewed for this story declared no relevant financial relationships.

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

BARCELONA – Running therapy rivals antidepressant medication for the treatment of depression and anxiety, results of a new study show. However, running provides greater physical health benefits while adherence is greater with drug treatment.

“Both interventions helped with the depression to around the same extent,” study presenter Brenda W.J.H. Penninx, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam said in a release.

However, medication “generally had worse impact on body weight, heart rate variability, and blood pressure, whereas running therapy led to improved effect on general fitness and heart rate,” Dr. Penninx added.

The findings were presented at the annual congress of the European College of Neuropsychopharmacology and recently published in the Journal of Affective Disorders.
 

Research gap

Previous research suggests exercise interventions can have a therapeutic effect equivalent to antidepressants, but their impact on physical health has been “poorly examined in a psychiatric population, the investigators note.

The authors note that depressive and anxiety disorders “cause immense suffering by compromising both mental and physical health,” and the need for effective treatments is “pressing.”

Although antidepressant medication is considered a “standard first-line treatment” alongside psychotherapy, the drugs are “not effective for all and [are] often associated with side effects.”

The Mood Treatment with Antidepressant or Running (MOTAR) study was a partially randomized pragmatic trial in adults with depression and/or anxiety disorder, as determined using the DSM-IV algorithms with the Composite International Diagnostic Interview (CIDI).

The 16-week intervention study included 141 patients with depression and/or anxiety. The mean age was 38.2 years and 58% were women. Participants were offered a choice of treatment: 16 weeks of treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram (Lexapro) or a 16-week group-based running therapy.

Patients without a strong preference for treatment allocation were randomly assigned to either antidepressant medication or running therapy, while those unwilling to be randomized were allocated to their preferred intervention.

A total of 22 patients were randomly assigned to receive antidepressant treatment and 13 to running therapy. A total of 36 participants chose antidepressant treatment, while 83 chose the running therapy.

Running therapy involved 16 weeks of supervised 45-minute outdoor running sessions to a target of two to three sessions per week, in line with U.S. Centers for Disease Control and Prevention/American College of Sports Medicine recommendations.
 

Physical health benefits

Treatment adherence in the antidepressant group, defined as still using treatment at the posttreatment assessment, was 82.2% vs. 52.1% among running therapy participants, where adherence was specified as completing more than 22 sessions.

Remission was defined as no longer meeting the criteria of a current depressive or anxiety disorder via CIDI at week 16.

On intention-to-treat analysis, this requirement was met by 44.8% of patients taking antidepressants and 43.3% of those in the running therapy group (P = .88).

However, running therapy patients showed significant improvements in weight (P = .001), waist circumference (P = .011), systolic and diastolic blood pressure (P = .011 and P = .002, respectively), heart rate (P = .033), and heart rate variability (P = .006).

The investigators note the more favorable physical health changes in the running therapy group were attributable to “larger improvements in the running therapy group but also due to larger deterioration in the antidepressant group.”

Antidepressants are generally safe and effective and work for most people, said Dr. Penninx. She also noted that untreated depression leads to worse outcomes, so “antidepressants are generally a good choice.”

Nevertheless, she said, “we need to extend our treatment arsenal as not all patients respond to antidepressants or are willing to take them.”

The study’s results, she added, suggest that “implementing exercise therapy is something we should take much more seriously, as it could be a good, and maybe even better, choice for some of our patients.”

Francesca Cirulli, PhD, senior researcher and group leader at the National Institute of Health, Rome, said in an interview that the study is notable because it is one of the first to prospectively measure the effects of antidepressants and running on physical health.

Dr. Cirulli suggested that running therapy could be tried ahead of treatment with antidepressants if patients prefer physical exercise and can adhere to it. However, she said, the findings also suggest that an increase in physical activity should accompany treatment with antidepressant medications.

Overall, Dr. Cirulli said “the message should not be that everyone can be helped by running and antidepressants are bad,” but rather “these are both helpful, but not excellent, interventions against depression.”
 

‘Important limitations’

In a comment, Eduard Vieta, MD, PhD, chair of the department of psychiatry and psychology at the University of Barcelona Hospital Clinic, noted the study has “very important limitations.”

Among the limitations: the inclusion of nonrandomized patients who received the treatment of their choice, causing obvious bias and the “lack of binding and power issues” over the number of patients enrolled. 

Dr. Vieta also said that the results “seem obvious, because it is known that exercise improves physical health.”

The trial therefore shows, “if you can find people who are able to do exercise while depressed and adhere to it, those would benefit from that practice,” he noted.

Also commenting on the research, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said the results are confirmatory and “again show physical health can influence mental health.”

However, Dr. Ruhe underlined, while it is “common practice” to allow patients to follow their treatment preference and is “understandable from a pragmatic point of view,” the group comparison may be “biased,” compared with a “truly randomized study.”

“For example, patients in the antidepressant group were more depressed, which might be associated with less chance of persisting engagement in the exercises,” he said. “So, we have to be careful not to overinterpret the comparisons between groups, which the authors acknowledge properly.”

Turning to the difference in adherence between the two interventions, Dr. Ruhe said the results show adopting, and adhering to, a lifestyle habit is more difficult than taking a pill.

“This is not exclusively found in psychiatry, indicating that we also have to focus on how to improve compliance to healthy behavior. This could have tremendous impact on health care more generally, but also on psychiatric diseases,” Dr. Ruhe said.

The MOTAR study was funded by a NWO-VICI grant. Funding for the inflammatory markers was provided by ZonMw: The Netherlands Organization for Health Research and Development. The study authors and clinicians interviewed for this story declared no relevant financial relationships.

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

BARCELONA – Running therapy rivals antidepressant medication for the treatment of depression and anxiety, results of a new study show. However, running provides greater physical health benefits while adherence is greater with drug treatment.

“Both interventions helped with the depression to around the same extent,” study presenter Brenda W.J.H. Penninx, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam said in a release.

However, medication “generally had worse impact on body weight, heart rate variability, and blood pressure, whereas running therapy led to improved effect on general fitness and heart rate,” Dr. Penninx added.

The findings were presented at the annual congress of the European College of Neuropsychopharmacology and recently published in the Journal of Affective Disorders.
 

Research gap

Previous research suggests exercise interventions can have a therapeutic effect equivalent to antidepressants, but their impact on physical health has been “poorly examined in a psychiatric population, the investigators note.

The authors note that depressive and anxiety disorders “cause immense suffering by compromising both mental and physical health,” and the need for effective treatments is “pressing.”

Although antidepressant medication is considered a “standard first-line treatment” alongside psychotherapy, the drugs are “not effective for all and [are] often associated with side effects.”

The Mood Treatment with Antidepressant or Running (MOTAR) study was a partially randomized pragmatic trial in adults with depression and/or anxiety disorder, as determined using the DSM-IV algorithms with the Composite International Diagnostic Interview (CIDI).

The 16-week intervention study included 141 patients with depression and/or anxiety. The mean age was 38.2 years and 58% were women. Participants were offered a choice of treatment: 16 weeks of treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram (Lexapro) or a 16-week group-based running therapy.

Patients without a strong preference for treatment allocation were randomly assigned to either antidepressant medication or running therapy, while those unwilling to be randomized were allocated to their preferred intervention.

A total of 22 patients were randomly assigned to receive antidepressant treatment and 13 to running therapy. A total of 36 participants chose antidepressant treatment, while 83 chose the running therapy.

Running therapy involved 16 weeks of supervised 45-minute outdoor running sessions to a target of two to three sessions per week, in line with U.S. Centers for Disease Control and Prevention/American College of Sports Medicine recommendations.
 

Physical health benefits

Treatment adherence in the antidepressant group, defined as still using treatment at the posttreatment assessment, was 82.2% vs. 52.1% among running therapy participants, where adherence was specified as completing more than 22 sessions.

Remission was defined as no longer meeting the criteria of a current depressive or anxiety disorder via CIDI at week 16.

On intention-to-treat analysis, this requirement was met by 44.8% of patients taking antidepressants and 43.3% of those in the running therapy group (P = .88).

However, running therapy patients showed significant improvements in weight (P = .001), waist circumference (P = .011), systolic and diastolic blood pressure (P = .011 and P = .002, respectively), heart rate (P = .033), and heart rate variability (P = .006).

The investigators note the more favorable physical health changes in the running therapy group were attributable to “larger improvements in the running therapy group but also due to larger deterioration in the antidepressant group.”

Antidepressants are generally safe and effective and work for most people, said Dr. Penninx. She also noted that untreated depression leads to worse outcomes, so “antidepressants are generally a good choice.”

Nevertheless, she said, “we need to extend our treatment arsenal as not all patients respond to antidepressants or are willing to take them.”

The study’s results, she added, suggest that “implementing exercise therapy is something we should take much more seriously, as it could be a good, and maybe even better, choice for some of our patients.”

Francesca Cirulli, PhD, senior researcher and group leader at the National Institute of Health, Rome, said in an interview that the study is notable because it is one of the first to prospectively measure the effects of antidepressants and running on physical health.

Dr. Cirulli suggested that running therapy could be tried ahead of treatment with antidepressants if patients prefer physical exercise and can adhere to it. However, she said, the findings also suggest that an increase in physical activity should accompany treatment with antidepressant medications.

Overall, Dr. Cirulli said “the message should not be that everyone can be helped by running and antidepressants are bad,” but rather “these are both helpful, but not excellent, interventions against depression.”
 

‘Important limitations’

In a comment, Eduard Vieta, MD, PhD, chair of the department of psychiatry and psychology at the University of Barcelona Hospital Clinic, noted the study has “very important limitations.”

Among the limitations: the inclusion of nonrandomized patients who received the treatment of their choice, causing obvious bias and the “lack of binding and power issues” over the number of patients enrolled. 

Dr. Vieta also said that the results “seem obvious, because it is known that exercise improves physical health.”

The trial therefore shows, “if you can find people who are able to do exercise while depressed and adhere to it, those would benefit from that practice,” he noted.

Also commenting on the research, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said the results are confirmatory and “again show physical health can influence mental health.”

However, Dr. Ruhe underlined, while it is “common practice” to allow patients to follow their treatment preference and is “understandable from a pragmatic point of view,” the group comparison may be “biased,” compared with a “truly randomized study.”

“For example, patients in the antidepressant group were more depressed, which might be associated with less chance of persisting engagement in the exercises,” he said. “So, we have to be careful not to overinterpret the comparisons between groups, which the authors acknowledge properly.”

Turning to the difference in adherence between the two interventions, Dr. Ruhe said the results show adopting, and adhering to, a lifestyle habit is more difficult than taking a pill.

“This is not exclusively found in psychiatry, indicating that we also have to focus on how to improve compliance to healthy behavior. This could have tremendous impact on health care more generally, but also on psychiatric diseases,” Dr. Ruhe said.

The MOTAR study was funded by a NWO-VICI grant. Funding for the inflammatory markers was provided by ZonMw: The Netherlands Organization for Health Research and Development. The study authors and clinicians interviewed for this story declared no relevant financial relationships.

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

TOPLINE:

The risk for dementia before age 90 years was significantly higher among people with a history of proton pump inhibitor (PPI) use and was highest among those diagnosed before age 70 years regardless of when PPI treatment was initiated.

METHODOLOGY:

• Researchers used four Danish registries to collect data on dementia diagnoses and prescription PPI use among 1,983,785 individuals aged 60-75 years between 2000 and 2018.
• The median follow-up time was 10.3 years.

TAKEAWAY:

• There were 99,384 (5.0%) cases of all-cause dementia during follow-up, with a median age of diagnosis of 79 years.
• Twenty-one-point-two percent of dementia cases and 18.9% of controls reported a history of PPI use.
• Risk for all-cause dementia before age 90 years was 36% higher with PPI use in people aged 60-69 years at baseline (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.29-1.43) and 6% higher in those who were age 80-89 years at baseline (aIRR, 1.06; 95% CI, 1.03-1.09).
• Investigators found significant increased dementia risk before age 90 years with PPI use regardless of when PPI treatment began and found no link between PPI use and dementia diagnoses after age 90 years.

IN PRACTICE:

“The association between PPI use and dementia was unambiguously largest among the youngest cases of dementia, potentially suggestive of a critical window of exposure where midlife PPI use affects dementia risk to a larger degree compared to late-life use,” the authors wrote. “Further, the finding could signify a declining impact of individual risk factors with advancing age owing to lengthy ongoing neuropathological processes.”

SOURCE:

Lead author of the study was Nelsan Pourhadi, MD, Danish Dementia Research Centre, department of neurology, Copenhagen University Hospital–Rigshospitalet. It was published online in Alzheimer’s and Dementia.

LIMITATIONS:

The study did not include data on PPI prescriptions before 1995, over-the-counter PPI use, and in-hospital intravenous use of PPI during the study period.

DISCLOSURES:

The study was funded by the Danish Ministry of Health. The authors reported no relevant conflicts.

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

TOPLINE:

The risk for dementia before age 90 years was significantly higher among people with a history of proton pump inhibitor (PPI) use and was highest among those diagnosed before age 70 years regardless of when PPI treatment was initiated.

METHODOLOGY:

• Researchers used four Danish registries to collect data on dementia diagnoses and prescription PPI use among 1,983,785 individuals aged 60-75 years between 2000 and 2018.
• The median follow-up time was 10.3 years.

TAKEAWAY:

• There were 99,384 (5.0%) cases of all-cause dementia during follow-up, with a median age of diagnosis of 79 years.
• Twenty-one-point-two percent of dementia cases and 18.9% of controls reported a history of PPI use.
• Risk for all-cause dementia before age 90 years was 36% higher with PPI use in people aged 60-69 years at baseline (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.29-1.43) and 6% higher in those who were age 80-89 years at baseline (aIRR, 1.06; 95% CI, 1.03-1.09).
• Investigators found significant increased dementia risk before age 90 years with PPI use regardless of when PPI treatment began and found no link between PPI use and dementia diagnoses after age 90 years.

IN PRACTICE:

“The association between PPI use and dementia was unambiguously largest among the youngest cases of dementia, potentially suggestive of a critical window of exposure where midlife PPI use affects dementia risk to a larger degree compared to late-life use,” the authors wrote. “Further, the finding could signify a declining impact of individual risk factors with advancing age owing to lengthy ongoing neuropathological processes.”

SOURCE:

Lead author of the study was Nelsan Pourhadi, MD, Danish Dementia Research Centre, department of neurology, Copenhagen University Hospital–Rigshospitalet. It was published online in Alzheimer’s and Dementia.

LIMITATIONS:

The study did not include data on PPI prescriptions before 1995, over-the-counter PPI use, and in-hospital intravenous use of PPI during the study period.

DISCLOSURES:

The study was funded by the Danish Ministry of Health. The authors reported no relevant conflicts.

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

TOPLINE:

The risk for dementia before age 90 years was significantly higher among people with a history of proton pump inhibitor (PPI) use and was highest among those diagnosed before age 70 years regardless of when PPI treatment was initiated.

METHODOLOGY:

• Researchers used four Danish registries to collect data on dementia diagnoses and prescription PPI use among 1,983,785 individuals aged 60-75 years between 2000 and 2018.
• The median follow-up time was 10.3 years.

TAKEAWAY:

• There were 99,384 (5.0%) cases of all-cause dementia during follow-up, with a median age of diagnosis of 79 years.
• Twenty-one-point-two percent of dementia cases and 18.9% of controls reported a history of PPI use.
• Risk for all-cause dementia before age 90 years was 36% higher with PPI use in people aged 60-69 years at baseline (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.29-1.43) and 6% higher in those who were age 80-89 years at baseline (aIRR, 1.06; 95% CI, 1.03-1.09).
• Investigators found significant increased dementia risk before age 90 years with PPI use regardless of when PPI treatment began and found no link between PPI use and dementia diagnoses after age 90 years.

IN PRACTICE:

“The association between PPI use and dementia was unambiguously largest among the youngest cases of dementia, potentially suggestive of a critical window of exposure where midlife PPI use affects dementia risk to a larger degree compared to late-life use,” the authors wrote. “Further, the finding could signify a declining impact of individual risk factors with advancing age owing to lengthy ongoing neuropathological processes.”

SOURCE:

Lead author of the study was Nelsan Pourhadi, MD, Danish Dementia Research Centre, department of neurology, Copenhagen University Hospital–Rigshospitalet. It was published online in Alzheimer’s and Dementia.

LIMITATIONS:

The study did not include data on PPI prescriptions before 1995, over-the-counter PPI use, and in-hospital intravenous use of PPI during the study period.

DISCLOSURES:

The study was funded by the Danish Ministry of Health. The authors reported no relevant conflicts.

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

TOPLINE:

While the prevalence of attention-deficit/hyperactivity disorder in U.S. children increased from the late 1990s to 2016, more recent data show rates remained steady at around 10% from 2017 to 2022.

METHODOLOGY:

• Based on prior data, the prevalence of ADHD in children rose from 6.1% in 1997-1998 to 10.2% in 2015-2016, with a 42.0% increase from 2003 to 2011. The new report provides updated prevalence data for 2017-2022.
• The cross-sectional analysis used data from the National Health Interview Survey (NHIS) from 2017 to 2022 for more than 37,609 U.S. children and adolescents 4-17 years old (52% male, 53% non-Hispanic White, 24% Hispanic, 11% non-Hispanic Black, and 12% non-Hispanic other race).
• Information on health care provider–diagnosed ADHD was reported by a parent or guardian.

TAKEAWAY:

• A total of 4,098 children and adolescents (10.9%) were reported to have an ADHD diagnosis during the study period.
• The weighted prevalence of ADHD ranged from 10.08% to 10.47% from 2017 to 2022, which is similar to the prevalence in 2015-2016 (10.20%).
• There was no significant change on an annual basis or in all subgroups evaluated. Notably, the estimated prevalence of ADHD among U.S. children and adolescents was higher than worldwide estimates (5.3%) in earlier years (1978-2005).
• The prevalence of ADHD in U.S. children differed significantly by age, sex, race/ethnicity, and family income, in line with previous findings, with higher rates in those 12-17 years (vs. 4-11 years), males, non-Hispanic populations, and those with higher family income.

IN PRACTICE:

The estimated ADHD prevalence remains “high” and “further investigation is warranted to assess potentially modifiable risk factors and provide adequate resources for treatment of individuals with ADHD in the future,” the authors write.

SOURCE:

The study, with first author Yanmei Li, Guangdong Pharmaceutical University, Guangzhou, China, was published online in JAMA Network Open.

LIMITATIONS:

Information on ADHD relied on parent-reported diagnosis, which may lead to misreporting and recall bias. The NHIS underwent a major redesign in 2019, which may affect comparability with prior years, and the COVID-19 pandemic affected collection in 2020.

DISCLOSURES:

The study had no specific funding. The authors reported no relevant financial relationships.

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

TOPLINE:

While the prevalence of attention-deficit/hyperactivity disorder in U.S. children increased from the late 1990s to 2016, more recent data show rates remained steady at around 10% from 2017 to 2022.

METHODOLOGY:

• Based on prior data, the prevalence of ADHD in children rose from 6.1% in 1997-1998 to 10.2% in 2015-2016, with a 42.0% increase from 2003 to 2011. The new report provides updated prevalence data for 2017-2022.
• The cross-sectional analysis used data from the National Health Interview Survey (NHIS) from 2017 to 2022 for more than 37,609 U.S. children and adolescents 4-17 years old (52% male, 53% non-Hispanic White, 24% Hispanic, 11% non-Hispanic Black, and 12% non-Hispanic other race).
• Information on health care provider–diagnosed ADHD was reported by a parent or guardian.

TAKEAWAY:

• A total of 4,098 children and adolescents (10.9%) were reported to have an ADHD diagnosis during the study period.
• The weighted prevalence of ADHD ranged from 10.08% to 10.47% from 2017 to 2022, which is similar to the prevalence in 2015-2016 (10.20%).
• There was no significant change on an annual basis or in all subgroups evaluated. Notably, the estimated prevalence of ADHD among U.S. children and adolescents was higher than worldwide estimates (5.3%) in earlier years (1978-2005).
• The prevalence of ADHD in U.S. children differed significantly by age, sex, race/ethnicity, and family income, in line with previous findings, with higher rates in those 12-17 years (vs. 4-11 years), males, non-Hispanic populations, and those with higher family income.

IN PRACTICE:

The estimated ADHD prevalence remains “high” and “further investigation is warranted to assess potentially modifiable risk factors and provide adequate resources for treatment of individuals with ADHD in the future,” the authors write.

SOURCE:

The study, with first author Yanmei Li, Guangdong Pharmaceutical University, Guangzhou, China, was published online in JAMA Network Open.

LIMITATIONS:

Information on ADHD relied on parent-reported diagnosis, which may lead to misreporting and recall bias. The NHIS underwent a major redesign in 2019, which may affect comparability with prior years, and the COVID-19 pandemic affected collection in 2020.

DISCLOSURES:

The study had no specific funding. The authors reported no relevant financial relationships.

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

TOPLINE:

While the prevalence of attention-deficit/hyperactivity disorder in U.S. children increased from the late 1990s to 2016, more recent data show rates remained steady at around 10% from 2017 to 2022.

METHODOLOGY:

• Based on prior data, the prevalence of ADHD in children rose from 6.1% in 1997-1998 to 10.2% in 2015-2016, with a 42.0% increase from 2003 to 2011. The new report provides updated prevalence data for 2017-2022.
• The cross-sectional analysis used data from the National Health Interview Survey (NHIS) from 2017 to 2022 for more than 37,609 U.S. children and adolescents 4-17 years old (52% male, 53% non-Hispanic White, 24% Hispanic, 11% non-Hispanic Black, and 12% non-Hispanic other race).
• Information on health care provider–diagnosed ADHD was reported by a parent or guardian.

TAKEAWAY:

• A total of 4,098 children and adolescents (10.9%) were reported to have an ADHD diagnosis during the study period.
• The weighted prevalence of ADHD ranged from 10.08% to 10.47% from 2017 to 2022, which is similar to the prevalence in 2015-2016 (10.20%).
• There was no significant change on an annual basis or in all subgroups evaluated. Notably, the estimated prevalence of ADHD among U.S. children and adolescents was higher than worldwide estimates (5.3%) in earlier years (1978-2005).
• The prevalence of ADHD in U.S. children differed significantly by age, sex, race/ethnicity, and family income, in line with previous findings, with higher rates in those 12-17 years (vs. 4-11 years), males, non-Hispanic populations, and those with higher family income.

IN PRACTICE:

The estimated ADHD prevalence remains “high” and “further investigation is warranted to assess potentially modifiable risk factors and provide adequate resources for treatment of individuals with ADHD in the future,” the authors write.

SOURCE:

The study, with first author Yanmei Li, Guangdong Pharmaceutical University, Guangzhou, China, was published online in JAMA Network Open.

LIMITATIONS:

Information on ADHD relied on parent-reported diagnosis, which may lead to misreporting and recall bias. The NHIS underwent a major redesign in 2019, which may affect comparability with prior years, and the COVID-19 pandemic affected collection in 2020.

DISCLOSURES:

The study had no specific funding. The authors reported no relevant financial relationships.

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