Mental Health

Children in foster care are far more likely to be prescribed psychotropic medication, compared with children who are not in foster care, an analysis of Medicaid claims data shows.

Different rates of mental health disorders in these groups do not fully explain the “alarming trend,” which persists across psychotropic medication classes, said study author Rachael J. Keefe, MD, MPH.

Misdiagnosis, overprescribing, and frequent transitions to new doctors may contribute to this phenomenon, doctors suggested.

Dr. Keefe, with Baylor College of Medicine, Houston, and colleagues analyzed Medicaid claims data from two managed care organizations to compare the prevalence of psychotropic medication use among children in foster care versus children insured by Medicaid but not in foster care. The study focused on claims from the same region in southeast Texas between July 2014 and June 2016.

The researchers included 388,914 children in Medicaid and 8,426 children in foster care in their analysis. They excluded children with a seizure or epilepsy diagnosis.

About 8% of children not in foster care received psychotropic medications, compared with 35% of those in foster care.

Children in foster care were 27 times more likely to receive antipsychotic medication (21.2% of children in foster care vs. 0.8% of children not in foster care) and twice as likely to receive antianxiety medication (6% vs. 3%).

For children in foster care, the rate of alpha-agonist use was 15 times higher, the rate of antidepressant use was 13 times higher, the rate of mood stabilizer use was 26 times higher, and the rate of stimulant use was 6 times higher.

The researchers have a limited understanding of the full context in which these medications were prescribed, and psychotropic medications have a role in the treatment of children in foster care, Dr. Keefe acknowledged.

“We have to be careful not to have a knee-jerk reaction” and inappropriately withhold medication from children in foster care, she said in an interview.

But overprescribing has been a concern. Dr. Keefe leads a foster care clinical service at Texas Children’s Hospital in Houston.

“The overprescribing of psychotropic medications to children in foster care is something I feel every day in my clinical practice, but it’s different to see it on paper,” Dr. Keefe said in a news release highlighting the research, which she presented on Oct. 11 at the annual meeting of the American Academy of Pediatrics. “It’s especially shocking to see these dramatic differences in children of preschool and elementary age.”

Misdiagnosis can be a common problem among children in foster care, said Danielle Shaw, MD, a child and adolescent psychiatrist in Camarillo, Calif., during a question-and-answer period following the presentation.

“I see incorrect diagnoses very frequently,” Dr. Shaw said. “The history of trauma or [adverse childhood experiences] is not even included in the assessment. Mood lability from trauma is misdiagnosed as bipolar disorder, despite not meeting criteria. This will justify the use of antipsychotic medication and mood stabilizers. Flashbacks can be mistaken for a psychotic disorder, which again justifies the use of antipsychotic medication.”

Children in foster care have experienced numerous traumatic experiences that affect brain development and the hypothalamic-pituitary-adrenal axis, Dr. Keefe said.

“Although from previous research we know that children in foster care are more likely to carry mental health and developmental disorder diagnoses, this does not account for the significant difference in prescribing practices in this population,” Dr. Keefe said in an interview.

Although the study focused on data in Texas, Dr. Keefe expects similar patterns exist in other regions, based on anecdotal reports. “I work with foster care pediatricians across the country, and many have seen similar concerning trends within their own clinical practices,” she said.

The use of appropriate therapies, minimizing transitions between providers, improved record keeping, the development of deprescribing algorithms, and placement of children in foster care in long-term homes as early as possible are measures that potentially could reduce inappropriate psychotropic prescribing for children in foster care, Dr. Keefe suggested.

The research was funded by a Texas Medical Center Health Policy Research Grant. The study authors and Dr. Shaw had no relevant financial disclosures.

jremaly@mdedge.com

Children in foster care are far more likely to be prescribed psychotropic medication, compared with children who are not in foster care, an analysis of Medicaid claims data shows.

Different rates of mental health disorders in these groups do not fully explain the “alarming trend,” which persists across psychotropic medication classes, said study author Rachael J. Keefe, MD, MPH.

Misdiagnosis, overprescribing, and frequent transitions to new doctors may contribute to this phenomenon, doctors suggested.

Dr. Keefe, with Baylor College of Medicine, Houston, and colleagues analyzed Medicaid claims data from two managed care organizations to compare the prevalence of psychotropic medication use among children in foster care versus children insured by Medicaid but not in foster care. The study focused on claims from the same region in southeast Texas between July 2014 and June 2016.

The researchers included 388,914 children in Medicaid and 8,426 children in foster care in their analysis. They excluded children with a seizure or epilepsy diagnosis.

About 8% of children not in foster care received psychotropic medications, compared with 35% of those in foster care.

Children in foster care were 27 times more likely to receive antipsychotic medication (21.2% of children in foster care vs. 0.8% of children not in foster care) and twice as likely to receive antianxiety medication (6% vs. 3%).

For children in foster care, the rate of alpha-agonist use was 15 times higher, the rate of antidepressant use was 13 times higher, the rate of mood stabilizer use was 26 times higher, and the rate of stimulant use was 6 times higher.

The researchers have a limited understanding of the full context in which these medications were prescribed, and psychotropic medications have a role in the treatment of children in foster care, Dr. Keefe acknowledged.

“We have to be careful not to have a knee-jerk reaction” and inappropriately withhold medication from children in foster care, she said in an interview.

But overprescribing has been a concern. Dr. Keefe leads a foster care clinical service at Texas Children’s Hospital in Houston.

“The overprescribing of psychotropic medications to children in foster care is something I feel every day in my clinical practice, but it’s different to see it on paper,” Dr. Keefe said in a news release highlighting the research, which she presented on Oct. 11 at the annual meeting of the American Academy of Pediatrics. “It’s especially shocking to see these dramatic differences in children of preschool and elementary age.”

Misdiagnosis can be a common problem among children in foster care, said Danielle Shaw, MD, a child and adolescent psychiatrist in Camarillo, Calif., during a question-and-answer period following the presentation.

“I see incorrect diagnoses very frequently,” Dr. Shaw said. “The history of trauma or [adverse childhood experiences] is not even included in the assessment. Mood lability from trauma is misdiagnosed as bipolar disorder, despite not meeting criteria. This will justify the use of antipsychotic medication and mood stabilizers. Flashbacks can be mistaken for a psychotic disorder, which again justifies the use of antipsychotic medication.”

Children in foster care have experienced numerous traumatic experiences that affect brain development and the hypothalamic-pituitary-adrenal axis, Dr. Keefe said.

“Although from previous research we know that children in foster care are more likely to carry mental health and developmental disorder diagnoses, this does not account for the significant difference in prescribing practices in this population,” Dr. Keefe said in an interview.

Although the study focused on data in Texas, Dr. Keefe expects similar patterns exist in other regions, based on anecdotal reports. “I work with foster care pediatricians across the country, and many have seen similar concerning trends within their own clinical practices,” she said.

The use of appropriate therapies, minimizing transitions between providers, improved record keeping, the development of deprescribing algorithms, and placement of children in foster care in long-term homes as early as possible are measures that potentially could reduce inappropriate psychotropic prescribing for children in foster care, Dr. Keefe suggested.

The research was funded by a Texas Medical Center Health Policy Research Grant. The study authors and Dr. Shaw had no relevant financial disclosures.

jremaly@mdedge.com

Children in foster care are far more likely to be prescribed psychotropic medication, compared with children who are not in foster care, an analysis of Medicaid claims data shows.

Different rates of mental health disorders in these groups do not fully explain the “alarming trend,” which persists across psychotropic medication classes, said study author Rachael J. Keefe, MD, MPH.

Misdiagnosis, overprescribing, and frequent transitions to new doctors may contribute to this phenomenon, doctors suggested.

Dr. Keefe, with Baylor College of Medicine, Houston, and colleagues analyzed Medicaid claims data from two managed care organizations to compare the prevalence of psychotropic medication use among children in foster care versus children insured by Medicaid but not in foster care. The study focused on claims from the same region in southeast Texas between July 2014 and June 2016.

The researchers included 388,914 children in Medicaid and 8,426 children in foster care in their analysis. They excluded children with a seizure or epilepsy diagnosis.

About 8% of children not in foster care received psychotropic medications, compared with 35% of those in foster care.

Children in foster care were 27 times more likely to receive antipsychotic medication (21.2% of children in foster care vs. 0.8% of children not in foster care) and twice as likely to receive antianxiety medication (6% vs. 3%).

For children in foster care, the rate of alpha-agonist use was 15 times higher, the rate of antidepressant use was 13 times higher, the rate of mood stabilizer use was 26 times higher, and the rate of stimulant use was 6 times higher.

The researchers have a limited understanding of the full context in which these medications were prescribed, and psychotropic medications have a role in the treatment of children in foster care, Dr. Keefe acknowledged.

“We have to be careful not to have a knee-jerk reaction” and inappropriately withhold medication from children in foster care, she said in an interview.

But overprescribing has been a concern. Dr. Keefe leads a foster care clinical service at Texas Children’s Hospital in Houston.

“The overprescribing of psychotropic medications to children in foster care is something I feel every day in my clinical practice, but it’s different to see it on paper,” Dr. Keefe said in a news release highlighting the research, which she presented on Oct. 11 at the annual meeting of the American Academy of Pediatrics. “It’s especially shocking to see these dramatic differences in children of preschool and elementary age.”

Misdiagnosis can be a common problem among children in foster care, said Danielle Shaw, MD, a child and adolescent psychiatrist in Camarillo, Calif., during a question-and-answer period following the presentation.

“I see incorrect diagnoses very frequently,” Dr. Shaw said. “The history of trauma or [adverse childhood experiences] is not even included in the assessment. Mood lability from trauma is misdiagnosed as bipolar disorder, despite not meeting criteria. This will justify the use of antipsychotic medication and mood stabilizers. Flashbacks can be mistaken for a psychotic disorder, which again justifies the use of antipsychotic medication.”

Children in foster care have experienced numerous traumatic experiences that affect brain development and the hypothalamic-pituitary-adrenal axis, Dr. Keefe said.

“Although from previous research we know that children in foster care are more likely to carry mental health and developmental disorder diagnoses, this does not account for the significant difference in prescribing practices in this population,” Dr. Keefe said in an interview.

Although the study focused on data in Texas, Dr. Keefe expects similar patterns exist in other regions, based on anecdotal reports. “I work with foster care pediatricians across the country, and many have seen similar concerning trends within their own clinical practices,” she said.

The use of appropriate therapies, minimizing transitions between providers, improved record keeping, the development of deprescribing algorithms, and placement of children in foster care in long-term homes as early as possible are measures that potentially could reduce inappropriate psychotropic prescribing for children in foster care, Dr. Keefe suggested.

The research was funded by a Texas Medical Center Health Policy Research Grant. The study authors and Dr. Shaw had no relevant financial disclosures.

jremaly@mdedge.com

Transgender and nonbinary young people experienced less depression and fewer suicidal thoughts after a year of gender-affirming care with hormones or puberty blockers, according to new research.

“Given the high rates of adverse mental health comorbidities, these data provide critical evidence that expansion of gender-affirming care can save lives,” said David J. Inwards-Breland, MD, MPH, chief of adolescent and young adult medicine and codirector of the Center for Gender-Affirming Care at Rady Children’s Hospital in San Diego, during his presentation.

The findings, presented October 11 at the American Academy of Pediatrics 2021 National Conference, were not at all surprising to Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.

“The younger we can provide gender-affirming care, the less likely they’re going to have depression, and then the negative outcomes from untreated depression, which includes suicide intent or even suicide completion,” Dr. Breuner told this news organization. “It’s so obvious that we are saving lives by providing gender-affirming care.”

For their study, Dr. Inwards-Breland and his colleagues tracked depression, anxiety, and suicidality in 104 trans and nonbinary people 13 to 21 years of age who received care at the Seattle Children’s gender clinic between August 2017 and June 2018.

The study population consisted of 63 transgender male or male participants, 27 transgender female or female participants, 10 nonbinary participants, and four participants who had not defined their gender identity. Of this cohort, 62.5% were receiving mental health therapy, and 34.7% reported some substance use.

Participants completed the nine-item Patient Health Questionnaire (PHQ-9) and the seven-item Generalized Anxiety Disorder scale (GAD-7) at baseline and then at 3, 6, and 12 months. The researchers defined severe depression and severe anxiety as a score of 10 or greater on either scale.

At baseline, 56.7% of the participants had moderate to severe depression, 43.3% reported thoughts of self-harm or suicidal in the previous 2 weeks, and 50.0% had moderate to severe anxiety.

After 12 months of care, participants experienced a 60% decrease in depression (adjusted odds ratio, 0.4) and a 73% decrease in suicidality (aOR, 0.27), after adjustment for temporal trends and sex assigned at birth, race/ethnicity, level of parental support, ongoing mental health therapy, substance use, and victimization, including bullying, interpersonal violence, neglect, and abuse.

Although the decline in depression and suicidality after gender-affirming treatment was not a surprise, “those drops are huge,” Dr. Inwards-Breland said in an interview.

He said he attributes the improvement to a health care system that “affirms who these young people are” and enables changes that allow their outward appearance to reflect “who they know they are inside.”

There were no significant changes in anxiety during the study period. “Anxiety, I think, is just a little harder to treat, and it takes a little longer to treat,” he explained. And a lot of factors can trigger anxiety, and those can continue during treatment.

The slow pace of changes to gender identity can have an effect on people’s moods. “Since they’re not happening quickly, these young people are still being misgendered, they’re still seeing the body that they don’t feel like they should have, and they have to go to school and go out in public. I think that continues to fuel anxiety with a lot of these young people.”

Family support is important in reducing depression and suicidal thoughts in this population. Parents will often see positive changes after their child receives gender-affirming care, which can help contribute to positive changes in parents’ attitudes, Dr. Inwards-Breland said.

Such changes reinforce “that protective factor of connectedness with family,” he noted. “Families are crucial for any health care, and if there’s that connectedness with families, we know that, clinically, patients do better.”
 

Balancing risks

Although there are risks associated with gender-affirming hormones and puberty blockers, the risks of not receiving treatment must also be considered.

“Our young people are killing themselves,” he said. “Our young people are developing severe eating disorders that are killing them. Our young people are increasing their substance abuse, homelessness, depression. The list just goes on.”

For trans-masculine and nonbinary masculine patients, the potential permanent changes of hormone therapy include a deeper voice, hair growth, enlargement of the clitoris, and, in some patients, the development of male pattern baldness. In trans and nonbinary feminine patients, potential long-term effects include breast development and an increased risk for fertility issues.

The consent forms required for young people who want gender-affirming hormones or puberty blockers are extensive, with every possible reversible and irreversible effect described in detail, Dr. Breuner said.

“Parents sign them because they want their child to stay alive,” she explained. “When you compare the cost of someone who has severe debilitating depression and dying by suicide with some of the risks associated with gender-affirming hormone therapy, that’s a no-brainer to me.”

This study is limited by the fact that screening tests, not diagnostic tests, were used to identify depression, anxiety, and suicidality, and the fact that the use of antidepression or antianxiety medications was not taken into account, Dr. Inwards-Breland acknowledged.

“I think future studies should look at a mental health evaluation and diagnosis by a mental health provider,” he added. And mental health, gender dysphoria, suicidality, and self-harm should be tracked over the course of treatment.

He also acknowledged the study’s selection bias. All participants sought care at a multidisciplinary gender clinic, so were likely to be privileged and to have supportive families. “There’s a good chance that if we had more trans and nonbinary youth of color, we may have different findings,” he said.

More qualitative research is needed to assess the effect of gender-affirming therapy on the mental health of these patients, Dr. Breuner said.

“Being able to finally come into who you think you are and enjoy expressing who you are in a gender-affirming way has to be positive in such a way that you’re not depressed anymore,” she added. “It has to be tragic for people who cannot stand the body they’re in and cannot talk about it to anybody or express themselves without fear of recourse, to the point that they would be so devastated that they’d want to die by suicide.”

This research was funded by the Seattle Children’s Center for Diversity and Health Equity and the Pacific Hospital Development and Port Authority. Dr. Inwards-Breland and Dr. Breuner have disclosed no relevant financial relationships.

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

Transgender and nonbinary young people experienced less depression and fewer suicidal thoughts after a year of gender-affirming care with hormones or puberty blockers, according to new research.

“Given the high rates of adverse mental health comorbidities, these data provide critical evidence that expansion of gender-affirming care can save lives,” said David J. Inwards-Breland, MD, MPH, chief of adolescent and young adult medicine and codirector of the Center for Gender-Affirming Care at Rady Children’s Hospital in San Diego, during his presentation.

The findings, presented October 11 at the American Academy of Pediatrics 2021 National Conference, were not at all surprising to Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.

“The younger we can provide gender-affirming care, the less likely they’re going to have depression, and then the negative outcomes from untreated depression, which includes suicide intent or even suicide completion,” Dr. Breuner told this news organization. “It’s so obvious that we are saving lives by providing gender-affirming care.”

For their study, Dr. Inwards-Breland and his colleagues tracked depression, anxiety, and suicidality in 104 trans and nonbinary people 13 to 21 years of age who received care at the Seattle Children’s gender clinic between August 2017 and June 2018.

The study population consisted of 63 transgender male or male participants, 27 transgender female or female participants, 10 nonbinary participants, and four participants who had not defined their gender identity. Of this cohort, 62.5% were receiving mental health therapy, and 34.7% reported some substance use.

Participants completed the nine-item Patient Health Questionnaire (PHQ-9) and the seven-item Generalized Anxiety Disorder scale (GAD-7) at baseline and then at 3, 6, and 12 months. The researchers defined severe depression and severe anxiety as a score of 10 or greater on either scale.

At baseline, 56.7% of the participants had moderate to severe depression, 43.3% reported thoughts of self-harm or suicidal in the previous 2 weeks, and 50.0% had moderate to severe anxiety.

After 12 months of care, participants experienced a 60% decrease in depression (adjusted odds ratio, 0.4) and a 73% decrease in suicidality (aOR, 0.27), after adjustment for temporal trends and sex assigned at birth, race/ethnicity, level of parental support, ongoing mental health therapy, substance use, and victimization, including bullying, interpersonal violence, neglect, and abuse.

Although the decline in depression and suicidality after gender-affirming treatment was not a surprise, “those drops are huge,” Dr. Inwards-Breland said in an interview.

He said he attributes the improvement to a health care system that “affirms who these young people are” and enables changes that allow their outward appearance to reflect “who they know they are inside.”

There were no significant changes in anxiety during the study period. “Anxiety, I think, is just a little harder to treat, and it takes a little longer to treat,” he explained. And a lot of factors can trigger anxiety, and those can continue during treatment.

The slow pace of changes to gender identity can have an effect on people’s moods. “Since they’re not happening quickly, these young people are still being misgendered, they’re still seeing the body that they don’t feel like they should have, and they have to go to school and go out in public. I think that continues to fuel anxiety with a lot of these young people.”

Family support is important in reducing depression and suicidal thoughts in this population. Parents will often see positive changes after their child receives gender-affirming care, which can help contribute to positive changes in parents’ attitudes, Dr. Inwards-Breland said.

Such changes reinforce “that protective factor of connectedness with family,” he noted. “Families are crucial for any health care, and if there’s that connectedness with families, we know that, clinically, patients do better.”
 

Balancing risks

Although there are risks associated with gender-affirming hormones and puberty blockers, the risks of not receiving treatment must also be considered.

“Our young people are killing themselves,” he said. “Our young people are developing severe eating disorders that are killing them. Our young people are increasing their substance abuse, homelessness, depression. The list just goes on.”

For trans-masculine and nonbinary masculine patients, the potential permanent changes of hormone therapy include a deeper voice, hair growth, enlargement of the clitoris, and, in some patients, the development of male pattern baldness. In trans and nonbinary feminine patients, potential long-term effects include breast development and an increased risk for fertility issues.

The consent forms required for young people who want gender-affirming hormones or puberty blockers are extensive, with every possible reversible and irreversible effect described in detail, Dr. Breuner said.

“Parents sign them because they want their child to stay alive,” she explained. “When you compare the cost of someone who has severe debilitating depression and dying by suicide with some of the risks associated with gender-affirming hormone therapy, that’s a no-brainer to me.”

This study is limited by the fact that screening tests, not diagnostic tests, were used to identify depression, anxiety, and suicidality, and the fact that the use of antidepression or antianxiety medications was not taken into account, Dr. Inwards-Breland acknowledged.

“I think future studies should look at a mental health evaluation and diagnosis by a mental health provider,” he added. And mental health, gender dysphoria, suicidality, and self-harm should be tracked over the course of treatment.

He also acknowledged the study’s selection bias. All participants sought care at a multidisciplinary gender clinic, so were likely to be privileged and to have supportive families. “There’s a good chance that if we had more trans and nonbinary youth of color, we may have different findings,” he said.

More qualitative research is needed to assess the effect of gender-affirming therapy on the mental health of these patients, Dr. Breuner said.

“Being able to finally come into who you think you are and enjoy expressing who you are in a gender-affirming way has to be positive in such a way that you’re not depressed anymore,” she added. “It has to be tragic for people who cannot stand the body they’re in and cannot talk about it to anybody or express themselves without fear of recourse, to the point that they would be so devastated that they’d want to die by suicide.”

This research was funded by the Seattle Children’s Center for Diversity and Health Equity and the Pacific Hospital Development and Port Authority. Dr. Inwards-Breland and Dr. Breuner have disclosed no relevant financial relationships.

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

Transgender and nonbinary young people experienced less depression and fewer suicidal thoughts after a year of gender-affirming care with hormones or puberty blockers, according to new research.

“Given the high rates of adverse mental health comorbidities, these data provide critical evidence that expansion of gender-affirming care can save lives,” said David J. Inwards-Breland, MD, MPH, chief of adolescent and young adult medicine and codirector of the Center for Gender-Affirming Care at Rady Children’s Hospital in San Diego, during his presentation.

The findings, presented October 11 at the American Academy of Pediatrics 2021 National Conference, were not at all surprising to Cora Breuner, MD, MPH, professor of pediatrics at Seattle Children’s Hospital.

“The younger we can provide gender-affirming care, the less likely they’re going to have depression, and then the negative outcomes from untreated depression, which includes suicide intent or even suicide completion,” Dr. Breuner told this news organization. “It’s so obvious that we are saving lives by providing gender-affirming care.”

For their study, Dr. Inwards-Breland and his colleagues tracked depression, anxiety, and suicidality in 104 trans and nonbinary people 13 to 21 years of age who received care at the Seattle Children’s gender clinic between August 2017 and June 2018.

The study population consisted of 63 transgender male or male participants, 27 transgender female or female participants, 10 nonbinary participants, and four participants who had not defined their gender identity. Of this cohort, 62.5% were receiving mental health therapy, and 34.7% reported some substance use.

Participants completed the nine-item Patient Health Questionnaire (PHQ-9) and the seven-item Generalized Anxiety Disorder scale (GAD-7) at baseline and then at 3, 6, and 12 months. The researchers defined severe depression and severe anxiety as a score of 10 or greater on either scale.

At baseline, 56.7% of the participants had moderate to severe depression, 43.3% reported thoughts of self-harm or suicidal in the previous 2 weeks, and 50.0% had moderate to severe anxiety.

After 12 months of care, participants experienced a 60% decrease in depression (adjusted odds ratio, 0.4) and a 73% decrease in suicidality (aOR, 0.27), after adjustment for temporal trends and sex assigned at birth, race/ethnicity, level of parental support, ongoing mental health therapy, substance use, and victimization, including bullying, interpersonal violence, neglect, and abuse.

Although the decline in depression and suicidality after gender-affirming treatment was not a surprise, “those drops are huge,” Dr. Inwards-Breland said in an interview.

He said he attributes the improvement to a health care system that “affirms who these young people are” and enables changes that allow their outward appearance to reflect “who they know they are inside.”

There were no significant changes in anxiety during the study period. “Anxiety, I think, is just a little harder to treat, and it takes a little longer to treat,” he explained. And a lot of factors can trigger anxiety, and those can continue during treatment.

The slow pace of changes to gender identity can have an effect on people’s moods. “Since they’re not happening quickly, these young people are still being misgendered, they’re still seeing the body that they don’t feel like they should have, and they have to go to school and go out in public. I think that continues to fuel anxiety with a lot of these young people.”

Family support is important in reducing depression and suicidal thoughts in this population. Parents will often see positive changes after their child receives gender-affirming care, which can help contribute to positive changes in parents’ attitudes, Dr. Inwards-Breland said.

Such changes reinforce “that protective factor of connectedness with family,” he noted. “Families are crucial for any health care, and if there’s that connectedness with families, we know that, clinically, patients do better.”
 

Balancing risks

Although there are risks associated with gender-affirming hormones and puberty blockers, the risks of not receiving treatment must also be considered.

“Our young people are killing themselves,” he said. “Our young people are developing severe eating disorders that are killing them. Our young people are increasing their substance abuse, homelessness, depression. The list just goes on.”

For trans-masculine and nonbinary masculine patients, the potential permanent changes of hormone therapy include a deeper voice, hair growth, enlargement of the clitoris, and, in some patients, the development of male pattern baldness. In trans and nonbinary feminine patients, potential long-term effects include breast development and an increased risk for fertility issues.

The consent forms required for young people who want gender-affirming hormones or puberty blockers are extensive, with every possible reversible and irreversible effect described in detail, Dr. Breuner said.

“Parents sign them because they want their child to stay alive,” she explained. “When you compare the cost of someone who has severe debilitating depression and dying by suicide with some of the risks associated with gender-affirming hormone therapy, that’s a no-brainer to me.”

This study is limited by the fact that screening tests, not diagnostic tests, were used to identify depression, anxiety, and suicidality, and the fact that the use of antidepression or antianxiety medications was not taken into account, Dr. Inwards-Breland acknowledged.

“I think future studies should look at a mental health evaluation and diagnosis by a mental health provider,” he added. And mental health, gender dysphoria, suicidality, and self-harm should be tracked over the course of treatment.

He also acknowledged the study’s selection bias. All participants sought care at a multidisciplinary gender clinic, so were likely to be privileged and to have supportive families. “There’s a good chance that if we had more trans and nonbinary youth of color, we may have different findings,” he said.

More qualitative research is needed to assess the effect of gender-affirming therapy on the mental health of these patients, Dr. Breuner said.

“Being able to finally come into who you think you are and enjoy expressing who you are in a gender-affirming way has to be positive in such a way that you’re not depressed anymore,” she added. “It has to be tragic for people who cannot stand the body they’re in and cannot talk about it to anybody or express themselves without fear of recourse, to the point that they would be so devastated that they’d want to die by suicide.”

This research was funded by the Seattle Children’s Center for Diversity and Health Equity and the Pacific Hospital Development and Port Authority. Dr. Inwards-Breland and Dr. Breuner have disclosed no relevant financial relationships.

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

Given that approximately 9.5% of youth aged 13-17 in the United States identify as lesbian, gay, bisexual, transgender, or queer (LGBTQ),¹ it is likely that a general pediatrician or pediatric subspecialist is going to encounter at least one LGBTQ patient during the course of the average workweek. By having an easy way to identify these patients and store this data in a user-friendly manner, you can ensure that your practice is LGBTQ friendly and an affirming environment for all sexual- and gender-minority youth.

One way to do this is to look over any paper or electronic forms your practice uses and make sure that they provide patients and families a range of options to identify themselves. For example, you could provide more options for gender, other than male or female, including a nonbinary or “other” (with a free text line) option. This allows your patients to give you an accurate description of what their affirmed gender is. Instead of having a space for mother’s name and father’s name, you could list these fields as “parent/guardian #1” and “parent/guardian #2.” These labels allow for more inclusivity and to reflect the diverse makeup of modern families. Providing a space for a patient to put the name and pronouns that they use allows your staff to make sure that you are calling a patient by the correct name and using the correct pronouns.

Within your EMR, there may be editable fields that allow for you or your staff to list the patient’s affirmed name and pronouns. Making this small change allows any staff member who accesses the chart to have that information displayed correctly for them and reduces the chances of staff misgendering or dead-naming a patient. Underscoring the importance of this, Sequeira et al. found that in a sample of youth from a gender clinic, only 9% of those adolescents reported that they were asked their name/pronouns outside of the gender clinic.² If those fields are not there, you may check with your IT staff or your EMR vendor to see if these fields may be added in. However, staff needs to make sure that they check with the child/adolescent first to discern with whom the patient has discussed their gender identity. If you were to put a patient’s affirmed name into the chart and then call the patient by that name in front of the parent/guardian, the parent/guardian may look at you quizzically about why you are calling their child by that name. This could then cause an uncomfortable conversation in the exam room or result in harm to the patient after the visit.

It is not just good clinical practice to ensure that you use a patient’s affirmed name and pronouns. Russell et al. looked at the relationship between depressive symptoms and suicidal ideation and whether an adolescent’s name/pronouns were used in the context of their home, school, work, and/or friend group. They found that use of an adolescent’s affirmed name in at least one of these contexts was associated with a decrease in depressive symptoms and a 29% decrease in suicidal ideation.³ Therefore, the use of an adolescent’s affirmed name and pronouns in your office contributes to the overall mental well-being of your patients.

Fortunately, there are many guides to help you and your practice be successful at implementing some of these changes. The Gay, Lesbian, Bisexual and Transgender Health Access Project put together its “Community Standards of Practice for the Provision of Quality Health Care Services to Lesbian, Gay, Bisexual, and Transgender Clients” to aid practices in developing environments that are LGBTQ affirming. The National LGBTQIA+ Health Education Center, a part of the Fenway Institute, has a series of learning modules that you and your staff can view for interactive training and tips for best practices. These resources offer pediatricians and their practices free resources to improve their policies and procedures. By instituting these small changes, you can ensure that your practice continues to be an affirming environment for your LGBTQ children and adolescents.
 

Dr. Cooper is assistant professor of pediatrics at University of Texas Southwestern, Dallas, and an adolescent medicine specialist at Children’s Medical Center Dallas.

References

1. Conran KJ. LGBT youth population in the United States, UCLA School of Law, Williams Institute, 2020 Sep.

2. Sequeira GM et al. Affirming transgender youths’ names and pronouns in the electronic medical record. JAMA Pediatr. 2020;174(5):501-3.

3. Russell ST et al. Chosen name use is linked to reduced depressive symptoms, suicidal ideation, and suicidal behavior among transgender youth. J Adolesc Health. 2018;63(4):503-5.

Given that approximately 9.5% of youth aged 13-17 in the United States identify as lesbian, gay, bisexual, transgender, or queer (LGBTQ),¹ it is likely that a general pediatrician or pediatric subspecialist is going to encounter at least one LGBTQ patient during the course of the average workweek. By having an easy way to identify these patients and store this data in a user-friendly manner, you can ensure that your practice is LGBTQ friendly and an affirming environment for all sexual- and gender-minority youth.

One way to do this is to look over any paper or electronic forms your practice uses and make sure that they provide patients and families a range of options to identify themselves. For example, you could provide more options for gender, other than male or female, including a nonbinary or “other” (with a free text line) option. This allows your patients to give you an accurate description of what their affirmed gender is. Instead of having a space for mother’s name and father’s name, you could list these fields as “parent/guardian #1” and “parent/guardian #2.” These labels allow for more inclusivity and to reflect the diverse makeup of modern families. Providing a space for a patient to put the name and pronouns that they use allows your staff to make sure that you are calling a patient by the correct name and using the correct pronouns.

Within your EMR, there may be editable fields that allow for you or your staff to list the patient’s affirmed name and pronouns. Making this small change allows any staff member who accesses the chart to have that information displayed correctly for them and reduces the chances of staff misgendering or dead-naming a patient. Underscoring the importance of this, Sequeira et al. found that in a sample of youth from a gender clinic, only 9% of those adolescents reported that they were asked their name/pronouns outside of the gender clinic.² If those fields are not there, you may check with your IT staff or your EMR vendor to see if these fields may be added in. However, staff needs to make sure that they check with the child/adolescent first to discern with whom the patient has discussed their gender identity. If you were to put a patient’s affirmed name into the chart and then call the patient by that name in front of the parent/guardian, the parent/guardian may look at you quizzically about why you are calling their child by that name. This could then cause an uncomfortable conversation in the exam room or result in harm to the patient after the visit.

It is not just good clinical practice to ensure that you use a patient’s affirmed name and pronouns. Russell et al. looked at the relationship between depressive symptoms and suicidal ideation and whether an adolescent’s name/pronouns were used in the context of their home, school, work, and/or friend group. They found that use of an adolescent’s affirmed name in at least one of these contexts was associated with a decrease in depressive symptoms and a 29% decrease in suicidal ideation.³ Therefore, the use of an adolescent’s affirmed name and pronouns in your office contributes to the overall mental well-being of your patients.

Fortunately, there are many guides to help you and your practice be successful at implementing some of these changes. The Gay, Lesbian, Bisexual and Transgender Health Access Project put together its “Community Standards of Practice for the Provision of Quality Health Care Services to Lesbian, Gay, Bisexual, and Transgender Clients” to aid practices in developing environments that are LGBTQ affirming. The National LGBTQIA+ Health Education Center, a part of the Fenway Institute, has a series of learning modules that you and your staff can view for interactive training and tips for best practices. These resources offer pediatricians and their practices free resources to improve their policies and procedures. By instituting these small changes, you can ensure that your practice continues to be an affirming environment for your LGBTQ children and adolescents.
 

Dr. Cooper is assistant professor of pediatrics at University of Texas Southwestern, Dallas, and an adolescent medicine specialist at Children’s Medical Center Dallas.

References

1. Conran KJ. LGBT youth population in the United States, UCLA School of Law, Williams Institute, 2020 Sep.

2. Sequeira GM et al. Affirming transgender youths’ names and pronouns in the electronic medical record. JAMA Pediatr. 2020;174(5):501-3.

3. Russell ST et al. Chosen name use is linked to reduced depressive symptoms, suicidal ideation, and suicidal behavior among transgender youth. J Adolesc Health. 2018;63(4):503-5.

Given that approximately 9.5% of youth aged 13-17 in the United States identify as lesbian, gay, bisexual, transgender, or queer (LGBTQ),¹ it is likely that a general pediatrician or pediatric subspecialist is going to encounter at least one LGBTQ patient during the course of the average workweek. By having an easy way to identify these patients and store this data in a user-friendly manner, you can ensure that your practice is LGBTQ friendly and an affirming environment for all sexual- and gender-minority youth.

One way to do this is to look over any paper or electronic forms your practice uses and make sure that they provide patients and families a range of options to identify themselves. For example, you could provide more options for gender, other than male or female, including a nonbinary or “other” (with a free text line) option. This allows your patients to give you an accurate description of what their affirmed gender is. Instead of having a space for mother’s name and father’s name, you could list these fields as “parent/guardian #1” and “parent/guardian #2.” These labels allow for more inclusivity and to reflect the diverse makeup of modern families. Providing a space for a patient to put the name and pronouns that they use allows your staff to make sure that you are calling a patient by the correct name and using the correct pronouns.

Within your EMR, there may be editable fields that allow for you or your staff to list the patient’s affirmed name and pronouns. Making this small change allows any staff member who accesses the chart to have that information displayed correctly for them and reduces the chances of staff misgendering or dead-naming a patient. Underscoring the importance of this, Sequeira et al. found that in a sample of youth from a gender clinic, only 9% of those adolescents reported that they were asked their name/pronouns outside of the gender clinic.² If those fields are not there, you may check with your IT staff or your EMR vendor to see if these fields may be added in. However, staff needs to make sure that they check with the child/adolescent first to discern with whom the patient has discussed their gender identity. If you were to put a patient’s affirmed name into the chart and then call the patient by that name in front of the parent/guardian, the parent/guardian may look at you quizzically about why you are calling their child by that name. This could then cause an uncomfortable conversation in the exam room or result in harm to the patient after the visit.

It is not just good clinical practice to ensure that you use a patient’s affirmed name and pronouns. Russell et al. looked at the relationship between depressive symptoms and suicidal ideation and whether an adolescent’s name/pronouns were used in the context of their home, school, work, and/or friend group. They found that use of an adolescent’s affirmed name in at least one of these contexts was associated with a decrease in depressive symptoms and a 29% decrease in suicidal ideation.³ Therefore, the use of an adolescent’s affirmed name and pronouns in your office contributes to the overall mental well-being of your patients.

Fortunately, there are many guides to help you and your practice be successful at implementing some of these changes. The Gay, Lesbian, Bisexual and Transgender Health Access Project put together its “Community Standards of Practice for the Provision of Quality Health Care Services to Lesbian, Gay, Bisexual, and Transgender Clients” to aid practices in developing environments that are LGBTQ affirming. The National LGBTQIA+ Health Education Center, a part of the Fenway Institute, has a series of learning modules that you and your staff can view for interactive training and tips for best practices. These resources offer pediatricians and their practices free resources to improve their policies and procedures. By instituting these small changes, you can ensure that your practice continues to be an affirming environment for your LGBTQ children and adolescents.
 

Dr. Cooper is assistant professor of pediatrics at University of Texas Southwestern, Dallas, and an adolescent medicine specialist at Children’s Medical Center Dallas.

References

1. Conran KJ. LGBT youth population in the United States, UCLA School of Law, Williams Institute, 2020 Sep.

2. Sequeira GM et al. Affirming transgender youths’ names and pronouns in the electronic medical record. JAMA Pediatr. 2020;174(5):501-3.

3. Russell ST et al. Chosen name use is linked to reduced depressive symptoms, suicidal ideation, and suicidal behavior among transgender youth. J Adolesc Health. 2018;63(4):503-5.

It’s well known that levels of anxiety and depression in youth are on the rise. While some of this increase may be because of other things, such as a lowering of the threshold for what counts as clinically relevant symptoms and decreased stigma when it comes to seeking out mental health services, there seems little debate that the number of children and adolescents who are actually struggling with their mental health is taking a sharp turn for the worse.

What is much less certain are the causes behind this surge. The answer to this important question will likely defy a clear answer from a definitive study. In its place then are a number of different theories that have been circulated and discussed. Each comes with some evidence to support the hypothesis, but none seems able to make a truly compelling argument as the single driving force behind this trend. This column briefly describes and examines some of the factors that may be contributing to the rise in anxiety and depression while providing some explanation for why each factor is unlikely to be the sole culprit.

Some of the biggest suggested causes for the rise in child and adolescent mental health problems include the following:

• COVID. Multiple studies have documented increases in mood and anxiety associated with the pandemic, which in turn, may be because of a number of factors such as social isolation, loss of family members, family financial stressors, and many other contributors.¹ Yet, while it certainly makes sense that COVID is a powerful instigator of mood and anxiety problems, there is good evidence that the upward tic in emotional-behavioral problems began well before the COVID pandemic.²
• Smartphones. In 2017, psychologist Jean Twenge penned a provocative essay in the Atlantic with the title “Have Smartphones Destroyed a Generation?” and the basic answer was yes.³ The foundation for this conclusion was the tracking between the rise in mood and anxiety problems and the meteoric rise of smartphone use in youth. None of these associations, however, can be proven as casual, and more experimental data on the link between smartphone usage and mental health have been inconsistent.
• Bullying. The toxic effect of bullying and, in particular, online or “cyberbullying” has frequently been brought up as a potential cause. Yet while the negative effects of bullying have been well documented, there is evidence that overall bullying has actually decreased over recent years.⁴

These three factors have arguably been the most discussed, but a few others also probably deserve mention.

• Helicopter parenting. Critics of this common and increasingly popular approach to parenting are concerned that all the parental hovering and stepping in convey the message that the world is a very dangerous place while depriving children of opportunities to gain the exposure and competence they need to succeed. The critique is certainly logical and even has been supported in some studies but lacks the needed evidence for a more definitive conclusion.⁵
• Medications. Of course there will be stories blaming the mental health treatment itself, rather than the reasons people seek treatment, for this disturbing trend. And while it is always important to consider that medications can be part of the problem rather than the solution, the majority of evidence points overall to a lack of treatment rather than too much. A recent important study, for example, found that the peak of suicidal thoughts and behaviors occurred a month before medications were started, rather than after.⁶
• Cannabis. While there seems to be a lot of geographic variability with regard to whether or not the number of youth using cannabis is increasing or not, it’s clear that the product now being consumed is considerably stronger than what was used in decades past. This high-potency cannabis now being used has been shown to increase the risk for later mental health problems including psychosis and suicidal behavior.⁷ Unfortunately, these risks are not being heard as a powerful industry fights to increase their market share.

Putting all this together, it seems likely that a tidy and simple explanation for the alarming increase in youth mental health problems will be hard to pin down. It’s also worth pointing out that many of the above factors could work in a synergistic manner. For example, helicopter parenting may be keeping kids more confined to their rooms where they interact more and more on their phones and are exposed to higher amounts of online bullying, all of which has been magnified recently with the COVID pandemic. Obviously, understanding the causes behind this surge is much more than an academic exercise as the amount of stress and suffering rises and treatment resources get overwhelmed. In the meantime, addressing all of the above factors in both primary and specialty care is worthwhile in an effort to reverse this worrying and wide-ranging pattern.

Dr. Rettew is a child and adolescent psychiatrist and medical director of Lane County Behavioral Health in Eugene, Ore. He is the author of the 2021 book, “Parenting Made Complicated: What Science Really Knows about the Greatest Debates of Early Childhood.” You can follow him on Twitter and Facebook @PediPsych.

References

1. Hawes MT et al. Psychol Med. 2021;13:1-9.

2. Twenge JM et al. J Abnorm Psych. 2019;128(3):185-99.

3. Twenge JM. Have Smartphones Destroyed a Generation? The Atlantic. 2017:September.

4. Rettew DC. Bullying: An update. Child Psych Clin North Am. 2021; in press.

5. Van Der Bruggen CO et al. J Child Psychol Psychiatry. 2008;49(12):1257-69.

6. Lagerberg T et al. Selective serotonin reuptake inhibitors and suicidal behaviour: A population-based cohort study. Neuropsychopharmacology 2021 Sep 24.

7. Gobbi G et al. JAMA Psychiatry. 2019;76(4):426-34.

It’s well known that levels of anxiety and depression in youth are on the rise. While some of this increase may be because of other things, such as a lowering of the threshold for what counts as clinically relevant symptoms and decreased stigma when it comes to seeking out mental health services, there seems little debate that the number of children and adolescents who are actually struggling with their mental health is taking a sharp turn for the worse.

What is much less certain are the causes behind this surge. The answer to this important question will likely defy a clear answer from a definitive study. In its place then are a number of different theories that have been circulated and discussed. Each comes with some evidence to support the hypothesis, but none seems able to make a truly compelling argument as the single driving force behind this trend. This column briefly describes and examines some of the factors that may be contributing to the rise in anxiety and depression while providing some explanation for why each factor is unlikely to be the sole culprit.

Some of the biggest suggested causes for the rise in child and adolescent mental health problems include the following:

• COVID. Multiple studies have documented increases in mood and anxiety associated with the pandemic, which in turn, may be because of a number of factors such as social isolation, loss of family members, family financial stressors, and many other contributors.¹ Yet, while it certainly makes sense that COVID is a powerful instigator of mood and anxiety problems, there is good evidence that the upward tic in emotional-behavioral problems began well before the COVID pandemic.²
• Smartphones. In 2017, psychologist Jean Twenge penned a provocative essay in the Atlantic with the title “Have Smartphones Destroyed a Generation?” and the basic answer was yes.³ The foundation for this conclusion was the tracking between the rise in mood and anxiety problems and the meteoric rise of smartphone use in youth. None of these associations, however, can be proven as casual, and more experimental data on the link between smartphone usage and mental health have been inconsistent.
• Bullying. The toxic effect of bullying and, in particular, online or “cyberbullying” has frequently been brought up as a potential cause. Yet while the negative effects of bullying have been well documented, there is evidence that overall bullying has actually decreased over recent years.⁴

These three factors have arguably been the most discussed, but a few others also probably deserve mention.

• Helicopter parenting. Critics of this common and increasingly popular approach to parenting are concerned that all the parental hovering and stepping in convey the message that the world is a very dangerous place while depriving children of opportunities to gain the exposure and competence they need to succeed. The critique is certainly logical and even has been supported in some studies but lacks the needed evidence for a more definitive conclusion.⁵
• Medications. Of course there will be stories blaming the mental health treatment itself, rather than the reasons people seek treatment, for this disturbing trend. And while it is always important to consider that medications can be part of the problem rather than the solution, the majority of evidence points overall to a lack of treatment rather than too much. A recent important study, for example, found that the peak of suicidal thoughts and behaviors occurred a month before medications were started, rather than after.⁶
• Cannabis. While there seems to be a lot of geographic variability with regard to whether or not the number of youth using cannabis is increasing or not, it’s clear that the product now being consumed is considerably stronger than what was used in decades past. This high-potency cannabis now being used has been shown to increase the risk for later mental health problems including psychosis and suicidal behavior.⁷ Unfortunately, these risks are not being heard as a powerful industry fights to increase their market share.

Putting all this together, it seems likely that a tidy and simple explanation for the alarming increase in youth mental health problems will be hard to pin down. It’s also worth pointing out that many of the above factors could work in a synergistic manner. For example, helicopter parenting may be keeping kids more confined to their rooms where they interact more and more on their phones and are exposed to higher amounts of online bullying, all of which has been magnified recently with the COVID pandemic. Obviously, understanding the causes behind this surge is much more than an academic exercise as the amount of stress and suffering rises and treatment resources get overwhelmed. In the meantime, addressing all of the above factors in both primary and specialty care is worthwhile in an effort to reverse this worrying and wide-ranging pattern.

Dr. Rettew is a child and adolescent psychiatrist and medical director of Lane County Behavioral Health in Eugene, Ore. He is the author of the 2021 book, “Parenting Made Complicated: What Science Really Knows about the Greatest Debates of Early Childhood.” You can follow him on Twitter and Facebook @PediPsych.

References

1. Hawes MT et al. Psychol Med. 2021;13:1-9.

2. Twenge JM et al. J Abnorm Psych. 2019;128(3):185-99.

3. Twenge JM. Have Smartphones Destroyed a Generation? The Atlantic. 2017:September.

4. Rettew DC. Bullying: An update. Child Psych Clin North Am. 2021; in press.

5. Van Der Bruggen CO et al. J Child Psychol Psychiatry. 2008;49(12):1257-69.

6. Lagerberg T et al. Selective serotonin reuptake inhibitors and suicidal behaviour: A population-based cohort study. Neuropsychopharmacology 2021 Sep 24.

7. Gobbi G et al. JAMA Psychiatry. 2019;76(4):426-34.

It’s well known that levels of anxiety and depression in youth are on the rise. While some of this increase may be because of other things, such as a lowering of the threshold for what counts as clinically relevant symptoms and decreased stigma when it comes to seeking out mental health services, there seems little debate that the number of children and adolescents who are actually struggling with their mental health is taking a sharp turn for the worse.

What is much less certain are the causes behind this surge. The answer to this important question will likely defy a clear answer from a definitive study. In its place then are a number of different theories that have been circulated and discussed. Each comes with some evidence to support the hypothesis, but none seems able to make a truly compelling argument as the single driving force behind this trend. This column briefly describes and examines some of the factors that may be contributing to the rise in anxiety and depression while providing some explanation for why each factor is unlikely to be the sole culprit.

Some of the biggest suggested causes for the rise in child and adolescent mental health problems include the following:

• COVID. Multiple studies have documented increases in mood and anxiety associated with the pandemic, which in turn, may be because of a number of factors such as social isolation, loss of family members, family financial stressors, and many other contributors.¹ Yet, while it certainly makes sense that COVID is a powerful instigator of mood and anxiety problems, there is good evidence that the upward tic in emotional-behavioral problems began well before the COVID pandemic.²
• Smartphones. In 2017, psychologist Jean Twenge penned a provocative essay in the Atlantic with the title “Have Smartphones Destroyed a Generation?” and the basic answer was yes.³ The foundation for this conclusion was the tracking between the rise in mood and anxiety problems and the meteoric rise of smartphone use in youth. None of these associations, however, can be proven as casual, and more experimental data on the link between smartphone usage and mental health have been inconsistent.
• Bullying. The toxic effect of bullying and, in particular, online or “cyberbullying” has frequently been brought up as a potential cause. Yet while the negative effects of bullying have been well documented, there is evidence that overall bullying has actually decreased over recent years.⁴

These three factors have arguably been the most discussed, but a few others also probably deserve mention.

• Helicopter parenting. Critics of this common and increasingly popular approach to parenting are concerned that all the parental hovering and stepping in convey the message that the world is a very dangerous place while depriving children of opportunities to gain the exposure and competence they need to succeed. The critique is certainly logical and even has been supported in some studies but lacks the needed evidence for a more definitive conclusion.⁵
• Medications. Of course there will be stories blaming the mental health treatment itself, rather than the reasons people seek treatment, for this disturbing trend. And while it is always important to consider that medications can be part of the problem rather than the solution, the majority of evidence points overall to a lack of treatment rather than too much. A recent important study, for example, found that the peak of suicidal thoughts and behaviors occurred a month before medications were started, rather than after.⁶
• Cannabis. While there seems to be a lot of geographic variability with regard to whether or not the number of youth using cannabis is increasing or not, it’s clear that the product now being consumed is considerably stronger than what was used in decades past. This high-potency cannabis now being used has been shown to increase the risk for later mental health problems including psychosis and suicidal behavior.⁷ Unfortunately, these risks are not being heard as a powerful industry fights to increase their market share.

Putting all this together, it seems likely that a tidy and simple explanation for the alarming increase in youth mental health problems will be hard to pin down. It’s also worth pointing out that many of the above factors could work in a synergistic manner. For example, helicopter parenting may be keeping kids more confined to their rooms where they interact more and more on their phones and are exposed to higher amounts of online bullying, all of which has been magnified recently with the COVID pandemic. Obviously, understanding the causes behind this surge is much more than an academic exercise as the amount of stress and suffering rises and treatment resources get overwhelmed. In the meantime, addressing all of the above factors in both primary and specialty care is worthwhile in an effort to reverse this worrying and wide-ranging pattern.

Dr. Rettew is a child and adolescent psychiatrist and medical director of Lane County Behavioral Health in Eugene, Ore. He is the author of the 2021 book, “Parenting Made Complicated: What Science Really Knows about the Greatest Debates of Early Childhood.” You can follow him on Twitter and Facebook @PediPsych.

References

1. Hawes MT et al. Psychol Med. 2021;13:1-9.

2. Twenge JM et al. J Abnorm Psych. 2019;128(3):185-99.

3. Twenge JM. Have Smartphones Destroyed a Generation? The Atlantic. 2017:September.

4. Rettew DC. Bullying: An update. Child Psych Clin North Am. 2021; in press.

5. Van Der Bruggen CO et al. J Child Psychol Psychiatry. 2008;49(12):1257-69.

6. Lagerberg T et al. Selective serotonin reuptake inhibitors and suicidal behaviour: A population-based cohort study. Neuropsychopharmacology 2021 Sep 24.

7. Gobbi G et al. JAMA Psychiatry. 2019;76(4):426-34.

A novel antidepressant (AXS-05, Axsome Therapeutics) appears to have a rapid and durable effect in patients with major depressive disorder (MDD), results of an open label, phase 3 trial, show. Yet, its new drug application (NDA) remains in limbo with the U.S. Food and Drug Administration for reasons that are unclear.

In the study, which included 876 patients with MDD, results showed the drug, a combination of dextromethorphan and bupropion, had a clinical response rate of 80% and a remission rate of almost 70%. In addition, functional improvements were “substantial” and AXS-05 was determined to be “generally safe and well-tolerated.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

The study

The COMET trial was a phase 3, multicenter, U.S. trial, in which patients with MDD were treated with AXS-05 twice daily for up to 12 months. Patients had to have a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 25. They could have completed a prior AXS-05 study or be newly enrolled.

Of 876 patients included in the study, 611 were newly enrolled. The mean age was 42.4 years, and 62.4% were women. Just over half (58.1%) were White, with 35.6% Black, and 2.0% Asian. The mean body mass index was 31.4 kg/m².

The mean MADRS total score at baseline was 32.7 and the Sheehan Disability Scale (SDS) score was 20.0.

Presenting efficacy data in 609 newly enrolled patients, the team showed that MADRS total scores fell sharply on starting AXS-05, by 9.1 points at week 1, 14.0 points at week 2, and 21.2 points at week 6.

By 6 months, the reduction over baseline was 23.9 points, which was maintained out to 12 months, at a mean reduction of 23.0 points.

The proportion of patients achieving a clinical response, defined as a greater than or equal to 50% improvement in MADRS scores, was 18.8% at week 1, 39.7% at week 2, and 73.2% at week 6. There was a clinical response in 84.6% of patients at 6 months and in 82.8% at 12 months.

Clinical remission, defined as a MADRS score less than or equal to 10, was achieved in 8.3% of patients at week 1, rising to 21.5% at week 2, and 52.5% at week 6. At 6 months, 68.7% of patients were in clinical remission, reaching 69.0% at 12 months.

These benefits were accompanied by substantial improvements in depressive symptoms on the Clinical Global Impression of Improvement scale, with a marked or moderate improvement seen in 86.7% of patients at 6 months and 93.1% at 12 months.

Moreover, a clinical response in functioning on the SDS was achieved by 80.6% of patients at 6 months and 75.9% at 12 months.

The safety analysis of AXS-05 in the entire cohort suggested it was well-tolerated, with dizziness seen in 12.7% of patients, along with nausea in 11.9%, headache in 8.8%, dry mouth in 7.1%, and decreased appetite in 6.1%.

The rate of discontinuation due to adverse events was 8.4%, and there were no signs of psychotomimetic effects, cognitive impairment, weight gain, or increased sexual dysfunction.

Other research presented at the meeting also showed that the drug was associated with a reduction in suicidal ideation and increased rates of suicidal ideation resolution, and was also effective for treatment-resistant depression.

Results from an analysis of the ASCEND phase 2 and GEMINI phase 3 trials also suggested that AXS-05 was superior to both bupropion and placebo in achieving rapid and sustained improvements in depression symptoms.

FDA delay

Yet despite these seemingly positive findings, the FDA appears to have issues with the agent’s new drug application.

As reported in August, the agency reviewed the NDA for AXS-05 for the treatment of MDD, but at that time the drug’s manufacturer revealed that the agency had identified “deficiencies that preclude labeling discussions at this time.”

With the latest results presented at ECNP 2021, this news organization asked Axsome about the status of the NDA and whether there had been any further discussions and/or movement with the FDA.

Instead of a direct reply from the drug company, this news organization was directed to a statement released by Axsome in August announcing that the FDA had informed the company that its NDA review “would not be completed by the Prescription Drug User Fee Act target action date of August 22, 2021.”

“The FDA did not request additional information from the company, and the review of the application is ongoing,” the statement said. Axsome did not respond to further questions.
 

‘Impressive’ remission rate

Commenting on the research, Marin Jukic, PhD, department of physiology and pharmacology, Karolinska Institutet, Stockholm, who was not involved in the research, said AXS-05 “looks promising in relation to the efficacy and tolerability results” with a remission rate that is “truly impressive.”

However, Dr. Jukic cautioned that it was an open-label trial and therefore had no placebo or active comparator arms.

He noted that it would be “interesting to compare the efficacy with placebo and escitalopram, for example, to evaluate the potential for the benefits and efficacy better.”

The research was funded by Axsome Therapeutics, and, except for one, the researchers for the four studies are employees of Axsome Therapeutics.

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

A novel antidepressant (AXS-05, Axsome Therapeutics) appears to have a rapid and durable effect in patients with major depressive disorder (MDD), results of an open label, phase 3 trial, show. Yet, its new drug application (NDA) remains in limbo with the U.S. Food and Drug Administration for reasons that are unclear.

In the study, which included 876 patients with MDD, results showed the drug, a combination of dextromethorphan and bupropion, had a clinical response rate of 80% and a remission rate of almost 70%. In addition, functional improvements were “substantial” and AXS-05 was determined to be “generally safe and well-tolerated.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

The study

The COMET trial was a phase 3, multicenter, U.S. trial, in which patients with MDD were treated with AXS-05 twice daily for up to 12 months. Patients had to have a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 25. They could have completed a prior AXS-05 study or be newly enrolled.

Of 876 patients included in the study, 611 were newly enrolled. The mean age was 42.4 years, and 62.4% were women. Just over half (58.1%) were White, with 35.6% Black, and 2.0% Asian. The mean body mass index was 31.4 kg/m².

The mean MADRS total score at baseline was 32.7 and the Sheehan Disability Scale (SDS) score was 20.0.

Presenting efficacy data in 609 newly enrolled patients, the team showed that MADRS total scores fell sharply on starting AXS-05, by 9.1 points at week 1, 14.0 points at week 2, and 21.2 points at week 6.

By 6 months, the reduction over baseline was 23.9 points, which was maintained out to 12 months, at a mean reduction of 23.0 points.

The proportion of patients achieving a clinical response, defined as a greater than or equal to 50% improvement in MADRS scores, was 18.8% at week 1, 39.7% at week 2, and 73.2% at week 6. There was a clinical response in 84.6% of patients at 6 months and in 82.8% at 12 months.

Clinical remission, defined as a MADRS score less than or equal to 10, was achieved in 8.3% of patients at week 1, rising to 21.5% at week 2, and 52.5% at week 6. At 6 months, 68.7% of patients were in clinical remission, reaching 69.0% at 12 months.

These benefits were accompanied by substantial improvements in depressive symptoms on the Clinical Global Impression of Improvement scale, with a marked or moderate improvement seen in 86.7% of patients at 6 months and 93.1% at 12 months.

Moreover, a clinical response in functioning on the SDS was achieved by 80.6% of patients at 6 months and 75.9% at 12 months.

The safety analysis of AXS-05 in the entire cohort suggested it was well-tolerated, with dizziness seen in 12.7% of patients, along with nausea in 11.9%, headache in 8.8%, dry mouth in 7.1%, and decreased appetite in 6.1%.

The rate of discontinuation due to adverse events was 8.4%, and there were no signs of psychotomimetic effects, cognitive impairment, weight gain, or increased sexual dysfunction.

Other research presented at the meeting also showed that the drug was associated with a reduction in suicidal ideation and increased rates of suicidal ideation resolution, and was also effective for treatment-resistant depression.

Results from an analysis of the ASCEND phase 2 and GEMINI phase 3 trials also suggested that AXS-05 was superior to both bupropion and placebo in achieving rapid and sustained improvements in depression symptoms.

FDA delay

Yet despite these seemingly positive findings, the FDA appears to have issues with the agent’s new drug application.

As reported in August, the agency reviewed the NDA for AXS-05 for the treatment of MDD, but at that time the drug’s manufacturer revealed that the agency had identified “deficiencies that preclude labeling discussions at this time.”

With the latest results presented at ECNP 2021, this news organization asked Axsome about the status of the NDA and whether there had been any further discussions and/or movement with the FDA.

Instead of a direct reply from the drug company, this news organization was directed to a statement released by Axsome in August announcing that the FDA had informed the company that its NDA review “would not be completed by the Prescription Drug User Fee Act target action date of August 22, 2021.”

“The FDA did not request additional information from the company, and the review of the application is ongoing,” the statement said. Axsome did not respond to further questions.
 

‘Impressive’ remission rate

Commenting on the research, Marin Jukic, PhD, department of physiology and pharmacology, Karolinska Institutet, Stockholm, who was not involved in the research, said AXS-05 “looks promising in relation to the efficacy and tolerability results” with a remission rate that is “truly impressive.”

However, Dr. Jukic cautioned that it was an open-label trial and therefore had no placebo or active comparator arms.

He noted that it would be “interesting to compare the efficacy with placebo and escitalopram, for example, to evaluate the potential for the benefits and efficacy better.”

The research was funded by Axsome Therapeutics, and, except for one, the researchers for the four studies are employees of Axsome Therapeutics.

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

A novel antidepressant (AXS-05, Axsome Therapeutics) appears to have a rapid and durable effect in patients with major depressive disorder (MDD), results of an open label, phase 3 trial, show. Yet, its new drug application (NDA) remains in limbo with the U.S. Food and Drug Administration for reasons that are unclear.

In the study, which included 876 patients with MDD, results showed the drug, a combination of dextromethorphan and bupropion, had a clinical response rate of 80% and a remission rate of almost 70%. In addition, functional improvements were “substantial” and AXS-05 was determined to be “generally safe and well-tolerated.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

The study

The COMET trial was a phase 3, multicenter, U.S. trial, in which patients with MDD were treated with AXS-05 twice daily for up to 12 months. Patients had to have a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 25. They could have completed a prior AXS-05 study or be newly enrolled.

Of 876 patients included in the study, 611 were newly enrolled. The mean age was 42.4 years, and 62.4% were women. Just over half (58.1%) were White, with 35.6% Black, and 2.0% Asian. The mean body mass index was 31.4 kg/m².

The mean MADRS total score at baseline was 32.7 and the Sheehan Disability Scale (SDS) score was 20.0.

Presenting efficacy data in 609 newly enrolled patients, the team showed that MADRS total scores fell sharply on starting AXS-05, by 9.1 points at week 1, 14.0 points at week 2, and 21.2 points at week 6.

By 6 months, the reduction over baseline was 23.9 points, which was maintained out to 12 months, at a mean reduction of 23.0 points.

The proportion of patients achieving a clinical response, defined as a greater than or equal to 50% improvement in MADRS scores, was 18.8% at week 1, 39.7% at week 2, and 73.2% at week 6. There was a clinical response in 84.6% of patients at 6 months and in 82.8% at 12 months.

Clinical remission, defined as a MADRS score less than or equal to 10, was achieved in 8.3% of patients at week 1, rising to 21.5% at week 2, and 52.5% at week 6. At 6 months, 68.7% of patients were in clinical remission, reaching 69.0% at 12 months.

These benefits were accompanied by substantial improvements in depressive symptoms on the Clinical Global Impression of Improvement scale, with a marked or moderate improvement seen in 86.7% of patients at 6 months and 93.1% at 12 months.

Moreover, a clinical response in functioning on the SDS was achieved by 80.6% of patients at 6 months and 75.9% at 12 months.

The safety analysis of AXS-05 in the entire cohort suggested it was well-tolerated, with dizziness seen in 12.7% of patients, along with nausea in 11.9%, headache in 8.8%, dry mouth in 7.1%, and decreased appetite in 6.1%.

The rate of discontinuation due to adverse events was 8.4%, and there were no signs of psychotomimetic effects, cognitive impairment, weight gain, or increased sexual dysfunction.

Other research presented at the meeting also showed that the drug was associated with a reduction in suicidal ideation and increased rates of suicidal ideation resolution, and was also effective for treatment-resistant depression.

Results from an analysis of the ASCEND phase 2 and GEMINI phase 3 trials also suggested that AXS-05 was superior to both bupropion and placebo in achieving rapid and sustained improvements in depression symptoms.

FDA delay

Yet despite these seemingly positive findings, the FDA appears to have issues with the agent’s new drug application.

As reported in August, the agency reviewed the NDA for AXS-05 for the treatment of MDD, but at that time the drug’s manufacturer revealed that the agency had identified “deficiencies that preclude labeling discussions at this time.”

With the latest results presented at ECNP 2021, this news organization asked Axsome about the status of the NDA and whether there had been any further discussions and/or movement with the FDA.

Instead of a direct reply from the drug company, this news organization was directed to a statement released by Axsome in August announcing that the FDA had informed the company that its NDA review “would not be completed by the Prescription Drug User Fee Act target action date of August 22, 2021.”

“The FDA did not request additional information from the company, and the review of the application is ongoing,” the statement said. Axsome did not respond to further questions.
 

‘Impressive’ remission rate

Commenting on the research, Marin Jukic, PhD, department of physiology and pharmacology, Karolinska Institutet, Stockholm, who was not involved in the research, said AXS-05 “looks promising in relation to the efficacy and tolerability results” with a remission rate that is “truly impressive.”

However, Dr. Jukic cautioned that it was an open-label trial and therefore had no placebo or active comparator arms.

He noted that it would be “interesting to compare the efficacy with placebo and escitalopram, for example, to evaluate the potential for the benefits and efficacy better.”

The research was funded by Axsome Therapeutics, and, except for one, the researchers for the four studies are employees of Axsome Therapeutics.

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

Patients with comorbid anxiety and mood disorders who have reduced, albeit “normal” serum levels of thyroid-stimulating hormone (TSH) may be at increased risk for suicidal ideation, new research suggests.

In a cross-sectional study, clinical data on diagnosis, medication use, and symptom scores were gathered, along with assessments of blood levels of thyroid axis hormones, in patients with both anxiety and mood disorders.

After investigators accounted for age, gender, symptoms, medication use, and other potential confounders, patients with suicidal ideation were 54% less likely to have higher TSH levels. There was no association found with other thyroid hormones.

Based on the results, the assessment of thyroid hormone levels “may be important for suicide prevention and might allow clinicians to evaluate the potential of the suicidal ideation risk in individuals with [anxiety and mood disorders],” co-investigator Vilma Liaugaudaite, PhD student, Neuroscience Institute of the Lithuanian University of Health Sciences, Palanga, and colleagues note.

The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress.
 

‘Complex mechanism’

Ms. Liaugaudaite told this news organization that thyroid hormones are known to have a “profound” effect on mood and behavior.

Recent studies show “various degrees of hypothalamic-pituitary-thyroid axis dysregulation are associated with suicidal behavior” in patients with depression, she added.

Noting that disturbances in the serotonin system “constitute the most common biochemical abnormality associated with suicidal behavior,” Ms. Liaugaudaite said it is thought thyroid hormones “are involved in a complex compensatory mechanism to correct reduced central 5-hydroxytryptamine activity” via lower TSH levels.

In addition, hypersecretion of thyrotropin-releasing hormone, which stimulates the release of TSH, “has been considered a compensatory mechanism to maintain normal thyroid hormone secretion and normalize serotonin activity in depressed patients,” she said.

To investigate associations between thyroid axis hormones and suicidality in individuals with comorbid anxiety and mood disorders, the researchers assessed consecutive patients attending a stress disorders clinic.

Sociodemographic and clinical information was gathered, and patients completed the Mini International Neuropsychiatric Interview, the Patient Health Questionnaire-9 (PHQ-9), and the General Anxiety Disorder-7 (GAD-7) scale.

Fasting blood samples were also tested for free thyroxine (FT4), free triiodothyronine (FT3), and TSH levels.

Significant association

Seventy-seven patients aged 18 to 73 years participated in the study. Of these, 59 were women. Suicidal ideation was identified in 42 participants. Serum FT4, FT3, and TSH levels were within the normal range.

Badmanproduction/Thinkstock

There were no significant differences between patients with and without suicidal ideation in terms of age, gender, education, obesity, smoking, and medication use.

Suicidal ideation was associated with higher scores on the PHQ-9 (15.5 vs. 13.3; P = .085), and with lower TSH levels (1.54 IU/L vs. 2.04 IU/L; P = .092).

The association between serum TSH levels and suicidal ideation was significant after multivariate logistic regression analysis accounted for age, gender, PHQ-9 and GAD-7 scores, education, body mass index, smoking, and use of antidepressants, tranquilizers, mood stabilizers, and neuroleptics.

Specifically, patients with suicidal ideation were significantly less likely to have higher TSH levels than those without, at an odds ratio of 0.46 (P = .027).

There were no significant associations between serum FT4 and FT3 levels and suicidal ideation.


 

Interesting, but preliminary

Commenting on the findings, Sanjeev Sockalingam, MD, vice chair and professor of psychiatry at the University of Toronto, said it is an “interesting study” because the literature on trying to identify individuals at risk for suicidal ideation or behaviors is “quite mixed, in terms of the results.”

However, it was a cross-sectional study with a relatively small sample size, and studies of this nature typically include patients with hypothyroidism “who end up having suicidal thoughts,” said Dr. Sockalingam, who was not involved with the research.

“I do wonder, given the sample size and patient population, if there may be other factors that may have been related to this,” he added.

Dr. Sockalingam noted that he would like to see more data on the medications the patients were taking, and he underlined that the thyroid levels were in the normal range, “so it’s a bit difficult to untangle what that means in terms of these subtle changes in thyroid levels.”

Robert Levitan, MD, Cameron Wilson Chair in Depression Research at the Centre for Addiction and Mental Health, Toronto, also emphasized that the thyroid levels were in the normal range.

He commented that it therefore “seems unlikely that there’s going to be some biological effect that’s going to affect the brain in a significant enough way” to influence suicidal ideation.

Dr. Levitan continued, “What’s probably happening is there’s some other clinical issue here that they just haven’t picked up on that’s leading in one direction to the suicidal ideation and perhaps affecting the TSH to some extent.”

Although the study is, therefore, “preliminary,” the findings are nevertheless “interesting,” he concluded.

The study received no funding. Ms. Liaugaudaite, Dr. Sockalingam, and Dr. Levitan have disclosed no relevant financial relationships.

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

Patients with comorbid anxiety and mood disorders who have reduced, albeit “normal” serum levels of thyroid-stimulating hormone (TSH) may be at increased risk for suicidal ideation, new research suggests.

In a cross-sectional study, clinical data on diagnosis, medication use, and symptom scores were gathered, along with assessments of blood levels of thyroid axis hormones, in patients with both anxiety and mood disorders.

After investigators accounted for age, gender, symptoms, medication use, and other potential confounders, patients with suicidal ideation were 54% less likely to have higher TSH levels. There was no association found with other thyroid hormones.

Based on the results, the assessment of thyroid hormone levels “may be important for suicide prevention and might allow clinicians to evaluate the potential of the suicidal ideation risk in individuals with [anxiety and mood disorders],” co-investigator Vilma Liaugaudaite, PhD student, Neuroscience Institute of the Lithuanian University of Health Sciences, Palanga, and colleagues note.

The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress.
 

‘Complex mechanism’

Ms. Liaugaudaite told this news organization that thyroid hormones are known to have a “profound” effect on mood and behavior.

Recent studies show “various degrees of hypothalamic-pituitary-thyroid axis dysregulation are associated with suicidal behavior” in patients with depression, she added.

Noting that disturbances in the serotonin system “constitute the most common biochemical abnormality associated with suicidal behavior,” Ms. Liaugaudaite said it is thought thyroid hormones “are involved in a complex compensatory mechanism to correct reduced central 5-hydroxytryptamine activity” via lower TSH levels.

In addition, hypersecretion of thyrotropin-releasing hormone, which stimulates the release of TSH, “has been considered a compensatory mechanism to maintain normal thyroid hormone secretion and normalize serotonin activity in depressed patients,” she said.

To investigate associations between thyroid axis hormones and suicidality in individuals with comorbid anxiety and mood disorders, the researchers assessed consecutive patients attending a stress disorders clinic.

Sociodemographic and clinical information was gathered, and patients completed the Mini International Neuropsychiatric Interview, the Patient Health Questionnaire-9 (PHQ-9), and the General Anxiety Disorder-7 (GAD-7) scale.

Fasting blood samples were also tested for free thyroxine (FT4), free triiodothyronine (FT3), and TSH levels.

Significant association

Seventy-seven patients aged 18 to 73 years participated in the study. Of these, 59 were women. Suicidal ideation was identified in 42 participants. Serum FT4, FT3, and TSH levels were within the normal range.

Badmanproduction/Thinkstock

There were no significant differences between patients with and without suicidal ideation in terms of age, gender, education, obesity, smoking, and medication use.

Suicidal ideation was associated with higher scores on the PHQ-9 (15.5 vs. 13.3; P = .085), and with lower TSH levels (1.54 IU/L vs. 2.04 IU/L; P = .092).

The association between serum TSH levels and suicidal ideation was significant after multivariate logistic regression analysis accounted for age, gender, PHQ-9 and GAD-7 scores, education, body mass index, smoking, and use of antidepressants, tranquilizers, mood stabilizers, and neuroleptics.

Specifically, patients with suicidal ideation were significantly less likely to have higher TSH levels than those without, at an odds ratio of 0.46 (P = .027).

There were no significant associations between serum FT4 and FT3 levels and suicidal ideation.


 

Interesting, but preliminary

Commenting on the findings, Sanjeev Sockalingam, MD, vice chair and professor of psychiatry at the University of Toronto, said it is an “interesting study” because the literature on trying to identify individuals at risk for suicidal ideation or behaviors is “quite mixed, in terms of the results.”

However, it was a cross-sectional study with a relatively small sample size, and studies of this nature typically include patients with hypothyroidism “who end up having suicidal thoughts,” said Dr. Sockalingam, who was not involved with the research.

“I do wonder, given the sample size and patient population, if there may be other factors that may have been related to this,” he added.

Dr. Sockalingam noted that he would like to see more data on the medications the patients were taking, and he underlined that the thyroid levels were in the normal range, “so it’s a bit difficult to untangle what that means in terms of these subtle changes in thyroid levels.”

Robert Levitan, MD, Cameron Wilson Chair in Depression Research at the Centre for Addiction and Mental Health, Toronto, also emphasized that the thyroid levels were in the normal range.

He commented that it therefore “seems unlikely that there’s going to be some biological effect that’s going to affect the brain in a significant enough way” to influence suicidal ideation.

Dr. Levitan continued, “What’s probably happening is there’s some other clinical issue here that they just haven’t picked up on that’s leading in one direction to the suicidal ideation and perhaps affecting the TSH to some extent.”

Although the study is, therefore, “preliminary,” the findings are nevertheless “interesting,” he concluded.

The study received no funding. Ms. Liaugaudaite, Dr. Sockalingam, and Dr. Levitan have disclosed no relevant financial relationships.

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

Patients with comorbid anxiety and mood disorders who have reduced, albeit “normal” serum levels of thyroid-stimulating hormone (TSH) may be at increased risk for suicidal ideation, new research suggests.

In a cross-sectional study, clinical data on diagnosis, medication use, and symptom scores were gathered, along with assessments of blood levels of thyroid axis hormones, in patients with both anxiety and mood disorders.

After investigators accounted for age, gender, symptoms, medication use, and other potential confounders, patients with suicidal ideation were 54% less likely to have higher TSH levels. There was no association found with other thyroid hormones.

Based on the results, the assessment of thyroid hormone levels “may be important for suicide prevention and might allow clinicians to evaluate the potential of the suicidal ideation risk in individuals with [anxiety and mood disorders],” co-investigator Vilma Liaugaudaite, PhD student, Neuroscience Institute of the Lithuanian University of Health Sciences, Palanga, and colleagues note.

The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress.
 

‘Complex mechanism’

Ms. Liaugaudaite told this news organization that thyroid hormones are known to have a “profound” effect on mood and behavior.

Recent studies show “various degrees of hypothalamic-pituitary-thyroid axis dysregulation are associated with suicidal behavior” in patients with depression, she added.

Noting that disturbances in the serotonin system “constitute the most common biochemical abnormality associated with suicidal behavior,” Ms. Liaugaudaite said it is thought thyroid hormones “are involved in a complex compensatory mechanism to correct reduced central 5-hydroxytryptamine activity” via lower TSH levels.

In addition, hypersecretion of thyrotropin-releasing hormone, which stimulates the release of TSH, “has been considered a compensatory mechanism to maintain normal thyroid hormone secretion and normalize serotonin activity in depressed patients,” she said.

To investigate associations between thyroid axis hormones and suicidality in individuals with comorbid anxiety and mood disorders, the researchers assessed consecutive patients attending a stress disorders clinic.

Sociodemographic and clinical information was gathered, and patients completed the Mini International Neuropsychiatric Interview, the Patient Health Questionnaire-9 (PHQ-9), and the General Anxiety Disorder-7 (GAD-7) scale.

Fasting blood samples were also tested for free thyroxine (FT4), free triiodothyronine (FT3), and TSH levels.

Significant association

Seventy-seven patients aged 18 to 73 years participated in the study. Of these, 59 were women. Suicidal ideation was identified in 42 participants. Serum FT4, FT3, and TSH levels were within the normal range.

Badmanproduction/Thinkstock

There were no significant differences between patients with and without suicidal ideation in terms of age, gender, education, obesity, smoking, and medication use.

Suicidal ideation was associated with higher scores on the PHQ-9 (15.5 vs. 13.3; P = .085), and with lower TSH levels (1.54 IU/L vs. 2.04 IU/L; P = .092).

The association between serum TSH levels and suicidal ideation was significant after multivariate logistic regression analysis accounted for age, gender, PHQ-9 and GAD-7 scores, education, body mass index, smoking, and use of antidepressants, tranquilizers, mood stabilizers, and neuroleptics.

Specifically, patients with suicidal ideation were significantly less likely to have higher TSH levels than those without, at an odds ratio of 0.46 (P = .027).

There were no significant associations between serum FT4 and FT3 levels and suicidal ideation.


 

Interesting, but preliminary

Commenting on the findings, Sanjeev Sockalingam, MD, vice chair and professor of psychiatry at the University of Toronto, said it is an “interesting study” because the literature on trying to identify individuals at risk for suicidal ideation or behaviors is “quite mixed, in terms of the results.”

However, it was a cross-sectional study with a relatively small sample size, and studies of this nature typically include patients with hypothyroidism “who end up having suicidal thoughts,” said Dr. Sockalingam, who was not involved with the research.

“I do wonder, given the sample size and patient population, if there may be other factors that may have been related to this,” he added.

Dr. Sockalingam noted that he would like to see more data on the medications the patients were taking, and he underlined that the thyroid levels were in the normal range, “so it’s a bit difficult to untangle what that means in terms of these subtle changes in thyroid levels.”

Robert Levitan, MD, Cameron Wilson Chair in Depression Research at the Centre for Addiction and Mental Health, Toronto, also emphasized that the thyroid levels were in the normal range.

He commented that it therefore “seems unlikely that there’s going to be some biological effect that’s going to affect the brain in a significant enough way” to influence suicidal ideation.

Dr. Levitan continued, “What’s probably happening is there’s some other clinical issue here that they just haven’t picked up on that’s leading in one direction to the suicidal ideation and perhaps affecting the TSH to some extent.”

Although the study is, therefore, “preliminary,” the findings are nevertheless “interesting,” he concluded.

The study received no funding. Ms. Liaugaudaite, Dr. Sockalingam, and Dr. Levitan have disclosed no relevant financial relationships.

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

With all the lockdowns and social distancing of the pandemic, millions of people have had a lot of time to themselves. Many may have filled that time with baking, long walks, or video games, but minds wandering during these periods was inevitable. Coincident with these experiences were increases in depression and anxiety, which could be linked to the same brain network that is thought to support a meandering mind, called the default mode network.

©Thinkstock

Scientists interested in this network wanted to understand how wandering thoughts can lead some people to a state of brooding in which the same negative thoughts resurface repeatedly. To gain some insight into these patterns, they recorded more than 2,000 thoughts spoken aloud by 78 study participants who did nothing but let their minds wander for 10 minutes.

Senior researcher Jessica Andrews-Hanna, PhD, assistant professor of psychology, University of Arizona, Tucson, and colleagues hoped that analyzing these stream-of-consciousness thoughts could yield insights into how people become stuck in negative mental spirals.

They found that most participants thought about the present or future in words that were neither particularly negative nor positive. Almost three-quarters of the thoughts were focused inward on the person or were imaginative.
 

Negativity breeds negativity

But the investigators found an interesting pattern with regard to negative thoughts. The more negative someone’s thoughts became, the more likely that their next idea would be related to their previous one. In other words, negative thoughts created a chain reaction of more negative thoughts.

Positive thoughts, in contrast, tended to be followed by completely unrelated ruminations, indicating true mental meandering. The pattern suggested that negativity tends to narrow the range of thoughts, whereas positivity tends to expand it during periods in which the mind wanders.

The researchers also found, unsurprisingly, that negative thoughts that were focused on the self and on the past were more likely to result in brooding and that positive thoughts were less likely to arise.

Most study participants were young and educated and may have only said things that they were comfortable allowing the researchers to hear. And because the authors didn’t ask participants about their moods, the investigators could not associate specific patterns of thought with any mental health conditions.

Although the findings, published in Scientific Reports, do not on their own point to solutions for depression or anxiety, they may offer a starting point for future research into how negative trains of thoughts begin – and perhaps how to derail them.

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

With all the lockdowns and social distancing of the pandemic, millions of people have had a lot of time to themselves. Many may have filled that time with baking, long walks, or video games, but minds wandering during these periods was inevitable. Coincident with these experiences were increases in depression and anxiety, which could be linked to the same brain network that is thought to support a meandering mind, called the default mode network.

©Thinkstock

Scientists interested in this network wanted to understand how wandering thoughts can lead some people to a state of brooding in which the same negative thoughts resurface repeatedly. To gain some insight into these patterns, they recorded more than 2,000 thoughts spoken aloud by 78 study participants who did nothing but let their minds wander for 10 minutes.

Senior researcher Jessica Andrews-Hanna, PhD, assistant professor of psychology, University of Arizona, Tucson, and colleagues hoped that analyzing these stream-of-consciousness thoughts could yield insights into how people become stuck in negative mental spirals.

They found that most participants thought about the present or future in words that were neither particularly negative nor positive. Almost three-quarters of the thoughts were focused inward on the person or were imaginative.
 

Negativity breeds negativity

But the investigators found an interesting pattern with regard to negative thoughts. The more negative someone’s thoughts became, the more likely that their next idea would be related to their previous one. In other words, negative thoughts created a chain reaction of more negative thoughts.

Positive thoughts, in contrast, tended to be followed by completely unrelated ruminations, indicating true mental meandering. The pattern suggested that negativity tends to narrow the range of thoughts, whereas positivity tends to expand it during periods in which the mind wanders.

The researchers also found, unsurprisingly, that negative thoughts that were focused on the self and on the past were more likely to result in brooding and that positive thoughts were less likely to arise.

Most study participants were young and educated and may have only said things that they were comfortable allowing the researchers to hear. And because the authors didn’t ask participants about their moods, the investigators could not associate specific patterns of thought with any mental health conditions.

Although the findings, published in Scientific Reports, do not on their own point to solutions for depression or anxiety, they may offer a starting point for future research into how negative trains of thoughts begin – and perhaps how to derail them.

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

With all the lockdowns and social distancing of the pandemic, millions of people have had a lot of time to themselves. Many may have filled that time with baking, long walks, or video games, but minds wandering during these periods was inevitable. Coincident with these experiences were increases in depression and anxiety, which could be linked to the same brain network that is thought to support a meandering mind, called the default mode network.

©Thinkstock

Scientists interested in this network wanted to understand how wandering thoughts can lead some people to a state of brooding in which the same negative thoughts resurface repeatedly. To gain some insight into these patterns, they recorded more than 2,000 thoughts spoken aloud by 78 study participants who did nothing but let their minds wander for 10 minutes.

Senior researcher Jessica Andrews-Hanna, PhD, assistant professor of psychology, University of Arizona, Tucson, and colleagues hoped that analyzing these stream-of-consciousness thoughts could yield insights into how people become stuck in negative mental spirals.

They found that most participants thought about the present or future in words that were neither particularly negative nor positive. Almost three-quarters of the thoughts were focused inward on the person or were imaginative.
 

Negativity breeds negativity

But the investigators found an interesting pattern with regard to negative thoughts. The more negative someone’s thoughts became, the more likely that their next idea would be related to their previous one. In other words, negative thoughts created a chain reaction of more negative thoughts.

Positive thoughts, in contrast, tended to be followed by completely unrelated ruminations, indicating true mental meandering. The pattern suggested that negativity tends to narrow the range of thoughts, whereas positivity tends to expand it during periods in which the mind wanders.

The researchers also found, unsurprisingly, that negative thoughts that were focused on the self and on the past were more likely to result in brooding and that positive thoughts were less likely to arise.

Most study participants were young and educated and may have only said things that they were comfortable allowing the researchers to hear. And because the authors didn’t ask participants about their moods, the investigators could not associate specific patterns of thought with any mental health conditions.

Although the findings, published in Scientific Reports, do not on their own point to solutions for depression or anxiety, they may offer a starting point for future research into how negative trains of thoughts begin – and perhaps how to derail them.

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

A simple caregiver education intervention reduced the use of psychotropic medications and associated drugs costs in long-term care facilities for the elderly in a new study.

The effect of the intervention was transient, possibly because of high staff turnover, according to the investigators in the new randomized, controlled trial.

The findings were presented by Ulla Aalto, MD, PhD, during a session at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

There was a significant reduction in the use of psychotropic agents at 6 months in long-term care wards where the nursing staff had undergone a short training session on drug therapy for older patients, but there was no improvement in wards that were randomly assigned to serve as controls, Dr. Aalto, from Helsinki Hospital, reported during the session.

“Future research would be investigating how we could maintain the positive effects that were gained at 6 months but not seen any more at 1 year, and how to implement the good practice in nursing homes by this kind of staff training,” she said.

Heavy drug use

Psychotropic medications are widely used in long-term care settings, but their indiscriminate use or use of the wrong drug for the wrong patient can be harmful. Inappropriate drug use in long-term care settings is also associated with higher costs, Dr. Aalto said.

To see whether a staff-training intervention could reduce drugs use and lower costs, the investigators conducted a randomized clinical trial in assisted living facilities in Helsinki in 2011, with a total of 227 patients 65 years and older.

Long-term care wards were randomly assigned to either an intervention for nursing staff consisting of two 4-hour sessions on good drug-therapy practice for older adults, or to serve as controls (10 wards in each group).

Drug use and costs were monitored at both 6 and 12 months after randomization. Psychotropic drugs included antipsychotics, antidepressants, anxiolytics, and hypnotics as classified by the World Health Organization. For the purposes of comparison, actual doses were counted and converted into relative proportions of defined daily doses.

The baseline characteristics of patients in each group were generally similar, with a mean age of around 83 years. In each study arm, nearly two-thirds of patients were on at least one psychotropic drug, and of this group, a third had been prescribed 2 or more psychotropic agents.

Nearly half of the patients were on at least one antipsychotic agent and/or antidepressant.
 

Short-term benefit

As noted before, in the wards randomized to staff training, there was a significant reduction in use of all psychotropics from baseline at 6 months after randomization (P = .045), but there was no change among the control wards.

By 12 months, however, the differences between the intervention and control arms narrowed, and drug use in the intervention arm was no longer significantly lower over baseline.

Drugs costs significantly decreased in the intervention group at 6 months (P = .027) and were numerically but not statistically lower over baseline at 12 months.

In contrast, drug costs in the control arm were numerically (but not statistically) higher at both 6 and 12 months of follow-up.

Annual drug costs in the intervention group decreased by mean of 12.3 euros ($14.22) whereas costs in the control group increased by a mean of 20.6 euros ($23.81).

“This quite light and feasible intervention succeeded in reducing overall defined daily doses of psychotropics in the short term,” Dr. Aalto said.

The waning of the intervention’s effect on drug use and costs may be caused partly by the high employee turnover rate in long-term care facilities and to the dilution effect, she said, referring to a form of judgment bias in which people tend to devalue diagnostic information when other, nondiagnostic information is also available.
 

Randomized design

In the question-and-answer session following her presentation, audience member Jesper Ryg, MD, PhD from Odense (Denmark) University Hospital and the University of Southern Denmark, also in Odense, commented: “It’s a great study, doing a [randomized, controlled trial] on deprescribing, we need more of those.”

“But what we know now is that a lot of studies show it is possible to deprescribe and get less drugs, but do we have any clinical data? Does this deprescribing lead to less falls, did it lead to lower mortality?” he asked.

Dr. Aalto replied that, in an earlier report from this study, investigators showed that harmful medication use was reduced and negative outcomes were reduced.

Another audience member asked why nursing staff were the target of the intervention, given that physicians do the actual drug prescribing.

Dr. Aalto responded: “It is the physician of course who prescribes, but in nursing homes and long-term care, nursing staff is there all the time, and the physicians are kind of consultants who just come there once in a while, so it’s important that the nurses also know about these harmful medications and can bring them to the doctor when he or she arrives there.”

Dr. Aalto and Dr. Ryg had no disclosures.

A simple caregiver education intervention reduced the use of psychotropic medications and associated drugs costs in long-term care facilities for the elderly in a new study.

The effect of the intervention was transient, possibly because of high staff turnover, according to the investigators in the new randomized, controlled trial.

The findings were presented by Ulla Aalto, MD, PhD, during a session at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

There was a significant reduction in the use of psychotropic agents at 6 months in long-term care wards where the nursing staff had undergone a short training session on drug therapy for older patients, but there was no improvement in wards that were randomly assigned to serve as controls, Dr. Aalto, from Helsinki Hospital, reported during the session.

“Future research would be investigating how we could maintain the positive effects that were gained at 6 months but not seen any more at 1 year, and how to implement the good practice in nursing homes by this kind of staff training,” she said.

Heavy drug use

Psychotropic medications are widely used in long-term care settings, but their indiscriminate use or use of the wrong drug for the wrong patient can be harmful. Inappropriate drug use in long-term care settings is also associated with higher costs, Dr. Aalto said.

To see whether a staff-training intervention could reduce drugs use and lower costs, the investigators conducted a randomized clinical trial in assisted living facilities in Helsinki in 2011, with a total of 227 patients 65 years and older.

Long-term care wards were randomly assigned to either an intervention for nursing staff consisting of two 4-hour sessions on good drug-therapy practice for older adults, or to serve as controls (10 wards in each group).

Drug use and costs were monitored at both 6 and 12 months after randomization. Psychotropic drugs included antipsychotics, antidepressants, anxiolytics, and hypnotics as classified by the World Health Organization. For the purposes of comparison, actual doses were counted and converted into relative proportions of defined daily doses.

The baseline characteristics of patients in each group were generally similar, with a mean age of around 83 years. In each study arm, nearly two-thirds of patients were on at least one psychotropic drug, and of this group, a third had been prescribed 2 or more psychotropic agents.

Nearly half of the patients were on at least one antipsychotic agent and/or antidepressant.
 

Short-term benefit

As noted before, in the wards randomized to staff training, there was a significant reduction in use of all psychotropics from baseline at 6 months after randomization (P = .045), but there was no change among the control wards.

By 12 months, however, the differences between the intervention and control arms narrowed, and drug use in the intervention arm was no longer significantly lower over baseline.

Drugs costs significantly decreased in the intervention group at 6 months (P = .027) and were numerically but not statistically lower over baseline at 12 months.

In contrast, drug costs in the control arm were numerically (but not statistically) higher at both 6 and 12 months of follow-up.

Annual drug costs in the intervention group decreased by mean of 12.3 euros ($14.22) whereas costs in the control group increased by a mean of 20.6 euros ($23.81).

“This quite light and feasible intervention succeeded in reducing overall defined daily doses of psychotropics in the short term,” Dr. Aalto said.

The waning of the intervention’s effect on drug use and costs may be caused partly by the high employee turnover rate in long-term care facilities and to the dilution effect, she said, referring to a form of judgment bias in which people tend to devalue diagnostic information when other, nondiagnostic information is also available.
 

Randomized design

In the question-and-answer session following her presentation, audience member Jesper Ryg, MD, PhD from Odense (Denmark) University Hospital and the University of Southern Denmark, also in Odense, commented: “It’s a great study, doing a [randomized, controlled trial] on deprescribing, we need more of those.”

“But what we know now is that a lot of studies show it is possible to deprescribe and get less drugs, but do we have any clinical data? Does this deprescribing lead to less falls, did it lead to lower mortality?” he asked.

Dr. Aalto replied that, in an earlier report from this study, investigators showed that harmful medication use was reduced and negative outcomes were reduced.

Another audience member asked why nursing staff were the target of the intervention, given that physicians do the actual drug prescribing.

Dr. Aalto responded: “It is the physician of course who prescribes, but in nursing homes and long-term care, nursing staff is there all the time, and the physicians are kind of consultants who just come there once in a while, so it’s important that the nurses also know about these harmful medications and can bring them to the doctor when he or she arrives there.”

Dr. Aalto and Dr. Ryg had no disclosures.

A simple caregiver education intervention reduced the use of psychotropic medications and associated drugs costs in long-term care facilities for the elderly in a new study.

The effect of the intervention was transient, possibly because of high staff turnover, according to the investigators in the new randomized, controlled trial.

The findings were presented by Ulla Aalto, MD, PhD, during a session at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

There was a significant reduction in the use of psychotropic agents at 6 months in long-term care wards where the nursing staff had undergone a short training session on drug therapy for older patients, but there was no improvement in wards that were randomly assigned to serve as controls, Dr. Aalto, from Helsinki Hospital, reported during the session.

“Future research would be investigating how we could maintain the positive effects that were gained at 6 months but not seen any more at 1 year, and how to implement the good practice in nursing homes by this kind of staff training,” she said.

Heavy drug use

Psychotropic medications are widely used in long-term care settings, but their indiscriminate use or use of the wrong drug for the wrong patient can be harmful. Inappropriate drug use in long-term care settings is also associated with higher costs, Dr. Aalto said.

To see whether a staff-training intervention could reduce drugs use and lower costs, the investigators conducted a randomized clinical trial in assisted living facilities in Helsinki in 2011, with a total of 227 patients 65 years and older.

Long-term care wards were randomly assigned to either an intervention for nursing staff consisting of two 4-hour sessions on good drug-therapy practice for older adults, or to serve as controls (10 wards in each group).

Drug use and costs were monitored at both 6 and 12 months after randomization. Psychotropic drugs included antipsychotics, antidepressants, anxiolytics, and hypnotics as classified by the World Health Organization. For the purposes of comparison, actual doses were counted and converted into relative proportions of defined daily doses.

The baseline characteristics of patients in each group were generally similar, with a mean age of around 83 years. In each study arm, nearly two-thirds of patients were on at least one psychotropic drug, and of this group, a third had been prescribed 2 or more psychotropic agents.

Nearly half of the patients were on at least one antipsychotic agent and/or antidepressant.
 

Short-term benefit

As noted before, in the wards randomized to staff training, there was a significant reduction in use of all psychotropics from baseline at 6 months after randomization (P = .045), but there was no change among the control wards.

By 12 months, however, the differences between the intervention and control arms narrowed, and drug use in the intervention arm was no longer significantly lower over baseline.

Drugs costs significantly decreased in the intervention group at 6 months (P = .027) and were numerically but not statistically lower over baseline at 12 months.

In contrast, drug costs in the control arm were numerically (but not statistically) higher at both 6 and 12 months of follow-up.

Annual drug costs in the intervention group decreased by mean of 12.3 euros ($14.22) whereas costs in the control group increased by a mean of 20.6 euros ($23.81).

“This quite light and feasible intervention succeeded in reducing overall defined daily doses of psychotropics in the short term,” Dr. Aalto said.

The waning of the intervention’s effect on drug use and costs may be caused partly by the high employee turnover rate in long-term care facilities and to the dilution effect, she said, referring to a form of judgment bias in which people tend to devalue diagnostic information when other, nondiagnostic information is also available.
 

Randomized design

In the question-and-answer session following her presentation, audience member Jesper Ryg, MD, PhD from Odense (Denmark) University Hospital and the University of Southern Denmark, also in Odense, commented: “It’s a great study, doing a [randomized, controlled trial] on deprescribing, we need more of those.”

“But what we know now is that a lot of studies show it is possible to deprescribe and get less drugs, but do we have any clinical data? Does this deprescribing lead to less falls, did it lead to lower mortality?” he asked.

Dr. Aalto replied that, in an earlier report from this study, investigators showed that harmful medication use was reduced and negative outcomes were reduced.

Another audience member asked why nursing staff were the target of the intervention, given that physicians do the actual drug prescribing.

Dr. Aalto responded: “It is the physician of course who prescribes, but in nursing homes and long-term care, nursing staff is there all the time, and the physicians are kind of consultants who just come there once in a while, so it’s important that the nurses also know about these harmful medications and can bring them to the doctor when he or she arrives there.”

Dr. Aalto and Dr. Ryg had no disclosures.

Study results of an experimental agent that improves symptoms of major depression and boosts quality of life in as little as 3 days suggest it may be an effective short-term treatment option.

Jupiterimages/ThinkStock

Phase 3 results of a randomized, placebo-controlled trial compared zuranolone, an neuroactive steroid that binds to both synaptic and extra-synaptic GABA-A receptors, to placebo in patients with major depressive disorder (MDD). Overall, 30% of participants were already taking antidepressants.

Investigators found the drug was associated with a significant improvement in depression scores versus placebo, with benefit observed as early as day 3. This was accompanied by improved function and well-being.

The drug was also “generally well tolerated” and had a safety profile that was “consistent” with what has been seen previously with the drug, said study presenter Colville Brown, MD, Sage Therapeutics, Cambridge, Mass.

“These data continue to support the development of zuranolone as a potential 14-day short course treatment for major depressive disorder episodes.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

High placebo response

However, despite being significant, the drug’s benefit was only slightly higher than that of placebo, raising questions about the study design and the true performance of the drug.

Dr. Brown explained that patients with MDD were randomized to oral zuranolone 50 mg or placebo once daily for 14 days, with dose reductions to 40 mg or matching placebo permitted in case of perceived intolerance.

Patients were assessed at baseline and day 15 via the 17-item Hamilton Rating Scale for Depression (HAMD-17) before entering a 28-day follow-up period off the study drug.

Among the 268 participants who received zuranolone, 90.3% completed the study, compared with 87.4% of 269 patients in the placebo group.

The mean age of participants was 40 years. Women made up 69.4% of those who received zuranolone and 61.7% assigned to placebo.

The mean HAMD-17 score at baseline was 26.8 and 26.9 in the zuranolone and placebo groups, respectively. Dr. Brown noted that 29.5% of patients in the zuranolone group and 30.1% of those assigned to placebo were taking antidepressants at baseline.

The study’s primary endpoint was met, with patients taking the study drug experiencing a significantly greater reduction in HAMD-17 scores from baseline to day 15 versus those given placebo, at 14.1 versus 12.3 points (P = .0141).

Dr. Brown highlighted that the difference in reduction in HAMD-17 scores between the zuranolone and placebo groups was already significant at day 3 (P < .0001), and again at day 8 (P < .0001) and day 12 (P < .001).

At day 3, response rates on the HAMD-17 were significantly higher among zuranolone-treated patients than among those given placebo, at 29.3% versus 16.3% (P < .001). However, the differences on day 15 and on day 42 were no longer significant.

A similar effect was seen for HAMD-17 remissions, which were seen in 7.6% of zuranolone-treated patients and 2.3% of those given placebo at day 3 (P < .01), rising to 29.8% versus 27.1% at day 15, and 30.8% versus 29.6% at day 42, and neither difference was significant.

Dr. Brown also showed that, at all time points during the treatment and follow-up periods, improvements in response rates in Global Improvement on the Clinical Global Impression scale favored zuranolone.

On the SF-36v2 quality of life questionnaire, improvements again favored zuranolone on all domains, although the difference between active treatment and placebo was significant only for vitality on day 15, at 12.8 versus 9.7 points (P < .05).

Treatment-emergent adverse events were more common with zuranolone, with 60.1% of patients experiencing at least one event of any grade versus 44.6% with placebo. However, severe events were seen in only 3.0% versus 1.1% of patients, and serious adverse events were recorded in only two patients (0.7%) in both groups.

The most common adverse events were somnolence, dizziness, headache, sedation, and diarrhea, with no increase in suicidal ideation or withdrawal. Dr. Brown noted that there was “no change in the safety signal” between patients with or without prior antidepressant therapy.

From the audience, Marie-Josée Filteau, MD, department of psychiatry, Laval University, Quebec, drew attention to the similarity in the improvement in HAMD-17 scores between the zuranolone and placebo groups, asking: “How is that compelling?”

Dr. Brown replied that “what they are excited about is that change from baseline with zuranolone,” adding: “You do see it in the placebo group as well, and ... this isn’t new to psychiatry.

“This is a heterogeneous disease, and remember this [study] was conducted during COVID, so patients were being seen with clinic visits during COVID.

“What impact did that have? The placebo is not really placebo” in this case.

More effective than results suggest?

Approached for comment by this news organization, Maurizio Fava, MD, executive vice chair, department of psychiatry, and executive director, Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, noted there are several issues with the trial.

Because of those, the drug “is likely to be much more efficacious than it looks because it achieved statistical significance despite an extremely high placebo response,” he said

“Whenever your change on placebo is greater than 10 points on the HAMD, you have an excessive response ... and a very, very low chance of detecting a signal,” he said.

Dr. Fava said that another issue was including patients who were either on or off antidepressants, which meant the population was not sufficiently homogenous.

Another “flaw” was to assume that the placebo effect would be “transient” and deteriorate over time, whereas the results showed the opposite.

Nevertheless, “it’s a positive study because of the sample size ... that provides further evidence for the antidepressant activity of zuranolone” and the drug was “well tolerated.”

Dr. Fava expects zuranolone “will make it to the market,” as an indication from the Food and Drug Administration is likely, “but if you’re asking me: Is the drug as effective as shown in their studies? It’s probably much more effective.”

The study was funded by Sage Therapeutics and Biogen. Dr. Brown is an employee of Sage Therapeutics. Lead investigator Anita Clayton, MD, University of Virginia, Charlottesville, has reported relationships with Dario Bioscience, Janssen, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Fabre-Kramer, MindCure, Ovoca Bio, PureTech Health, S1 Biopharma, Vella Bioscience, WCG MedAvante-ProPhase, Ballantine Books/Random House, Guilford Publications, Euthymics, and Mediflix.

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

Study results of an experimental agent that improves symptoms of major depression and boosts quality of life in as little as 3 days suggest it may be an effective short-term treatment option.

Jupiterimages/ThinkStock

Phase 3 results of a randomized, placebo-controlled trial compared zuranolone, an neuroactive steroid that binds to both synaptic and extra-synaptic GABA-A receptors, to placebo in patients with major depressive disorder (MDD). Overall, 30% of participants were already taking antidepressants.

Investigators found the drug was associated with a significant improvement in depression scores versus placebo, with benefit observed as early as day 3. This was accompanied by improved function and well-being.

The drug was also “generally well tolerated” and had a safety profile that was “consistent” with what has been seen previously with the drug, said study presenter Colville Brown, MD, Sage Therapeutics, Cambridge, Mass.

“These data continue to support the development of zuranolone as a potential 14-day short course treatment for major depressive disorder episodes.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

High placebo response

However, despite being significant, the drug’s benefit was only slightly higher than that of placebo, raising questions about the study design and the true performance of the drug.

Dr. Brown explained that patients with MDD were randomized to oral zuranolone 50 mg or placebo once daily for 14 days, with dose reductions to 40 mg or matching placebo permitted in case of perceived intolerance.

Patients were assessed at baseline and day 15 via the 17-item Hamilton Rating Scale for Depression (HAMD-17) before entering a 28-day follow-up period off the study drug.

Among the 268 participants who received zuranolone, 90.3% completed the study, compared with 87.4% of 269 patients in the placebo group.

The mean age of participants was 40 years. Women made up 69.4% of those who received zuranolone and 61.7% assigned to placebo.

The mean HAMD-17 score at baseline was 26.8 and 26.9 in the zuranolone and placebo groups, respectively. Dr. Brown noted that 29.5% of patients in the zuranolone group and 30.1% of those assigned to placebo were taking antidepressants at baseline.

The study’s primary endpoint was met, with patients taking the study drug experiencing a significantly greater reduction in HAMD-17 scores from baseline to day 15 versus those given placebo, at 14.1 versus 12.3 points (P = .0141).

Dr. Brown highlighted that the difference in reduction in HAMD-17 scores between the zuranolone and placebo groups was already significant at day 3 (P < .0001), and again at day 8 (P < .0001) and day 12 (P < .001).

At day 3, response rates on the HAMD-17 were significantly higher among zuranolone-treated patients than among those given placebo, at 29.3% versus 16.3% (P < .001). However, the differences on day 15 and on day 42 were no longer significant.

A similar effect was seen for HAMD-17 remissions, which were seen in 7.6% of zuranolone-treated patients and 2.3% of those given placebo at day 3 (P < .01), rising to 29.8% versus 27.1% at day 15, and 30.8% versus 29.6% at day 42, and neither difference was significant.

Dr. Brown also showed that, at all time points during the treatment and follow-up periods, improvements in response rates in Global Improvement on the Clinical Global Impression scale favored zuranolone.

On the SF-36v2 quality of life questionnaire, improvements again favored zuranolone on all domains, although the difference between active treatment and placebo was significant only for vitality on day 15, at 12.8 versus 9.7 points (P < .05).

Treatment-emergent adverse events were more common with zuranolone, with 60.1% of patients experiencing at least one event of any grade versus 44.6% with placebo. However, severe events were seen in only 3.0% versus 1.1% of patients, and serious adverse events were recorded in only two patients (0.7%) in both groups.

The most common adverse events were somnolence, dizziness, headache, sedation, and diarrhea, with no increase in suicidal ideation or withdrawal. Dr. Brown noted that there was “no change in the safety signal” between patients with or without prior antidepressant therapy.

From the audience, Marie-Josée Filteau, MD, department of psychiatry, Laval University, Quebec, drew attention to the similarity in the improvement in HAMD-17 scores between the zuranolone and placebo groups, asking: “How is that compelling?”

Dr. Brown replied that “what they are excited about is that change from baseline with zuranolone,” adding: “You do see it in the placebo group as well, and ... this isn’t new to psychiatry.

“This is a heterogeneous disease, and remember this [study] was conducted during COVID, so patients were being seen with clinic visits during COVID.

“What impact did that have? The placebo is not really placebo” in this case.

More effective than results suggest?

Approached for comment by this news organization, Maurizio Fava, MD, executive vice chair, department of psychiatry, and executive director, Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, noted there are several issues with the trial.

Because of those, the drug “is likely to be much more efficacious than it looks because it achieved statistical significance despite an extremely high placebo response,” he said

“Whenever your change on placebo is greater than 10 points on the HAMD, you have an excessive response ... and a very, very low chance of detecting a signal,” he said.

Dr. Fava said that another issue was including patients who were either on or off antidepressants, which meant the population was not sufficiently homogenous.

Another “flaw” was to assume that the placebo effect would be “transient” and deteriorate over time, whereas the results showed the opposite.

Nevertheless, “it’s a positive study because of the sample size ... that provides further evidence for the antidepressant activity of zuranolone” and the drug was “well tolerated.”

Dr. Fava expects zuranolone “will make it to the market,” as an indication from the Food and Drug Administration is likely, “but if you’re asking me: Is the drug as effective as shown in their studies? It’s probably much more effective.”

The study was funded by Sage Therapeutics and Biogen. Dr. Brown is an employee of Sage Therapeutics. Lead investigator Anita Clayton, MD, University of Virginia, Charlottesville, has reported relationships with Dario Bioscience, Janssen, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Fabre-Kramer, MindCure, Ovoca Bio, PureTech Health, S1 Biopharma, Vella Bioscience, WCG MedAvante-ProPhase, Ballantine Books/Random House, Guilford Publications, Euthymics, and Mediflix.

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

Study results of an experimental agent that improves symptoms of major depression and boosts quality of life in as little as 3 days suggest it may be an effective short-term treatment option.

Jupiterimages/ThinkStock

Phase 3 results of a randomized, placebo-controlled trial compared zuranolone, an neuroactive steroid that binds to both synaptic and extra-synaptic GABA-A receptors, to placebo in patients with major depressive disorder (MDD). Overall, 30% of participants were already taking antidepressants.

Investigators found the drug was associated with a significant improvement in depression scores versus placebo, with benefit observed as early as day 3. This was accompanied by improved function and well-being.

The drug was also “generally well tolerated” and had a safety profile that was “consistent” with what has been seen previously with the drug, said study presenter Colville Brown, MD, Sage Therapeutics, Cambridge, Mass.

“These data continue to support the development of zuranolone as a potential 14-day short course treatment for major depressive disorder episodes.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

High placebo response

However, despite being significant, the drug’s benefit was only slightly higher than that of placebo, raising questions about the study design and the true performance of the drug.

Dr. Brown explained that patients with MDD were randomized to oral zuranolone 50 mg or placebo once daily for 14 days, with dose reductions to 40 mg or matching placebo permitted in case of perceived intolerance.

Patients were assessed at baseline and day 15 via the 17-item Hamilton Rating Scale for Depression (HAMD-17) before entering a 28-day follow-up period off the study drug.

Among the 268 participants who received zuranolone, 90.3% completed the study, compared with 87.4% of 269 patients in the placebo group.

The mean age of participants was 40 years. Women made up 69.4% of those who received zuranolone and 61.7% assigned to placebo.

The mean HAMD-17 score at baseline was 26.8 and 26.9 in the zuranolone and placebo groups, respectively. Dr. Brown noted that 29.5% of patients in the zuranolone group and 30.1% of those assigned to placebo were taking antidepressants at baseline.

The study’s primary endpoint was met, with patients taking the study drug experiencing a significantly greater reduction in HAMD-17 scores from baseline to day 15 versus those given placebo, at 14.1 versus 12.3 points (P = .0141).

Dr. Brown highlighted that the difference in reduction in HAMD-17 scores between the zuranolone and placebo groups was already significant at day 3 (P < .0001), and again at day 8 (P < .0001) and day 12 (P < .001).

At day 3, response rates on the HAMD-17 were significantly higher among zuranolone-treated patients than among those given placebo, at 29.3% versus 16.3% (P < .001). However, the differences on day 15 and on day 42 were no longer significant.

A similar effect was seen for HAMD-17 remissions, which were seen in 7.6% of zuranolone-treated patients and 2.3% of those given placebo at day 3 (P < .01), rising to 29.8% versus 27.1% at day 15, and 30.8% versus 29.6% at day 42, and neither difference was significant.

Dr. Brown also showed that, at all time points during the treatment and follow-up periods, improvements in response rates in Global Improvement on the Clinical Global Impression scale favored zuranolone.

On the SF-36v2 quality of life questionnaire, improvements again favored zuranolone on all domains, although the difference between active treatment and placebo was significant only for vitality on day 15, at 12.8 versus 9.7 points (P < .05).

Treatment-emergent adverse events were more common with zuranolone, with 60.1% of patients experiencing at least one event of any grade versus 44.6% with placebo. However, severe events were seen in only 3.0% versus 1.1% of patients, and serious adverse events were recorded in only two patients (0.7%) in both groups.

The most common adverse events were somnolence, dizziness, headache, sedation, and diarrhea, with no increase in suicidal ideation or withdrawal. Dr. Brown noted that there was “no change in the safety signal” between patients with or without prior antidepressant therapy.

From the audience, Marie-Josée Filteau, MD, department of psychiatry, Laval University, Quebec, drew attention to the similarity in the improvement in HAMD-17 scores between the zuranolone and placebo groups, asking: “How is that compelling?”

Dr. Brown replied that “what they are excited about is that change from baseline with zuranolone,” adding: “You do see it in the placebo group as well, and ... this isn’t new to psychiatry.

“This is a heterogeneous disease, and remember this [study] was conducted during COVID, so patients were being seen with clinic visits during COVID.

“What impact did that have? The placebo is not really placebo” in this case.

More effective than results suggest?

Approached for comment by this news organization, Maurizio Fava, MD, executive vice chair, department of psychiatry, and executive director, Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, noted there are several issues with the trial.

Because of those, the drug “is likely to be much more efficacious than it looks because it achieved statistical significance despite an extremely high placebo response,” he said

“Whenever your change on placebo is greater than 10 points on the HAMD, you have an excessive response ... and a very, very low chance of detecting a signal,” he said.

Dr. Fava said that another issue was including patients who were either on or off antidepressants, which meant the population was not sufficiently homogenous.

Another “flaw” was to assume that the placebo effect would be “transient” and deteriorate over time, whereas the results showed the opposite.

Nevertheless, “it’s a positive study because of the sample size ... that provides further evidence for the antidepressant activity of zuranolone” and the drug was “well tolerated.”

Dr. Fava expects zuranolone “will make it to the market,” as an indication from the Food and Drug Administration is likely, “but if you’re asking me: Is the drug as effective as shown in their studies? It’s probably much more effective.”

The study was funded by Sage Therapeutics and Biogen. Dr. Brown is an employee of Sage Therapeutics. Lead investigator Anita Clayton, MD, University of Virginia, Charlottesville, has reported relationships with Dario Bioscience, Janssen, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Fabre-Kramer, MindCure, Ovoca Bio, PureTech Health, S1 Biopharma, Vella Bioscience, WCG MedAvante-ProPhase, Ballantine Books/Random House, Guilford Publications, Euthymics, and Mediflix.

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

After a concussion, resuming aerobic exercise relatively early on – at an intensity that does not worsen symptoms – may help young athletes recover sooner, compared with stretching, a randomized controlled trial (RCT) shows.

Douglas Levere/University at Buffalo

The study adds to emerging evidence that clinicians should prescribe exercise, rather than strict rest, to facilitate concussion recovery, researchers said.

Tamara McLeod, PhD, ATC, professor and director of athletic training programs at A.T. Still University in Mesa, Ariz., hopes the findings help clinicians see that “this is an approach that should be taken.”

“Too often with concussion, patients are given a laundry list of things they are NOT allowed to do,” including sports, school, and social activities, said Dr. McLeod, who was not involved in the study.

The research, published in The Lancet Child & Adolescent Health, largely replicates the findings of a prior trial while addressing limitations of the previous study’s design, researchers said.

For the trial, John J. Leddy, MD, with the State University of New York at Buffalo and colleagues recruited 118 male and female adolescent athletes aged 13-18 years who had had a sport-related concussion in the past 10 days. Investigators at three community and hospital-affiliated sports medicine concussion centers in the United States randomly assigned the athletes to individualized subsymptom-threshold aerobic exercise (61 participants) or stretching exercise (57 participants) at least 20 minutes per day for up to 4 weeks. Aerobic exercise included walking, jogging, or stationary cycling at home.

“It is important that the general clinician community appreciates that prolonged rest and avoidance of physical activity until spontaneous symptom resolution is no longer an acceptable approach to caring for adolescents with concussion,” Dr. Leddy and coauthors said.

The investigators improved on the “the scientific rigor of their previous RCT by including intention-to-treat and per-protocol analyses, daily symptom reporting, objective exercise adherence measurements, and greater heterogeneity of concussion severity,” said Carolyn A. Emery, PhD, and Jonathan Smirl, PhD, both with the University of Calgary (Alta.), in a related commentary. The new study is the first to show that early targeted heart rate subsymptom-threshold aerobic exercise, relative to stretching, shortened recovery time within 4 weeks after sport-related concussion (hazard ratio, 0.52) when controlling for sex, study site, and average daily exercise time, Dr. Emery and Dr. Smirl said.

A larger proportion of athletes assigned to stretching did not recover by 4 weeks, compared with those assigned to aerobic exercise (32% vs. 21%). The median time to full recovery was longer for the stretching group than for the aerobic exercise group (19 days vs. 14 days).

Among athletes who adhered to their assigned regimens, the differences were more pronounced: The median recovery time was 21 days for the stretching group, compared with 12 days for the aerobic exercise group. The rate of postconcussion symptoms beyond 28 days was 9% in the aerobic exercise group versus 31% in the stretching group, among adherent participants.

More research is needed to establish the efficacy of postconcussion aerobic exercise in adults and for nonsport injury, the researchers noted. Possible mechanisms underlying aerobic exercise’s benefits could include increased parasympathetic autonomic tone, improved cerebral blood flow regulation, or enhanced neuron repair, they suggested.

The right amount and timing of exercise, and doing so at an intensity that does not exacerbate symptoms, may be key. Other research has suggested that too much exercise, too soon may delay recovery, Dr. Emery said in an interview. “But there is now a lot of evidence to support low and moderate levels of physical activity to expedite recovery,” she said.

The study was funded by the American Medical Society for Sports Medicine. The study and commentary authors and Dr. McLeod had no disclosures.

jremaly@mdedge.com

After a concussion, resuming aerobic exercise relatively early on – at an intensity that does not worsen symptoms – may help young athletes recover sooner, compared with stretching, a randomized controlled trial (RCT) shows.

Douglas Levere/University at Buffalo

The study adds to emerging evidence that clinicians should prescribe exercise, rather than strict rest, to facilitate concussion recovery, researchers said.

Tamara McLeod, PhD, ATC, professor and director of athletic training programs at A.T. Still University in Mesa, Ariz., hopes the findings help clinicians see that “this is an approach that should be taken.”

“Too often with concussion, patients are given a laundry list of things they are NOT allowed to do,” including sports, school, and social activities, said Dr. McLeod, who was not involved in the study.

The research, published in The Lancet Child & Adolescent Health, largely replicates the findings of a prior trial while addressing limitations of the previous study’s design, researchers said.

For the trial, John J. Leddy, MD, with the State University of New York at Buffalo and colleagues recruited 118 male and female adolescent athletes aged 13-18 years who had had a sport-related concussion in the past 10 days. Investigators at three community and hospital-affiliated sports medicine concussion centers in the United States randomly assigned the athletes to individualized subsymptom-threshold aerobic exercise (61 participants) or stretching exercise (57 participants) at least 20 minutes per day for up to 4 weeks. Aerobic exercise included walking, jogging, or stationary cycling at home.

“It is important that the general clinician community appreciates that prolonged rest and avoidance of physical activity until spontaneous symptom resolution is no longer an acceptable approach to caring for adolescents with concussion,” Dr. Leddy and coauthors said.

The investigators improved on the “the scientific rigor of their previous RCT by including intention-to-treat and per-protocol analyses, daily symptom reporting, objective exercise adherence measurements, and greater heterogeneity of concussion severity,” said Carolyn A. Emery, PhD, and Jonathan Smirl, PhD, both with the University of Calgary (Alta.), in a related commentary. The new study is the first to show that early targeted heart rate subsymptom-threshold aerobic exercise, relative to stretching, shortened recovery time within 4 weeks after sport-related concussion (hazard ratio, 0.52) when controlling for sex, study site, and average daily exercise time, Dr. Emery and Dr. Smirl said.

A larger proportion of athletes assigned to stretching did not recover by 4 weeks, compared with those assigned to aerobic exercise (32% vs. 21%). The median time to full recovery was longer for the stretching group than for the aerobic exercise group (19 days vs. 14 days).

Among athletes who adhered to their assigned regimens, the differences were more pronounced: The median recovery time was 21 days for the stretching group, compared with 12 days for the aerobic exercise group. The rate of postconcussion symptoms beyond 28 days was 9% in the aerobic exercise group versus 31% in the stretching group, among adherent participants.

More research is needed to establish the efficacy of postconcussion aerobic exercise in adults and for nonsport injury, the researchers noted. Possible mechanisms underlying aerobic exercise’s benefits could include increased parasympathetic autonomic tone, improved cerebral blood flow regulation, or enhanced neuron repair, they suggested.

The right amount and timing of exercise, and doing so at an intensity that does not exacerbate symptoms, may be key. Other research has suggested that too much exercise, too soon may delay recovery, Dr. Emery said in an interview. “But there is now a lot of evidence to support low and moderate levels of physical activity to expedite recovery,” she said.

The study was funded by the American Medical Society for Sports Medicine. The study and commentary authors and Dr. McLeod had no disclosures.

jremaly@mdedge.com

After a concussion, resuming aerobic exercise relatively early on – at an intensity that does not worsen symptoms – may help young athletes recover sooner, compared with stretching, a randomized controlled trial (RCT) shows.

Douglas Levere/University at Buffalo

The study adds to emerging evidence that clinicians should prescribe exercise, rather than strict rest, to facilitate concussion recovery, researchers said.

Tamara McLeod, PhD, ATC, professor and director of athletic training programs at A.T. Still University in Mesa, Ariz., hopes the findings help clinicians see that “this is an approach that should be taken.”

“Too often with concussion, patients are given a laundry list of things they are NOT allowed to do,” including sports, school, and social activities, said Dr. McLeod, who was not involved in the study.

The research, published in The Lancet Child & Adolescent Health, largely replicates the findings of a prior trial while addressing limitations of the previous study’s design, researchers said.

For the trial, John J. Leddy, MD, with the State University of New York at Buffalo and colleagues recruited 118 male and female adolescent athletes aged 13-18 years who had had a sport-related concussion in the past 10 days. Investigators at three community and hospital-affiliated sports medicine concussion centers in the United States randomly assigned the athletes to individualized subsymptom-threshold aerobic exercise (61 participants) or stretching exercise (57 participants) at least 20 minutes per day for up to 4 weeks. Aerobic exercise included walking, jogging, or stationary cycling at home.

“It is important that the general clinician community appreciates that prolonged rest and avoidance of physical activity until spontaneous symptom resolution is no longer an acceptable approach to caring for adolescents with concussion,” Dr. Leddy and coauthors said.

The investigators improved on the “the scientific rigor of their previous RCT by including intention-to-treat and per-protocol analyses, daily symptom reporting, objective exercise adherence measurements, and greater heterogeneity of concussion severity,” said Carolyn A. Emery, PhD, and Jonathan Smirl, PhD, both with the University of Calgary (Alta.), in a related commentary. The new study is the first to show that early targeted heart rate subsymptom-threshold aerobic exercise, relative to stretching, shortened recovery time within 4 weeks after sport-related concussion (hazard ratio, 0.52) when controlling for sex, study site, and average daily exercise time, Dr. Emery and Dr. Smirl said.

A larger proportion of athletes assigned to stretching did not recover by 4 weeks, compared with those assigned to aerobic exercise (32% vs. 21%). The median time to full recovery was longer for the stretching group than for the aerobic exercise group (19 days vs. 14 days).

Among athletes who adhered to their assigned regimens, the differences were more pronounced: The median recovery time was 21 days for the stretching group, compared with 12 days for the aerobic exercise group. The rate of postconcussion symptoms beyond 28 days was 9% in the aerobic exercise group versus 31% in the stretching group, among adherent participants.

More research is needed to establish the efficacy of postconcussion aerobic exercise in adults and for nonsport injury, the researchers noted. Possible mechanisms underlying aerobic exercise’s benefits could include increased parasympathetic autonomic tone, improved cerebral blood flow regulation, or enhanced neuron repair, they suggested.

The right amount and timing of exercise, and doing so at an intensity that does not exacerbate symptoms, may be key. Other research has suggested that too much exercise, too soon may delay recovery, Dr. Emery said in an interview. “But there is now a lot of evidence to support low and moderate levels of physical activity to expedite recovery,” she said.

The study was funded by the American Medical Society for Sports Medicine. The study and commentary authors and Dr. McLeod had no disclosures.

jremaly@mdedge.com