Mental Health

Last year, my husband and I took a 16-day road trip from Kentucky through Massachusetts to Maine. On our first morning in Boston, we exited the Park Street Station en route to Boston Common, but instead of being greeted by the aroma of molasses, we were hit full-on with a pungent, repulsive odor. “That’s skunk weed,” my husband chuckled as we stepped right into the middle of the Boston Freedom Rally, a celebration of all things cannabis.

As we boarded a hop-on-hop-off bus, we learned that this was the one week of the year that the city skips testing tour bus drivers for tetrahydrocannabinol (THC), “because we all test positive,” the driver quipped. As our open-air bus circled the Common, a crowd of pot enthusiasts displayed signs in support of relaxed regulation for public consumption.

The 34-year-old Boston Freedom Rally is a sign that U.S. culture has transformed forever. Mary Jane is no friend of emergency physicians nor of staff on hospital wards and offices. Health care workers should brace for the true impact of THC as its adoption by all ages rises.
 

Toking boomers and millennials

Researchers at the University of California, San Diego, looked at cannabis-related emergency department visits from all acute-care hospitals in the state from 2005 to 2019 and found an 1,808% increase in patients aged 65 or older (that is not a typo) who were there for complications from cannabis use.

The lead author said in an interview that, “older patients taking marijuana or related products may have dizziness and falls, heart palpitations, panic attacks, confusion, anxiety or worsening of underlying lung diseases, such as asthma or [chronic obstructive pulmonary disease].”

A recent study from Canada suggests that commercialization has been associated with an increase in related hospitalizations, including cannabis-induced psychosis.

According to a National Study of Drug Use and Health, marijuana use in young adults reached an all-time high (pun intended) in 2021. Nearly 10% of eighth graders and 20% of 10th graders reported using marijuana this past year.

The full downside of any drug, legal or illegal, is largely unknown until it infiltrates the mainstream market, but these are the typical cases we see:

Let’s start with the demotivated high school honors student who dropped out of college to work at the local cinema. He stumbled and broke his clavicle outside a bar at 2 AM, but he wasn’t sure if he passed out, so a cardiology consult was requested to “rule out” arrhythmia associated with syncope. He related that his plan to become a railway conductor had been upended because he knew he would be drug tested and just couldn’t give up pot. After a normal cardiac exam, ECG, labs, a Holter, and an echocardiogram were also requested and normal at a significant cost.
 

Cannabinoid hyperemesis syndrome

One of my Midwest colleagues related her encounter with two middle-aged pot users with ventricular tachycardia (VT). These episodes coincided with potassium levels less than 3.0 mEq/L in the setting of repetitive vomiting. The QTc interval didn’t normalize despite a corrected potassium level in one patient. They were both informed that they should never smoke pot because vomiting would predictably drop their K+ levels again and prolong their QTc intervals. Then began “the circular argument,” as my friend described it. The patient claims, “I smoke pot to relieve my nausea,” to which she explains that “in many folks, pot use induces nausea.” Of course, the classic reply is, “Not me.” Predictably one of these stoners soon returned with more VT, more puking, and more hypokalemia. “Consider yourself ‘allergic’ to pot smoke,” my friend advised, but “was met with no meaningful hint of understanding or hope for transformative change,” she told me.

I’ve seen cannabinoid hyperemesis syndrome several times in the past few years. It occurs in daily to weekly pot users. Very rarely, it can cause cerebral edema, but it is also associated with seizures and dehydration that can lead to hypovolemic shock and kidney failure.
 

Heart and brain harm

Then there are the young patients who for various reasons have developed heart failure. Unfortunately, some are repetitively tox screen positive with varying trifectas of methamphetamine (meth), cocaine, and THC; opiates, meth, and THC; alcohol, meth, and THC; or heroin, meth, and THC. THC, the ever present and essential third leg of the stool of stupor. These unfortunate patients often need heart failure medications that they can’t afford or won’t take because illicit drug use is expensive and dulls their ability to prioritize their health. Some desperately need a heart transplant, but the necessary negative drug screen is a pipe dream.

And it’s not just the heart that is affected. There are data linking cannabis use to a higher risk for both ischemic and hemorrhagic stroke. A retrospective study published in Stroke, of more than 1,000 people diagnosed with an aneurysmal subarachnoid hemorrhage, found that more than half of the 46 who tested positive for THC at admission developed delayed cerebral ischemia (DCI), which increases the risk for disability or early death. This was after adjusting for several patient characteristics as well as recent exposure to other illicit substances; cocaine, meth, and tobacco use were not associated with DCI.
 

Natural my ...

I’m certain my anti-cannabis stance will strike a nerve with those who love their recreational THC and push for its legal sale; after all, “It’s perfectly natural.” But I counter with the fact that tornadoes, earthquakes, cyanide, and appendicitis are all natural but certainly not optimal. And what we are seeing in the vascular specialties is completely unnatural. We are treating a different mix of complications than before pot was readily accessible across several states.

Our most effective action is to educate our patients. We should encourage those who don’t currently smoke cannabis to never start and those who do to quit. People who require marijuana for improved quality of life for terminal care or true (not supposed) disorders that mainstream medicine fails should be approached with empathy and caution.

A good rule of thumb is to never breathe anything you can see. Never put anything in your body that comes off the street: Drug dealers who sell cannabis cut with fentanyl will be ecstatic to take someone’s money then merely keep scrolling when their obituary comes up.

Let’s try to reverse the rise of vascular complications, orthopedic injuries, and vomiting across America. We can start by encouraging our patients to avoid “skunk weed” and get back to the sweet smells of nature in our cities and parks.

Some details have been changed to protect the patients’ identities, but the essence of their diagnoses has been preserved.

Dr. Walton-Shirley is a retired clinical cardiologist from Nashville, Tenn. She disclosed no relevant conflicts of interest.

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

Last year, my husband and I took a 16-day road trip from Kentucky through Massachusetts to Maine. On our first morning in Boston, we exited the Park Street Station en route to Boston Common, but instead of being greeted by the aroma of molasses, we were hit full-on with a pungent, repulsive odor. “That’s skunk weed,” my husband chuckled as we stepped right into the middle of the Boston Freedom Rally, a celebration of all things cannabis.

As we boarded a hop-on-hop-off bus, we learned that this was the one week of the year that the city skips testing tour bus drivers for tetrahydrocannabinol (THC), “because we all test positive,” the driver quipped. As our open-air bus circled the Common, a crowd of pot enthusiasts displayed signs in support of relaxed regulation for public consumption.

The 34-year-old Boston Freedom Rally is a sign that U.S. culture has transformed forever. Mary Jane is no friend of emergency physicians nor of staff on hospital wards and offices. Health care workers should brace for the true impact of THC as its adoption by all ages rises.
 

Toking boomers and millennials

Researchers at the University of California, San Diego, looked at cannabis-related emergency department visits from all acute-care hospitals in the state from 2005 to 2019 and found an 1,808% increase in patients aged 65 or older (that is not a typo) who were there for complications from cannabis use.

The lead author said in an interview that, “older patients taking marijuana or related products may have dizziness and falls, heart palpitations, panic attacks, confusion, anxiety or worsening of underlying lung diseases, such as asthma or [chronic obstructive pulmonary disease].”

A recent study from Canada suggests that commercialization has been associated with an increase in related hospitalizations, including cannabis-induced psychosis.

According to a National Study of Drug Use and Health, marijuana use in young adults reached an all-time high (pun intended) in 2021. Nearly 10% of eighth graders and 20% of 10th graders reported using marijuana this past year.

The full downside of any drug, legal or illegal, is largely unknown until it infiltrates the mainstream market, but these are the typical cases we see:

Let’s start with the demotivated high school honors student who dropped out of college to work at the local cinema. He stumbled and broke his clavicle outside a bar at 2 AM, but he wasn’t sure if he passed out, so a cardiology consult was requested to “rule out” arrhythmia associated with syncope. He related that his plan to become a railway conductor had been upended because he knew he would be drug tested and just couldn’t give up pot. After a normal cardiac exam, ECG, labs, a Holter, and an echocardiogram were also requested and normal at a significant cost.
 

Cannabinoid hyperemesis syndrome

One of my Midwest colleagues related her encounter with two middle-aged pot users with ventricular tachycardia (VT). These episodes coincided with potassium levels less than 3.0 mEq/L in the setting of repetitive vomiting. The QTc interval didn’t normalize despite a corrected potassium level in one patient. They were both informed that they should never smoke pot because vomiting would predictably drop their K+ levels again and prolong their QTc intervals. Then began “the circular argument,” as my friend described it. The patient claims, “I smoke pot to relieve my nausea,” to which she explains that “in many folks, pot use induces nausea.” Of course, the classic reply is, “Not me.” Predictably one of these stoners soon returned with more VT, more puking, and more hypokalemia. “Consider yourself ‘allergic’ to pot smoke,” my friend advised, but “was met with no meaningful hint of understanding or hope for transformative change,” she told me.

I’ve seen cannabinoid hyperemesis syndrome several times in the past few years. It occurs in daily to weekly pot users. Very rarely, it can cause cerebral edema, but it is also associated with seizures and dehydration that can lead to hypovolemic shock and kidney failure.
 

Heart and brain harm

Then there are the young patients who for various reasons have developed heart failure. Unfortunately, some are repetitively tox screen positive with varying trifectas of methamphetamine (meth), cocaine, and THC; opiates, meth, and THC; alcohol, meth, and THC; or heroin, meth, and THC. THC, the ever present and essential third leg of the stool of stupor. These unfortunate patients often need heart failure medications that they can’t afford or won’t take because illicit drug use is expensive and dulls their ability to prioritize their health. Some desperately need a heart transplant, but the necessary negative drug screen is a pipe dream.

And it’s not just the heart that is affected. There are data linking cannabis use to a higher risk for both ischemic and hemorrhagic stroke. A retrospective study published in Stroke, of more than 1,000 people diagnosed with an aneurysmal subarachnoid hemorrhage, found that more than half of the 46 who tested positive for THC at admission developed delayed cerebral ischemia (DCI), which increases the risk for disability or early death. This was after adjusting for several patient characteristics as well as recent exposure to other illicit substances; cocaine, meth, and tobacco use were not associated with DCI.
 

Natural my ...

I’m certain my anti-cannabis stance will strike a nerve with those who love their recreational THC and push for its legal sale; after all, “It’s perfectly natural.” But I counter with the fact that tornadoes, earthquakes, cyanide, and appendicitis are all natural but certainly not optimal. And what we are seeing in the vascular specialties is completely unnatural. We are treating a different mix of complications than before pot was readily accessible across several states.

Our most effective action is to educate our patients. We should encourage those who don’t currently smoke cannabis to never start and those who do to quit. People who require marijuana for improved quality of life for terminal care or true (not supposed) disorders that mainstream medicine fails should be approached with empathy and caution.

A good rule of thumb is to never breathe anything you can see. Never put anything in your body that comes off the street: Drug dealers who sell cannabis cut with fentanyl will be ecstatic to take someone’s money then merely keep scrolling when their obituary comes up.

Let’s try to reverse the rise of vascular complications, orthopedic injuries, and vomiting across America. We can start by encouraging our patients to avoid “skunk weed” and get back to the sweet smells of nature in our cities and parks.

Some details have been changed to protect the patients’ identities, but the essence of their diagnoses has been preserved.

Dr. Walton-Shirley is a retired clinical cardiologist from Nashville, Tenn. She disclosed no relevant conflicts of interest.

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

Last year, my husband and I took a 16-day road trip from Kentucky through Massachusetts to Maine. On our first morning in Boston, we exited the Park Street Station en route to Boston Common, but instead of being greeted by the aroma of molasses, we were hit full-on with a pungent, repulsive odor. “That’s skunk weed,” my husband chuckled as we stepped right into the middle of the Boston Freedom Rally, a celebration of all things cannabis.

As we boarded a hop-on-hop-off bus, we learned that this was the one week of the year that the city skips testing tour bus drivers for tetrahydrocannabinol (THC), “because we all test positive,” the driver quipped. As our open-air bus circled the Common, a crowd of pot enthusiasts displayed signs in support of relaxed regulation for public consumption.

The 34-year-old Boston Freedom Rally is a sign that U.S. culture has transformed forever. Mary Jane is no friend of emergency physicians nor of staff on hospital wards and offices. Health care workers should brace for the true impact of THC as its adoption by all ages rises.
 

Toking boomers and millennials

Researchers at the University of California, San Diego, looked at cannabis-related emergency department visits from all acute-care hospitals in the state from 2005 to 2019 and found an 1,808% increase in patients aged 65 or older (that is not a typo) who were there for complications from cannabis use.

The lead author said in an interview that, “older patients taking marijuana or related products may have dizziness and falls, heart palpitations, panic attacks, confusion, anxiety or worsening of underlying lung diseases, such as asthma or [chronic obstructive pulmonary disease].”

A recent study from Canada suggests that commercialization has been associated with an increase in related hospitalizations, including cannabis-induced psychosis.

According to a National Study of Drug Use and Health, marijuana use in young adults reached an all-time high (pun intended) in 2021. Nearly 10% of eighth graders and 20% of 10th graders reported using marijuana this past year.

The full downside of any drug, legal or illegal, is largely unknown until it infiltrates the mainstream market, but these are the typical cases we see:

Let’s start with the demotivated high school honors student who dropped out of college to work at the local cinema. He stumbled and broke his clavicle outside a bar at 2 AM, but he wasn’t sure if he passed out, so a cardiology consult was requested to “rule out” arrhythmia associated with syncope. He related that his plan to become a railway conductor had been upended because he knew he would be drug tested and just couldn’t give up pot. After a normal cardiac exam, ECG, labs, a Holter, and an echocardiogram were also requested and normal at a significant cost.
 

Cannabinoid hyperemesis syndrome

One of my Midwest colleagues related her encounter with two middle-aged pot users with ventricular tachycardia (VT). These episodes coincided with potassium levels less than 3.0 mEq/L in the setting of repetitive vomiting. The QTc interval didn’t normalize despite a corrected potassium level in one patient. They were both informed that they should never smoke pot because vomiting would predictably drop their K+ levels again and prolong their QTc intervals. Then began “the circular argument,” as my friend described it. The patient claims, “I smoke pot to relieve my nausea,” to which she explains that “in many folks, pot use induces nausea.” Of course, the classic reply is, “Not me.” Predictably one of these stoners soon returned with more VT, more puking, and more hypokalemia. “Consider yourself ‘allergic’ to pot smoke,” my friend advised, but “was met with no meaningful hint of understanding or hope for transformative change,” she told me.

I’ve seen cannabinoid hyperemesis syndrome several times in the past few years. It occurs in daily to weekly pot users. Very rarely, it can cause cerebral edema, but it is also associated with seizures and dehydration that can lead to hypovolemic shock and kidney failure.
 

Heart and brain harm

Then there are the young patients who for various reasons have developed heart failure. Unfortunately, some are repetitively tox screen positive with varying trifectas of methamphetamine (meth), cocaine, and THC; opiates, meth, and THC; alcohol, meth, and THC; or heroin, meth, and THC. THC, the ever present and essential third leg of the stool of stupor. These unfortunate patients often need heart failure medications that they can’t afford or won’t take because illicit drug use is expensive and dulls their ability to prioritize their health. Some desperately need a heart transplant, but the necessary negative drug screen is a pipe dream.

And it’s not just the heart that is affected. There are data linking cannabis use to a higher risk for both ischemic and hemorrhagic stroke. A retrospective study published in Stroke, of more than 1,000 people diagnosed with an aneurysmal subarachnoid hemorrhage, found that more than half of the 46 who tested positive for THC at admission developed delayed cerebral ischemia (DCI), which increases the risk for disability or early death. This was after adjusting for several patient characteristics as well as recent exposure to other illicit substances; cocaine, meth, and tobacco use were not associated with DCI.
 

Natural my ...

I’m certain my anti-cannabis stance will strike a nerve with those who love their recreational THC and push for its legal sale; after all, “It’s perfectly natural.” But I counter with the fact that tornadoes, earthquakes, cyanide, and appendicitis are all natural but certainly not optimal. And what we are seeing in the vascular specialties is completely unnatural. We are treating a different mix of complications than before pot was readily accessible across several states.

Our most effective action is to educate our patients. We should encourage those who don’t currently smoke cannabis to never start and those who do to quit. People who require marijuana for improved quality of life for terminal care or true (not supposed) disorders that mainstream medicine fails should be approached with empathy and caution.

A good rule of thumb is to never breathe anything you can see. Never put anything in your body that comes off the street: Drug dealers who sell cannabis cut with fentanyl will be ecstatic to take someone’s money then merely keep scrolling when their obituary comes up.

Let’s try to reverse the rise of vascular complications, orthopedic injuries, and vomiting across America. We can start by encouraging our patients to avoid “skunk weed” and get back to the sweet smells of nature in our cities and parks.

Some details have been changed to protect the patients’ identities, but the essence of their diagnoses has been preserved.

Dr. Walton-Shirley is a retired clinical cardiologist from Nashville, Tenn. She disclosed no relevant conflicts of interest.

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

Checking on the well-being of mothers is one of the important acknowledged aspects of primary pediatric care. “How are you doing?” directed to the child’s mother has long been considered an appropriate question. The AAP recommends several checks in the Bright Futures Guidelines, including conducting several formal screens for depression and asking about “getting time alone with your partner” as well as other supports.

But I have recently become aware of new data that changes my ideas about what we pediatricians need to be doing as part of our care for children and their families, especially in the first year: Considering the risks to the mother of dying.

Maternal mortality increased by 26.6% from 2000 to 2014 across the United States such that it is higher now than it was for our own mothers. The U.S. now has the highest rates of maternal mortality among high-income nations, especially for Black, American Indian, or Alaska Native women, those of lower socioeconomic status, and those under 18 or over 35 years old.

You may be thinking, well, that is an issue for ob.gyns. Indeed, the most common reasons for maternal death are cardiovascular: hemorrhage, hypertensive disorders, deep vein thrombosis, and stroke, all usually occurring at or in the first week after birth. You may have heard about sudden unexpected heart failure from postpartum cardiomyopathy, although rare (1 in 1,000-4,000), presenting from 1 month pre birth to 5 months post delivery, which is when we may be the main clinicians seeing the mother, not the ob.gyns. This can be easily missed since it presents with shortness of breath and decreased exercise tolerance, fatigue, palpitations, and/or leg swelling. Serious eclampsia may have only symptoms of headache or abdominal pain. All of these may easily be mistaken for lingering pregnancy symptoms. But in higher income countries, such as the U.S., 38% of maternal deaths occur from 8 to 42 days after birth, the period for fatal infections as well as cardiac complications. Elevated risk for all of these causes of mortality include Black race, obesity, tobacco use, congenital heart disease, and being older than 40.

As pediatric providers, we may see mothers along with their infants as newborns in the hospital, at day 2, at 2 weeks, or even at 1-2 months after birth, potentially before their one recommended postnatal obstetric visit at 3-8 weeks. Asking the mother how she is feeling at those times should not just be a social nicety but rather an additional check for serious postnatal complications.
 

Additional concerns

But wait, it gets worse.

Did you know that the leading cause of maternal death from pregnancy up to 1 year after a birth is homicide?

Maternal perinatal mortality figures have not usually included “perinatal-associated” deaths, a maternal death attributable to a condition that is unaffected by the pregnancy and occurring within 1 year of delivery (that I will cite as perinatal henceforth). While half of maternal deaths occur during pregnancy, another half occur in the year following. There were 3.62 homicides per 100,000 live births among females who were pregnant or within 1 year postpartum, 16% more than for similarly aged nonpregnant and nonpostpartum women (3.12 deaths/100,000 population, P < .05). Homicides made up 8.4% of reported perinatal maternal deaths from all causes, with a rate of 1.7 per 100,000 live births, twice the rate of any one of the other leading causes noted above. Black women had seven times the risk of perinatal homicide as that of White women. Females under 20, many of them our own pediatric patients, had a greater than six times higher risk and those aged 20-24 had a 65% higher risk of pregnancy-associated homicide across race and ethnic groups. Homicide is most likely before 21 weeks of pregnancy, decreases in the third trimester, but increases again after birth. Two-thirds of pregnancy-associated homicide deaths occurred in the home, with the perpetrator a current or prior partner (> 59%, with 98% being male), 45%-50% were associated with reported intimate partner violence (IPV), and the most common method was a firearm (55%). Often the same women had histories of substance abuse, serious mental illness, and/or prior IPV, all risk factors for pregnancy-associated deaths, including from homicide.

Homicide? “Not the mothers in my practice,” you may say, but, if not homicide, drug-related deaths (3.68 per 100,000 person-years) and suicide (1.42 per 100,000 person-years) together comprise 18% of all maternal deaths. Non-Hispanic White women, Medicaid-insured women, and women residing in smaller cities were especially likely to die from drugs or suicide. More than half (54.3%) of perinatal suicides involve intimate partner conflict, which increases the risk ninefold. Perinatal mood disorders, affecting up to 15% of pregnant and postpartum U.S. women, is also a risk factor in substance abuse, opioid overdose death, and suicide.

And substance use has gotten more dangerous with the increase in fentanyl lacing. Pregnancy-associated deaths (4%-10% of deaths) involving opioids more than doubled between 2007 and 2016, and, although the rates are higher for Black women, the increase has been greater for non-Hispanic White women. Two-thirds of those deaths occur between 6 and 12 months postpartum, on our watch. Although many women decrease substance use during pregnancy, they may fall back into substance use (rates increase 4 times by 7-12 months after delivery) and not continue to receive treatment. Although pharmacotherapy (e.g., methadone, buprenorphine treatment) is the current standard of care for opioid use disorder (OUD) during pregnancy, nearly half receiving treatment in publicly funded centers are not receiving these medications and others may lose insurance or access to pregnancy-related treatment programs after delivery, increasing risk of relapse. Stigma, and punitive or discriminatory approaches to pregnant women with OUD (e.g., jail, removal of children) can dissuade them from participating in treatment, increasing overdose risk.

It is important to note that in more than half of the 41 deaths from violent trauma in one study (including 22 homicides), obstetrical providers knew of or suspected IPV. Also, the vast majority (74%) of those who died by drugs or suicide had made one or more emergency department or hospital visit between their delivery and death, and 39% had made three or more visits. Without knowing if anything was done in those cases, we also know that, in addition to thorough, compassionate providers, there is sometimes segmentation of responsibility, insensitivity, discrimination, racism, stigma, inequity, lack of resources, lack of access, lack of payment mechanisms, legal issues for immigrants, time constraints, and other systemic deficits that may hinder effective care for these and subsequent women.
 

Awareness and action

What should we, who are primary care pediatric providers, do about these threats to the mothers and pregnant young women we care for? Clearly, their children, our main patients, would be terribly and permanently hurt by harm coming to their mothers – the extreme adverse childhood experiences and social determinants of health to which we are already committed.

I hope this article will help alert pediatric providers to what is being published, mainly as women’s health and public health issues.

First, we need awareness of the physical symptoms that may come up in our interactions with pregnant and postpartum women so that we can educate them and expedite any indicated emergency care.

Next, we need to expand our routine screening of mothers and pregnant women from just the most impactful social determinants of health (including depression, substance use, and IPV) to include anxiety, past suicide attempts and current suicidal ideation, and the presence of firearms, early and repeatedly in the first year of the child’s life. Adults and teens are more likely to disclose risk for sensitive issues through questionnaires than through interviews, perhaps even more so when the identified patient is their child rather than themselves. Any screen can have false negatives, so asking directly when risk is suspected is important. The reason for screening could be framed as caring for the caregiver who is the most important person for the child. It could be accompanied by acknowledging that pregnancy and the first year of life can be difficult for mothers and their partners and that we want to support them and connect them to resources, if needed. When substance use disorder is acknowledged, we should prescribe and teach about Narcan for overdose. When there is IPV, we should discuss firearm removal/locking as well as counseling on a personal safety plan.

Working as part of an on-site or virtual team that includes professionals who know about community resources and can coordinate care is essential, in addition to educating about 211 for services and 988 for suicide risk.

Finally, we can advocate and vote for programs, people, and laws that support and safeguard women and families, address substance use, and reduce access to firearms.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Checking on the well-being of mothers is one of the important acknowledged aspects of primary pediatric care. “How are you doing?” directed to the child’s mother has long been considered an appropriate question. The AAP recommends several checks in the Bright Futures Guidelines, including conducting several formal screens for depression and asking about “getting time alone with your partner” as well as other supports.

But I have recently become aware of new data that changes my ideas about what we pediatricians need to be doing as part of our care for children and their families, especially in the first year: Considering the risks to the mother of dying.

Maternal mortality increased by 26.6% from 2000 to 2014 across the United States such that it is higher now than it was for our own mothers. The U.S. now has the highest rates of maternal mortality among high-income nations, especially for Black, American Indian, or Alaska Native women, those of lower socioeconomic status, and those under 18 or over 35 years old.

You may be thinking, well, that is an issue for ob.gyns. Indeed, the most common reasons for maternal death are cardiovascular: hemorrhage, hypertensive disorders, deep vein thrombosis, and stroke, all usually occurring at or in the first week after birth. You may have heard about sudden unexpected heart failure from postpartum cardiomyopathy, although rare (1 in 1,000-4,000), presenting from 1 month pre birth to 5 months post delivery, which is when we may be the main clinicians seeing the mother, not the ob.gyns. This can be easily missed since it presents with shortness of breath and decreased exercise tolerance, fatigue, palpitations, and/or leg swelling. Serious eclampsia may have only symptoms of headache or abdominal pain. All of these may easily be mistaken for lingering pregnancy symptoms. But in higher income countries, such as the U.S., 38% of maternal deaths occur from 8 to 42 days after birth, the period for fatal infections as well as cardiac complications. Elevated risk for all of these causes of mortality include Black race, obesity, tobacco use, congenital heart disease, and being older than 40.

As pediatric providers, we may see mothers along with their infants as newborns in the hospital, at day 2, at 2 weeks, or even at 1-2 months after birth, potentially before their one recommended postnatal obstetric visit at 3-8 weeks. Asking the mother how she is feeling at those times should not just be a social nicety but rather an additional check for serious postnatal complications.
 

Additional concerns

But wait, it gets worse.

Did you know that the leading cause of maternal death from pregnancy up to 1 year after a birth is homicide?

Maternal perinatal mortality figures have not usually included “perinatal-associated” deaths, a maternal death attributable to a condition that is unaffected by the pregnancy and occurring within 1 year of delivery (that I will cite as perinatal henceforth). While half of maternal deaths occur during pregnancy, another half occur in the year following. There were 3.62 homicides per 100,000 live births among females who were pregnant or within 1 year postpartum, 16% more than for similarly aged nonpregnant and nonpostpartum women (3.12 deaths/100,000 population, P < .05). Homicides made up 8.4% of reported perinatal maternal deaths from all causes, with a rate of 1.7 per 100,000 live births, twice the rate of any one of the other leading causes noted above. Black women had seven times the risk of perinatal homicide as that of White women. Females under 20, many of them our own pediatric patients, had a greater than six times higher risk and those aged 20-24 had a 65% higher risk of pregnancy-associated homicide across race and ethnic groups. Homicide is most likely before 21 weeks of pregnancy, decreases in the third trimester, but increases again after birth. Two-thirds of pregnancy-associated homicide deaths occurred in the home, with the perpetrator a current or prior partner (> 59%, with 98% being male), 45%-50% were associated with reported intimate partner violence (IPV), and the most common method was a firearm (55%). Often the same women had histories of substance abuse, serious mental illness, and/or prior IPV, all risk factors for pregnancy-associated deaths, including from homicide.

Homicide? “Not the mothers in my practice,” you may say, but, if not homicide, drug-related deaths (3.68 per 100,000 person-years) and suicide (1.42 per 100,000 person-years) together comprise 18% of all maternal deaths. Non-Hispanic White women, Medicaid-insured women, and women residing in smaller cities were especially likely to die from drugs or suicide. More than half (54.3%) of perinatal suicides involve intimate partner conflict, which increases the risk ninefold. Perinatal mood disorders, affecting up to 15% of pregnant and postpartum U.S. women, is also a risk factor in substance abuse, opioid overdose death, and suicide.

And substance use has gotten more dangerous with the increase in fentanyl lacing. Pregnancy-associated deaths (4%-10% of deaths) involving opioids more than doubled between 2007 and 2016, and, although the rates are higher for Black women, the increase has been greater for non-Hispanic White women. Two-thirds of those deaths occur between 6 and 12 months postpartum, on our watch. Although many women decrease substance use during pregnancy, they may fall back into substance use (rates increase 4 times by 7-12 months after delivery) and not continue to receive treatment. Although pharmacotherapy (e.g., methadone, buprenorphine treatment) is the current standard of care for opioid use disorder (OUD) during pregnancy, nearly half receiving treatment in publicly funded centers are not receiving these medications and others may lose insurance or access to pregnancy-related treatment programs after delivery, increasing risk of relapse. Stigma, and punitive or discriminatory approaches to pregnant women with OUD (e.g., jail, removal of children) can dissuade them from participating in treatment, increasing overdose risk.

It is important to note that in more than half of the 41 deaths from violent trauma in one study (including 22 homicides), obstetrical providers knew of or suspected IPV. Also, the vast majority (74%) of those who died by drugs or suicide had made one or more emergency department or hospital visit between their delivery and death, and 39% had made three or more visits. Without knowing if anything was done in those cases, we also know that, in addition to thorough, compassionate providers, there is sometimes segmentation of responsibility, insensitivity, discrimination, racism, stigma, inequity, lack of resources, lack of access, lack of payment mechanisms, legal issues for immigrants, time constraints, and other systemic deficits that may hinder effective care for these and subsequent women.
 

Awareness and action

What should we, who are primary care pediatric providers, do about these threats to the mothers and pregnant young women we care for? Clearly, their children, our main patients, would be terribly and permanently hurt by harm coming to their mothers – the extreme adverse childhood experiences and social determinants of health to which we are already committed.

I hope this article will help alert pediatric providers to what is being published, mainly as women’s health and public health issues.

First, we need awareness of the physical symptoms that may come up in our interactions with pregnant and postpartum women so that we can educate them and expedite any indicated emergency care.

Next, we need to expand our routine screening of mothers and pregnant women from just the most impactful social determinants of health (including depression, substance use, and IPV) to include anxiety, past suicide attempts and current suicidal ideation, and the presence of firearms, early and repeatedly in the first year of the child’s life. Adults and teens are more likely to disclose risk for sensitive issues through questionnaires than through interviews, perhaps even more so when the identified patient is their child rather than themselves. Any screen can have false negatives, so asking directly when risk is suspected is important. The reason for screening could be framed as caring for the caregiver who is the most important person for the child. It could be accompanied by acknowledging that pregnancy and the first year of life can be difficult for mothers and their partners and that we want to support them and connect them to resources, if needed. When substance use disorder is acknowledged, we should prescribe and teach about Narcan for overdose. When there is IPV, we should discuss firearm removal/locking as well as counseling on a personal safety plan.

Working as part of an on-site or virtual team that includes professionals who know about community resources and can coordinate care is essential, in addition to educating about 211 for services and 988 for suicide risk.

Finally, we can advocate and vote for programs, people, and laws that support and safeguard women and families, address substance use, and reduce access to firearms.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Checking on the well-being of mothers is one of the important acknowledged aspects of primary pediatric care. “How are you doing?” directed to the child’s mother has long been considered an appropriate question. The AAP recommends several checks in the Bright Futures Guidelines, including conducting several formal screens for depression and asking about “getting time alone with your partner” as well as other supports.

But I have recently become aware of new data that changes my ideas about what we pediatricians need to be doing as part of our care for children and their families, especially in the first year: Considering the risks to the mother of dying.

Maternal mortality increased by 26.6% from 2000 to 2014 across the United States such that it is higher now than it was for our own mothers. The U.S. now has the highest rates of maternal mortality among high-income nations, especially for Black, American Indian, or Alaska Native women, those of lower socioeconomic status, and those under 18 or over 35 years old.

You may be thinking, well, that is an issue for ob.gyns. Indeed, the most common reasons for maternal death are cardiovascular: hemorrhage, hypertensive disorders, deep vein thrombosis, and stroke, all usually occurring at or in the first week after birth. You may have heard about sudden unexpected heart failure from postpartum cardiomyopathy, although rare (1 in 1,000-4,000), presenting from 1 month pre birth to 5 months post delivery, which is when we may be the main clinicians seeing the mother, not the ob.gyns. This can be easily missed since it presents with shortness of breath and decreased exercise tolerance, fatigue, palpitations, and/or leg swelling. Serious eclampsia may have only symptoms of headache or abdominal pain. All of these may easily be mistaken for lingering pregnancy symptoms. But in higher income countries, such as the U.S., 38% of maternal deaths occur from 8 to 42 days after birth, the period for fatal infections as well as cardiac complications. Elevated risk for all of these causes of mortality include Black race, obesity, tobacco use, congenital heart disease, and being older than 40.

As pediatric providers, we may see mothers along with their infants as newborns in the hospital, at day 2, at 2 weeks, or even at 1-2 months after birth, potentially before their one recommended postnatal obstetric visit at 3-8 weeks. Asking the mother how she is feeling at those times should not just be a social nicety but rather an additional check for serious postnatal complications.
 

Additional concerns

But wait, it gets worse.

Did you know that the leading cause of maternal death from pregnancy up to 1 year after a birth is homicide?

Maternal perinatal mortality figures have not usually included “perinatal-associated” deaths, a maternal death attributable to a condition that is unaffected by the pregnancy and occurring within 1 year of delivery (that I will cite as perinatal henceforth). While half of maternal deaths occur during pregnancy, another half occur in the year following. There were 3.62 homicides per 100,000 live births among females who were pregnant or within 1 year postpartum, 16% more than for similarly aged nonpregnant and nonpostpartum women (3.12 deaths/100,000 population, P < .05). Homicides made up 8.4% of reported perinatal maternal deaths from all causes, with a rate of 1.7 per 100,000 live births, twice the rate of any one of the other leading causes noted above. Black women had seven times the risk of perinatal homicide as that of White women. Females under 20, many of them our own pediatric patients, had a greater than six times higher risk and those aged 20-24 had a 65% higher risk of pregnancy-associated homicide across race and ethnic groups. Homicide is most likely before 21 weeks of pregnancy, decreases in the third trimester, but increases again after birth. Two-thirds of pregnancy-associated homicide deaths occurred in the home, with the perpetrator a current or prior partner (> 59%, with 98% being male), 45%-50% were associated with reported intimate partner violence (IPV), and the most common method was a firearm (55%). Often the same women had histories of substance abuse, serious mental illness, and/or prior IPV, all risk factors for pregnancy-associated deaths, including from homicide.

Homicide? “Not the mothers in my practice,” you may say, but, if not homicide, drug-related deaths (3.68 per 100,000 person-years) and suicide (1.42 per 100,000 person-years) together comprise 18% of all maternal deaths. Non-Hispanic White women, Medicaid-insured women, and women residing in smaller cities were especially likely to die from drugs or suicide. More than half (54.3%) of perinatal suicides involve intimate partner conflict, which increases the risk ninefold. Perinatal mood disorders, affecting up to 15% of pregnant and postpartum U.S. women, is also a risk factor in substance abuse, opioid overdose death, and suicide.

And substance use has gotten more dangerous with the increase in fentanyl lacing. Pregnancy-associated deaths (4%-10% of deaths) involving opioids more than doubled between 2007 and 2016, and, although the rates are higher for Black women, the increase has been greater for non-Hispanic White women. Two-thirds of those deaths occur between 6 and 12 months postpartum, on our watch. Although many women decrease substance use during pregnancy, they may fall back into substance use (rates increase 4 times by 7-12 months after delivery) and not continue to receive treatment. Although pharmacotherapy (e.g., methadone, buprenorphine treatment) is the current standard of care for opioid use disorder (OUD) during pregnancy, nearly half receiving treatment in publicly funded centers are not receiving these medications and others may lose insurance or access to pregnancy-related treatment programs after delivery, increasing risk of relapse. Stigma, and punitive or discriminatory approaches to pregnant women with OUD (e.g., jail, removal of children) can dissuade them from participating in treatment, increasing overdose risk.

It is important to note that in more than half of the 41 deaths from violent trauma in one study (including 22 homicides), obstetrical providers knew of or suspected IPV. Also, the vast majority (74%) of those who died by drugs or suicide had made one or more emergency department or hospital visit between their delivery and death, and 39% had made three or more visits. Without knowing if anything was done in those cases, we also know that, in addition to thorough, compassionate providers, there is sometimes segmentation of responsibility, insensitivity, discrimination, racism, stigma, inequity, lack of resources, lack of access, lack of payment mechanisms, legal issues for immigrants, time constraints, and other systemic deficits that may hinder effective care for these and subsequent women.
 

Awareness and action

What should we, who are primary care pediatric providers, do about these threats to the mothers and pregnant young women we care for? Clearly, their children, our main patients, would be terribly and permanently hurt by harm coming to their mothers – the extreme adverse childhood experiences and social determinants of health to which we are already committed.

I hope this article will help alert pediatric providers to what is being published, mainly as women’s health and public health issues.

First, we need awareness of the physical symptoms that may come up in our interactions with pregnant and postpartum women so that we can educate them and expedite any indicated emergency care.

Next, we need to expand our routine screening of mothers and pregnant women from just the most impactful social determinants of health (including depression, substance use, and IPV) to include anxiety, past suicide attempts and current suicidal ideation, and the presence of firearms, early and repeatedly in the first year of the child’s life. Adults and teens are more likely to disclose risk for sensitive issues through questionnaires than through interviews, perhaps even more so when the identified patient is their child rather than themselves. Any screen can have false negatives, so asking directly when risk is suspected is important. The reason for screening could be framed as caring for the caregiver who is the most important person for the child. It could be accompanied by acknowledging that pregnancy and the first year of life can be difficult for mothers and their partners and that we want to support them and connect them to resources, if needed. When substance use disorder is acknowledged, we should prescribe and teach about Narcan for overdose. When there is IPV, we should discuss firearm removal/locking as well as counseling on a personal safety plan.

Working as part of an on-site or virtual team that includes professionals who know about community resources and can coordinate care is essential, in addition to educating about 211 for services and 988 for suicide risk.

Finally, we can advocate and vote for programs, people, and laws that support and safeguard women and families, address substance use, and reduce access to firearms.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

TOPLINE:

Solriamfetol – a medication approved for excessive daytime sleepiness caused by narcolepsy or obstructive sleep apnea – significantly improved symptoms of attention-deficit/hyperactivity disorder (ADHD) and clinical impression of ADHD severity in a pilot study of adults with ADHD.

METHODOLOGY:

• Solriamfetol is a dopamine and norepinephrine reuptake inhibitor that shares some of the properties of current ADHD medications.
• Researchers conducted a randomized, double-blind, placebo-controlled, dose-optimization trial of 75- or 150-mg solriamfetol in 60 adults with ADHD. For nearly all of the individuals who received solriamfetol, doses increased to 150 mg after the first week.
• The primary outcome was change in scores on the Adult ADHD Investigator Symptom Rating Scale (AISRS).
• Secondary outcomes included scores on the Clinical Global Impressions (CGI) scale and standard measures of executive function, behavior, and sleep.

TAKEAWAY:

• By week 6, total AISRS score improved 25% for 52% of individuals to took solriamfetol, vs. 17% of those who received placebo. Total AISRS score improved 50% by week 6 in 28% of those who took solriamfetol, vs. 3.4% of those who received placebo.
• By week 6, CGI ratings of “much improved” or “very much improved” occurred in significantly more individuals who received solriamfetol than those who took placebo (45% vs. 7%).
• Significantly more individuals who received solriamfetol than placebo self-reported improvements in executive function (69% vs. 34%). Improvement in wakefulness was noted with solriamfetol, but that did not moderate the change in ADHD symptom burden.
• Solriamfetol was well tolerated, with no significant effect on sleep quality or blood pressure. Adverse effects that occurred at a higher rate in the treatment group than in the placebo group were typical for solriamfetol and sympathomimetic agents used for ADHD.

IN PRACTICE:

Massachusetts General Hospital

“Solriamfetol may be a safe and effective treatment for ADHD in adults. Larger studies replicating these findings could confirm the strong evidence of benefit and the tolerability of this agent as a treatment,” lead author Craig B.H. Surman, MD, director of the clinical and research program in adult ADHD, Massachusetts General Hospital, Boston, said in a statement.

SOURCE:

The study was published online in The Journal of Clinical Psychiatry.

LIMITATIONS:

Limitations include the small sample size and short 6-week duration. More women than men received solriamfetol; it’s unclear how this could have affected the results.

DISCLOSURES:

The study was an investigator-initiated trial supported by Jazz Pharmaceuticals and Axsome Therapeutics. Dr. Surman has received consultant fees, research support, and royalties from multiple companies.

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

TOPLINE:

Solriamfetol – a medication approved for excessive daytime sleepiness caused by narcolepsy or obstructive sleep apnea – significantly improved symptoms of attention-deficit/hyperactivity disorder (ADHD) and clinical impression of ADHD severity in a pilot study of adults with ADHD.

METHODOLOGY:

• Solriamfetol is a dopamine and norepinephrine reuptake inhibitor that shares some of the properties of current ADHD medications.
• Researchers conducted a randomized, double-blind, placebo-controlled, dose-optimization trial of 75- or 150-mg solriamfetol in 60 adults with ADHD. For nearly all of the individuals who received solriamfetol, doses increased to 150 mg after the first week.
• The primary outcome was change in scores on the Adult ADHD Investigator Symptom Rating Scale (AISRS).
• Secondary outcomes included scores on the Clinical Global Impressions (CGI) scale and standard measures of executive function, behavior, and sleep.

TAKEAWAY:

• By week 6, total AISRS score improved 25% for 52% of individuals to took solriamfetol, vs. 17% of those who received placebo. Total AISRS score improved 50% by week 6 in 28% of those who took solriamfetol, vs. 3.4% of those who received placebo.
• By week 6, CGI ratings of “much improved” or “very much improved” occurred in significantly more individuals who received solriamfetol than those who took placebo (45% vs. 7%).
• Significantly more individuals who received solriamfetol than placebo self-reported improvements in executive function (69% vs. 34%). Improvement in wakefulness was noted with solriamfetol, but that did not moderate the change in ADHD symptom burden.
• Solriamfetol was well tolerated, with no significant effect on sleep quality or blood pressure. Adverse effects that occurred at a higher rate in the treatment group than in the placebo group were typical for solriamfetol and sympathomimetic agents used for ADHD.

IN PRACTICE:

Massachusetts General Hospital

“Solriamfetol may be a safe and effective treatment for ADHD in adults. Larger studies replicating these findings could confirm the strong evidence of benefit and the tolerability of this agent as a treatment,” lead author Craig B.H. Surman, MD, director of the clinical and research program in adult ADHD, Massachusetts General Hospital, Boston, said in a statement.

SOURCE:

The study was published online in The Journal of Clinical Psychiatry.

LIMITATIONS:

Limitations include the small sample size and short 6-week duration. More women than men received solriamfetol; it’s unclear how this could have affected the results.

DISCLOSURES:

The study was an investigator-initiated trial supported by Jazz Pharmaceuticals and Axsome Therapeutics. Dr. Surman has received consultant fees, research support, and royalties from multiple companies.

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

TOPLINE:

Solriamfetol – a medication approved for excessive daytime sleepiness caused by narcolepsy or obstructive sleep apnea – significantly improved symptoms of attention-deficit/hyperactivity disorder (ADHD) and clinical impression of ADHD severity in a pilot study of adults with ADHD.

METHODOLOGY:

• Solriamfetol is a dopamine and norepinephrine reuptake inhibitor that shares some of the properties of current ADHD medications.
• Researchers conducted a randomized, double-blind, placebo-controlled, dose-optimization trial of 75- or 150-mg solriamfetol in 60 adults with ADHD. For nearly all of the individuals who received solriamfetol, doses increased to 150 mg after the first week.
• The primary outcome was change in scores on the Adult ADHD Investigator Symptom Rating Scale (AISRS).
• Secondary outcomes included scores on the Clinical Global Impressions (CGI) scale and standard measures of executive function, behavior, and sleep.

TAKEAWAY:

• By week 6, total AISRS score improved 25% for 52% of individuals to took solriamfetol, vs. 17% of those who received placebo. Total AISRS score improved 50% by week 6 in 28% of those who took solriamfetol, vs. 3.4% of those who received placebo.
• By week 6, CGI ratings of “much improved” or “very much improved” occurred in significantly more individuals who received solriamfetol than those who took placebo (45% vs. 7%).
• Significantly more individuals who received solriamfetol than placebo self-reported improvements in executive function (69% vs. 34%). Improvement in wakefulness was noted with solriamfetol, but that did not moderate the change in ADHD symptom burden.
• Solriamfetol was well tolerated, with no significant effect on sleep quality or blood pressure. Adverse effects that occurred at a higher rate in the treatment group than in the placebo group were typical for solriamfetol and sympathomimetic agents used for ADHD.

IN PRACTICE:

Massachusetts General Hospital

“Solriamfetol may be a safe and effective treatment for ADHD in adults. Larger studies replicating these findings could confirm the strong evidence of benefit and the tolerability of this agent as a treatment,” lead author Craig B.H. Surman, MD, director of the clinical and research program in adult ADHD, Massachusetts General Hospital, Boston, said in a statement.

SOURCE:

The study was published online in The Journal of Clinical Psychiatry.

LIMITATIONS:

Limitations include the small sample size and short 6-week duration. More women than men received solriamfetol; it’s unclear how this could have affected the results.

DISCLOSURES:

The study was an investigator-initiated trial supported by Jazz Pharmaceuticals and Axsome Therapeutics. Dr. Surman has received consultant fees, research support, and royalties from multiple companies.

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

According to the CDC, the prevalence of autism spectrum disorders (ASD) has gone from roughly 1 in 68 children in 2010 to 1 in 36 children in 2020.¹ This is nearly a 50% increase over that 10-year period. Over the last several years, there has been evidence suggesting that increasing numbers of young people with ASD or other neurodivergent conditions identify as transgender or gender diverse.² Experts agree more careful attention must be paid to these patients.

UT Southwestern Medical Center

Clinical work with neurodivergent youth, especially those with ASD, can be complicated. This includes things such as difficulty with communication, possible concrete thinking, and obsessive interests. While earlier research has shown a higher incidence of ASD in those referred to specialized gender medical clinics, it is important to realize that not all of these youth are seeking medical care. They may be brought to the attention of a primary care pediatrician (PCP) if the child has discussed their gender identity at home. It is important that PCPs approach these young people with an open mind and address any coexisting mental health conditions. PCPs must be careful not to dismiss any gender identity concerns as another of the patient’s “obsessions”; rather, they should ensure the patient receives the appropriate mental health care that they need to explore these concerns. One challenge for PCPs is that there is a dearth of mental health professionals who have experience in working with young people who have both gender dysphoria and a neurodivergent condition.

For those clinicians who provide gender-affirming medical care to these young people, it is imperative that they have a thorough understanding of the patient’s gender identity and medical goals before starting any treatment. This may require extensive collaboration with the patient’s mental health provider. The clinician providing medical care may also choose to proceed slower with the introduction of hormones and their subsequent dosing to allow the young person time to continue discussing their effects with their mental health provider. To help clinicians, Dr. John Strang and a multidisciplinary group of collaborators developed a set of guidelines for co-occurring ASD and gender dysphoria in adolescents.³ More recently, Dr. Strang and other collaborators have also developed a questionnaire that can be used by clinicians in the care of these patients.⁴ The goal of this questionnaire is to allow the young people to “communicate their experiences and needs in a report format attuned to common autistic thinking and communication styles.”

In summary, pediatricians and those who care for children and adolescents need to be aware of the increased association between those with ASD or other neurodivergent conditions and gender dysphoria. To ensure that these young people receive optimal care, it is important to connect them to experts (if possible) in coexisting ASD and gender dysphoria. If such experts are not readily available, the National LGBTQIA+ Health Education Center has developed a resource for providing an affirmative approach to care for these young people.⁵ While more research is needed to better understand young people with coexisting ASD (or other neurodivergent conditions), taking an individualized approach to their care can help ensure optimal outcomes.
 

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. Data & Statistics on Autism Spectrum Disorder. https://www.cdc.gov/ncbddd/autism/data.html.

2. Glidden D et al. Gender dysphoria and autism spectrum disorder: A systematic review of the literature. Sex Med Rev. 2016;4(1):3-14. doi:10.1016/j.sxmr.2015.10.003.

3. Strang JF et al. Initial clinical guidelines for co-occurring autism spectrum disorder and gender dysphoria or incongruence in adolescents. J Clin Child Adolesc Psychol. 2018;47(1):105-15. doi:10.1080/15374416.2016.1228462.

4. Strang JF et. al. The Gender-Diversity and Autism Questionnaire: A Community-Developed Clinical, Research, and Self-Advocacy Tool for Autistic Transgender and Gender-Diverse Young Adults. Autism Adulthood. 2023 Jun 1;5(2):175-90. doi: 10.1089/aut.2023.0002.

5. National LGBT Health Education Center. Neurodiversity & gender-diverse youth: An affirming approach to care 2020. https://www.lgbtqiahealtheducation.org/publication/neurodiversity-gender-diverse-youth-an-affirming-approach-to-care-2020/download

According to the CDC, the prevalence of autism spectrum disorders (ASD) has gone from roughly 1 in 68 children in 2010 to 1 in 36 children in 2020.¹ This is nearly a 50% increase over that 10-year period. Over the last several years, there has been evidence suggesting that increasing numbers of young people with ASD or other neurodivergent conditions identify as transgender or gender diverse.² Experts agree more careful attention must be paid to these patients.

UT Southwestern Medical Center

Clinical work with neurodivergent youth, especially those with ASD, can be complicated. This includes things such as difficulty with communication, possible concrete thinking, and obsessive interests. While earlier research has shown a higher incidence of ASD in those referred to specialized gender medical clinics, it is important to realize that not all of these youth are seeking medical care. They may be brought to the attention of a primary care pediatrician (PCP) if the child has discussed their gender identity at home. It is important that PCPs approach these young people with an open mind and address any coexisting mental health conditions. PCPs must be careful not to dismiss any gender identity concerns as another of the patient’s “obsessions”; rather, they should ensure the patient receives the appropriate mental health care that they need to explore these concerns. One challenge for PCPs is that there is a dearth of mental health professionals who have experience in working with young people who have both gender dysphoria and a neurodivergent condition.

For those clinicians who provide gender-affirming medical care to these young people, it is imperative that they have a thorough understanding of the patient’s gender identity and medical goals before starting any treatment. This may require extensive collaboration with the patient’s mental health provider. The clinician providing medical care may also choose to proceed slower with the introduction of hormones and their subsequent dosing to allow the young person time to continue discussing their effects with their mental health provider. To help clinicians, Dr. John Strang and a multidisciplinary group of collaborators developed a set of guidelines for co-occurring ASD and gender dysphoria in adolescents.³ More recently, Dr. Strang and other collaborators have also developed a questionnaire that can be used by clinicians in the care of these patients.⁴ The goal of this questionnaire is to allow the young people to “communicate their experiences and needs in a report format attuned to common autistic thinking and communication styles.”

In summary, pediatricians and those who care for children and adolescents need to be aware of the increased association between those with ASD or other neurodivergent conditions and gender dysphoria. To ensure that these young people receive optimal care, it is important to connect them to experts (if possible) in coexisting ASD and gender dysphoria. If such experts are not readily available, the National LGBTQIA+ Health Education Center has developed a resource for providing an affirmative approach to care for these young people.⁵ While more research is needed to better understand young people with coexisting ASD (or other neurodivergent conditions), taking an individualized approach to their care can help ensure optimal outcomes.
 

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. Data & Statistics on Autism Spectrum Disorder. https://www.cdc.gov/ncbddd/autism/data.html.

2. Glidden D et al. Gender dysphoria and autism spectrum disorder: A systematic review of the literature. Sex Med Rev. 2016;4(1):3-14. doi:10.1016/j.sxmr.2015.10.003.

3. Strang JF et al. Initial clinical guidelines for co-occurring autism spectrum disorder and gender dysphoria or incongruence in adolescents. J Clin Child Adolesc Psychol. 2018;47(1):105-15. doi:10.1080/15374416.2016.1228462.

4. Strang JF et. al. The Gender-Diversity and Autism Questionnaire: A Community-Developed Clinical, Research, and Self-Advocacy Tool for Autistic Transgender and Gender-Diverse Young Adults. Autism Adulthood. 2023 Jun 1;5(2):175-90. doi: 10.1089/aut.2023.0002.

5. National LGBT Health Education Center. Neurodiversity & gender-diverse youth: An affirming approach to care 2020. https://www.lgbtqiahealtheducation.org/publication/neurodiversity-gender-diverse-youth-an-affirming-approach-to-care-2020/download

According to the CDC, the prevalence of autism spectrum disorders (ASD) has gone from roughly 1 in 68 children in 2010 to 1 in 36 children in 2020.¹ This is nearly a 50% increase over that 10-year period. Over the last several years, there has been evidence suggesting that increasing numbers of young people with ASD or other neurodivergent conditions identify as transgender or gender diverse.² Experts agree more careful attention must be paid to these patients.

UT Southwestern Medical Center

Clinical work with neurodivergent youth, especially those with ASD, can be complicated. This includes things such as difficulty with communication, possible concrete thinking, and obsessive interests. While earlier research has shown a higher incidence of ASD in those referred to specialized gender medical clinics, it is important to realize that not all of these youth are seeking medical care. They may be brought to the attention of a primary care pediatrician (PCP) if the child has discussed their gender identity at home. It is important that PCPs approach these young people with an open mind and address any coexisting mental health conditions. PCPs must be careful not to dismiss any gender identity concerns as another of the patient’s “obsessions”; rather, they should ensure the patient receives the appropriate mental health care that they need to explore these concerns. One challenge for PCPs is that there is a dearth of mental health professionals who have experience in working with young people who have both gender dysphoria and a neurodivergent condition.

For those clinicians who provide gender-affirming medical care to these young people, it is imperative that they have a thorough understanding of the patient’s gender identity and medical goals before starting any treatment. This may require extensive collaboration with the patient’s mental health provider. The clinician providing medical care may also choose to proceed slower with the introduction of hormones and their subsequent dosing to allow the young person time to continue discussing their effects with their mental health provider. To help clinicians, Dr. John Strang and a multidisciplinary group of collaborators developed a set of guidelines for co-occurring ASD and gender dysphoria in adolescents.³ More recently, Dr. Strang and other collaborators have also developed a questionnaire that can be used by clinicians in the care of these patients.⁴ The goal of this questionnaire is to allow the young people to “communicate their experiences and needs in a report format attuned to common autistic thinking and communication styles.”

In summary, pediatricians and those who care for children and adolescents need to be aware of the increased association between those with ASD or other neurodivergent conditions and gender dysphoria. To ensure that these young people receive optimal care, it is important to connect them to experts (if possible) in coexisting ASD and gender dysphoria. If such experts are not readily available, the National LGBTQIA+ Health Education Center has developed a resource for providing an affirmative approach to care for these young people.⁵ While more research is needed to better understand young people with coexisting ASD (or other neurodivergent conditions), taking an individualized approach to their care can help ensure optimal outcomes.
 

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. Data & Statistics on Autism Spectrum Disorder. https://www.cdc.gov/ncbddd/autism/data.html.

2. Glidden D et al. Gender dysphoria and autism spectrum disorder: A systematic review of the literature. Sex Med Rev. 2016;4(1):3-14. doi:10.1016/j.sxmr.2015.10.003.

3. Strang JF et al. Initial clinical guidelines for co-occurring autism spectrum disorder and gender dysphoria or incongruence in adolescents. J Clin Child Adolesc Psychol. 2018;47(1):105-15. doi:10.1080/15374416.2016.1228462.

4. Strang JF et. al. The Gender-Diversity and Autism Questionnaire: A Community-Developed Clinical, Research, and Self-Advocacy Tool for Autistic Transgender and Gender-Diverse Young Adults. Autism Adulthood. 2023 Jun 1;5(2):175-90. doi: 10.1089/aut.2023.0002.

5. National LGBT Health Education Center. Neurodiversity & gender-diverse youth: An affirming approach to care 2020. https://www.lgbtqiahealtheducation.org/publication/neurodiversity-gender-diverse-youth-an-affirming-approach-to-care-2020/download

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Oregon Health &amp; Science University (OHSU)

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

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

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

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

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

Countering social media diagnoses

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

Another case

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

Discussion

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

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

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

Oregon Health &amp; Science University (OHSU)

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

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

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

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

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

Countering social media diagnoses

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

Another case

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

Discussion

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

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

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

Oregon Health &amp; Science University (OHSU)

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

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

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

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

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

Countering social media diagnoses

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

Another case

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

Discussion

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

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

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

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

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

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

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

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

Wide range of adverse outcomes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Sex differences

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

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

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

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

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

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

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

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

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

Confirmatory research

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Wide range of adverse outcomes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Sex differences

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

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

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

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

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

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

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

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

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

Confirmatory research

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Wide range of adverse outcomes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Sex differences

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

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

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

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

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

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

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

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

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

Confirmatory research

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

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

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

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

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

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

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

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

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

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

courtesy UNC-Chapel Hill

What is zuranolone?

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

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

What does zuranolone treat?

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

How does zuranolone work?

courtesy UNC-Chapel Hill

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

How was it studied?

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

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

When will we be able to start using it?

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

Who can prescribe it?

courtesy UNC-Chapel Hill

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

How much will it cost?

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

What sort of doses and duration is recommended?

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

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

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

What are the side effects?

courtesy UNC-Chapel Hill

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

Are there any boxed warnings?

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

Can it be used with other medications?

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

Are there any medicines to avoid?

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

Can it be used with birth control?

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

Can it be used in pregnancy?

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

Long-term side effects?

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

Breastfeeding?

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

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

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

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

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

Anxiety?

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

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

Insomnia?

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

How is it different from brexanolone?

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

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

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

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

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

Where can I find more information?

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

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

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

References

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

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

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

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

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

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

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

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

courtesy UNC-Chapel Hill

What is zuranolone?

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

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

What does zuranolone treat?

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

How does zuranolone work?

courtesy UNC-Chapel Hill

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

How was it studied?

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

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

When will we be able to start using it?

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

Who can prescribe it?

courtesy UNC-Chapel Hill

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

How much will it cost?

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

What sort of doses and duration is recommended?

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

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

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

What are the side effects?

courtesy UNC-Chapel Hill

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

Are there any boxed warnings?

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

Can it be used with other medications?

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

Are there any medicines to avoid?

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

Can it be used with birth control?

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

Can it be used in pregnancy?

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

Long-term side effects?

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

Breastfeeding?

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

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

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

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

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

Anxiety?

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

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

Insomnia?

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

How is it different from brexanolone?

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

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

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

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

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

Where can I find more information?

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

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

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

References

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

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

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

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

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

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

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

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

courtesy UNC-Chapel Hill

What is zuranolone?

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

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

What does zuranolone treat?

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

How does zuranolone work?

courtesy UNC-Chapel Hill

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

How was it studied?

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

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

When will we be able to start using it?

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

Who can prescribe it?

courtesy UNC-Chapel Hill

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

How much will it cost?

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

What sort of doses and duration is recommended?

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

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

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

What are the side effects?

courtesy UNC-Chapel Hill

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

Are there any boxed warnings?

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

Can it be used with other medications?

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

Are there any medicines to avoid?

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

Can it be used with birth control?

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

Can it be used in pregnancy?

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

Long-term side effects?

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

Breastfeeding?

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

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

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

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

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

Anxiety?

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

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

Insomnia?

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

How is it different from brexanolone?

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

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

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

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

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

Where can I find more information?

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

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

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

References

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

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

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

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

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

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

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

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

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

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

Research gap

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

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

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

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

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

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

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

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

Physical health benefits

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

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

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

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

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

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

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

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

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

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

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

‘Important limitations’

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Research gap

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

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

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

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

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

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

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

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

Physical health benefits

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

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

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

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

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

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

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

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

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

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

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

‘Important limitations’

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Research gap

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

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

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

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

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

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

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

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

Physical health benefits

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

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

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

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

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

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

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

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

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

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

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

‘Important limitations’

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

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

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

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

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

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

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

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

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

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

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

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

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

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

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

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

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