Mental Health

With youth obesity on the rise – an estimated 1 in 5 youths are impacted by obesity, according to the Centers for Disease Control and Prevention – conversations about healthy weight are becoming more commonplace, not only in the pediatrician’s office, but at home, too. But the language we use around this sensitive topic is important, as youths are acutely aware that words have a direct impact on their mental health.

Sixteen-year-old Avery DiCocco of Northbrook, Ill., knows how vulnerable teenagers feel. 

“I think it definitely matters the way that parents and doctors address weight,” she said. “You never know who may be insecure, and using negative words could go a lot further than they think with impacting self-esteem.” 

A new study published in Pediatrics brings light to the words that parents (and providers) use when speaking to youths (ages 10-17) about their weight.

Researchers from the University of Connecticut Rudd Center for Food Policy & Health, Hartford, led an online survey of youths and their parents. Those who took part were asked about 27  terms related to body weight. Parents were asked to comment on their use of these words, while youths commented on the emotional response. The researchers said 1,936 parents and 2,032 adolescents were surveyed between September and December 2021.

Although results skewed toward the use of more positive words, such as “healthy weight,” over terms like “obese,” “fat” or “large,” there was variation across ethnicity, sexual orientation, and weight status. For example, it was noted in the study, funded by WW International, that preference for the word “curvy” was higher among Hispanic/Latino youths, sexual minority youths, and those with a body mass index in the 95th percentile, compared with their White, heterosexual, and lower-weight peers.
 

Words matter

In 2017, the American Academy of Pediatrics came out with a policy statement on weight stigma and the need for doctors to use more neutral language and less stigmatizing terms in practice when discussing weight among youths.

But one of the reasons this new study is important, said Gregory Germain, MD, associate chief of pediatrics at Yale New Haven (Conn.) Children’s Hospital, is that this study focuses on parents who interact with their kids much more often than a pediatrician who sees them a few times a year.

“Parental motivation, discussion, interaction on a consistent basis – that dialogue is so critical in kids with obesity,” said Germain, who stresses that all adults, coaches, and educators should consider this study as well.

“When we think about those detrimental impacts on mental health when more stigmatizing language is used, just us being more mindful in how we are talking to youth can make such a profound impact,” said Rebecca Kamody, PhD, a clinical psychologist at Yale University, with a research and clinical focus on eating and weight disorders.

“In essence, this is a low-hanging fruit intervention,” she said. 

Dr. Kamody recommends we take a lesson from “cultural humility” in psychology to understand how to approach this with kids, calling for “the humbleness as parents or providers in asking someone what they want used to make it the safest place for a discussion with our youth.”
 

One piece of the puzzle 

Dr. Germain and Dr. Kamody agreed that language in discussing this topic is important but that we need to recognize that this topic in general is extremely tricky.

For one, “there are these very real metabolic complications of having high weight at a young age,” said Kamody, who stresses the need for balance to make real change.

Dr. Germain agreed. “Finding a fine line between discussing obesity and not kicking your kid into disordered eating is important.”

The researchers also recognize the limits of an online study, where self-reporting parents may not want to admit using negative weight terminology, but certainly believe it’s a start in identifying some of the undesirable patterns that may be occurring when it comes to weight.

“The overarching message is a positive one, that with our preteens and teenage kids, we need to watch our language, to create a nonjudgmental and safe environment to discuss weight and any issue involved with taking care of themselves,” said Dr. Germain.

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

With youth obesity on the rise – an estimated 1 in 5 youths are impacted by obesity, according to the Centers for Disease Control and Prevention – conversations about healthy weight are becoming more commonplace, not only in the pediatrician’s office, but at home, too. But the language we use around this sensitive topic is important, as youths are acutely aware that words have a direct impact on their mental health.

Sixteen-year-old Avery DiCocco of Northbrook, Ill., knows how vulnerable teenagers feel. 

“I think it definitely matters the way that parents and doctors address weight,” she said. “You never know who may be insecure, and using negative words could go a lot further than they think with impacting self-esteem.” 

A new study published in Pediatrics brings light to the words that parents (and providers) use when speaking to youths (ages 10-17) about their weight.

Researchers from the University of Connecticut Rudd Center for Food Policy & Health, Hartford, led an online survey of youths and their parents. Those who took part were asked about 27  terms related to body weight. Parents were asked to comment on their use of these words, while youths commented on the emotional response. The researchers said 1,936 parents and 2,032 adolescents were surveyed between September and December 2021.

Although results skewed toward the use of more positive words, such as “healthy weight,” over terms like “obese,” “fat” or “large,” there was variation across ethnicity, sexual orientation, and weight status. For example, it was noted in the study, funded by WW International, that preference for the word “curvy” was higher among Hispanic/Latino youths, sexual minority youths, and those with a body mass index in the 95th percentile, compared with their White, heterosexual, and lower-weight peers.
 

Words matter

In 2017, the American Academy of Pediatrics came out with a policy statement on weight stigma and the need for doctors to use more neutral language and less stigmatizing terms in practice when discussing weight among youths.

But one of the reasons this new study is important, said Gregory Germain, MD, associate chief of pediatrics at Yale New Haven (Conn.) Children’s Hospital, is that this study focuses on parents who interact with their kids much more often than a pediatrician who sees them a few times a year.

“Parental motivation, discussion, interaction on a consistent basis – that dialogue is so critical in kids with obesity,” said Germain, who stresses that all adults, coaches, and educators should consider this study as well.

“When we think about those detrimental impacts on mental health when more stigmatizing language is used, just us being more mindful in how we are talking to youth can make such a profound impact,” said Rebecca Kamody, PhD, a clinical psychologist at Yale University, with a research and clinical focus on eating and weight disorders.

“In essence, this is a low-hanging fruit intervention,” she said. 

Dr. Kamody recommends we take a lesson from “cultural humility” in psychology to understand how to approach this with kids, calling for “the humbleness as parents or providers in asking someone what they want used to make it the safest place for a discussion with our youth.”
 

One piece of the puzzle 

Dr. Germain and Dr. Kamody agreed that language in discussing this topic is important but that we need to recognize that this topic in general is extremely tricky.

For one, “there are these very real metabolic complications of having high weight at a young age,” said Kamody, who stresses the need for balance to make real change.

Dr. Germain agreed. “Finding a fine line between discussing obesity and not kicking your kid into disordered eating is important.”

The researchers also recognize the limits of an online study, where self-reporting parents may not want to admit using negative weight terminology, but certainly believe it’s a start in identifying some of the undesirable patterns that may be occurring when it comes to weight.

“The overarching message is a positive one, that with our preteens and teenage kids, we need to watch our language, to create a nonjudgmental and safe environment to discuss weight and any issue involved with taking care of themselves,” said Dr. Germain.

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

With youth obesity on the rise – an estimated 1 in 5 youths are impacted by obesity, according to the Centers for Disease Control and Prevention – conversations about healthy weight are becoming more commonplace, not only in the pediatrician’s office, but at home, too. But the language we use around this sensitive topic is important, as youths are acutely aware that words have a direct impact on their mental health.

Sixteen-year-old Avery DiCocco of Northbrook, Ill., knows how vulnerable teenagers feel. 

“I think it definitely matters the way that parents and doctors address weight,” she said. “You never know who may be insecure, and using negative words could go a lot further than they think with impacting self-esteem.” 

A new study published in Pediatrics brings light to the words that parents (and providers) use when speaking to youths (ages 10-17) about their weight.

Researchers from the University of Connecticut Rudd Center for Food Policy & Health, Hartford, led an online survey of youths and their parents. Those who took part were asked about 27  terms related to body weight. Parents were asked to comment on their use of these words, while youths commented on the emotional response. The researchers said 1,936 parents and 2,032 adolescents were surveyed between September and December 2021.

Although results skewed toward the use of more positive words, such as “healthy weight,” over terms like “obese,” “fat” or “large,” there was variation across ethnicity, sexual orientation, and weight status. For example, it was noted in the study, funded by WW International, that preference for the word “curvy” was higher among Hispanic/Latino youths, sexual minority youths, and those with a body mass index in the 95th percentile, compared with their White, heterosexual, and lower-weight peers.
 

Words matter

In 2017, the American Academy of Pediatrics came out with a policy statement on weight stigma and the need for doctors to use more neutral language and less stigmatizing terms in practice when discussing weight among youths.

But one of the reasons this new study is important, said Gregory Germain, MD, associate chief of pediatrics at Yale New Haven (Conn.) Children’s Hospital, is that this study focuses on parents who interact with their kids much more often than a pediatrician who sees them a few times a year.

“Parental motivation, discussion, interaction on a consistent basis – that dialogue is so critical in kids with obesity,” said Germain, who stresses that all adults, coaches, and educators should consider this study as well.

“When we think about those detrimental impacts on mental health when more stigmatizing language is used, just us being more mindful in how we are talking to youth can make such a profound impact,” said Rebecca Kamody, PhD, a clinical psychologist at Yale University, with a research and clinical focus on eating and weight disorders.

“In essence, this is a low-hanging fruit intervention,” she said. 

Dr. Kamody recommends we take a lesson from “cultural humility” in psychology to understand how to approach this with kids, calling for “the humbleness as parents or providers in asking someone what they want used to make it the safest place for a discussion with our youth.”
 

One piece of the puzzle 

Dr. Germain and Dr. Kamody agreed that language in discussing this topic is important but that we need to recognize that this topic in general is extremely tricky.

For one, “there are these very real metabolic complications of having high weight at a young age,” said Kamody, who stresses the need for balance to make real change.

Dr. Germain agreed. “Finding a fine line between discussing obesity and not kicking your kid into disordered eating is important.”

The researchers also recognize the limits of an online study, where self-reporting parents may not want to admit using negative weight terminology, but certainly believe it’s a start in identifying some of the undesirable patterns that may be occurring when it comes to weight.

“The overarching message is a positive one, that with our preteens and teenage kids, we need to watch our language, to create a nonjudgmental and safe environment to discuss weight and any issue involved with taking care of themselves,” said Dr. Germain.

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

Recently the U.S. Preventive Services Task Force issued a formal recommendation that adolescents and children as young as 8 should be screened for anxiety.¹ The advice was based on a review of the research that concluded that anxiety disorders were common in youth (prevalence around 8%), screening was not overly burdensome or dangerous, and treatments were available and effective.

While pediatricians fully appreciate how common clinically significant anxiety is and its impact on the lives of youth, the reception for the recommendations have been mixed. Some are concerned that it could lead to the overprescribing of medications. Arguably, the biggest pushback, however, relates to the question of what to do when a child screens positive in a time when finding an available child and adolescent psychiatrist or other type of pediatric mental health professional can feel next to impossible. The hope of this article is to fill in some of those gaps.

Screening for anxiety disorders

The recommendations suggest using a rating scale as part of the screen but doesn’t dictate which one. A common instrument that has been employed is the Screen for Child Anxiety and Related Disorders, which is a freely available 41-item instrument that has versions for youth self-report and parent-report. A shorter 7-item rating scale, the General Anxiety Disorder–7, and the even shorter GAD-2 (the first two questions of the GAD-7), are also popular but focus, as the name applies, on general anxiety disorder and not related conditions such as social or separation anxiety that can have some different symptoms. These instruments can be given to patients and families in the waiting room or administered with the help of a nurse, physician, or embedded mental health professional. The recommendations do not include specific guidance on how often the screening should be done but repeated screenings are likely important at some interval.

Confirming the diagnosis

Of course, a screening isn’t a formal diagnosis. The American Academy of Pediatrics has expressed the view that the initial diagnosis and treatment for anxiety disorders is well within a pediatrician’s scope of practice, which means further steps are likely required beyond a referral. Fortunately, going from a positive screen to an initial diagnosis does not have to overly laborious and can focus on reviewing the DSM-5 criteria for key anxiety disorders while also ensuring that there isn’t a nonpsychiatric cause driving the symptoms, such as the often cited but rarely seen pheochromocytoma. More common rule-outs include medication-induced anxiety or substance use, excessive caffeine intake, and cardiac arrhythmias. Assessing for current and past trauma or specific causes of the anxiety such as bullying are also important.

It is important to note that it is the rule rather than the exception that youth with clinical levels of anxiety will frequently endorse a number of criteria that span multiple diagnoses including generalized anxiety disorder, social anxiety disorder, and separation anxiety disorder.² Spending a lot of effort to narrow things down to a single anxiety diagnosis often is unnecessary, as both pharmacologic and nonpharmacologic treatments don’t change all that much between individual diagnoses.
 

Explaining the diagnosis

In general, I’m a strong proponent of trying to explain any behavioral diagnoses that you make to kids in a way that is accurate but nonstigmatizing. When it comes to anxiety, one parallel I often draw is to our immune system, which most youth understand at least in basic terms. Both our immune system and our anxiety networks are natural and important; as a species, we wouldn’t have lasted long without them. Both are built to assess and respond to threats. Problems can arise, however, if the response is too strong relative to the threat or the response is activated when it doesn’t need to be. Treatment is directed not at ridding ourselves of anxiety but at helping regulate it so it works for us and not against us. Spending a few minutes going through a discussion like this can be very helpful, and perhaps more so than some dry summary of DSM-5 criteria.

Starting treatment

It is important to note that best practice recommendations when it comes to the treatment of anxiety disorder in youth do not suggest medications as the only type of treatment and often urge clinicians to try nonpharmacological interventions first.³ A specific type of psychotherapy called cognitive-behavioral therapy has the strongest scientific support as an effective treatment for anxiety but other modalities, including parenting guidance, can be helpful as well. Consequently, a referral to a good psychotherapist is paramount. For many kids, the key to overcoming anxiety is exposure: which means confronting anxiety slowly, with support, and with specific skills.

If there is a traumatic source of the anxiety, addressing that as much as possible is obviously critical and could involve working with the family or school. For some kids, this may involve frightening things they are seeing online or through other media. Finally, some health promotion activities such as exercise or mindfulness can also be quite useful.

Despite the fact that SSRIs are referred to as antidepressants, there is increasing appreciation that these medications are useful for anxiety, perhaps even more so than for mood. While only one medication, duloxetine, has Food and Drug Administration approval to treat anxiety in children as young as 7, there is good evidence to support the use of many of the most common SSRIs in treating clinical anxiety. Buspirone, beta-blockers, and antihistamine medications like hydroxyzine also can have their place in treatment, while benzodiazepines and antipsychotic medications are generally best avoided for anxious youth, especially in the primary care setting. A short but helpful medication guide with regard to pediatric anxiety has been published by the American Academy of Child and Adolescent Psychiatry.⁴

Conclusions

Clinical levels of anxiety in children and adolescents are both common and quite treatable, which has prompted new recommendations that primary care clinicians screen for them starting at age 8. While this recommendation may at first seem like yet one more task to fit in, following the guidance can be accomplished with the help of short screening tools and a managed multimodal approach to treatment.

Dr. Rettew is a child and adolescent psychiatrist with Lane County Behavioral Health in Eugene, Ore., and Oregon Health & Science University, Portland. You can follow him on Twitter and Facebook @PediPsych.

References

1. U.S. Preventive Services Task Force. JAMA. 2022;328(14):1438-44.

2. Strawn JR. Curr Psychiatry. 2012;11(9):16-21.

3. Walter HJ et al. J Am Acad Child Adolesc Psychiatry. 2020;59(10):1107-24.

4. Anxiety Disorders: Parents’ Medication Guide Workgroup. “Anxiety disorders: Parents’ medication guide.” Washington D.C.: American Academy of Child & Adolescent Psychiatry, 2020.

Recently the U.S. Preventive Services Task Force issued a formal recommendation that adolescents and children as young as 8 should be screened for anxiety.¹ The advice was based on a review of the research that concluded that anxiety disorders were common in youth (prevalence around 8%), screening was not overly burdensome or dangerous, and treatments were available and effective.

While pediatricians fully appreciate how common clinically significant anxiety is and its impact on the lives of youth, the reception for the recommendations have been mixed. Some are concerned that it could lead to the overprescribing of medications. Arguably, the biggest pushback, however, relates to the question of what to do when a child screens positive in a time when finding an available child and adolescent psychiatrist or other type of pediatric mental health professional can feel next to impossible. The hope of this article is to fill in some of those gaps.

Screening for anxiety disorders

The recommendations suggest using a rating scale as part of the screen but doesn’t dictate which one. A common instrument that has been employed is the Screen for Child Anxiety and Related Disorders, which is a freely available 41-item instrument that has versions for youth self-report and parent-report. A shorter 7-item rating scale, the General Anxiety Disorder–7, and the even shorter GAD-2 (the first two questions of the GAD-7), are also popular but focus, as the name applies, on general anxiety disorder and not related conditions such as social or separation anxiety that can have some different symptoms. These instruments can be given to patients and families in the waiting room or administered with the help of a nurse, physician, or embedded mental health professional. The recommendations do not include specific guidance on how often the screening should be done but repeated screenings are likely important at some interval.

Confirming the diagnosis

Of course, a screening isn’t a formal diagnosis. The American Academy of Pediatrics has expressed the view that the initial diagnosis and treatment for anxiety disorders is well within a pediatrician’s scope of practice, which means further steps are likely required beyond a referral. Fortunately, going from a positive screen to an initial diagnosis does not have to overly laborious and can focus on reviewing the DSM-5 criteria for key anxiety disorders while also ensuring that there isn’t a nonpsychiatric cause driving the symptoms, such as the often cited but rarely seen pheochromocytoma. More common rule-outs include medication-induced anxiety or substance use, excessive caffeine intake, and cardiac arrhythmias. Assessing for current and past trauma or specific causes of the anxiety such as bullying are also important.

It is important to note that it is the rule rather than the exception that youth with clinical levels of anxiety will frequently endorse a number of criteria that span multiple diagnoses including generalized anxiety disorder, social anxiety disorder, and separation anxiety disorder.² Spending a lot of effort to narrow things down to a single anxiety diagnosis often is unnecessary, as both pharmacologic and nonpharmacologic treatments don’t change all that much between individual diagnoses.
 

Explaining the diagnosis

In general, I’m a strong proponent of trying to explain any behavioral diagnoses that you make to kids in a way that is accurate but nonstigmatizing. When it comes to anxiety, one parallel I often draw is to our immune system, which most youth understand at least in basic terms. Both our immune system and our anxiety networks are natural and important; as a species, we wouldn’t have lasted long without them. Both are built to assess and respond to threats. Problems can arise, however, if the response is too strong relative to the threat or the response is activated when it doesn’t need to be. Treatment is directed not at ridding ourselves of anxiety but at helping regulate it so it works for us and not against us. Spending a few minutes going through a discussion like this can be very helpful, and perhaps more so than some dry summary of DSM-5 criteria.

Starting treatment

It is important to note that best practice recommendations when it comes to the treatment of anxiety disorder in youth do not suggest medications as the only type of treatment and often urge clinicians to try nonpharmacological interventions first.³ A specific type of psychotherapy called cognitive-behavioral therapy has the strongest scientific support as an effective treatment for anxiety but other modalities, including parenting guidance, can be helpful as well. Consequently, a referral to a good psychotherapist is paramount. For many kids, the key to overcoming anxiety is exposure: which means confronting anxiety slowly, with support, and with specific skills.

If there is a traumatic source of the anxiety, addressing that as much as possible is obviously critical and could involve working with the family or school. For some kids, this may involve frightening things they are seeing online or through other media. Finally, some health promotion activities such as exercise or mindfulness can also be quite useful.

Despite the fact that SSRIs are referred to as antidepressants, there is increasing appreciation that these medications are useful for anxiety, perhaps even more so than for mood. While only one medication, duloxetine, has Food and Drug Administration approval to treat anxiety in children as young as 7, there is good evidence to support the use of many of the most common SSRIs in treating clinical anxiety. Buspirone, beta-blockers, and antihistamine medications like hydroxyzine also can have their place in treatment, while benzodiazepines and antipsychotic medications are generally best avoided for anxious youth, especially in the primary care setting. A short but helpful medication guide with regard to pediatric anxiety has been published by the American Academy of Child and Adolescent Psychiatry.⁴

Conclusions

Clinical levels of anxiety in children and adolescents are both common and quite treatable, which has prompted new recommendations that primary care clinicians screen for them starting at age 8. While this recommendation may at first seem like yet one more task to fit in, following the guidance can be accomplished with the help of short screening tools and a managed multimodal approach to treatment.

Dr. Rettew is a child and adolescent psychiatrist with Lane County Behavioral Health in Eugene, Ore., and Oregon Health & Science University, Portland. You can follow him on Twitter and Facebook @PediPsych.

References

1. U.S. Preventive Services Task Force. JAMA. 2022;328(14):1438-44.

2. Strawn JR. Curr Psychiatry. 2012;11(9):16-21.

3. Walter HJ et al. J Am Acad Child Adolesc Psychiatry. 2020;59(10):1107-24.

4. Anxiety Disorders: Parents’ Medication Guide Workgroup. “Anxiety disorders: Parents’ medication guide.” Washington D.C.: American Academy of Child & Adolescent Psychiatry, 2020.

Recently the U.S. Preventive Services Task Force issued a formal recommendation that adolescents and children as young as 8 should be screened for anxiety.¹ The advice was based on a review of the research that concluded that anxiety disorders were common in youth (prevalence around 8%), screening was not overly burdensome or dangerous, and treatments were available and effective.

While pediatricians fully appreciate how common clinically significant anxiety is and its impact on the lives of youth, the reception for the recommendations have been mixed. Some are concerned that it could lead to the overprescribing of medications. Arguably, the biggest pushback, however, relates to the question of what to do when a child screens positive in a time when finding an available child and adolescent psychiatrist or other type of pediatric mental health professional can feel next to impossible. The hope of this article is to fill in some of those gaps.

Screening for anxiety disorders

The recommendations suggest using a rating scale as part of the screen but doesn’t dictate which one. A common instrument that has been employed is the Screen for Child Anxiety and Related Disorders, which is a freely available 41-item instrument that has versions for youth self-report and parent-report. A shorter 7-item rating scale, the General Anxiety Disorder–7, and the even shorter GAD-2 (the first two questions of the GAD-7), are also popular but focus, as the name applies, on general anxiety disorder and not related conditions such as social or separation anxiety that can have some different symptoms. These instruments can be given to patients and families in the waiting room or administered with the help of a nurse, physician, or embedded mental health professional. The recommendations do not include specific guidance on how often the screening should be done but repeated screenings are likely important at some interval.

Confirming the diagnosis

Of course, a screening isn’t a formal diagnosis. The American Academy of Pediatrics has expressed the view that the initial diagnosis and treatment for anxiety disorders is well within a pediatrician’s scope of practice, which means further steps are likely required beyond a referral. Fortunately, going from a positive screen to an initial diagnosis does not have to overly laborious and can focus on reviewing the DSM-5 criteria for key anxiety disorders while also ensuring that there isn’t a nonpsychiatric cause driving the symptoms, such as the often cited but rarely seen pheochromocytoma. More common rule-outs include medication-induced anxiety or substance use, excessive caffeine intake, and cardiac arrhythmias. Assessing for current and past trauma or specific causes of the anxiety such as bullying are also important.

It is important to note that it is the rule rather than the exception that youth with clinical levels of anxiety will frequently endorse a number of criteria that span multiple diagnoses including generalized anxiety disorder, social anxiety disorder, and separation anxiety disorder.² Spending a lot of effort to narrow things down to a single anxiety diagnosis often is unnecessary, as both pharmacologic and nonpharmacologic treatments don’t change all that much between individual diagnoses.
 

Explaining the diagnosis

In general, I’m a strong proponent of trying to explain any behavioral diagnoses that you make to kids in a way that is accurate but nonstigmatizing. When it comes to anxiety, one parallel I often draw is to our immune system, which most youth understand at least in basic terms. Both our immune system and our anxiety networks are natural and important; as a species, we wouldn’t have lasted long without them. Both are built to assess and respond to threats. Problems can arise, however, if the response is too strong relative to the threat or the response is activated when it doesn’t need to be. Treatment is directed not at ridding ourselves of anxiety but at helping regulate it so it works for us and not against us. Spending a few minutes going through a discussion like this can be very helpful, and perhaps more so than some dry summary of DSM-5 criteria.

Starting treatment

It is important to note that best practice recommendations when it comes to the treatment of anxiety disorder in youth do not suggest medications as the only type of treatment and often urge clinicians to try nonpharmacological interventions first.³ A specific type of psychotherapy called cognitive-behavioral therapy has the strongest scientific support as an effective treatment for anxiety but other modalities, including parenting guidance, can be helpful as well. Consequently, a referral to a good psychotherapist is paramount. For many kids, the key to overcoming anxiety is exposure: which means confronting anxiety slowly, with support, and with specific skills.

If there is a traumatic source of the anxiety, addressing that as much as possible is obviously critical and could involve working with the family or school. For some kids, this may involve frightening things they are seeing online or through other media. Finally, some health promotion activities such as exercise or mindfulness can also be quite useful.

Despite the fact that SSRIs are referred to as antidepressants, there is increasing appreciation that these medications are useful for anxiety, perhaps even more so than for mood. While only one medication, duloxetine, has Food and Drug Administration approval to treat anxiety in children as young as 7, there is good evidence to support the use of many of the most common SSRIs in treating clinical anxiety. Buspirone, beta-blockers, and antihistamine medications like hydroxyzine also can have their place in treatment, while benzodiazepines and antipsychotic medications are generally best avoided for anxious youth, especially in the primary care setting. A short but helpful medication guide with regard to pediatric anxiety has been published by the American Academy of Child and Adolescent Psychiatry.⁴

Conclusions

Clinical levels of anxiety in children and adolescents are both common and quite treatable, which has prompted new recommendations that primary care clinicians screen for them starting at age 8. While this recommendation may at first seem like yet one more task to fit in, following the guidance can be accomplished with the help of short screening tools and a managed multimodal approach to treatment.

Dr. Rettew is a child and adolescent psychiatrist with Lane County Behavioral Health in Eugene, Ore., and Oregon Health & Science University, Portland. You can follow him on Twitter and Facebook @PediPsych.

References

1. U.S. Preventive Services Task Force. JAMA. 2022;328(14):1438-44.

2. Strawn JR. Curr Psychiatry. 2012;11(9):16-21.

3. Walter HJ et al. J Am Acad Child Adolesc Psychiatry. 2020;59(10):1107-24.

4. Anxiety Disorders: Parents’ Medication Guide Workgroup. “Anxiety disorders: Parents’ medication guide.” Washington D.C.: American Academy of Child & Adolescent Psychiatry, 2020.

A large Danish study supports a robust and long-term bidirectional relationship between epilepsy and depression, with implications for diagnosis and patient care. The findings “strongly support previous observations of a bidirectional association between these two brain disorders,” said Eva Bølling-Ladegaard, MD, a PhD student, department of clinical medicine (Neurology), Aarhus (Denmark) University.

“We add to the existing evidence in temporal range, showing that the increased risks of depression following epilepsy, and vice versa, are sustained over a much more extended time period than previously shown; that is, 20 years on both sides of receiving a diagnosis of the index disorder,” Ms. Bølling-Ladegaard said.

The study was published online in Neurology.
 

Epilepsy then depression

The researchers examined the magnitude and long-term temporal association between epilepsy and depression. They compared the risk of the two brain disorders following another chronic disorder (asthma) in a nationwide, register-based, matched cohort study.

In a population of more than 8.7 million people, they identified 139,014 persons with epilepsy (54% males; median age at diagnosis, 43 years), 219,990 with depression (37% males; median age at diagnosis, 43 years), and 358,821 with asthma (49% males; median age at diagnosis, 29 years).

The rate of developing depression was increased nearly twofold among people with epilepsy compared with the matched population who did not have epilepsy (adjusted hazard ratio, 1.88; 95% confidence interval, 1.82-1.95).

The rate of depression was highest during the first months and years after epilepsy diagnosis. It declined over time, yet remained significantly elevated throughout the 20+ years of observation.

The cumulative incidence of depression at 5 and 35 years’ follow-up in the epilepsy cohort was 1.37% and 6.05%, respectively, compared with 0.59% and 3.92% in the reference population.

The highest rate of depression after epilepsy was among individuals aged 40-59 years, and the lowest was among those aged 0-19 years at first epilepsy diagnosis.
 

Depression then epilepsy

The rate of developing epilepsy was increased more than twofold among patients with incident depression compared with the matched population who were without depression (aHR, 2.35; 95% CI, 2.25-2.44).

As in the opposite analysis, the rate of epilepsy was highest during the first months and years after depression diagnosis and declined over time.

The cumulative incidence of epilepsy at 5 and 35 years after depression diagnosis was 1.10% and 4.19%, respectively, compared with 0.32% and 2.06% in the reference population.

The rate of epilepsy was highest among those aged 0-19 years at time of first depression diagnosis and was lowest among those aged 80+ at first depression diagnosis.

For comparison, after asthma diagnosis, rates of depression and epilepsy were increased 1.63-fold (95% CI, 1.59-1.67) and 1.48-fold (95% CI, 1.44-1.53), respectively, compared with matched individuals without asthma.

Using admission with seizures as a proxy for treatment failure, the researchers observed an increased risk of treatment failure among people with epilepsy who were diagnosed with depression.

“Our results support previous findings indicating worse seizure outcomes in people with epilepsy and coexisting depression,” said Ms. Bølling-Ladegaard.

“Increased clinical awareness of the association between epilepsy and depression is therefore needed in order to increase the proportion of patients that receive appropriate treatment and improve outcomes for these patient groups,” she said.
 

Clinical implications

Reached for comment, Zulfi Haneef, MBBS, MD, associate professor of neurology, Baylor College of Medicine, Houston, noted that the link between epilepsy and depression is “well-known.”

“However, typically one thinks of epilepsy as leading to depression, not vice versa. Here they show the risk of epilepsy following depression to be high (highest of the risks given), which is thought provoking. However, association does not imply causation,” Dr. Haneef said.

“Prima facie, there is no biological rationale for depression to lead to epilepsy,” he said. He noted that some antidepressants can reduce the seizure threshold.

The findings do have implications for care, he said.

“For neurologists, this is another study that exhorts them to screen for depression and treat adequately in all patients with epilepsy,” Dr. Haneef said.

“For psychiatrists, this study may give guidance to watch more carefully for seizures in patients with depression, especially when using antidepressant medications that induce seizures.

“For the general public with either epilepsy or depression, it would help them be aware about this bidirectional association,” Dr. Haneef said.

The study was funded by the Lundbeck Foundation, the Danish Epilepsy Association, and the Novo Nordisk Foundation. Ms. Bølling-Ladegaard and Dr. Haneef have disclosed no relevant financial relationships.

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

A large Danish study supports a robust and long-term bidirectional relationship between epilepsy and depression, with implications for diagnosis and patient care. The findings “strongly support previous observations of a bidirectional association between these two brain disorders,” said Eva Bølling-Ladegaard, MD, a PhD student, department of clinical medicine (Neurology), Aarhus (Denmark) University.

“We add to the existing evidence in temporal range, showing that the increased risks of depression following epilepsy, and vice versa, are sustained over a much more extended time period than previously shown; that is, 20 years on both sides of receiving a diagnosis of the index disorder,” Ms. Bølling-Ladegaard said.

The study was published online in Neurology.
 

Epilepsy then depression

The researchers examined the magnitude and long-term temporal association between epilepsy and depression. They compared the risk of the two brain disorders following another chronic disorder (asthma) in a nationwide, register-based, matched cohort study.

In a population of more than 8.7 million people, they identified 139,014 persons with epilepsy (54% males; median age at diagnosis, 43 years), 219,990 with depression (37% males; median age at diagnosis, 43 years), and 358,821 with asthma (49% males; median age at diagnosis, 29 years).

The rate of developing depression was increased nearly twofold among people with epilepsy compared with the matched population who did not have epilepsy (adjusted hazard ratio, 1.88; 95% confidence interval, 1.82-1.95).

The rate of depression was highest during the first months and years after epilepsy diagnosis. It declined over time, yet remained significantly elevated throughout the 20+ years of observation.

The cumulative incidence of depression at 5 and 35 years’ follow-up in the epilepsy cohort was 1.37% and 6.05%, respectively, compared with 0.59% and 3.92% in the reference population.

The highest rate of depression after epilepsy was among individuals aged 40-59 years, and the lowest was among those aged 0-19 years at first epilepsy diagnosis.
 

Depression then epilepsy

The rate of developing epilepsy was increased more than twofold among patients with incident depression compared with the matched population who were without depression (aHR, 2.35; 95% CI, 2.25-2.44).

As in the opposite analysis, the rate of epilepsy was highest during the first months and years after depression diagnosis and declined over time.

The cumulative incidence of epilepsy at 5 and 35 years after depression diagnosis was 1.10% and 4.19%, respectively, compared with 0.32% and 2.06% in the reference population.

The rate of epilepsy was highest among those aged 0-19 years at time of first depression diagnosis and was lowest among those aged 80+ at first depression diagnosis.

For comparison, after asthma diagnosis, rates of depression and epilepsy were increased 1.63-fold (95% CI, 1.59-1.67) and 1.48-fold (95% CI, 1.44-1.53), respectively, compared with matched individuals without asthma.

Using admission with seizures as a proxy for treatment failure, the researchers observed an increased risk of treatment failure among people with epilepsy who were diagnosed with depression.

“Our results support previous findings indicating worse seizure outcomes in people with epilepsy and coexisting depression,” said Ms. Bølling-Ladegaard.

“Increased clinical awareness of the association between epilepsy and depression is therefore needed in order to increase the proportion of patients that receive appropriate treatment and improve outcomes for these patient groups,” she said.
 

Clinical implications

Reached for comment, Zulfi Haneef, MBBS, MD, associate professor of neurology, Baylor College of Medicine, Houston, noted that the link between epilepsy and depression is “well-known.”

“However, typically one thinks of epilepsy as leading to depression, not vice versa. Here they show the risk of epilepsy following depression to be high (highest of the risks given), which is thought provoking. However, association does not imply causation,” Dr. Haneef said.

“Prima facie, there is no biological rationale for depression to lead to epilepsy,” he said. He noted that some antidepressants can reduce the seizure threshold.

The findings do have implications for care, he said.

“For neurologists, this is another study that exhorts them to screen for depression and treat adequately in all patients with epilepsy,” Dr. Haneef said.

“For psychiatrists, this study may give guidance to watch more carefully for seizures in patients with depression, especially when using antidepressant medications that induce seizures.

“For the general public with either epilepsy or depression, it would help them be aware about this bidirectional association,” Dr. Haneef said.

The study was funded by the Lundbeck Foundation, the Danish Epilepsy Association, and the Novo Nordisk Foundation. Ms. Bølling-Ladegaard and Dr. Haneef have disclosed no relevant financial relationships.

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

A large Danish study supports a robust and long-term bidirectional relationship between epilepsy and depression, with implications for diagnosis and patient care. The findings “strongly support previous observations of a bidirectional association between these two brain disorders,” said Eva Bølling-Ladegaard, MD, a PhD student, department of clinical medicine (Neurology), Aarhus (Denmark) University.

“We add to the existing evidence in temporal range, showing that the increased risks of depression following epilepsy, and vice versa, are sustained over a much more extended time period than previously shown; that is, 20 years on both sides of receiving a diagnosis of the index disorder,” Ms. Bølling-Ladegaard said.

The study was published online in Neurology.
 

Epilepsy then depression

The researchers examined the magnitude and long-term temporal association between epilepsy and depression. They compared the risk of the two brain disorders following another chronic disorder (asthma) in a nationwide, register-based, matched cohort study.

In a population of more than 8.7 million people, they identified 139,014 persons with epilepsy (54% males; median age at diagnosis, 43 years), 219,990 with depression (37% males; median age at diagnosis, 43 years), and 358,821 with asthma (49% males; median age at diagnosis, 29 years).

The rate of developing depression was increased nearly twofold among people with epilepsy compared with the matched population who did not have epilepsy (adjusted hazard ratio, 1.88; 95% confidence interval, 1.82-1.95).

The rate of depression was highest during the first months and years after epilepsy diagnosis. It declined over time, yet remained significantly elevated throughout the 20+ years of observation.

The cumulative incidence of depression at 5 and 35 years’ follow-up in the epilepsy cohort was 1.37% and 6.05%, respectively, compared with 0.59% and 3.92% in the reference population.

The highest rate of depression after epilepsy was among individuals aged 40-59 years, and the lowest was among those aged 0-19 years at first epilepsy diagnosis.
 

Depression then epilepsy

The rate of developing epilepsy was increased more than twofold among patients with incident depression compared with the matched population who were without depression (aHR, 2.35; 95% CI, 2.25-2.44).

As in the opposite analysis, the rate of epilepsy was highest during the first months and years after depression diagnosis and declined over time.

The cumulative incidence of epilepsy at 5 and 35 years after depression diagnosis was 1.10% and 4.19%, respectively, compared with 0.32% and 2.06% in the reference population.

The rate of epilepsy was highest among those aged 0-19 years at time of first depression diagnosis and was lowest among those aged 80+ at first depression diagnosis.

For comparison, after asthma diagnosis, rates of depression and epilepsy were increased 1.63-fold (95% CI, 1.59-1.67) and 1.48-fold (95% CI, 1.44-1.53), respectively, compared with matched individuals without asthma.

Using admission with seizures as a proxy for treatment failure, the researchers observed an increased risk of treatment failure among people with epilepsy who were diagnosed with depression.

“Our results support previous findings indicating worse seizure outcomes in people with epilepsy and coexisting depression,” said Ms. Bølling-Ladegaard.

“Increased clinical awareness of the association between epilepsy and depression is therefore needed in order to increase the proportion of patients that receive appropriate treatment and improve outcomes for these patient groups,” she said.
 

Clinical implications

Reached for comment, Zulfi Haneef, MBBS, MD, associate professor of neurology, Baylor College of Medicine, Houston, noted that the link between epilepsy and depression is “well-known.”

“However, typically one thinks of epilepsy as leading to depression, not vice versa. Here they show the risk of epilepsy following depression to be high (highest of the risks given), which is thought provoking. However, association does not imply causation,” Dr. Haneef said.

“Prima facie, there is no biological rationale for depression to lead to epilepsy,” he said. He noted that some antidepressants can reduce the seizure threshold.

The findings do have implications for care, he said.

“For neurologists, this is another study that exhorts them to screen for depression and treat adequately in all patients with epilepsy,” Dr. Haneef said.

“For psychiatrists, this study may give guidance to watch more carefully for seizures in patients with depression, especially when using antidepressant medications that induce seizures.

“For the general public with either epilepsy or depression, it would help them be aware about this bidirectional association,” Dr. Haneef said.

The study was funded by the Lundbeck Foundation, the Danish Epilepsy Association, and the Novo Nordisk Foundation. Ms. Bølling-Ladegaard and Dr. Haneef have disclosed no relevant financial relationships.

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

The American Academy of Pediatrics is cautioning physicians and parents to be on the lookout for unnecessary diagnostic testing associated with several common pediatric conditions.

Children seen for these conditions in emergency settings and even in primary care offices could experience avoidable pain, exposure to harmful radiation, and other harms, according to the group.

“The emergency department has the ability to rapidly perform myriad diagnostic tests and receive results quickly,” said Paul Mullan, MD, MPH, chair of the AAP’s Section of Emergency Medicine’s Choosing Wisely task force. “However, this comes with the danger of diagnostic overtesting.”

The five recommendations are as follows:

• Radiographs should not be obtained for children with bronchiolitis, croup, asthma, or first-time wheezing.
• Laboratory tests for screening should not be undertaken in the medical clearance process of children who require inpatient psychiatric admission unless clinically indicated.
• Laboratory testing or a CT scan of the head should not be ordered for a child with an unprovoked, generalized seizure or a simple febrile seizure whose mental status has returned to baseline.
• Abdominal radiographs should not be obtained for suspected constipation.
• Comprehensive viral panel testing should not be undertaken for children who are suspected of having respiratory viral illnesses.

The AAP task force partnered with Choosing Wisely Canada to create the recommendations. The list is the first of its kind to be published jointly by two countries, according to the release.

“We hope this Choosing Wisely list will encourage clinicians to rely on their clinical skills and avoid unnecessary tests,” said Dr. Mullan, who is also a physician at Children’s Hospital of the King’s Daughters and professor of pediatrics at Eastern Virginia Medical School, Norfolk.

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

The American Academy of Pediatrics is cautioning physicians and parents to be on the lookout for unnecessary diagnostic testing associated with several common pediatric conditions.

Children seen for these conditions in emergency settings and even in primary care offices could experience avoidable pain, exposure to harmful radiation, and other harms, according to the group.

“The emergency department has the ability to rapidly perform myriad diagnostic tests and receive results quickly,” said Paul Mullan, MD, MPH, chair of the AAP’s Section of Emergency Medicine’s Choosing Wisely task force. “However, this comes with the danger of diagnostic overtesting.”

The five recommendations are as follows:

• Radiographs should not be obtained for children with bronchiolitis, croup, asthma, or first-time wheezing.
• Laboratory tests for screening should not be undertaken in the medical clearance process of children who require inpatient psychiatric admission unless clinically indicated.
• Laboratory testing or a CT scan of the head should not be ordered for a child with an unprovoked, generalized seizure or a simple febrile seizure whose mental status has returned to baseline.
• Abdominal radiographs should not be obtained for suspected constipation.
• Comprehensive viral panel testing should not be undertaken for children who are suspected of having respiratory viral illnesses.

The AAP task force partnered with Choosing Wisely Canada to create the recommendations. The list is the first of its kind to be published jointly by two countries, according to the release.

“We hope this Choosing Wisely list will encourage clinicians to rely on their clinical skills and avoid unnecessary tests,” said Dr. Mullan, who is also a physician at Children’s Hospital of the King’s Daughters and professor of pediatrics at Eastern Virginia Medical School, Norfolk.

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

The American Academy of Pediatrics is cautioning physicians and parents to be on the lookout for unnecessary diagnostic testing associated with several common pediatric conditions.

Children seen for these conditions in emergency settings and even in primary care offices could experience avoidable pain, exposure to harmful radiation, and other harms, according to the group.

“The emergency department has the ability to rapidly perform myriad diagnostic tests and receive results quickly,” said Paul Mullan, MD, MPH, chair of the AAP’s Section of Emergency Medicine’s Choosing Wisely task force. “However, this comes with the danger of diagnostic overtesting.”

The five recommendations are as follows:

• Radiographs should not be obtained for children with bronchiolitis, croup, asthma, or first-time wheezing.
• Laboratory tests for screening should not be undertaken in the medical clearance process of children who require inpatient psychiatric admission unless clinically indicated.
• Laboratory testing or a CT scan of the head should not be ordered for a child with an unprovoked, generalized seizure or a simple febrile seizure whose mental status has returned to baseline.
• Abdominal radiographs should not be obtained for suspected constipation.
• Comprehensive viral panel testing should not be undertaken for children who are suspected of having respiratory viral illnesses.

The AAP task force partnered with Choosing Wisely Canada to create the recommendations. The list is the first of its kind to be published jointly by two countries, according to the release.

“We hope this Choosing Wisely list will encourage clinicians to rely on their clinical skills and avoid unnecessary tests,” said Dr. Mullan, who is also a physician at Children’s Hospital of the King’s Daughters and professor of pediatrics at Eastern Virginia Medical School, Norfolk.

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

As fentanyl-related overdose deaths continue to increase, clinicians should take note of important differences that set the drug apart from the other drugs of misuse – and the troubling reality that fentanyl now contaminates most of them.

“It would be fair to tell patients, if you’re buying any illicit drugs – pills, powder, liquid, whatever it is, you’ve got to assume it’s either contaminated with or replaced by fentanyl,” said Edwin Salsitz, MD, an associate clinical professor at the Icahn School of Medicine at Mount Sinai, New York, during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

In many if not most cases, he noted, patients become addicted to fentanyl unknowingly. They assume they are ingesting oxycodone, cocaine, or another drug, and have no realization that they are even exposed to fentanyl until they test positive for it – or overdose.

Meanwhile, the high potency of fentanyl can overcome the opioid blockade of addiction treatment therapies – methadone and buprenorphine – that take away the high that users get from less potent drugs such as heroin.

“Fentanyl is overcoming this blockade that methadone and buprenorphine used to provide,” Dr. Salsitz said. “With fentanyl having such a higher potency, patients are saying ‘no, I still feel the fentanyl effects,’ and they continue feeling it even with 200 milligrams of methadone or 24 milligrams of buprenorphine.”
 

‘Wooden chest syndrome’

Among the lesser-known dangers of fentanyl is the possibility that some overdose deaths may occur as the result of a syndrome previously reported as a rare complication following the medical use of fentanyl in critically ill patients – fentanyl-induced chest-wall rigidity, or “wooden chest syndrome,” Dr. Salsitz explained.

In such cases, the muscles of respiration become rigid and paralyzed, causing suffocation within a matter of minutes – too soon to benefit from the overdose rescue medication naloxone.

In one recent study published in Clinical Toxicology , nearly half of fentanyl overdose deaths were found to have occurred even before the body had a chance to produce norfentanyl, a metabolite of fentanyl that takes only about 2-3 minutes to appear in the system, suggesting the deaths occurred rapidly.

In the study of 48 fentanyl deaths, no appreciable concentrations of norfentanyl could be detected in 20 of the 48 overdose deaths (42%), and concentrations were less than 1 ng/mL in 25 cases (52%).

“The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity,” the authors reported.

“In several cases fentanyl concentrations were strikingly high (22 ng/mL and 20 ng/mL) with no norfentanyl detected,” they said.

Dr. Salsitz noted that the syndrome is not well known among the addiction treatment community.

“This is different than the usual respiratory opioid overdose where there’s a gradual decrease in the breathing rate and a gradual decrease in how much air is going in and out of the lungs,” Dr. Salsitz explained.

“With those cases, some may survive for an hour or longer, allowing time for someone to administer naloxone or to get the patient to the emergency room,” he said. “But with this, breathing stops and people can die within minutes.

“I think that this is one of the reasons that fentanyl deaths keep going up despite more and more naloxone availability out there,” he said.
 

Clearance may take longer

In toxicology testing for fentanyl, clinicians should also note the important difference between fentanyl and other opioids – that fentanyl, because of its high lipophilicity, may be detected in urine toxicology testing up to 3 weeks after last use. This is much longer than the 2- to 4-day clearance observed with other opioids, possibly causing patients to continue to test positive for the drug weeks after cessation.

This effect was observed in one recent study of 12 opioid use disorder patients in a residential treatment program who had previously been exposed to daily fentanyl.

The study showed the mean amount of time of fentanyl clearance was 2 weeks, with a range of 4-26 days after last use.

The authors pointed out that the findings “might explain recent reports of difficulty in buprenorphine inductions for persons who use fentanyl, and point to a need to better understand the pharmacokinetics of fentanyl in the context of opioid withdrawal in persons who regularly use fentanyl.”

Though the study was small, Dr. Salsitz said “that’s not a stumbling block to the important finding that, with regular use of fentanyl, the drug may stay in the urine for a long time.”

Dr. Salsitz noted that similar observations have been made at his center, with clinicians logically assuming that patients were still somehow getting fentanyl.

“When we initially found this in patients, we thought that they were using on the unit, perhaps that they brought in the fentanyl, because otherwise how could it stay in the urine that long,” he noted. “But fentanyl appears to be more lipophilic and gets into the fat; it’s then excreted very slowly and then stays in the urine.”

Dr. Salsitz said most practitioners think of fentanyl as a short-acting drug, so “it’s important to realize that people may continue to test positive and it should be thought of as a long-acting opioid.”
 

Opiate screening tests don’t work

Dr. Salsitz warned of another misconception in fentanyl testing – the common mistake of assuming that fentanyl should show up in a test for opiates – when in fact fentanyl is not, technically, an opiate.

“The word opiate only refers to morphine, codeine, heroin and sometimes hydrocodone,” he explained. “Other opioids are classified as semisynthetic, such as oxycodone, or synthetics, such as fentanyl and methadone, buprenorphine.”

“In order to detect the synthetics, you must have a separate strip for each one of those drugs. They will not show up positive on a screen for opiates,” he noted.

The belief that fentanyl and other synthetic and semisynthetic opioids will show positive on an opiate screen is a common misconception, he said. “The misunderstanding in toxicology interpretation is a problem for many practitioners, [but] it’s essential to understand because otherwise false assumptions about the patient will be considered.”

Another important testing misreading can occur with the antidepressant drug trazodone, which Dr. Salsitz cautioned may falsely test as positive for fentanyl on immunoassays.

“Trazodone is very commonly used in addiction treatment centers, but it can give a false positive on the fentanyl immunoassay and we’ve had a number of those cases,” he said.

Dr. Salsitz had no disclosures to report.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

As fentanyl-related overdose deaths continue to increase, clinicians should take note of important differences that set the drug apart from the other drugs of misuse – and the troubling reality that fentanyl now contaminates most of them.

“It would be fair to tell patients, if you’re buying any illicit drugs – pills, powder, liquid, whatever it is, you’ve got to assume it’s either contaminated with or replaced by fentanyl,” said Edwin Salsitz, MD, an associate clinical professor at the Icahn School of Medicine at Mount Sinai, New York, during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

In many if not most cases, he noted, patients become addicted to fentanyl unknowingly. They assume they are ingesting oxycodone, cocaine, or another drug, and have no realization that they are even exposed to fentanyl until they test positive for it – or overdose.

Meanwhile, the high potency of fentanyl can overcome the opioid blockade of addiction treatment therapies – methadone and buprenorphine – that take away the high that users get from less potent drugs such as heroin.

“Fentanyl is overcoming this blockade that methadone and buprenorphine used to provide,” Dr. Salsitz said. “With fentanyl having such a higher potency, patients are saying ‘no, I still feel the fentanyl effects,’ and they continue feeling it even with 200 milligrams of methadone or 24 milligrams of buprenorphine.”
 

‘Wooden chest syndrome’

Among the lesser-known dangers of fentanyl is the possibility that some overdose deaths may occur as the result of a syndrome previously reported as a rare complication following the medical use of fentanyl in critically ill patients – fentanyl-induced chest-wall rigidity, or “wooden chest syndrome,” Dr. Salsitz explained.

In such cases, the muscles of respiration become rigid and paralyzed, causing suffocation within a matter of minutes – too soon to benefit from the overdose rescue medication naloxone.

In one recent study published in Clinical Toxicology , nearly half of fentanyl overdose deaths were found to have occurred even before the body had a chance to produce norfentanyl, a metabolite of fentanyl that takes only about 2-3 minutes to appear in the system, suggesting the deaths occurred rapidly.

In the study of 48 fentanyl deaths, no appreciable concentrations of norfentanyl could be detected in 20 of the 48 overdose deaths (42%), and concentrations were less than 1 ng/mL in 25 cases (52%).

“The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity,” the authors reported.

“In several cases fentanyl concentrations were strikingly high (22 ng/mL and 20 ng/mL) with no norfentanyl detected,” they said.

Dr. Salsitz noted that the syndrome is not well known among the addiction treatment community.

“This is different than the usual respiratory opioid overdose where there’s a gradual decrease in the breathing rate and a gradual decrease in how much air is going in and out of the lungs,” Dr. Salsitz explained.

“With those cases, some may survive for an hour or longer, allowing time for someone to administer naloxone or to get the patient to the emergency room,” he said. “But with this, breathing stops and people can die within minutes.

“I think that this is one of the reasons that fentanyl deaths keep going up despite more and more naloxone availability out there,” he said.
 

Clearance may take longer

In toxicology testing for fentanyl, clinicians should also note the important difference between fentanyl and other opioids – that fentanyl, because of its high lipophilicity, may be detected in urine toxicology testing up to 3 weeks after last use. This is much longer than the 2- to 4-day clearance observed with other opioids, possibly causing patients to continue to test positive for the drug weeks after cessation.

This effect was observed in one recent study of 12 opioid use disorder patients in a residential treatment program who had previously been exposed to daily fentanyl.

The study showed the mean amount of time of fentanyl clearance was 2 weeks, with a range of 4-26 days after last use.

The authors pointed out that the findings “might explain recent reports of difficulty in buprenorphine inductions for persons who use fentanyl, and point to a need to better understand the pharmacokinetics of fentanyl in the context of opioid withdrawal in persons who regularly use fentanyl.”

Though the study was small, Dr. Salsitz said “that’s not a stumbling block to the important finding that, with regular use of fentanyl, the drug may stay in the urine for a long time.”

Dr. Salsitz noted that similar observations have been made at his center, with clinicians logically assuming that patients were still somehow getting fentanyl.

“When we initially found this in patients, we thought that they were using on the unit, perhaps that they brought in the fentanyl, because otherwise how could it stay in the urine that long,” he noted. “But fentanyl appears to be more lipophilic and gets into the fat; it’s then excreted very slowly and then stays in the urine.”

Dr. Salsitz said most practitioners think of fentanyl as a short-acting drug, so “it’s important to realize that people may continue to test positive and it should be thought of as a long-acting opioid.”
 

Opiate screening tests don’t work

Dr. Salsitz warned of another misconception in fentanyl testing – the common mistake of assuming that fentanyl should show up in a test for opiates – when in fact fentanyl is not, technically, an opiate.

“The word opiate only refers to morphine, codeine, heroin and sometimes hydrocodone,” he explained. “Other opioids are classified as semisynthetic, such as oxycodone, or synthetics, such as fentanyl and methadone, buprenorphine.”

“In order to detect the synthetics, you must have a separate strip for each one of those drugs. They will not show up positive on a screen for opiates,” he noted.

The belief that fentanyl and other synthetic and semisynthetic opioids will show positive on an opiate screen is a common misconception, he said. “The misunderstanding in toxicology interpretation is a problem for many practitioners, [but] it’s essential to understand because otherwise false assumptions about the patient will be considered.”

Another important testing misreading can occur with the antidepressant drug trazodone, which Dr. Salsitz cautioned may falsely test as positive for fentanyl on immunoassays.

“Trazodone is very commonly used in addiction treatment centers, but it can give a false positive on the fentanyl immunoassay and we’ve had a number of those cases,” he said.

Dr. Salsitz had no disclosures to report.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

As fentanyl-related overdose deaths continue to increase, clinicians should take note of important differences that set the drug apart from the other drugs of misuse – and the troubling reality that fentanyl now contaminates most of them.

“It would be fair to tell patients, if you’re buying any illicit drugs – pills, powder, liquid, whatever it is, you’ve got to assume it’s either contaminated with or replaced by fentanyl,” said Edwin Salsitz, MD, an associate clinical professor at the Icahn School of Medicine at Mount Sinai, New York, during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

In many if not most cases, he noted, patients become addicted to fentanyl unknowingly. They assume they are ingesting oxycodone, cocaine, or another drug, and have no realization that they are even exposed to fentanyl until they test positive for it – or overdose.

Meanwhile, the high potency of fentanyl can overcome the opioid blockade of addiction treatment therapies – methadone and buprenorphine – that take away the high that users get from less potent drugs such as heroin.

“Fentanyl is overcoming this blockade that methadone and buprenorphine used to provide,” Dr. Salsitz said. “With fentanyl having such a higher potency, patients are saying ‘no, I still feel the fentanyl effects,’ and they continue feeling it even with 200 milligrams of methadone or 24 milligrams of buprenorphine.”
 

‘Wooden chest syndrome’

Among the lesser-known dangers of fentanyl is the possibility that some overdose deaths may occur as the result of a syndrome previously reported as a rare complication following the medical use of fentanyl in critically ill patients – fentanyl-induced chest-wall rigidity, or “wooden chest syndrome,” Dr. Salsitz explained.

In such cases, the muscles of respiration become rigid and paralyzed, causing suffocation within a matter of minutes – too soon to benefit from the overdose rescue medication naloxone.

In one recent study published in Clinical Toxicology , nearly half of fentanyl overdose deaths were found to have occurred even before the body had a chance to produce norfentanyl, a metabolite of fentanyl that takes only about 2-3 minutes to appear in the system, suggesting the deaths occurred rapidly.

In the study of 48 fentanyl deaths, no appreciable concentrations of norfentanyl could be detected in 20 of the 48 overdose deaths (42%), and concentrations were less than 1 ng/mL in 25 cases (52%).

“The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity,” the authors reported.

“In several cases fentanyl concentrations were strikingly high (22 ng/mL and 20 ng/mL) with no norfentanyl detected,” they said.

Dr. Salsitz noted that the syndrome is not well known among the addiction treatment community.

“This is different than the usual respiratory opioid overdose where there’s a gradual decrease in the breathing rate and a gradual decrease in how much air is going in and out of the lungs,” Dr. Salsitz explained.

“With those cases, some may survive for an hour or longer, allowing time for someone to administer naloxone or to get the patient to the emergency room,” he said. “But with this, breathing stops and people can die within minutes.

“I think that this is one of the reasons that fentanyl deaths keep going up despite more and more naloxone availability out there,” he said.
 

Clearance may take longer

In toxicology testing for fentanyl, clinicians should also note the important difference between fentanyl and other opioids – that fentanyl, because of its high lipophilicity, may be detected in urine toxicology testing up to 3 weeks after last use. This is much longer than the 2- to 4-day clearance observed with other opioids, possibly causing patients to continue to test positive for the drug weeks after cessation.

This effect was observed in one recent study of 12 opioid use disorder patients in a residential treatment program who had previously been exposed to daily fentanyl.

The study showed the mean amount of time of fentanyl clearance was 2 weeks, with a range of 4-26 days after last use.

The authors pointed out that the findings “might explain recent reports of difficulty in buprenorphine inductions for persons who use fentanyl, and point to a need to better understand the pharmacokinetics of fentanyl in the context of opioid withdrawal in persons who regularly use fentanyl.”

Though the study was small, Dr. Salsitz said “that’s not a stumbling block to the important finding that, with regular use of fentanyl, the drug may stay in the urine for a long time.”

Dr. Salsitz noted that similar observations have been made at his center, with clinicians logically assuming that patients were still somehow getting fentanyl.

“When we initially found this in patients, we thought that they were using on the unit, perhaps that they brought in the fentanyl, because otherwise how could it stay in the urine that long,” he noted. “But fentanyl appears to be more lipophilic and gets into the fat; it’s then excreted very slowly and then stays in the urine.”

Dr. Salsitz said most practitioners think of fentanyl as a short-acting drug, so “it’s important to realize that people may continue to test positive and it should be thought of as a long-acting opioid.”
 

Opiate screening tests don’t work

Dr. Salsitz warned of another misconception in fentanyl testing – the common mistake of assuming that fentanyl should show up in a test for opiates – when in fact fentanyl is not, technically, an opiate.

“The word opiate only refers to morphine, codeine, heroin and sometimes hydrocodone,” he explained. “Other opioids are classified as semisynthetic, such as oxycodone, or synthetics, such as fentanyl and methadone, buprenorphine.”

“In order to detect the synthetics, you must have a separate strip for each one of those drugs. They will not show up positive on a screen for opiates,” he noted.

The belief that fentanyl and other synthetic and semisynthetic opioids will show positive on an opiate screen is a common misconception, he said. “The misunderstanding in toxicology interpretation is a problem for many practitioners, [but] it’s essential to understand because otherwise false assumptions about the patient will be considered.”

Another important testing misreading can occur with the antidepressant drug trazodone, which Dr. Salsitz cautioned may falsely test as positive for fentanyl on immunoassays.

“Trazodone is very commonly used in addiction treatment centers, but it can give a false positive on the fentanyl immunoassay and we’ve had a number of those cases,” he said.

Dr. Salsitz had no disclosures to report.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

SAN FRANCISCO – Widely anticipated data from a phase 3 trial of the monoclonal antibody lecanemab suggest the drug “modestly” relieved cognitive impairment in patients with early Alzheimer’s disease (AD) – but at a cost.

In the CLARITY AD trial, adverse events (AEs) were common compared with placebo, including amyloid-related edema and effusions; and a recent news report linked a second death to the drug.

Moving forward, “longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease,” wrote Christopher H. van Dyck, MD, Yale University, New Haven, Conn., and colleagues.

The full trial findings were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference, with simultaneous publication on Nov. 29 in the New England Journal of Medicine.
 

Complications in the field

The phase 3 trial of lecanemab has been closely watched in AD circles, especially considering positive early data released in September and reported by this news organization at that time.

The Food and Drug Administration is expected to make a decision about possible approval of the drug in January 2023. Only one other antiamyloid treatment, the highly controversial and expensive aducanumab (Aduhelm), is currently approved by the FDA.

For the new 18-month, randomized, double-blind CLARITY AD trial, researchers enrolled 1,795 patients aged 50-90 years (average age, 71 years) with early AD. All were randomly assigned to receive either a placebo (n = 898) or intravenous lecanemab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively targets amyloid beta (A-beta) protofibrils, at 10 mg/kg of body weight every 2 weeks (n = 897).

The study ran from 2019 to 2021. The participants (52% women, 20% non-White) were recruited in North America, Europe, and Asia. Safety data included all participants, and the modified intention-to-treat group included 1,734 participants, with 859 receiving lecanemab and 875 receiving placebo.

The primary endpoint was the Clinical Dementia Rating–Sum of Boxes (CDR-SB). Scores from 0.5 to 6 are signs of early AD, according to the study. The mean baseline score for both groups was 3.2. The adjusted mean change at 18 months was 1.21 for lecanemab versus 1.66 for placebo (difference, –0.45; 95% confidence interval [CI], –0.67 to –0.23; P < .001).

As Dr. van Dyck noted in his presentation at the CTAD meting, this represents a 27% slowing of the decline in the lecanemab group.

The published findings do not speculate about how this difference would affect the day-to-day life of participants who took the drug, although it does refer to “modestly less decline” of cognition/function in the lecanemab group.

Other measurements that suggest cognitive improvements in the lecanemab group versus placebo include the Alzheimer’s Disease Assessment Scale–Cognitive Subscale score (mean difference, –1.44; 95% CI, –2.27 to –0.61), the Alzheimer’s Disease Composite Score (mean difference, –0.05; 95% CI, –.074 to –.027,), and the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment score (mean difference, 2.0; 95% CI, 1.2-2.8; all, P < .001).

Overall, Dr. van Dyck said, “Lecanemab met the primary and secondary endpoints versus placebo at 18 months, with highly significant differences starting at 6 months.”

In a substudy of 698 participants, results showed that amyloid burden fell at a higher rate in the lecanemab group than in the placebo group (difference, –59.1 centiloids; 95% CI, –62.6 to –55.6).

“Lecanemab has high selectivity for soluble aggregated species of A-beta as compared with monomeric amyloid, with moderate selectivity for fibrillar amyloid; this profile is considered to target the most toxic pathologic amyloid species,” the researchers wrote.
 

Concerning AE data

With respect to AEs, deaths occurred in both groups (0.7% in those who took lecanemab and 0.8% in those who took the placebo). The researchers did not attribute any deaths to the drug. However, according to a report in the journal Science published Nov. 27, a 65-year-old woman who was taking the drug as part of a clinical trial “recently died from a massive brain hemorrhage that some researchers link to the drug.”

The woman, the second person “whose death was linked to lecanemab,” died after suffering a stroke. Researchers summarized a case report as saying that the drug “contributed to her brain hemorrhage after biweekly infusions of lecanemab inflamed and weakened the blood vessels.”

Eisai, which sponsored the new trial, told Science that “all the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause.”

In a CTAD presentation, study coauthor Marwan Sabbagh, MD, Barrow Neurological Institute, Phoenix, said two hemorrhage-related deaths occurred in an open-label extension. One was in the context of a tissue plasminogen activator treatment for a stroke, which fits with the description of the case in the Science report. “Causality with lecanemab is a little difficult ...,” he said. “Patients on anticoagulation might need further consideration.”

In the CLARITY AD Trial, serious AEs occurred in 14% of the lecanemab group, leading to discontinuation 6.9% of the time, and in 11.3% of the placebo group, leading to discontinuation 2.9% of the time, the investigators reported.

They added that, in the lecanemab group, the most common AEs, defined as affecting more than 10% of participants, were infusion-related reactions (26.4% vs. 7.4% for placebo); amyloid-related imaging abnormalities with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (17.3% vs. 9%, respectively); amyloid-related imaging abnormalities with edema or effusions (12.6% vs. 1.7%); headache (11.1% vs. 8.1%); and falls (10.4% vs. 9.6%).

In addition, macrohemorrhage was reported in 0.6% of the lecanemab group and 0.1% of the placebo group.
 

Cautious optimism

In separate interviews, two Alzheimer’s specialists who weren’t involved in the study praised the trial and described the findings as “exciting.” But they also highlighted its limitations.

Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School and chief medical officer of Linus Health, said the study represents impressive progress after 60-plus trials examining anti-amyloid monoclonal antibodies. “This is the first trial that shows a clinical benefit that can be measured,” he said.

However, it’s unclear whether the changes “are really going to make a difference in people’s lives,” he said. The drug is likely to be expensive, owing to the large investment needed for research, he added, and patients will have to undergo costly testing, such as PET scans and spinal taps.

Still, “this could be a valuable adjunct to the armamentarium we have,” which includes interventions such as lifestyle changes, he said.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, noted that the trial reached its primary and secondary endpoints and that the drug had what he called a “modest” effect on cognition.

However, the drugmaker will need to explore the adverse effects, he said, especially among patients with atrial fibrillation who take anticoagulants. And, he said, medicine is still far from the ultimate goal – fully reversing cognitive decline.

Michael Weiner, MD, president of the CTAD22 Scientific Committee, noted in a press release that there is “growing evidence” that some antiamyloid therapies, “especially lecanemab and donanemab” have shown promising results.

“Unfortunately, these treatments are also associated with abnormal differences seen in imaging, including brain swelling and bleeding in the brain,” said Dr. Weiner, professor of radiology, medicine, and neurology at the University of California, San Francisco.

“There is considerable controversy concerning the significance and impact of these findings, including whether or not governments and medical insurance will provide financial coverage for such treatments,” he added.
 

Rave reviews from the Alzheimer’s Association

In a statement, the Alzheimer’s Association raved about lecanemab and declared that the FDA should approve lecanemab on an accelerated basis. The study “confirms this treatment can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease ...” the association said, adding that “it could mean many months more of recognizing their spouse, children and grandchildren.”

The association, which is a staunch supporter of aducanumab, called on the Centers for Medicare & Medicaid Services to cover the drug if the FDA approves it. The association’s statement did not address the drug’s potential high cost, the adverse effects, or the two reported deaths.

The trial was supported by Eisai (regulatory sponsor) with partial funding from Biogen. Dr. van Dyck reports having received research grants from Biogen, Eisai, Biohaven, Cerevel Therapeutics, Eli Lilly, Genentech, Janssen, Novartis, and UCB. He has been a consultant to Cerevel, Eisai, Ono Pharmaceutical, and Roche. Relevant financial relationships for the other investigators are fully listed in the original article.

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

SAN FRANCISCO – Widely anticipated data from a phase 3 trial of the monoclonal antibody lecanemab suggest the drug “modestly” relieved cognitive impairment in patients with early Alzheimer’s disease (AD) – but at a cost.

In the CLARITY AD trial, adverse events (AEs) were common compared with placebo, including amyloid-related edema and effusions; and a recent news report linked a second death to the drug.

Moving forward, “longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease,” wrote Christopher H. van Dyck, MD, Yale University, New Haven, Conn., and colleagues.

The full trial findings were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference, with simultaneous publication on Nov. 29 in the New England Journal of Medicine.
 

Complications in the field

The phase 3 trial of lecanemab has been closely watched in AD circles, especially considering positive early data released in September and reported by this news organization at that time.

The Food and Drug Administration is expected to make a decision about possible approval of the drug in January 2023. Only one other antiamyloid treatment, the highly controversial and expensive aducanumab (Aduhelm), is currently approved by the FDA.

For the new 18-month, randomized, double-blind CLARITY AD trial, researchers enrolled 1,795 patients aged 50-90 years (average age, 71 years) with early AD. All were randomly assigned to receive either a placebo (n = 898) or intravenous lecanemab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively targets amyloid beta (A-beta) protofibrils, at 10 mg/kg of body weight every 2 weeks (n = 897).

The study ran from 2019 to 2021. The participants (52% women, 20% non-White) were recruited in North America, Europe, and Asia. Safety data included all participants, and the modified intention-to-treat group included 1,734 participants, with 859 receiving lecanemab and 875 receiving placebo.

The primary endpoint was the Clinical Dementia Rating–Sum of Boxes (CDR-SB). Scores from 0.5 to 6 are signs of early AD, according to the study. The mean baseline score for both groups was 3.2. The adjusted mean change at 18 months was 1.21 for lecanemab versus 1.66 for placebo (difference, –0.45; 95% confidence interval [CI], –0.67 to –0.23; P < .001).

As Dr. van Dyck noted in his presentation at the CTAD meting, this represents a 27% slowing of the decline in the lecanemab group.

The published findings do not speculate about how this difference would affect the day-to-day life of participants who took the drug, although it does refer to “modestly less decline” of cognition/function in the lecanemab group.

Other measurements that suggest cognitive improvements in the lecanemab group versus placebo include the Alzheimer’s Disease Assessment Scale–Cognitive Subscale score (mean difference, –1.44; 95% CI, –2.27 to –0.61), the Alzheimer’s Disease Composite Score (mean difference, –0.05; 95% CI, –.074 to –.027,), and the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment score (mean difference, 2.0; 95% CI, 1.2-2.8; all, P < .001).

Overall, Dr. van Dyck said, “Lecanemab met the primary and secondary endpoints versus placebo at 18 months, with highly significant differences starting at 6 months.”

In a substudy of 698 participants, results showed that amyloid burden fell at a higher rate in the lecanemab group than in the placebo group (difference, –59.1 centiloids; 95% CI, –62.6 to –55.6).

“Lecanemab has high selectivity for soluble aggregated species of A-beta as compared with monomeric amyloid, with moderate selectivity for fibrillar amyloid; this profile is considered to target the most toxic pathologic amyloid species,” the researchers wrote.
 

Concerning AE data

With respect to AEs, deaths occurred in both groups (0.7% in those who took lecanemab and 0.8% in those who took the placebo). The researchers did not attribute any deaths to the drug. However, according to a report in the journal Science published Nov. 27, a 65-year-old woman who was taking the drug as part of a clinical trial “recently died from a massive brain hemorrhage that some researchers link to the drug.”

The woman, the second person “whose death was linked to lecanemab,” died after suffering a stroke. Researchers summarized a case report as saying that the drug “contributed to her brain hemorrhage after biweekly infusions of lecanemab inflamed and weakened the blood vessels.”

Eisai, which sponsored the new trial, told Science that “all the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause.”

In a CTAD presentation, study coauthor Marwan Sabbagh, MD, Barrow Neurological Institute, Phoenix, said two hemorrhage-related deaths occurred in an open-label extension. One was in the context of a tissue plasminogen activator treatment for a stroke, which fits with the description of the case in the Science report. “Causality with lecanemab is a little difficult ...,” he said. “Patients on anticoagulation might need further consideration.”

In the CLARITY AD Trial, serious AEs occurred in 14% of the lecanemab group, leading to discontinuation 6.9% of the time, and in 11.3% of the placebo group, leading to discontinuation 2.9% of the time, the investigators reported.

They added that, in the lecanemab group, the most common AEs, defined as affecting more than 10% of participants, were infusion-related reactions (26.4% vs. 7.4% for placebo); amyloid-related imaging abnormalities with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (17.3% vs. 9%, respectively); amyloid-related imaging abnormalities with edema or effusions (12.6% vs. 1.7%); headache (11.1% vs. 8.1%); and falls (10.4% vs. 9.6%).

In addition, macrohemorrhage was reported in 0.6% of the lecanemab group and 0.1% of the placebo group.
 

Cautious optimism

In separate interviews, two Alzheimer’s specialists who weren’t involved in the study praised the trial and described the findings as “exciting.” But they also highlighted its limitations.

Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School and chief medical officer of Linus Health, said the study represents impressive progress after 60-plus trials examining anti-amyloid monoclonal antibodies. “This is the first trial that shows a clinical benefit that can be measured,” he said.

However, it’s unclear whether the changes “are really going to make a difference in people’s lives,” he said. The drug is likely to be expensive, owing to the large investment needed for research, he added, and patients will have to undergo costly testing, such as PET scans and spinal taps.

Still, “this could be a valuable adjunct to the armamentarium we have,” which includes interventions such as lifestyle changes, he said.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, noted that the trial reached its primary and secondary endpoints and that the drug had what he called a “modest” effect on cognition.

However, the drugmaker will need to explore the adverse effects, he said, especially among patients with atrial fibrillation who take anticoagulants. And, he said, medicine is still far from the ultimate goal – fully reversing cognitive decline.

Michael Weiner, MD, president of the CTAD22 Scientific Committee, noted in a press release that there is “growing evidence” that some antiamyloid therapies, “especially lecanemab and donanemab” have shown promising results.

“Unfortunately, these treatments are also associated with abnormal differences seen in imaging, including brain swelling and bleeding in the brain,” said Dr. Weiner, professor of radiology, medicine, and neurology at the University of California, San Francisco.

“There is considerable controversy concerning the significance and impact of these findings, including whether or not governments and medical insurance will provide financial coverage for such treatments,” he added.
 

Rave reviews from the Alzheimer’s Association

In a statement, the Alzheimer’s Association raved about lecanemab and declared that the FDA should approve lecanemab on an accelerated basis. The study “confirms this treatment can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease ...” the association said, adding that “it could mean many months more of recognizing their spouse, children and grandchildren.”

The association, which is a staunch supporter of aducanumab, called on the Centers for Medicare & Medicaid Services to cover the drug if the FDA approves it. The association’s statement did not address the drug’s potential high cost, the adverse effects, or the two reported deaths.

The trial was supported by Eisai (regulatory sponsor) with partial funding from Biogen. Dr. van Dyck reports having received research grants from Biogen, Eisai, Biohaven, Cerevel Therapeutics, Eli Lilly, Genentech, Janssen, Novartis, and UCB. He has been a consultant to Cerevel, Eisai, Ono Pharmaceutical, and Roche. Relevant financial relationships for the other investigators are fully listed in the original article.

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

SAN FRANCISCO – Widely anticipated data from a phase 3 trial of the monoclonal antibody lecanemab suggest the drug “modestly” relieved cognitive impairment in patients with early Alzheimer’s disease (AD) – but at a cost.

In the CLARITY AD trial, adverse events (AEs) were common compared with placebo, including amyloid-related edema and effusions; and a recent news report linked a second death to the drug.

Moving forward, “longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease,” wrote Christopher H. van Dyck, MD, Yale University, New Haven, Conn., and colleagues.

The full trial findings were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference, with simultaneous publication on Nov. 29 in the New England Journal of Medicine.
 

Complications in the field

The phase 3 trial of lecanemab has been closely watched in AD circles, especially considering positive early data released in September and reported by this news organization at that time.

The Food and Drug Administration is expected to make a decision about possible approval of the drug in January 2023. Only one other antiamyloid treatment, the highly controversial and expensive aducanumab (Aduhelm), is currently approved by the FDA.

For the new 18-month, randomized, double-blind CLARITY AD trial, researchers enrolled 1,795 patients aged 50-90 years (average age, 71 years) with early AD. All were randomly assigned to receive either a placebo (n = 898) or intravenous lecanemab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively targets amyloid beta (A-beta) protofibrils, at 10 mg/kg of body weight every 2 weeks (n = 897).

The study ran from 2019 to 2021. The participants (52% women, 20% non-White) were recruited in North America, Europe, and Asia. Safety data included all participants, and the modified intention-to-treat group included 1,734 participants, with 859 receiving lecanemab and 875 receiving placebo.

The primary endpoint was the Clinical Dementia Rating–Sum of Boxes (CDR-SB). Scores from 0.5 to 6 are signs of early AD, according to the study. The mean baseline score for both groups was 3.2. The adjusted mean change at 18 months was 1.21 for lecanemab versus 1.66 for placebo (difference, –0.45; 95% confidence interval [CI], –0.67 to –0.23; P < .001).

As Dr. van Dyck noted in his presentation at the CTAD meting, this represents a 27% slowing of the decline in the lecanemab group.

The published findings do not speculate about how this difference would affect the day-to-day life of participants who took the drug, although it does refer to “modestly less decline” of cognition/function in the lecanemab group.

Other measurements that suggest cognitive improvements in the lecanemab group versus placebo include the Alzheimer’s Disease Assessment Scale–Cognitive Subscale score (mean difference, –1.44; 95% CI, –2.27 to –0.61), the Alzheimer’s Disease Composite Score (mean difference, –0.05; 95% CI, –.074 to –.027,), and the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment score (mean difference, 2.0; 95% CI, 1.2-2.8; all, P < .001).

Overall, Dr. van Dyck said, “Lecanemab met the primary and secondary endpoints versus placebo at 18 months, with highly significant differences starting at 6 months.”

In a substudy of 698 participants, results showed that amyloid burden fell at a higher rate in the lecanemab group than in the placebo group (difference, –59.1 centiloids; 95% CI, –62.6 to –55.6).

“Lecanemab has high selectivity for soluble aggregated species of A-beta as compared with monomeric amyloid, with moderate selectivity for fibrillar amyloid; this profile is considered to target the most toxic pathologic amyloid species,” the researchers wrote.
 

Concerning AE data

With respect to AEs, deaths occurred in both groups (0.7% in those who took lecanemab and 0.8% in those who took the placebo). The researchers did not attribute any deaths to the drug. However, according to a report in the journal Science published Nov. 27, a 65-year-old woman who was taking the drug as part of a clinical trial “recently died from a massive brain hemorrhage that some researchers link to the drug.”

The woman, the second person “whose death was linked to lecanemab,” died after suffering a stroke. Researchers summarized a case report as saying that the drug “contributed to her brain hemorrhage after biweekly infusions of lecanemab inflamed and weakened the blood vessels.”

Eisai, which sponsored the new trial, told Science that “all the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause.”

In a CTAD presentation, study coauthor Marwan Sabbagh, MD, Barrow Neurological Institute, Phoenix, said two hemorrhage-related deaths occurred in an open-label extension. One was in the context of a tissue plasminogen activator treatment for a stroke, which fits with the description of the case in the Science report. “Causality with lecanemab is a little difficult ...,” he said. “Patients on anticoagulation might need further consideration.”

In the CLARITY AD Trial, serious AEs occurred in 14% of the lecanemab group, leading to discontinuation 6.9% of the time, and in 11.3% of the placebo group, leading to discontinuation 2.9% of the time, the investigators reported.

They added that, in the lecanemab group, the most common AEs, defined as affecting more than 10% of participants, were infusion-related reactions (26.4% vs. 7.4% for placebo); amyloid-related imaging abnormalities with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (17.3% vs. 9%, respectively); amyloid-related imaging abnormalities with edema or effusions (12.6% vs. 1.7%); headache (11.1% vs. 8.1%); and falls (10.4% vs. 9.6%).

In addition, macrohemorrhage was reported in 0.6% of the lecanemab group and 0.1% of the placebo group.
 

Cautious optimism

In separate interviews, two Alzheimer’s specialists who weren’t involved in the study praised the trial and described the findings as “exciting.” But they also highlighted its limitations.

Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School and chief medical officer of Linus Health, said the study represents impressive progress after 60-plus trials examining anti-amyloid monoclonal antibodies. “This is the first trial that shows a clinical benefit that can be measured,” he said.

However, it’s unclear whether the changes “are really going to make a difference in people’s lives,” he said. The drug is likely to be expensive, owing to the large investment needed for research, he added, and patients will have to undergo costly testing, such as PET scans and spinal taps.

Still, “this could be a valuable adjunct to the armamentarium we have,” which includes interventions such as lifestyle changes, he said.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, noted that the trial reached its primary and secondary endpoints and that the drug had what he called a “modest” effect on cognition.

However, the drugmaker will need to explore the adverse effects, he said, especially among patients with atrial fibrillation who take anticoagulants. And, he said, medicine is still far from the ultimate goal – fully reversing cognitive decline.

Michael Weiner, MD, president of the CTAD22 Scientific Committee, noted in a press release that there is “growing evidence” that some antiamyloid therapies, “especially lecanemab and donanemab” have shown promising results.

“Unfortunately, these treatments are also associated with abnormal differences seen in imaging, including brain swelling and bleeding in the brain,” said Dr. Weiner, professor of radiology, medicine, and neurology at the University of California, San Francisco.

“There is considerable controversy concerning the significance and impact of these findings, including whether or not governments and medical insurance will provide financial coverage for such treatments,” he added.
 

Rave reviews from the Alzheimer’s Association

In a statement, the Alzheimer’s Association raved about lecanemab and declared that the FDA should approve lecanemab on an accelerated basis. The study “confirms this treatment can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease ...” the association said, adding that “it could mean many months more of recognizing their spouse, children and grandchildren.”

The association, which is a staunch supporter of aducanumab, called on the Centers for Medicare & Medicaid Services to cover the drug if the FDA approves it. The association’s statement did not address the drug’s potential high cost, the adverse effects, or the two reported deaths.

The trial was supported by Eisai (regulatory sponsor) with partial funding from Biogen. Dr. van Dyck reports having received research grants from Biogen, Eisai, Biohaven, Cerevel Therapeutics, Eli Lilly, Genentech, Janssen, Novartis, and UCB. He has been a consultant to Cerevel, Eisai, Ono Pharmaceutical, and Roche. Relevant financial relationships for the other investigators are fully listed in the original article.

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

Rates of youth suicides at the county level increased as mental health professional shortages increased, based on data from more than 5,000 youth suicides across all counties in the United States.

Suicide remains the second leading cause of death among adolescents in the United States, and shortages of pediatric mental health providers are well known, but the association between mental health workforce shortages and youth suicides at the local level has not been well studied, Jennifer A. Hoffmann, MD, of Northwestern University, Chicago, and colleagues wrote.

Previous studies have shown few or no child psychiatrists or child-focused mental health professionals in most counties across the United States, and shortages are more likely in rural and high-poverty counties, the researchers noted.

In a cross-sectional study published in JAMA Pediatrics, the researchers reviewed all youth suicide data from January 2015 to Dec. 31, 2016 using the Centers for Disease Control and Prevention’s Compressed Mortality File. They used a multivariate binomial regression model to examine the association between youth suicide rates and the presence or absence of mental health care. Mental health care shortages were based on data from the U.S. Health Resources and Services Administration’s assessment of the number of mental health professionals relative to the country population and the availability of nearby services. Areas identified as having shortages were designated as Health Professional Shortage Areas (HPSAs) and scored on a severity level of 0-25, with higher scores indicating greater shortages. Approximately two-thirds (67.6%) of the 3,133 counties included in the study met criteria for mental health workforce shortage areas.

The researchers identified 5,034 suicides in youth aged 5-19 years during the study period, for an annual rate of 3.99 per 100,000 individuals. Of these, 72.8% were male and 68.2% were non-Hispanic White.

Overall, a county designation of mental health care shortage was significantly associated with an increased rate of youth suicide (adjusted incidence rate ratio, 1.16) and also increased rate of youth firearm suicide (aIRR, 1.27) after controlling for county and socioeconomic characteristics including the presence of a children’s mental health hospital, the percentage of children without health insurance, median household income, and racial makeup of the county.

The adjusted youth suicide rate increased by 4% for every 1-point increase in the HPSA score in counties with designated mental health workforce shortages.

The adjusted youth suicide rates were higher in counties with a lower median household income, and youth suicides increased with increases in the percentages of uninsured children, the researchers wrote.

“Reducing poverty, addressing social determinants of health, and improving insurance coverage may be considered as components of a multipronged societal strategy to improve child health and reduce youth suicides,” they said. “Efforts are needed to enhance the mental health professional workforce to match current levels of need.” Possible strategies to increase the pediatric mental health workforce may include improving reimbursement and integrating mental health care into primary care and schools by expanding telehealth services.

The study findings were limited by several factors including the potential misclassification of demographics or cause of death, the researchers noted. Other limitations included the inability to assess actual use of mental health services or firearm ownership in a household, and the possible differences between county-level associations and those of a city, neighborhood, or individual.

However, the results indicate that mental health professional workforce shortages were associated with increased youth suicide rates, and the data may inform local-level suicide prevention efforts, they concluded.
 

Data support the need for early intervention

“It was very important to conduct this study at this time because mental health problems, to include suicidal ideation, continue to increase in adolescents,” Peter L. Loper Jr., MD, of the University of South Carolina, Columbia, said in an interview. “This study reinforces the immense import of sufficient mental health workforce to mitigate this increasing risk of suicide in adolescents.”

Dr. Loper said: “I believe that early intervention, or consistent access to mental health services, can go a very long way in preventing suicide in adolescents.

“I think the primary implications of this study are more relevant at the systems level, and reinforce the necessity of clinicians advocating for policies that address mental health workforce shortages in counties that are underserved,” he added.

However, “One primary barrier to increasing the number of mental health professionals at a local level, and specifically the number of child psychiatrists, is that demand is currently outpacing supply,” said Dr. Loper, a pediatrician and psychiatrist who was not involved in the study. “As the study authors cite, increasing telepsychiatry services and increasing mental health workforce specifically in the primary care setting may help offset these deficiencies,” he noted. Looking ahead, primary prevention of mental health problems by grassroots efforts is vital to stopping the trend in increased youth suicides and more mental health professionals are needed to mitigate the phenomenon of isolation and the degradation of community constructs.

As for additional research, Dr. Loper agreed with the study authors comments on the need for “more granular data” to better understand the correlation between mental health workforce and suicide in adolescents. “Data that captures city or neighborhood statistics related to mental health workforce and adolescent suicide could go a long way in our efforts to continue to better understand this very important correlation.”

The study was supported by an Academic Pediatric Association Young Investigator Award. Dr. Hoffmann disclosed research funding from the U.S. Agency for Healthcare Research and Quality unrelated to the current study. Dr. Loper had no financial conflicts to disclose.

Rates of youth suicides at the county level increased as mental health professional shortages increased, based on data from more than 5,000 youth suicides across all counties in the United States.

Suicide remains the second leading cause of death among adolescents in the United States, and shortages of pediatric mental health providers are well known, but the association between mental health workforce shortages and youth suicides at the local level has not been well studied, Jennifer A. Hoffmann, MD, of Northwestern University, Chicago, and colleagues wrote.

Previous studies have shown few or no child psychiatrists or child-focused mental health professionals in most counties across the United States, and shortages are more likely in rural and high-poverty counties, the researchers noted.

In a cross-sectional study published in JAMA Pediatrics, the researchers reviewed all youth suicide data from January 2015 to Dec. 31, 2016 using the Centers for Disease Control and Prevention’s Compressed Mortality File. They used a multivariate binomial regression model to examine the association between youth suicide rates and the presence or absence of mental health care. Mental health care shortages were based on data from the U.S. Health Resources and Services Administration’s assessment of the number of mental health professionals relative to the country population and the availability of nearby services. Areas identified as having shortages were designated as Health Professional Shortage Areas (HPSAs) and scored on a severity level of 0-25, with higher scores indicating greater shortages. Approximately two-thirds (67.6%) of the 3,133 counties included in the study met criteria for mental health workforce shortage areas.

The researchers identified 5,034 suicides in youth aged 5-19 years during the study period, for an annual rate of 3.99 per 100,000 individuals. Of these, 72.8% were male and 68.2% were non-Hispanic White.

Overall, a county designation of mental health care shortage was significantly associated with an increased rate of youth suicide (adjusted incidence rate ratio, 1.16) and also increased rate of youth firearm suicide (aIRR, 1.27) after controlling for county and socioeconomic characteristics including the presence of a children’s mental health hospital, the percentage of children without health insurance, median household income, and racial makeup of the county.

The adjusted youth suicide rate increased by 4% for every 1-point increase in the HPSA score in counties with designated mental health workforce shortages.

The adjusted youth suicide rates were higher in counties with a lower median household income, and youth suicides increased with increases in the percentages of uninsured children, the researchers wrote.

“Reducing poverty, addressing social determinants of health, and improving insurance coverage may be considered as components of a multipronged societal strategy to improve child health and reduce youth suicides,” they said. “Efforts are needed to enhance the mental health professional workforce to match current levels of need.” Possible strategies to increase the pediatric mental health workforce may include improving reimbursement and integrating mental health care into primary care and schools by expanding telehealth services.

The study findings were limited by several factors including the potential misclassification of demographics or cause of death, the researchers noted. Other limitations included the inability to assess actual use of mental health services or firearm ownership in a household, and the possible differences between county-level associations and those of a city, neighborhood, or individual.

However, the results indicate that mental health professional workforce shortages were associated with increased youth suicide rates, and the data may inform local-level suicide prevention efforts, they concluded.
 

Data support the need for early intervention

“It was very important to conduct this study at this time because mental health problems, to include suicidal ideation, continue to increase in adolescents,” Peter L. Loper Jr., MD, of the University of South Carolina, Columbia, said in an interview. “This study reinforces the immense import of sufficient mental health workforce to mitigate this increasing risk of suicide in adolescents.”

Dr. Loper said: “I believe that early intervention, or consistent access to mental health services, can go a very long way in preventing suicide in adolescents.

“I think the primary implications of this study are more relevant at the systems level, and reinforce the necessity of clinicians advocating for policies that address mental health workforce shortages in counties that are underserved,” he added.

However, “One primary barrier to increasing the number of mental health professionals at a local level, and specifically the number of child psychiatrists, is that demand is currently outpacing supply,” said Dr. Loper, a pediatrician and psychiatrist who was not involved in the study. “As the study authors cite, increasing telepsychiatry services and increasing mental health workforce specifically in the primary care setting may help offset these deficiencies,” he noted. Looking ahead, primary prevention of mental health problems by grassroots efforts is vital to stopping the trend in increased youth suicides and more mental health professionals are needed to mitigate the phenomenon of isolation and the degradation of community constructs.

As for additional research, Dr. Loper agreed with the study authors comments on the need for “more granular data” to better understand the correlation between mental health workforce and suicide in adolescents. “Data that captures city or neighborhood statistics related to mental health workforce and adolescent suicide could go a long way in our efforts to continue to better understand this very important correlation.”

The study was supported by an Academic Pediatric Association Young Investigator Award. Dr. Hoffmann disclosed research funding from the U.S. Agency for Healthcare Research and Quality unrelated to the current study. Dr. Loper had no financial conflicts to disclose.

Rates of youth suicides at the county level increased as mental health professional shortages increased, based on data from more than 5,000 youth suicides across all counties in the United States.

Suicide remains the second leading cause of death among adolescents in the United States, and shortages of pediatric mental health providers are well known, but the association between mental health workforce shortages and youth suicides at the local level has not been well studied, Jennifer A. Hoffmann, MD, of Northwestern University, Chicago, and colleagues wrote.

Previous studies have shown few or no child psychiatrists or child-focused mental health professionals in most counties across the United States, and shortages are more likely in rural and high-poverty counties, the researchers noted.

In a cross-sectional study published in JAMA Pediatrics, the researchers reviewed all youth suicide data from January 2015 to Dec. 31, 2016 using the Centers for Disease Control and Prevention’s Compressed Mortality File. They used a multivariate binomial regression model to examine the association between youth suicide rates and the presence or absence of mental health care. Mental health care shortages were based on data from the U.S. Health Resources and Services Administration’s assessment of the number of mental health professionals relative to the country population and the availability of nearby services. Areas identified as having shortages were designated as Health Professional Shortage Areas (HPSAs) and scored on a severity level of 0-25, with higher scores indicating greater shortages. Approximately two-thirds (67.6%) of the 3,133 counties included in the study met criteria for mental health workforce shortage areas.

The researchers identified 5,034 suicides in youth aged 5-19 years during the study period, for an annual rate of 3.99 per 100,000 individuals. Of these, 72.8% were male and 68.2% were non-Hispanic White.

Overall, a county designation of mental health care shortage was significantly associated with an increased rate of youth suicide (adjusted incidence rate ratio, 1.16) and also increased rate of youth firearm suicide (aIRR, 1.27) after controlling for county and socioeconomic characteristics including the presence of a children’s mental health hospital, the percentage of children without health insurance, median household income, and racial makeup of the county.

The adjusted youth suicide rate increased by 4% for every 1-point increase in the HPSA score in counties with designated mental health workforce shortages.

The adjusted youth suicide rates were higher in counties with a lower median household income, and youth suicides increased with increases in the percentages of uninsured children, the researchers wrote.

“Reducing poverty, addressing social determinants of health, and improving insurance coverage may be considered as components of a multipronged societal strategy to improve child health and reduce youth suicides,” they said. “Efforts are needed to enhance the mental health professional workforce to match current levels of need.” Possible strategies to increase the pediatric mental health workforce may include improving reimbursement and integrating mental health care into primary care and schools by expanding telehealth services.

The study findings were limited by several factors including the potential misclassification of demographics or cause of death, the researchers noted. Other limitations included the inability to assess actual use of mental health services or firearm ownership in a household, and the possible differences between county-level associations and those of a city, neighborhood, or individual.

However, the results indicate that mental health professional workforce shortages were associated with increased youth suicide rates, and the data may inform local-level suicide prevention efforts, they concluded.
 

Data support the need for early intervention

“It was very important to conduct this study at this time because mental health problems, to include suicidal ideation, continue to increase in adolescents,” Peter L. Loper Jr., MD, of the University of South Carolina, Columbia, said in an interview. “This study reinforces the immense import of sufficient mental health workforce to mitigate this increasing risk of suicide in adolescents.”

Dr. Loper said: “I believe that early intervention, or consistent access to mental health services, can go a very long way in preventing suicide in adolescents.

“I think the primary implications of this study are more relevant at the systems level, and reinforce the necessity of clinicians advocating for policies that address mental health workforce shortages in counties that are underserved,” he added.

However, “One primary barrier to increasing the number of mental health professionals at a local level, and specifically the number of child psychiatrists, is that demand is currently outpacing supply,” said Dr. Loper, a pediatrician and psychiatrist who was not involved in the study. “As the study authors cite, increasing telepsychiatry services and increasing mental health workforce specifically in the primary care setting may help offset these deficiencies,” he noted. Looking ahead, primary prevention of mental health problems by grassroots efforts is vital to stopping the trend in increased youth suicides and more mental health professionals are needed to mitigate the phenomenon of isolation and the degradation of community constructs.

As for additional research, Dr. Loper agreed with the study authors comments on the need for “more granular data” to better understand the correlation between mental health workforce and suicide in adolescents. “Data that captures city or neighborhood statistics related to mental health workforce and adolescent suicide could go a long way in our efforts to continue to better understand this very important correlation.”

The study was supported by an Academic Pediatric Association Young Investigator Award. Dr. Hoffmann disclosed research funding from the U.S. Agency for Healthcare Research and Quality unrelated to the current study. Dr. Loper had no financial conflicts to disclose.

Intermittent fasting (IF), defined as fasting for more than eight hours at a time, is a trend that is growing in popularity. Yet new research shows it may be linked to eating disorder (ED) behaviors.

Researchers from the University of Toronto analyzed data from more than 2700 adolescents and young adults from the Canadian Study of Adolescent Health Behaviors, and found that for women, IF was significantly associated with overeating, binge eating, vomiting, laxative use, and compulsive exercise.

IF in women was also associated with higher scores on the Eating Disorder Examination Questionnaire (EDE-Q), which was used to determine ED psychopathology.

Study investigator Kyle Ganson, PhD, assistant professor in the Factor-Inwentash Faculty of Social Work at the University of Toronto, said in an interview that evidence on the effectiveness of IF for weight loss and disease prevention is mixed, and that it’s important to understand the potential harms of IF – even if there are benefits for some.

“If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors, requiring health care professionals to be very aware of this contemporary and popular dietary trend, despite proponents on social media touting the effectiveness and benefits,” he said.

The study was published online in Eating Behaviors.
 

Touted for health benefits

The practice of IF has been gaining popularity partly because of reputable medical experts touting its health benefits. Johns Hopkins Medicine, for instance, cited evidence that IF boosts working memory, improves blood pressure, enhances physical performance, and prevents obesity. Yet there has been little research on its harms.

As part of the Canadian Study of Adolescent Health Behaviors, Dr. Ganson and associates analyzed data on 2,700 adolescents and young adults aged 16-30 recruited from social media ads in November and December 2021. The sample included women, men, and transgender or gender-nonconforming individuals.

Study participants answered questions about weight perception, current weight change behavior, engagement in IF, and participation in eating disorder behaviors. They were also administered the EDE-Q, which measures eating disorder psychopathology.

In total, 47% of women (n = 1,470), 38% of men (n = 1,060), and 52% transgender or gender-nonconforming individuals (n = 225) reported engaging in IF during the past year.

Dr. Ganson and associates found that, for women, IF in the past 12 months and past 30 days were significantly associated with all eating disorder behaviors, including overeating, loss of control, binge eating, vomiting, laxative use, compulsive exercise, and fasting – as well as higher overall EDE-Q global scores.

For men, IF in the past 12 months was significantly associated with compulsive exercise, and higher overall EDE-Q global scores.

The team found that for TGNC participants, IF was positively associated with higher EDE-Q global scores.

The investigators acknowledged some limitations with the study – the method of recruiting, which involved ads placed on social media, could cause selection bias. In addition to this, data collection methods relied heavily on participants’ self-reporting, which could also be susceptible to bias.

“Certainly, there needs to be more investigation on this dietary practice,” said Dr. Ganson. “If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors requiring healthcare professionals to be very aware of this contemporary and popular dietary trend – despite proponents on social media touting the effectiveness and benefits.”
 

Screening warranted

Dr. Ganson noted that additional research is needed to support the findings from his study, and to further illuminate the potential harms of IF.

Health care professionals “need to be aware of common, contemporary dietary trends that young people engage in and are commonly discussed on social media, such as IF,” he noted. In addition, he’d like to see health care professionals assess their patients for IF who are dieting and to follow-up with assessments for ED-related attitudes and behaviors.

“Additionally, there are likely bidirectional relationships between IF and ED attitudes and behaviors, so professionals should be aware the ways in which ED behaviors are masked as IF engagement,” Dr. Ganson said.
 

More research needed

Commenting on the findings, Angela Guarda, MD, professor of eating disorders at Johns Hopkins University and director of the eating disorders program at Johns Hopkins Hospital, both in Baltimore, said more research is needed on outcomes for IF.

“We lack a definitive answer. The reality is that IF may help some and harm others and is most likely not healthy for all,” she said, noting that the study results “support what many in the eating disorders field believe, namely that IF for someone who is at risk for an eating disorder is likely to be ill advised.”

She added that “continued research is needed to establish its safety, and for whom it may be a therapeutic versus an iatrogenic recommendation.”

The study was funded by the Connaught New Researcher Award. The authors reported no relevant financial relationships.

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

Intermittent fasting (IF), defined as fasting for more than eight hours at a time, is a trend that is growing in popularity. Yet new research shows it may be linked to eating disorder (ED) behaviors.

Researchers from the University of Toronto analyzed data from more than 2700 adolescents and young adults from the Canadian Study of Adolescent Health Behaviors, and found that for women, IF was significantly associated with overeating, binge eating, vomiting, laxative use, and compulsive exercise.

IF in women was also associated with higher scores on the Eating Disorder Examination Questionnaire (EDE-Q), which was used to determine ED psychopathology.

Study investigator Kyle Ganson, PhD, assistant professor in the Factor-Inwentash Faculty of Social Work at the University of Toronto, said in an interview that evidence on the effectiveness of IF for weight loss and disease prevention is mixed, and that it’s important to understand the potential harms of IF – even if there are benefits for some.

“If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors, requiring health care professionals to be very aware of this contemporary and popular dietary trend, despite proponents on social media touting the effectiveness and benefits,” he said.

The study was published online in Eating Behaviors.
 

Touted for health benefits

The practice of IF has been gaining popularity partly because of reputable medical experts touting its health benefits. Johns Hopkins Medicine, for instance, cited evidence that IF boosts working memory, improves blood pressure, enhances physical performance, and prevents obesity. Yet there has been little research on its harms.

As part of the Canadian Study of Adolescent Health Behaviors, Dr. Ganson and associates analyzed data on 2,700 adolescents and young adults aged 16-30 recruited from social media ads in November and December 2021. The sample included women, men, and transgender or gender-nonconforming individuals.

Study participants answered questions about weight perception, current weight change behavior, engagement in IF, and participation in eating disorder behaviors. They were also administered the EDE-Q, which measures eating disorder psychopathology.

In total, 47% of women (n = 1,470), 38% of men (n = 1,060), and 52% transgender or gender-nonconforming individuals (n = 225) reported engaging in IF during the past year.

Dr. Ganson and associates found that, for women, IF in the past 12 months and past 30 days were significantly associated with all eating disorder behaviors, including overeating, loss of control, binge eating, vomiting, laxative use, compulsive exercise, and fasting – as well as higher overall EDE-Q global scores.

For men, IF in the past 12 months was significantly associated with compulsive exercise, and higher overall EDE-Q global scores.

The team found that for TGNC participants, IF was positively associated with higher EDE-Q global scores.

The investigators acknowledged some limitations with the study – the method of recruiting, which involved ads placed on social media, could cause selection bias. In addition to this, data collection methods relied heavily on participants’ self-reporting, which could also be susceptible to bias.

“Certainly, there needs to be more investigation on this dietary practice,” said Dr. Ganson. “If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors requiring healthcare professionals to be very aware of this contemporary and popular dietary trend – despite proponents on social media touting the effectiveness and benefits.”
 

Screening warranted

Dr. Ganson noted that additional research is needed to support the findings from his study, and to further illuminate the potential harms of IF.

Health care professionals “need to be aware of common, contemporary dietary trends that young people engage in and are commonly discussed on social media, such as IF,” he noted. In addition, he’d like to see health care professionals assess their patients for IF who are dieting and to follow-up with assessments for ED-related attitudes and behaviors.

“Additionally, there are likely bidirectional relationships between IF and ED attitudes and behaviors, so professionals should be aware the ways in which ED behaviors are masked as IF engagement,” Dr. Ganson said.
 

More research needed

Commenting on the findings, Angela Guarda, MD, professor of eating disorders at Johns Hopkins University and director of the eating disorders program at Johns Hopkins Hospital, both in Baltimore, said more research is needed on outcomes for IF.

“We lack a definitive answer. The reality is that IF may help some and harm others and is most likely not healthy for all,” she said, noting that the study results “support what many in the eating disorders field believe, namely that IF for someone who is at risk for an eating disorder is likely to be ill advised.”

She added that “continued research is needed to establish its safety, and for whom it may be a therapeutic versus an iatrogenic recommendation.”

The study was funded by the Connaught New Researcher Award. The authors reported no relevant financial relationships.

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

Intermittent fasting (IF), defined as fasting for more than eight hours at a time, is a trend that is growing in popularity. Yet new research shows it may be linked to eating disorder (ED) behaviors.

Researchers from the University of Toronto analyzed data from more than 2700 adolescents and young adults from the Canadian Study of Adolescent Health Behaviors, and found that for women, IF was significantly associated with overeating, binge eating, vomiting, laxative use, and compulsive exercise.

IF in women was also associated with higher scores on the Eating Disorder Examination Questionnaire (EDE-Q), which was used to determine ED psychopathology.

Study investigator Kyle Ganson, PhD, assistant professor in the Factor-Inwentash Faculty of Social Work at the University of Toronto, said in an interview that evidence on the effectiveness of IF for weight loss and disease prevention is mixed, and that it’s important to understand the potential harms of IF – even if there are benefits for some.

“If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors, requiring health care professionals to be very aware of this contemporary and popular dietary trend, despite proponents on social media touting the effectiveness and benefits,” he said.

The study was published online in Eating Behaviors.
 

Touted for health benefits

The practice of IF has been gaining popularity partly because of reputable medical experts touting its health benefits. Johns Hopkins Medicine, for instance, cited evidence that IF boosts working memory, improves blood pressure, enhances physical performance, and prevents obesity. Yet there has been little research on its harms.

As part of the Canadian Study of Adolescent Health Behaviors, Dr. Ganson and associates analyzed data on 2,700 adolescents and young adults aged 16-30 recruited from social media ads in November and December 2021. The sample included women, men, and transgender or gender-nonconforming individuals.

Study participants answered questions about weight perception, current weight change behavior, engagement in IF, and participation in eating disorder behaviors. They were also administered the EDE-Q, which measures eating disorder psychopathology.

In total, 47% of women (n = 1,470), 38% of men (n = 1,060), and 52% transgender or gender-nonconforming individuals (n = 225) reported engaging in IF during the past year.

Dr. Ganson and associates found that, for women, IF in the past 12 months and past 30 days were significantly associated with all eating disorder behaviors, including overeating, loss of control, binge eating, vomiting, laxative use, compulsive exercise, and fasting – as well as higher overall EDE-Q global scores.

For men, IF in the past 12 months was significantly associated with compulsive exercise, and higher overall EDE-Q global scores.

The team found that for TGNC participants, IF was positively associated with higher EDE-Q global scores.

The investigators acknowledged some limitations with the study – the method of recruiting, which involved ads placed on social media, could cause selection bias. In addition to this, data collection methods relied heavily on participants’ self-reporting, which could also be susceptible to bias.

“Certainly, there needs to be more investigation on this dietary practice,” said Dr. Ganson. “If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors requiring healthcare professionals to be very aware of this contemporary and popular dietary trend – despite proponents on social media touting the effectiveness and benefits.”
 

Screening warranted

Dr. Ganson noted that additional research is needed to support the findings from his study, and to further illuminate the potential harms of IF.

Health care professionals “need to be aware of common, contemporary dietary trends that young people engage in and are commonly discussed on social media, such as IF,” he noted. In addition, he’d like to see health care professionals assess their patients for IF who are dieting and to follow-up with assessments for ED-related attitudes and behaviors.

“Additionally, there are likely bidirectional relationships between IF and ED attitudes and behaviors, so professionals should be aware the ways in which ED behaviors are masked as IF engagement,” Dr. Ganson said.
 

More research needed

Commenting on the findings, Angela Guarda, MD, professor of eating disorders at Johns Hopkins University and director of the eating disorders program at Johns Hopkins Hospital, both in Baltimore, said more research is needed on outcomes for IF.

“We lack a definitive answer. The reality is that IF may help some and harm others and is most likely not healthy for all,” she said, noting that the study results “support what many in the eating disorders field believe, namely that IF for someone who is at risk for an eating disorder is likely to be ill advised.”

She added that “continued research is needed to establish its safety, and for whom it may be a therapeutic versus an iatrogenic recommendation.”

The study was funded by the Connaught New Researcher Award. The authors reported no relevant financial relationships.

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

THE CASE

Alex T,* a 23-year-old first-time mom, presented to the family medicine office for her baby’s 2-week appointment. When asked how she was doing, she began to cry. She said, “I feel crazy” and indicated that she was feeling down and overwhelmed, and was struggling to bond with the baby. She filled out an Edinburgh Postnatal Depression Scale, a standard postpartum depression (PPD) screen; her score, 15 out of 30, was suggestive of depression. Ms. T had been coming to the practice for the past 3 years and had no significant physical or mental health history. She and the baby did not live with the baby’s father, and his degree of presence in their lives varied.

●How would you proceed with this patient?

* The patient’s name has been changed to protect her identity.

PPD, traditionally defined as depression in the postpartum period for as long as a year after childbirth, is a common, underdiagnosed outcome of both normal and complicated pregnancies.¹ Peripartum depression, which includes PPD and depression during pregnancy, occurs in approximately 10% of pregnancies.^2,3 When depression first appears in the postpartum period, most women develop symptoms in the first month after delivery (54% of cases) or in the next 2 to 4 months (40%).⁴

The most significant risk factor for PPD is previous depression, peripartum or otherwise.^1,4-6 Other common risk factors include major life events or stressors during or after pregnancy, domestic violence, poor social support, and preterm birth or an infant admission to the neonatal intensive care unit.^1,7 Women with a self-perceived negative birth experience are also likely to experience PPD.⁸ PPD can be associated with significant morbidity and mortality, with suicide a more common cause of maternal mortality than either hemorrhage or hypertensive disorders of pregnancy.⁹

Women with postpartum anemia and low ferritin stores are more prone to depression than are those with normal levels.

Early diagnosis and intervention are crucial to improving patient outcomes. Women with PPD initiate breastfeeding at lower rates and continue for shorter durations.¹⁰ PPD also affects maternal–infant bonding; may adversely affect an infant’s social, cognitive, and language development; and may lead to attachment disorders of infancy.^11,12 In severe cases, it can lead to failure to thrive or infanticide.¹¹

When to screen. The US Preventive Services Task Force (USPSTF) recommends clinicians screen for depression in pregnant and postpartum women (Grade B^a) and for women at increased risk, provide or refer to counseling interventions (Grade B^a).^13,14 The American College of Obstetricians and Gynecologists (ACOG) recommends screening at least once in the postpartum period.¹⁵ Repeat screening at follow-up in the later postpartum period increases the likelihood of diagnosis.¹⁶ Screening for PPD as part of well-child care improves maternal outcomes, and the American Academy of Pediatrics recommends screening at the 1-, 2-, 4-, and 6-month visits.^11,17 These screens are separately billable. Family physicians are uniquely suited to screening at both well-child and postpartum visits, as many women share a medical home with their child, and those who do not are equally willing to receive medical advice from their child’s physician.¹⁸

Continue to: Is it "the blues" or something else? Diagnosing PPD

Many new mothers experience postpartum blues, which manifest as tearfulness, insomnia, irritability, and anxiety. The postpartum blues, however, don’t meet the criteria for major depressive disorder and typically resolve within 14 days of delivery.^19-21 On the other end of the spectrum is postpartum psychosis, which is severe and rare, and can also affect new mothers.

Screening for PPD. The most commonly used screening tool for PPD is the Edinburgh Postnatal Depression Scale (EPDS 10), a free 10-item instrument scored out of 30 possible points, with any score ≥ 13 suggesting PPD.²² The EPDS 10 has a sensitivity of 74% and specificity of 97% for the diagnosis of PPD.²³ Other screening options include the Beck Depression Inventory II (BDI-II) and the Patient Health Questionnaire 9 (PHQ-9). The 21-item BDI-II takes longer to perform and is less sensitive (57%) than the EPDS.¹ The PHQ-9, which asks about some symptoms common to the postpartum period (including sleep changes), is less specific than the EPDS (sensitivity, 75%; specificity, 90%).¹ The EPDS also includes screening questions about anxiety.¹

A positive depression screen, or any positive response to a question on suicidal ideation, should be followed up for confirmation using the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) criteria for major depressive disorder with peripartum onset.²⁴ Women with PPD should also be asked about current or prior symptoms of bipolar disorder or mania.²⁵ Up to 67% of women with bipolar disorder may relapse postpartum, and they also have an elevated risk of postpartum psychosis.²⁶ The Mood Disorder Questionnaire is a useful tool if a concern for bipolar depression arises.²⁷

Refer any woman in whom bipolar depression is a concern to a clinician experienced with its management. The presence of auditory or visual hallucinations should also be assessed as indicators of postpartum psychosis. Active suicidal or homicidal ideation and postpartum psychosis all require emergent psychiatric care.^21,22 Intimate partner violence may also exist or escalate in the postpartum period and may exacerbate PPD. Both ACOG and the USPSTF recommend screening postpartum women for intimate partner violence.^28,29

Also consider possible medical causes of PPD symptoms. Hypothyroidism in the postpartum period may manifest with some similar symptoms to PPD and is commonly underdiagnosed.^22,30 Women with postpartum anemia and low ferritin stores also have a higher likelihood of PPD (odds ratio, 1.7-4.64), and postpartum iron supplementation may reduce this risk (number needed to treat = 4 in at least 1 randomized controlled trial).³¹ When anemia is present, ensure that it is properly treated.

Continue to: Steps you can take to manage pPD

Refer any woman who has PPD to a qualified therapist whenever possible. Generally, the psychological recommendations for treatment of PPD are very similar to recommendations for general treatment of depression. Psychotherapy on its own is considered a first-line treatment for mild-to-moderate PPD, and medication plus psychotherapy is considered first-line treatment for severe PPD.³² (Worth noting: It may also be useful to offer counseling to a patient who appears distressed, even if she does not fully meet all DSM-5 criteria.)

Of the psychotherapy options, cognitive behavioral therapy is supported by the most evidence.

Of the psychotherapy options, cognitive behavioral therapy (CBT) is supported by the most evidence. There is also evidence for the use of interpersonal therapy (IPT), especially in higher socioeconomic status populations.³³ Key therapeutic targets in IPT are increasing behavioral engagement (eg, reaching out to friends), decreasing negative self-talk (eg, “I am a bad mother”), and negotiating roles and support (eg, both mom’s and family members’ expectations of new motherhood). There is mixed evidence for recommending exercise as a treatment for PPD.^32,34 However, as exercise is a low-risk intervention, you may choose to make that recommendation to patients. Additionally, including partners/support people in treatment/visits for PPD has been shown to increase positive outcomes.³⁵

When medication is considered, selective serotonin reuptake inhibitors (SSRIs) are most commonly used. Research indicates that SSRIs are significantly more effective than placebo for treatment of women with PPD.³⁶ Sertraline, in particular, has shown to be both effective in treating PPD and safe in lactation.^37,38 Dosing and duration of therapy are equivalent to treatment of major depression outside the perinatal period. Consult a trusted source on medications in lactation before prescribing any antidepressant to a breastfeeding mother. One resource is the National Institutes of Health drugs and lactation database (LactMed; www.ncbi.nlm.nih.gov/books/NBK501922/), which provides detailed information on the levels of medications in breastmilk and their potential effects on an infant.

Women with severe, refractory PPD may require hospitalization. Additional treatment options for women with severe, refractory PPD include electroconvulsive therapy or the new medication brexanolone, which is administered as a 60-hour continuous infusion.^39,40

THE CASE

Further conversation with Ms. T revealed that she met the criteria for PPD (major depressive disorder with peripartum onset). She denied suicidal or homicidal ideation and was not experiencing any symptoms of psychosis. A complete blood count was drawn and showed no anemia, and her thyroid-stimulating hormone level was within normal limits. She had a good support network at home, with both her mom and sister taking shifts to help her get some extra rest and allow her to attend medical appointments. She said there was no domestic violence.

Ms. T was introduced to the clinic’s embedded counselor, who scheduled a follow-up appointment within the week to start CBT. After a discussion of risks and benefits, Ms. T also started a low dose of sertraline once daily. At follow-up postpartum visits, she reported significant improvement in her mood. She and her physician decided to taper her SSRI medication at 3 months postpartum. Screens for depression at her infant’s 4- and 6-month well-child visits in the office were reassuringly negative.

^a There is high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial.

CORRESPONDENCE
Katherine Buck, PhD, JPS Family Health Center, 1500 South Main Street, 4th Floor, Fort Worth, TX 76110; kbuck@jpshealth.org

THE CASE

Alex T,* a 23-year-old first-time mom, presented to the family medicine office for her baby’s 2-week appointment. When asked how she was doing, she began to cry. She said, “I feel crazy” and indicated that she was feeling down and overwhelmed, and was struggling to bond with the baby. She filled out an Edinburgh Postnatal Depression Scale, a standard postpartum depression (PPD) screen; her score, 15 out of 30, was suggestive of depression. Ms. T had been coming to the practice for the past 3 years and had no significant physical or mental health history. She and the baby did not live with the baby’s father, and his degree of presence in their lives varied.

●How would you proceed with this patient?

* The patient’s name has been changed to protect her identity.

PPD, traditionally defined as depression in the postpartum period for as long as a year after childbirth, is a common, underdiagnosed outcome of both normal and complicated pregnancies.¹ Peripartum depression, which includes PPD and depression during pregnancy, occurs in approximately 10% of pregnancies.^2,3 When depression first appears in the postpartum period, most women develop symptoms in the first month after delivery (54% of cases) or in the next 2 to 4 months (40%).⁴

The most significant risk factor for PPD is previous depression, peripartum or otherwise.^1,4-6 Other common risk factors include major life events or stressors during or after pregnancy, domestic violence, poor social support, and preterm birth or an infant admission to the neonatal intensive care unit.^1,7 Women with a self-perceived negative birth experience are also likely to experience PPD.⁸ PPD can be associated with significant morbidity and mortality, with suicide a more common cause of maternal mortality than either hemorrhage or hypertensive disorders of pregnancy.⁹

Women with postpartum anemia and low ferritin stores are more prone to depression than are those with normal levels.

Early diagnosis and intervention are crucial to improving patient outcomes. Women with PPD initiate breastfeeding at lower rates and continue for shorter durations.¹⁰ PPD also affects maternal–infant bonding; may adversely affect an infant’s social, cognitive, and language development; and may lead to attachment disorders of infancy.^11,12 In severe cases, it can lead to failure to thrive or infanticide.¹¹

When to screen. The US Preventive Services Task Force (USPSTF) recommends clinicians screen for depression in pregnant and postpartum women (Grade B^a) and for women at increased risk, provide or refer to counseling interventions (Grade B^a).^13,14 The American College of Obstetricians and Gynecologists (ACOG) recommends screening at least once in the postpartum period.¹⁵ Repeat screening at follow-up in the later postpartum period increases the likelihood of diagnosis.¹⁶ Screening for PPD as part of well-child care improves maternal outcomes, and the American Academy of Pediatrics recommends screening at the 1-, 2-, 4-, and 6-month visits.^11,17 These screens are separately billable. Family physicians are uniquely suited to screening at both well-child and postpartum visits, as many women share a medical home with their child, and those who do not are equally willing to receive medical advice from their child’s physician.¹⁸

Continue to: Is it "the blues" or something else? Diagnosing PPD

Many new mothers experience postpartum blues, which manifest as tearfulness, insomnia, irritability, and anxiety. The postpartum blues, however, don’t meet the criteria for major depressive disorder and typically resolve within 14 days of delivery.^19-21 On the other end of the spectrum is postpartum psychosis, which is severe and rare, and can also affect new mothers.

Screening for PPD. The most commonly used screening tool for PPD is the Edinburgh Postnatal Depression Scale (EPDS 10), a free 10-item instrument scored out of 30 possible points, with any score ≥ 13 suggesting PPD.²² The EPDS 10 has a sensitivity of 74% and specificity of 97% for the diagnosis of PPD.²³ Other screening options include the Beck Depression Inventory II (BDI-II) and the Patient Health Questionnaire 9 (PHQ-9). The 21-item BDI-II takes longer to perform and is less sensitive (57%) than the EPDS.¹ The PHQ-9, which asks about some symptoms common to the postpartum period (including sleep changes), is less specific than the EPDS (sensitivity, 75%; specificity, 90%).¹ The EPDS also includes screening questions about anxiety.¹

A positive depression screen, or any positive response to a question on suicidal ideation, should be followed up for confirmation using the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) criteria for major depressive disorder with peripartum onset.²⁴ Women with PPD should also be asked about current or prior symptoms of bipolar disorder or mania.²⁵ Up to 67% of women with bipolar disorder may relapse postpartum, and they also have an elevated risk of postpartum psychosis.²⁶ The Mood Disorder Questionnaire is a useful tool if a concern for bipolar depression arises.²⁷

Refer any woman in whom bipolar depression is a concern to a clinician experienced with its management. The presence of auditory or visual hallucinations should also be assessed as indicators of postpartum psychosis. Active suicidal or homicidal ideation and postpartum psychosis all require emergent psychiatric care.^21,22 Intimate partner violence may also exist or escalate in the postpartum period and may exacerbate PPD. Both ACOG and the USPSTF recommend screening postpartum women for intimate partner violence.^28,29

Also consider possible medical causes of PPD symptoms. Hypothyroidism in the postpartum period may manifest with some similar symptoms to PPD and is commonly underdiagnosed.^22,30 Women with postpartum anemia and low ferritin stores also have a higher likelihood of PPD (odds ratio, 1.7-4.64), and postpartum iron supplementation may reduce this risk (number needed to treat = 4 in at least 1 randomized controlled trial).³¹ When anemia is present, ensure that it is properly treated.

Continue to: Steps you can take to manage pPD

Refer any woman who has PPD to a qualified therapist whenever possible. Generally, the psychological recommendations for treatment of PPD are very similar to recommendations for general treatment of depression. Psychotherapy on its own is considered a first-line treatment for mild-to-moderate PPD, and medication plus psychotherapy is considered first-line treatment for severe PPD.³² (Worth noting: It may also be useful to offer counseling to a patient who appears distressed, even if she does not fully meet all DSM-5 criteria.)

Of the psychotherapy options, cognitive behavioral therapy is supported by the most evidence.

Of the psychotherapy options, cognitive behavioral therapy (CBT) is supported by the most evidence. There is also evidence for the use of interpersonal therapy (IPT), especially in higher socioeconomic status populations.³³ Key therapeutic targets in IPT are increasing behavioral engagement (eg, reaching out to friends), decreasing negative self-talk (eg, “I am a bad mother”), and negotiating roles and support (eg, both mom’s and family members’ expectations of new motherhood). There is mixed evidence for recommending exercise as a treatment for PPD.^32,34 However, as exercise is a low-risk intervention, you may choose to make that recommendation to patients. Additionally, including partners/support people in treatment/visits for PPD has been shown to increase positive outcomes.³⁵

When medication is considered, selective serotonin reuptake inhibitors (SSRIs) are most commonly used. Research indicates that SSRIs are significantly more effective than placebo for treatment of women with PPD.³⁶ Sertraline, in particular, has shown to be both effective in treating PPD and safe in lactation.^37,38 Dosing and duration of therapy are equivalent to treatment of major depression outside the perinatal period. Consult a trusted source on medications in lactation before prescribing any antidepressant to a breastfeeding mother. One resource is the National Institutes of Health drugs and lactation database (LactMed; www.ncbi.nlm.nih.gov/books/NBK501922/), which provides detailed information on the levels of medications in breastmilk and their potential effects on an infant.

Women with severe, refractory PPD may require hospitalization. Additional treatment options for women with severe, refractory PPD include electroconvulsive therapy or the new medication brexanolone, which is administered as a 60-hour continuous infusion.^39,40

THE CASE

Further conversation with Ms. T revealed that she met the criteria for PPD (major depressive disorder with peripartum onset). She denied suicidal or homicidal ideation and was not experiencing any symptoms of psychosis. A complete blood count was drawn and showed no anemia, and her thyroid-stimulating hormone level was within normal limits. She had a good support network at home, with both her mom and sister taking shifts to help her get some extra rest and allow her to attend medical appointments. She said there was no domestic violence.

Ms. T was introduced to the clinic’s embedded counselor, who scheduled a follow-up appointment within the week to start CBT. After a discussion of risks and benefits, Ms. T also started a low dose of sertraline once daily. At follow-up postpartum visits, she reported significant improvement in her mood. She and her physician decided to taper her SSRI medication at 3 months postpartum. Screens for depression at her infant’s 4- and 6-month well-child visits in the office were reassuringly negative.

^a There is high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial.

CORRESPONDENCE
Katherine Buck, PhD, JPS Family Health Center, 1500 South Main Street, 4th Floor, Fort Worth, TX 76110; kbuck@jpshealth.org

THE CASE

Alex T,* a 23-year-old first-time mom, presented to the family medicine office for her baby’s 2-week appointment. When asked how she was doing, she began to cry. She said, “I feel crazy” and indicated that she was feeling down and overwhelmed, and was struggling to bond with the baby. She filled out an Edinburgh Postnatal Depression Scale, a standard postpartum depression (PPD) screen; her score, 15 out of 30, was suggestive of depression. Ms. T had been coming to the practice for the past 3 years and had no significant physical or mental health history. She and the baby did not live with the baby’s father, and his degree of presence in their lives varied.

●How would you proceed with this patient?

* The patient’s name has been changed to protect her identity.

PPD, traditionally defined as depression in the postpartum period for as long as a year after childbirth, is a common, underdiagnosed outcome of both normal and complicated pregnancies.¹ Peripartum depression, which includes PPD and depression during pregnancy, occurs in approximately 10% of pregnancies.^2,3 When depression first appears in the postpartum period, most women develop symptoms in the first month after delivery (54% of cases) or in the next 2 to 4 months (40%).⁴

The most significant risk factor for PPD is previous depression, peripartum or otherwise.^1,4-6 Other common risk factors include major life events or stressors during or after pregnancy, domestic violence, poor social support, and preterm birth or an infant admission to the neonatal intensive care unit.^1,7 Women with a self-perceived negative birth experience are also likely to experience PPD.⁸ PPD can be associated with significant morbidity and mortality, with suicide a more common cause of maternal mortality than either hemorrhage or hypertensive disorders of pregnancy.⁹

Women with postpartum anemia and low ferritin stores are more prone to depression than are those with normal levels.

Early diagnosis and intervention are crucial to improving patient outcomes. Women with PPD initiate breastfeeding at lower rates and continue for shorter durations.¹⁰ PPD also affects maternal–infant bonding; may adversely affect an infant’s social, cognitive, and language development; and may lead to attachment disorders of infancy.^11,12 In severe cases, it can lead to failure to thrive or infanticide.¹¹

When to screen. The US Preventive Services Task Force (USPSTF) recommends clinicians screen for depression in pregnant and postpartum women (Grade B^a) and for women at increased risk, provide or refer to counseling interventions (Grade B^a).^13,14 The American College of Obstetricians and Gynecologists (ACOG) recommends screening at least once in the postpartum period.¹⁵ Repeat screening at follow-up in the later postpartum period increases the likelihood of diagnosis.¹⁶ Screening for PPD as part of well-child care improves maternal outcomes, and the American Academy of Pediatrics recommends screening at the 1-, 2-, 4-, and 6-month visits.^11,17 These screens are separately billable. Family physicians are uniquely suited to screening at both well-child and postpartum visits, as many women share a medical home with their child, and those who do not are equally willing to receive medical advice from their child’s physician.¹⁸

Continue to: Is it "the blues" or something else? Diagnosing PPD

Many new mothers experience postpartum blues, which manifest as tearfulness, insomnia, irritability, and anxiety. The postpartum blues, however, don’t meet the criteria for major depressive disorder and typically resolve within 14 days of delivery.^19-21 On the other end of the spectrum is postpartum psychosis, which is severe and rare, and can also affect new mothers.

Screening for PPD. The most commonly used screening tool for PPD is the Edinburgh Postnatal Depression Scale (EPDS 10), a free 10-item instrument scored out of 30 possible points, with any score ≥ 13 suggesting PPD.²² The EPDS 10 has a sensitivity of 74% and specificity of 97% for the diagnosis of PPD.²³ Other screening options include the Beck Depression Inventory II (BDI-II) and the Patient Health Questionnaire 9 (PHQ-9). The 21-item BDI-II takes longer to perform and is less sensitive (57%) than the EPDS.¹ The PHQ-9, which asks about some symptoms common to the postpartum period (including sleep changes), is less specific than the EPDS (sensitivity, 75%; specificity, 90%).¹ The EPDS also includes screening questions about anxiety.¹

A positive depression screen, or any positive response to a question on suicidal ideation, should be followed up for confirmation using the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) criteria for major depressive disorder with peripartum onset.²⁴ Women with PPD should also be asked about current or prior symptoms of bipolar disorder or mania.²⁵ Up to 67% of women with bipolar disorder may relapse postpartum, and they also have an elevated risk of postpartum psychosis.²⁶ The Mood Disorder Questionnaire is a useful tool if a concern for bipolar depression arises.²⁷

Refer any woman in whom bipolar depression is a concern to a clinician experienced with its management. The presence of auditory or visual hallucinations should also be assessed as indicators of postpartum psychosis. Active suicidal or homicidal ideation and postpartum psychosis all require emergent psychiatric care.^21,22 Intimate partner violence may also exist or escalate in the postpartum period and may exacerbate PPD. Both ACOG and the USPSTF recommend screening postpartum women for intimate partner violence.^28,29

Also consider possible medical causes of PPD symptoms. Hypothyroidism in the postpartum period may manifest with some similar symptoms to PPD and is commonly underdiagnosed.^22,30 Women with postpartum anemia and low ferritin stores also have a higher likelihood of PPD (odds ratio, 1.7-4.64), and postpartum iron supplementation may reduce this risk (number needed to treat = 4 in at least 1 randomized controlled trial).³¹ When anemia is present, ensure that it is properly treated.

Continue to: Steps you can take to manage pPD

Refer any woman who has PPD to a qualified therapist whenever possible. Generally, the psychological recommendations for treatment of PPD are very similar to recommendations for general treatment of depression. Psychotherapy on its own is considered a first-line treatment for mild-to-moderate PPD, and medication plus psychotherapy is considered first-line treatment for severe PPD.³² (Worth noting: It may also be useful to offer counseling to a patient who appears distressed, even if she does not fully meet all DSM-5 criteria.)

Of the psychotherapy options, cognitive behavioral therapy is supported by the most evidence.

Of the psychotherapy options, cognitive behavioral therapy (CBT) is supported by the most evidence. There is also evidence for the use of interpersonal therapy (IPT), especially in higher socioeconomic status populations.³³ Key therapeutic targets in IPT are increasing behavioral engagement (eg, reaching out to friends), decreasing negative self-talk (eg, “I am a bad mother”), and negotiating roles and support (eg, both mom’s and family members’ expectations of new motherhood). There is mixed evidence for recommending exercise as a treatment for PPD.^32,34 However, as exercise is a low-risk intervention, you may choose to make that recommendation to patients. Additionally, including partners/support people in treatment/visits for PPD has been shown to increase positive outcomes.³⁵

When medication is considered, selective serotonin reuptake inhibitors (SSRIs) are most commonly used. Research indicates that SSRIs are significantly more effective than placebo for treatment of women with PPD.³⁶ Sertraline, in particular, has shown to be both effective in treating PPD and safe in lactation.^37,38 Dosing and duration of therapy are equivalent to treatment of major depression outside the perinatal period. Consult a trusted source on medications in lactation before prescribing any antidepressant to a breastfeeding mother. One resource is the National Institutes of Health drugs and lactation database (LactMed; www.ncbi.nlm.nih.gov/books/NBK501922/), which provides detailed information on the levels of medications in breastmilk and their potential effects on an infant.

Women with severe, refractory PPD may require hospitalization. Additional treatment options for women with severe, refractory PPD include electroconvulsive therapy or the new medication brexanolone, which is administered as a 60-hour continuous infusion.^39,40

THE CASE

Further conversation with Ms. T revealed that she met the criteria for PPD (major depressive disorder with peripartum onset). She denied suicidal or homicidal ideation and was not experiencing any symptoms of psychosis. A complete blood count was drawn and showed no anemia, and her thyroid-stimulating hormone level was within normal limits. She had a good support network at home, with both her mom and sister taking shifts to help her get some extra rest and allow her to attend medical appointments. She said there was no domestic violence.

Ms. T was introduced to the clinic’s embedded counselor, who scheduled a follow-up appointment within the week to start CBT. After a discussion of risks and benefits, Ms. T also started a low dose of sertraline once daily. At follow-up postpartum visits, she reported significant improvement in her mood. She and her physician decided to taper her SSRI medication at 3 months postpartum. Screens for depression at her infant’s 4- and 6-month well-child visits in the office were reassuringly negative.

^a There is high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial.

CORRESPONDENCE
Katherine Buck, PhD, JPS Family Health Center, 1500 South Main Street, 4th Floor, Fort Worth, TX 76110; kbuck@jpshealth.org