Narcissists appear to be everywhere. A few minutes on the Internet shows the dangers of narcissistic romantic partners, friends, and employers. Identifying and limiting the reach of their manipulative and self-centered endeavors is cast as both urgent and necessary. The destructive powers of the narcissistic mother are viewed as especially in need of remedy, and any bookstore can reveal the risks they pose: “Will I Ever Be Good Enough? Healing the Daughters of Narcissistic Mothers;” “You’re Not Crazy – It’s Your Mother: Freedom for Daughters of Narcissistic Mothers;” “Healing for Daughters of Narcissistic Mothers: A Practical Guide on How to Recover from the Childhood Trauma of Toxic Relationship with Your Mother and How You Can Handle Her Abuse Now As An Adult” – to name just a few (there are more).

As a psychologist specializing in parental estrangement, I (Dr. Coleman) regularly see letters from adult children explaining their discovery-through-therapy that their mother is a narcissist. The proclamation often comes when the therapist has never met the mother. Typically, the discovery is presented as a justification for ending the relationship with the parent. While these mothers could rightly be accused of being anxious, over-involved, depressed, or hurt by the lack of gratitude or reciprocity, the vast majority are not narcissists.

Blaming mothers has a long reach. Mothers have been blamed for causing schizophrenia, autism, homosexuality, and effeminacy in men. While we used to call people selfish and “controlling,” narcissism is a more consequential label as it confers diagnostic validity from the mental health profession. Worse, it suggests an individual beyond reach, where the only answer is distance, containment, or estrangement.

The rise of the narcissistic mother comes during a time when, for the past 4 decades, the average working mother spends more time with her children than stay-at-home moms did in the supposed halcyon days of the 1960s’ middle class, before “parenting” was a common term. A variety of economists and sociologists observed that an increase in parental effort became necessary to launch children into adulthood given the retreat of governmental and corporate support for parents that began in the 1980s.

“The financial and emotional burden on families has grown in ways that were almost unimaginable just a half-century ago,” writes the University of Pennsylvania sociologist Frank Furstenberg in “On a New Schedule: Transitions to Adulthood and Family Change.” In addition, a view of children as vulnerable and in need of intense parental investment gained momentum over the course of the 20th century and has continued unabated into the present. As a result, an environment of intense maternal preoccupation, worry, guilt, and involvement with children’s grades, safety, health, and emotional states – referred to as “helicopter” and “tiger” mothering – grew into the norm across the classes.

While prior generations of parents could, by today’s standards, be viewed as being insufficiently involved, today’s parents have become “over-involved” – aided by the ability of parents to be in constant contact with their adult children through technology. While this shift to a more hands-on, more conscientious parenting has been a boon to parent–adult child relationships in the main, the downside has meant, for some, too much of a good thing. From that perspective, pathologizing a mother’s involvement or her expressions of hurt for that child’s lack of availability provides a shield against the child’s feelings of guilt or obligation.

Diagnoses can serve a social purpose: They can allow individuals to use the authority of our profession to decide who to be close to and who to let go. They can provide insulation against feelings of obligation or guilt. They create a way to label behavior as dysfunctional that in other eras or cultures would be considered normal, even valued. To that extent, diagnoses don’t occur in a cultural void. They are inextricably tied to larger ideals, be they individualistic – as exists in the United States – or collectivist, as exists in many other parts of the world.

While we have decided what parents owe our children, it is unclear what parents might ask in return. To that end, mothers who want more interest, availability, or gratitude today are vulnerable to being cast as selfish, uncaring, needy, and controlling. They can now be viewed as failing in their task of selfless devotion. Their desires for closeness or repair can be regarded as incompatible with the quest for the adult child’s self-fulfillment and identity; her identification with her children too great a barrier to their individuation.

There may well be good reasons to estrange family members for their intolerable behaviors, especially ones who have threatened personal safety. Yet, while there are plenty of problematic parents, few meet the diagnostic criteria of narcissistic personality disorder. More important, such labels can discourage a discussion of boundaries that both the parents and the adult children might find acceptable – which sometimes means asking family members to tolerate behavior or individuals not to their liking.

Diagnoses carry enormous social weight and can facilitate estrangements or negativity to mothers that are far more workable than our patients’ characterization of them might lead them or us to believe. Wrongly labeling mothers as narcissists greatly oversimplifies their lives and struggles; it devalues their years of love and dedication, however flawed; and it weakens the fabric of connection that could otherwise exist. Rather than provide a path toward compassion or understanding, “narcissistic mother” just becomes the latest form of mommy shaming.

Dr. Coleman is a clinical psychologist and author of “Rules of Estrangement: Why Adult Children Cut Ties and How to Heal the Conflict” (New York: Penguin Random House, 2021). Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University in Baltimore.

Narcissists appear to be everywhere. A few minutes on the Internet shows the dangers of narcissistic romantic partners, friends, and employers. Identifying and limiting the reach of their manipulative and self-centered endeavors is cast as both urgent and necessary. The destructive powers of the narcissistic mother are viewed as especially in need of remedy, and any bookstore can reveal the risks they pose: “Will I Ever Be Good Enough? Healing the Daughters of Narcissistic Mothers;” “You’re Not Crazy – It’s Your Mother: Freedom for Daughters of Narcissistic Mothers;” “Healing for Daughters of Narcissistic Mothers: A Practical Guide on How to Recover from the Childhood Trauma of Toxic Relationship with Your Mother and How You Can Handle Her Abuse Now As An Adult” – to name just a few (there are more).

As a psychologist specializing in parental estrangement, I (Dr. Coleman) regularly see letters from adult children explaining their discovery-through-therapy that their mother is a narcissist. The proclamation often comes when the therapist has never met the mother. Typically, the discovery is presented as a justification for ending the relationship with the parent. While these mothers could rightly be accused of being anxious, over-involved, depressed, or hurt by the lack of gratitude or reciprocity, the vast majority are not narcissists.

Blaming mothers has a long reach. Mothers have been blamed for causing schizophrenia, autism, homosexuality, and effeminacy in men. While we used to call people selfish and “controlling,” narcissism is a more consequential label as it confers diagnostic validity from the mental health profession. Worse, it suggests an individual beyond reach, where the only answer is distance, containment, or estrangement.

The rise of the narcissistic mother comes during a time when, for the past 4 decades, the average working mother spends more time with her children than stay-at-home moms did in the supposed halcyon days of the 1960s’ middle class, before “parenting” was a common term. A variety of economists and sociologists observed that an increase in parental effort became necessary to launch children into adulthood given the retreat of governmental and corporate support for parents that began in the 1980s.

“The financial and emotional burden on families has grown in ways that were almost unimaginable just a half-century ago,” writes the University of Pennsylvania sociologist Frank Furstenberg in “On a New Schedule: Transitions to Adulthood and Family Change.” In addition, a view of children as vulnerable and in need of intense parental investment gained momentum over the course of the 20th century and has continued unabated into the present. As a result, an environment of intense maternal preoccupation, worry, guilt, and involvement with children’s grades, safety, health, and emotional states – referred to as “helicopter” and “tiger” mothering – grew into the norm across the classes.

While prior generations of parents could, by today’s standards, be viewed as being insufficiently involved, today’s parents have become “over-involved” – aided by the ability of parents to be in constant contact with their adult children through technology. While this shift to a more hands-on, more conscientious parenting has been a boon to parent–adult child relationships in the main, the downside has meant, for some, too much of a good thing. From that perspective, pathologizing a mother’s involvement or her expressions of hurt for that child’s lack of availability provides a shield against the child’s feelings of guilt or obligation.

Diagnoses can serve a social purpose: They can allow individuals to use the authority of our profession to decide who to be close to and who to let go. They can provide insulation against feelings of obligation or guilt. They create a way to label behavior as dysfunctional that in other eras or cultures would be considered normal, even valued. To that extent, diagnoses don’t occur in a cultural void. They are inextricably tied to larger ideals, be they individualistic – as exists in the United States – or collectivist, as exists in many other parts of the world.

While we have decided what parents owe our children, it is unclear what parents might ask in return. To that end, mothers who want more interest, availability, or gratitude today are vulnerable to being cast as selfish, uncaring, needy, and controlling. They can now be viewed as failing in their task of selfless devotion. Their desires for closeness or repair can be regarded as incompatible with the quest for the adult child’s self-fulfillment and identity; her identification with her children too great a barrier to their individuation.

There may well be good reasons to estrange family members for their intolerable behaviors, especially ones who have threatened personal safety. Yet, while there are plenty of problematic parents, few meet the diagnostic criteria of narcissistic personality disorder. More important, such labels can discourage a discussion of boundaries that both the parents and the adult children might find acceptable – which sometimes means asking family members to tolerate behavior or individuals not to their liking.

Diagnoses carry enormous social weight and can facilitate estrangements or negativity to mothers that are far more workable than our patients’ characterization of them might lead them or us to believe. Wrongly labeling mothers as narcissists greatly oversimplifies their lives and struggles; it devalues their years of love and dedication, however flawed; and it weakens the fabric of connection that could otherwise exist. Rather than provide a path toward compassion or understanding, “narcissistic mother” just becomes the latest form of mommy shaming.

Dr. Coleman is a clinical psychologist and author of “Rules of Estrangement: Why Adult Children Cut Ties and How to Heal the Conflict” (New York: Penguin Random House, 2021). Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University in Baltimore.

Narcissists appear to be everywhere. A few minutes on the Internet shows the dangers of narcissistic romantic partners, friends, and employers. Identifying and limiting the reach of their manipulative and self-centered endeavors is cast as both urgent and necessary. The destructive powers of the narcissistic mother are viewed as especially in need of remedy, and any bookstore can reveal the risks they pose: “Will I Ever Be Good Enough? Healing the Daughters of Narcissistic Mothers;” “You’re Not Crazy – It’s Your Mother: Freedom for Daughters of Narcissistic Mothers;” “Healing for Daughters of Narcissistic Mothers: A Practical Guide on How to Recover from the Childhood Trauma of Toxic Relationship with Your Mother and How You Can Handle Her Abuse Now As An Adult” – to name just a few (there are more).

As a psychologist specializing in parental estrangement, I (Dr. Coleman) regularly see letters from adult children explaining their discovery-through-therapy that their mother is a narcissist. The proclamation often comes when the therapist has never met the mother. Typically, the discovery is presented as a justification for ending the relationship with the parent. While these mothers could rightly be accused of being anxious, over-involved, depressed, or hurt by the lack of gratitude or reciprocity, the vast majority are not narcissists.

Blaming mothers has a long reach. Mothers have been blamed for causing schizophrenia, autism, homosexuality, and effeminacy in men. While we used to call people selfish and “controlling,” narcissism is a more consequential label as it confers diagnostic validity from the mental health profession. Worse, it suggests an individual beyond reach, where the only answer is distance, containment, or estrangement.

The rise of the narcissistic mother comes during a time when, for the past 4 decades, the average working mother spends more time with her children than stay-at-home moms did in the supposed halcyon days of the 1960s’ middle class, before “parenting” was a common term. A variety of economists and sociologists observed that an increase in parental effort became necessary to launch children into adulthood given the retreat of governmental and corporate support for parents that began in the 1980s.

“The financial and emotional burden on families has grown in ways that were almost unimaginable just a half-century ago,” writes the University of Pennsylvania sociologist Frank Furstenberg in “On a New Schedule: Transitions to Adulthood and Family Change.” In addition, a view of children as vulnerable and in need of intense parental investment gained momentum over the course of the 20th century and has continued unabated into the present. As a result, an environment of intense maternal preoccupation, worry, guilt, and involvement with children’s grades, safety, health, and emotional states – referred to as “helicopter” and “tiger” mothering – grew into the norm across the classes.

While prior generations of parents could, by today’s standards, be viewed as being insufficiently involved, today’s parents have become “over-involved” – aided by the ability of parents to be in constant contact with their adult children through technology. While this shift to a more hands-on, more conscientious parenting has been a boon to parent–adult child relationships in the main, the downside has meant, for some, too much of a good thing. From that perspective, pathologizing a mother’s involvement or her expressions of hurt for that child’s lack of availability provides a shield against the child’s feelings of guilt or obligation.

Diagnoses can serve a social purpose: They can allow individuals to use the authority of our profession to decide who to be close to and who to let go. They can provide insulation against feelings of obligation or guilt. They create a way to label behavior as dysfunctional that in other eras or cultures would be considered normal, even valued. To that extent, diagnoses don’t occur in a cultural void. They are inextricably tied to larger ideals, be they individualistic – as exists in the United States – or collectivist, as exists in many other parts of the world.

While we have decided what parents owe our children, it is unclear what parents might ask in return. To that end, mothers who want more interest, availability, or gratitude today are vulnerable to being cast as selfish, uncaring, needy, and controlling. They can now be viewed as failing in their task of selfless devotion. Their desires for closeness or repair can be regarded as incompatible with the quest for the adult child’s self-fulfillment and identity; her identification with her children too great a barrier to their individuation.

There may well be good reasons to estrange family members for their intolerable behaviors, especially ones who have threatened personal safety. Yet, while there are plenty of problematic parents, few meet the diagnostic criteria of narcissistic personality disorder. More important, such labels can discourage a discussion of boundaries that both the parents and the adult children might find acceptable – which sometimes means asking family members to tolerate behavior or individuals not to their liking.

Diagnoses carry enormous social weight and can facilitate estrangements or negativity to mothers that are far more workable than our patients’ characterization of them might lead them or us to believe. Wrongly labeling mothers as narcissists greatly oversimplifies their lives and struggles; it devalues their years of love and dedication, however flawed; and it weakens the fabric of connection that could otherwise exist. Rather than provide a path toward compassion or understanding, “narcissistic mother” just becomes the latest form of mommy shaming.

Dr. Coleman is a clinical psychologist and author of “Rules of Estrangement: Why Adult Children Cut Ties and How to Heal the Conflict” (New York: Penguin Random House, 2021). Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University in Baltimore.

WASHINGTON –  Posttraumatic stress disorder (PTSD) is strongly linked to disordered eating, which in turn, impedes treatment for the anxiety disorder in new findings that underscore the need for better screening of eating disorder impairment (EDI).

“Eating-related and body-image concerns may be more prevalent than we think, and if not considered, these concerns can make psychotherapy treatment less effective,” study author Nick Powers, a doctoral student in clinical psychology, La Salle University, Philadelphia, told this news organization.

Nick Powers

The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Common bedfellows

Although many patients with PTSD also have an eating disorder, they are not always properly assessed for eating pathology and related functional impairment.

Some therapists don’t feel adequately equipped to target eating-related concerns in these patients and so may refer them to other providers. This, said Mr. Powers, can prolong symptoms and further distress patients.

Mr. Powers noted childhood physical or sexual abuse may affect eating patterns in patients with PTSD. “The evidence suggests these types of trauma exposure can be risk factors for the development of an eating disorder.”

Undiagnosed eating pathology may exacerbate functional impairment from PTSD and weaken the impact of evidence-based treatment.

Such patients are challenging to treat as they may not have the requisite skills to fully engage in exposure therapy, an evidence-based approach to treat PTSD, said Mr. Powers.

To determine whether PTSD would be significantly linked to greater eating disorder impairment (EDI) compared with other anxiety-related diagnoses and whether this would impair treatment, investigators studied 748 patients with an anxiety disorder who were attending a cognitive behavioral therapy (CBT) clinic. Anxiety disorders included PTSD, obsessive-compulsive disorder (OCD), social anxiety, and panic disorder.

Participants completed the 16-item Clinical Impairment Assessment (CIA) questionnaire, which includes questions about eating habits and feelings about food, body shape, and weight over the previous 4 weeks. Participants also reported anxiety symptom severity at the beginning, during, and end of treatment.
 

Need for better screening

Results showed that compared with those who had other anxiety disorders, patients with PTSD were three times more likely to have disordered eating (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.47-6.37; P = .003).

In addition, higher baseline CIA scores predicted poorer PTSD treatment outcome (beta = –1.4; 95% CI, –1.67 to –1.10; P < .01).

“Having higher baseline CIA scores meant that patients’ PTSD symptoms did not remit as strongly compared to those with lower scores,” said Mr. Powers.

Patients with both PTSD and an eating disorder may have difficulty with regulating emotions and tolerating distress, he said.

“They may use binge eating, purging, or food restriction as strategies to regulate emotions. These behaviors may allow patients to become numb to or avoid heightened emotions that come from having PTSD and an eating disorder.”

Prior research linked perfectionism tendencies to poorer response to PTSD treatment. Those with an eating disorder may share similar tendencies, said Mr. Powers.

“If someone is consistently thinking negatively about their eating or body to the point where it interrupts their functioning, they may not be as likely to fully engage with PTSD treatment,” he said.

Ideally, clinicians would screen all patients with PTSD for an eating disorder, said Mr. Powers. “If screening instruments aren’t feasible or available, even just inquiring about body image or history of maladaptive eating behaviors can be helpful.”

He added this could open up a conversation about a traumatic event in the patient’s past.
 

Confirmatory research

Commenting on the study, Karen S. Mitchell, PhD, clinical research psychologist, National Center for PTSD, VA Boston Healthcare System, and associate professor in psychiatry, Boston University, said she was “excited” to see this research.

Boston University

“Very few studies have examined the impact of baseline eating disorder symptoms on PTSD treatment outcomes or vice versa,” she said.

The study findings “add to the small but growing body of evidence suggesting that comorbid PTSD and eating disorder symptoms can impact recovery from each disorder,” she said.

She noted the importance of assessing comorbidity in patients presenting for treatment and of addressing comorbidity in both eating disorders and PTSD treatment. “But we need more research on how best to do this.”

Mr. Powers and Dr. Mitchell have reported no relevant financial relationships.
 

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

WASHINGTON –  Posttraumatic stress disorder (PTSD) is strongly linked to disordered eating, which in turn, impedes treatment for the anxiety disorder in new findings that underscore the need for better screening of eating disorder impairment (EDI).

“Eating-related and body-image concerns may be more prevalent than we think, and if not considered, these concerns can make psychotherapy treatment less effective,” study author Nick Powers, a doctoral student in clinical psychology, La Salle University, Philadelphia, told this news organization.

Nick Powers

The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Common bedfellows

Although many patients with PTSD also have an eating disorder, they are not always properly assessed for eating pathology and related functional impairment.

Some therapists don’t feel adequately equipped to target eating-related concerns in these patients and so may refer them to other providers. This, said Mr. Powers, can prolong symptoms and further distress patients.

Mr. Powers noted childhood physical or sexual abuse may affect eating patterns in patients with PTSD. “The evidence suggests these types of trauma exposure can be risk factors for the development of an eating disorder.”

Undiagnosed eating pathology may exacerbate functional impairment from PTSD and weaken the impact of evidence-based treatment.

Such patients are challenging to treat as they may not have the requisite skills to fully engage in exposure therapy, an evidence-based approach to treat PTSD, said Mr. Powers.

To determine whether PTSD would be significantly linked to greater eating disorder impairment (EDI) compared with other anxiety-related diagnoses and whether this would impair treatment, investigators studied 748 patients with an anxiety disorder who were attending a cognitive behavioral therapy (CBT) clinic. Anxiety disorders included PTSD, obsessive-compulsive disorder (OCD), social anxiety, and panic disorder.

Participants completed the 16-item Clinical Impairment Assessment (CIA) questionnaire, which includes questions about eating habits and feelings about food, body shape, and weight over the previous 4 weeks. Participants also reported anxiety symptom severity at the beginning, during, and end of treatment.
 

Need for better screening

Results showed that compared with those who had other anxiety disorders, patients with PTSD were three times more likely to have disordered eating (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.47-6.37; P = .003).

In addition, higher baseline CIA scores predicted poorer PTSD treatment outcome (beta = –1.4; 95% CI, –1.67 to –1.10; P < .01).

“Having higher baseline CIA scores meant that patients’ PTSD symptoms did not remit as strongly compared to those with lower scores,” said Mr. Powers.

Patients with both PTSD and an eating disorder may have difficulty with regulating emotions and tolerating distress, he said.

“They may use binge eating, purging, or food restriction as strategies to regulate emotions. These behaviors may allow patients to become numb to or avoid heightened emotions that come from having PTSD and an eating disorder.”

Prior research linked perfectionism tendencies to poorer response to PTSD treatment. Those with an eating disorder may share similar tendencies, said Mr. Powers.

“If someone is consistently thinking negatively about their eating or body to the point where it interrupts their functioning, they may not be as likely to fully engage with PTSD treatment,” he said.

Ideally, clinicians would screen all patients with PTSD for an eating disorder, said Mr. Powers. “If screening instruments aren’t feasible or available, even just inquiring about body image or history of maladaptive eating behaviors can be helpful.”

He added this could open up a conversation about a traumatic event in the patient’s past.
 

Confirmatory research

Commenting on the study, Karen S. Mitchell, PhD, clinical research psychologist, National Center for PTSD, VA Boston Healthcare System, and associate professor in psychiatry, Boston University, said she was “excited” to see this research.

Boston University

“Very few studies have examined the impact of baseline eating disorder symptoms on PTSD treatment outcomes or vice versa,” she said.

The study findings “add to the small but growing body of evidence suggesting that comorbid PTSD and eating disorder symptoms can impact recovery from each disorder,” she said.

She noted the importance of assessing comorbidity in patients presenting for treatment and of addressing comorbidity in both eating disorders and PTSD treatment. “But we need more research on how best to do this.”

Mr. Powers and Dr. Mitchell have reported no relevant financial relationships.
 

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

WASHINGTON –  Posttraumatic stress disorder (PTSD) is strongly linked to disordered eating, which in turn, impedes treatment for the anxiety disorder in new findings that underscore the need for better screening of eating disorder impairment (EDI).

“Eating-related and body-image concerns may be more prevalent than we think, and if not considered, these concerns can make psychotherapy treatment less effective,” study author Nick Powers, a doctoral student in clinical psychology, La Salle University, Philadelphia, told this news organization.

Nick Powers

The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

Common bedfellows

Although many patients with PTSD also have an eating disorder, they are not always properly assessed for eating pathology and related functional impairment.

Some therapists don’t feel adequately equipped to target eating-related concerns in these patients and so may refer them to other providers. This, said Mr. Powers, can prolong symptoms and further distress patients.

Mr. Powers noted childhood physical or sexual abuse may affect eating patterns in patients with PTSD. “The evidence suggests these types of trauma exposure can be risk factors for the development of an eating disorder.”

Undiagnosed eating pathology may exacerbate functional impairment from PTSD and weaken the impact of evidence-based treatment.

Such patients are challenging to treat as they may not have the requisite skills to fully engage in exposure therapy, an evidence-based approach to treat PTSD, said Mr. Powers.

To determine whether PTSD would be significantly linked to greater eating disorder impairment (EDI) compared with other anxiety-related diagnoses and whether this would impair treatment, investigators studied 748 patients with an anxiety disorder who were attending a cognitive behavioral therapy (CBT) clinic. Anxiety disorders included PTSD, obsessive-compulsive disorder (OCD), social anxiety, and panic disorder.

Participants completed the 16-item Clinical Impairment Assessment (CIA) questionnaire, which includes questions about eating habits and feelings about food, body shape, and weight over the previous 4 weeks. Participants also reported anxiety symptom severity at the beginning, during, and end of treatment.
 

Need for better screening

Results showed that compared with those who had other anxiety disorders, patients with PTSD were three times more likely to have disordered eating (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.47-6.37; P = .003).

In addition, higher baseline CIA scores predicted poorer PTSD treatment outcome (beta = –1.4; 95% CI, –1.67 to –1.10; P < .01).

“Having higher baseline CIA scores meant that patients’ PTSD symptoms did not remit as strongly compared to those with lower scores,” said Mr. Powers.

Patients with both PTSD and an eating disorder may have difficulty with regulating emotions and tolerating distress, he said.

“They may use binge eating, purging, or food restriction as strategies to regulate emotions. These behaviors may allow patients to become numb to or avoid heightened emotions that come from having PTSD and an eating disorder.”

Prior research linked perfectionism tendencies to poorer response to PTSD treatment. Those with an eating disorder may share similar tendencies, said Mr. Powers.

“If someone is consistently thinking negatively about their eating or body to the point where it interrupts their functioning, they may not be as likely to fully engage with PTSD treatment,” he said.

Ideally, clinicians would screen all patients with PTSD for an eating disorder, said Mr. Powers. “If screening instruments aren’t feasible or available, even just inquiring about body image or history of maladaptive eating behaviors can be helpful.”

He added this could open up a conversation about a traumatic event in the patient’s past.
 

Confirmatory research

Commenting on the study, Karen S. Mitchell, PhD, clinical research psychologist, National Center for PTSD, VA Boston Healthcare System, and associate professor in psychiatry, Boston University, said she was “excited” to see this research.

Boston University

“Very few studies have examined the impact of baseline eating disorder symptoms on PTSD treatment outcomes or vice versa,” she said.

The study findings “add to the small but growing body of evidence suggesting that comorbid PTSD and eating disorder symptoms can impact recovery from each disorder,” she said.

She noted the importance of assessing comorbidity in patients presenting for treatment and of addressing comorbidity in both eating disorders and PTSD treatment. “But we need more research on how best to do this.”

Mr. Powers and Dr. Mitchell have reported no relevant financial relationships.
 

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

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.

The differences between patients who have PsA with axial involvement (AxPsA) and patients who have axial spondyloarthritis with psoriasis (AxSpA+PsO) continue to remain a strong area of interest. Regierer and colleagues recently compared 359 patients with AxPsA vs 181 patients with AxSpA+PsO. These patients were enrolled into the RABBIT-SpA prospective longitudinal cohort study. Given the lack of definition of AxPsA, two definitions were used: 1) clinical judgment by the rheumatologist and 2) imaging (x-ray or MRI) findings. Regardless of clinical or imaging definition used, compared with patients who have AxSpA+PsO those with AxPsA were significantly more often women, were older, were less often HLA-B27 positive, and had more frequent peripheral manifestations but less frequent uveitis. The two diseases thus have significant differences; these should be carefully considered while making treatment decisions.

Another major research focus is on the influence of sex on PsA treatment response. Eder and colleagues conducted a post hoc analysis of pooled data from phase 3 randomized controlled trials that included 816 patients with PsA who received tofacitinib, adalimumab, or placebo. They demonstrate that at 3 months, tofacitinib was more efficacious than placebo, irrespective of sex. However, a higher proportion of men vs women receiving tofacitinib achieved minimal disease activity. This might be due to baseline differences in disease activity. The American College of Rheumatology 20/50/70 response rates were comparable. The incidence of treatment-emergent adverse events was similar in men and women receiving tofacitinib. Thus, sex significantly influences achieving low disease state. Understanding the mechanisms underlying sex differences will help improve treatment response rates in women with PsA.

Atherosclerotic vascular disease (ASVD) is an important comorbidity of PsA. Predicting ASVD remains difficult. The triglyceride-glucose (TyG) index — calculated as ln[fasting triglycerides (in mg/dL) × fasting glucose (in mg/dL)/2] — was recently identified as a marker of insulin resistance and ASVD. Xie and colleagues conducted a cross-sectional study in 165 patients with PsA who underwent carotid ultrasound and had data available for the TyG index. In a model that was adjusted for age, sex, comorbidities, smoking, BMI, low-density lipoprotein cholesterol, psoriasis area and severity index, and disease activity index for PsA, the TyG index was significantly associated with the presence of carotid atherosclerosis (adjusted odds ratio [aOR] 2.69; 95% CI 1.02-7.11) as well as carotid artery plaque (aOR 3.61; 95% CI 1.15-11.38). Thus, this easily calculated marker is associated with ASVD independent of demographic, traditional risk factors, and disease activity and needs further evaluation in prospective studies.

BOSTON – Atogepant helped reduce the number of mean migraine days among adults with episodic migraine who failed multiple other oral migraine medications, according to findings from a study presented at the 2023 annual meeting of the American Academy of Neurology.

Initial results from the double-blind ELEVATE trial showed the oral atogepant group had significantly fewer mean monthly migraine days (MMD) compared with a placebo group. There was also a significant difference in the number of participants who achieved 50% or greater reduction in the number of mean MMDs and a significant reduction in acute medication use days compared with the placebo group, according to Patricia Pozo-Rosich, MD, PhD, a headache specialist in the neurology department and director of the headache and craniofacial pain clinical unit and the Migraine Adaptive Brain Center at the Vall d’Hebron University Hospital in Barcelona, and colleagues.

Vall d’Hebron University Hospital

The oral calcitonin gene-related peptide (CGRP) receptor antagonist is currently approved in the United States by the Food and Drug Administration as a preventative for both episodic and chronic migraine.
 

Results from ELEVATE

Overall, ELEVATE’s initial efficacy analysis population consisted of 309 adults aged between 18 and 80 years from North America and Europe with episodic migraine who had 4-14 MMDs and had treatment failure with at least two classes of conventional oral medication. After a 28-day screening period, participants received either 60 mg of oral atogepant once per day (154 participants) or a placebo (155 participants). In the efficacy analysis population, 56.0% of participants had failed two oral migraine preventative medication classes, while 44.0% failed three or more classes of medication. Dr. Pozo-Rosich noted that participants were taking a number of different oral preventatives across different medication classes, including flunarizine, beta blockers, topiramate, and amitriptyline, but data are not yet available on which participants had received certain combinations of oral medications.

“[T]hese people have already taken some type of prevention, so they’re not naive patients,” she said. “They’re usually more or less well treated in the sense of having had a contact with specialists or a general neurologist, someone that actually tries to do some prevention.”

The researchers examined change from MMDs at baseline and at 12 weeks as a primary outcome, with 50% or greater MMD reduction, change in mean monthly headache days, and change in acute medication use days as secondary outcomes. Regarding the different acute medications used, Dr. Pozo-Rosich said the main three types were analgesics, nonsteroid anti-inflammatory drugs, and triptans, with participants excluded from the trial if they were taking opioids.

The results showed participants in the atogepant group had significantly fewer mean MMDs compared with the placebo group at 12 weeks compared with baseline (–4.20 vs. –1.85 days; P < .0001). Researchers also found statistically significant improvement in the atogepant group for 50% or greater reduction in MMD, change in mean monthly headache days, and change in acute medication use days across 12 weeks of treatment compared with the placebo group. While the specific data analyses for secondary outcomes were not conducted in the initial analysis, Dr. Pozo-Rosich said the numbers “correlate with the primary outcome” as seen in other migraine trials.

Compared with the placebo group, participants in the atogepant group had higher rates of constipation (10.3% vs. 2.5%), COVID-19 (9.6% vs. 8.3%), and nausea (7.1% vs. 3.2%), while the placebo group had a higher rate of nasopharyngitis (5.1% vs. 7.6%).*

Migraine is a prevalent and undertreated disease, and patients around the world with migraine are in need of treatment options that are both safe and effective, Dr. Pozo-Rosich said in an interview. “[E]ven in these hard-to-treat or difficult-to-treat migraine patients, you have a drug that works, and is safe, and well tolerated and effective,” she said.

That’s “kind of good news for all of us,” she said. Patients “need this type of good news and solution,” she explained, because they may not tolerate or have access to injectable medications. Atogepant would also give clinicians have another option to offer patients with difficult-to-treat migraine cases, she noted. “It makes life easier for many physicians and many patients for many different reasons,” she said.

Dr. Pozo-Rosich said the likely next step in the research is to conduct the main analysis as well as post hoc analyses with accumulated data from pathology trials “to understand patterns of response, understand the sustainability of the response, [and] adherence to the treatment in the long term.”
 

‘Exciting that it works well’ in difficult-to-treat patients

Commenting on the study, Alan M. Rapoport, MD, clinical professor of neurology at University of California, Los Angeles, and past president of the International Headache Society, agreed that better options in migraine treatment and prevention are needed.

“We needed something that was going to be better than what we had before,” he said.

Dr. Rapoport noted the study was well designed with strongly positive results. “It looks like it’s an effective drug, and it looks really good in that it’s effective for people that have failed all these preventives that have very little hope for the future,” he said.

He specifically praised the inclusion of older participants in the population. “You never see a study on 80-year-olds,” he said, “but I like that, because they felt it would be safe. There are 80-year-old patients – fewer of them than 40-year-old patients – but there are 80-year-old patients who still have migraine, so I’m really glad they put older patients in it,” he said.

For atogepant, he noted that “some patients won’t get the side effects, and some patients will tolerate the side effects because it’s working really well.” While the study was not a head-to-head comparison against other oral migraine preventatives, he pointed out the high rate of constipation among participants in the trial setting may be a warning sign of future issues, as seen with other CGRP receptor agonists.

“I can tell you that with erenumab, the monoclonal antibody that was injected in the double-blind studies, they didn’t find any significant increase in constipation,” he explained. However, some clinicians using erenumab in the real world have reported up to 20% of their patients are constipated. “It’s not good that they’re reporting 10% are constipated” in the study, he said.

Overall, “all you can really say is it does work well,” Dr. Rapoport said. “It’s exciting that it works well in such difficult-to-treat patients, and it does come with some side effects.”

Dr. Pozo-Rosich reports serving as a consultant and developing education materials for AbbVie, Eli Lilly, Novartis, Teva Pharmaceuticals, and Pfizer. Dr. Rapoport is the editor-in-chief of Neurology Reviews; he reports being a consultant for AbbVie, the developer of atogepant. The ELEVATE trial is supported by AbbVie.

*Correction, 5/4/23: An earlier version of this article misstated the percentage of COVID-positive patients in the study population. 

BOSTON – Atogepant helped reduce the number of mean migraine days among adults with episodic migraine who failed multiple other oral migraine medications, according to findings from a study presented at the 2023 annual meeting of the American Academy of Neurology.

Initial results from the double-blind ELEVATE trial showed the oral atogepant group had significantly fewer mean monthly migraine days (MMD) compared with a placebo group. There was also a significant difference in the number of participants who achieved 50% or greater reduction in the number of mean MMDs and a significant reduction in acute medication use days compared with the placebo group, according to Patricia Pozo-Rosich, MD, PhD, a headache specialist in the neurology department and director of the headache and craniofacial pain clinical unit and the Migraine Adaptive Brain Center at the Vall d’Hebron University Hospital in Barcelona, and colleagues.

Vall d’Hebron University Hospital

The oral calcitonin gene-related peptide (CGRP) receptor antagonist is currently approved in the United States by the Food and Drug Administration as a preventative for both episodic and chronic migraine.
 

Results from ELEVATE

Overall, ELEVATE’s initial efficacy analysis population consisted of 309 adults aged between 18 and 80 years from North America and Europe with episodic migraine who had 4-14 MMDs and had treatment failure with at least two classes of conventional oral medication. After a 28-day screening period, participants received either 60 mg of oral atogepant once per day (154 participants) or a placebo (155 participants). In the efficacy analysis population, 56.0% of participants had failed two oral migraine preventative medication classes, while 44.0% failed three or more classes of medication. Dr. Pozo-Rosich noted that participants were taking a number of different oral preventatives across different medication classes, including flunarizine, beta blockers, topiramate, and amitriptyline, but data are not yet available on which participants had received certain combinations of oral medications.

“[T]hese people have already taken some type of prevention, so they’re not naive patients,” she said. “They’re usually more or less well treated in the sense of having had a contact with specialists or a general neurologist, someone that actually tries to do some prevention.”

The researchers examined change from MMDs at baseline and at 12 weeks as a primary outcome, with 50% or greater MMD reduction, change in mean monthly headache days, and change in acute medication use days as secondary outcomes. Regarding the different acute medications used, Dr. Pozo-Rosich said the main three types were analgesics, nonsteroid anti-inflammatory drugs, and triptans, with participants excluded from the trial if they were taking opioids.

The results showed participants in the atogepant group had significantly fewer mean MMDs compared with the placebo group at 12 weeks compared with baseline (–4.20 vs. –1.85 days; P < .0001). Researchers also found statistically significant improvement in the atogepant group for 50% or greater reduction in MMD, change in mean monthly headache days, and change in acute medication use days across 12 weeks of treatment compared with the placebo group. While the specific data analyses for secondary outcomes were not conducted in the initial analysis, Dr. Pozo-Rosich said the numbers “correlate with the primary outcome” as seen in other migraine trials.

Compared with the placebo group, participants in the atogepant group had higher rates of constipation (10.3% vs. 2.5%), COVID-19 (9.6% vs. 8.3%), and nausea (7.1% vs. 3.2%), while the placebo group had a higher rate of nasopharyngitis (5.1% vs. 7.6%).*

Migraine is a prevalent and undertreated disease, and patients around the world with migraine are in need of treatment options that are both safe and effective, Dr. Pozo-Rosich said in an interview. “[E]ven in these hard-to-treat or difficult-to-treat migraine patients, you have a drug that works, and is safe, and well tolerated and effective,” she said.

That’s “kind of good news for all of us,” she said. Patients “need this type of good news and solution,” she explained, because they may not tolerate or have access to injectable medications. Atogepant would also give clinicians have another option to offer patients with difficult-to-treat migraine cases, she noted. “It makes life easier for many physicians and many patients for many different reasons,” she said.

Dr. Pozo-Rosich said the likely next step in the research is to conduct the main analysis as well as post hoc analyses with accumulated data from pathology trials “to understand patterns of response, understand the sustainability of the response, [and] adherence to the treatment in the long term.”
 

‘Exciting that it works well’ in difficult-to-treat patients

Commenting on the study, Alan M. Rapoport, MD, clinical professor of neurology at University of California, Los Angeles, and past president of the International Headache Society, agreed that better options in migraine treatment and prevention are needed.

“We needed something that was going to be better than what we had before,” he said.

Dr. Rapoport noted the study was well designed with strongly positive results. “It looks like it’s an effective drug, and it looks really good in that it’s effective for people that have failed all these preventives that have very little hope for the future,” he said.

He specifically praised the inclusion of older participants in the population. “You never see a study on 80-year-olds,” he said, “but I like that, because they felt it would be safe. There are 80-year-old patients – fewer of them than 40-year-old patients – but there are 80-year-old patients who still have migraine, so I’m really glad they put older patients in it,” he said.

For atogepant, he noted that “some patients won’t get the side effects, and some patients will tolerate the side effects because it’s working really well.” While the study was not a head-to-head comparison against other oral migraine preventatives, he pointed out the high rate of constipation among participants in the trial setting may be a warning sign of future issues, as seen with other CGRP receptor agonists.

“I can tell you that with erenumab, the monoclonal antibody that was injected in the double-blind studies, they didn’t find any significant increase in constipation,” he explained. However, some clinicians using erenumab in the real world have reported up to 20% of their patients are constipated. “It’s not good that they’re reporting 10% are constipated” in the study, he said.

Overall, “all you can really say is it does work well,” Dr. Rapoport said. “It’s exciting that it works well in such difficult-to-treat patients, and it does come with some side effects.”

Dr. Pozo-Rosich reports serving as a consultant and developing education materials for AbbVie, Eli Lilly, Novartis, Teva Pharmaceuticals, and Pfizer. Dr. Rapoport is the editor-in-chief of Neurology Reviews; he reports being a consultant for AbbVie, the developer of atogepant. The ELEVATE trial is supported by AbbVie.

*Correction, 5/4/23: An earlier version of this article misstated the percentage of COVID-positive patients in the study population. 

BOSTON – Atogepant helped reduce the number of mean migraine days among adults with episodic migraine who failed multiple other oral migraine medications, according to findings from a study presented at the 2023 annual meeting of the American Academy of Neurology.

Initial results from the double-blind ELEVATE trial showed the oral atogepant group had significantly fewer mean monthly migraine days (MMD) compared with a placebo group. There was also a significant difference in the number of participants who achieved 50% or greater reduction in the number of mean MMDs and a significant reduction in acute medication use days compared with the placebo group, according to Patricia Pozo-Rosich, MD, PhD, a headache specialist in the neurology department and director of the headache and craniofacial pain clinical unit and the Migraine Adaptive Brain Center at the Vall d’Hebron University Hospital in Barcelona, and colleagues.

Vall d’Hebron University Hospital

The oral calcitonin gene-related peptide (CGRP) receptor antagonist is currently approved in the United States by the Food and Drug Administration as a preventative for both episodic and chronic migraine.
 

Results from ELEVATE

Overall, ELEVATE’s initial efficacy analysis population consisted of 309 adults aged between 18 and 80 years from North America and Europe with episodic migraine who had 4-14 MMDs and had treatment failure with at least two classes of conventional oral medication. After a 28-day screening period, participants received either 60 mg of oral atogepant once per day (154 participants) or a placebo (155 participants). In the efficacy analysis population, 56.0% of participants had failed two oral migraine preventative medication classes, while 44.0% failed three or more classes of medication. Dr. Pozo-Rosich noted that participants were taking a number of different oral preventatives across different medication classes, including flunarizine, beta blockers, topiramate, and amitriptyline, but data are not yet available on which participants had received certain combinations of oral medications.

“[T]hese people have already taken some type of prevention, so they’re not naive patients,” she said. “They’re usually more or less well treated in the sense of having had a contact with specialists or a general neurologist, someone that actually tries to do some prevention.”

The researchers examined change from MMDs at baseline and at 12 weeks as a primary outcome, with 50% or greater MMD reduction, change in mean monthly headache days, and change in acute medication use days as secondary outcomes. Regarding the different acute medications used, Dr. Pozo-Rosich said the main three types were analgesics, nonsteroid anti-inflammatory drugs, and triptans, with participants excluded from the trial if they were taking opioids.

The results showed participants in the atogepant group had significantly fewer mean MMDs compared with the placebo group at 12 weeks compared with baseline (–4.20 vs. –1.85 days; P < .0001). Researchers also found statistically significant improvement in the atogepant group for 50% or greater reduction in MMD, change in mean monthly headache days, and change in acute medication use days across 12 weeks of treatment compared with the placebo group. While the specific data analyses for secondary outcomes were not conducted in the initial analysis, Dr. Pozo-Rosich said the numbers “correlate with the primary outcome” as seen in other migraine trials.

Compared with the placebo group, participants in the atogepant group had higher rates of constipation (10.3% vs. 2.5%), COVID-19 (9.6% vs. 8.3%), and nausea (7.1% vs. 3.2%), while the placebo group had a higher rate of nasopharyngitis (5.1% vs. 7.6%).*

Migraine is a prevalent and undertreated disease, and patients around the world with migraine are in need of treatment options that are both safe and effective, Dr. Pozo-Rosich said in an interview. “[E]ven in these hard-to-treat or difficult-to-treat migraine patients, you have a drug that works, and is safe, and well tolerated and effective,” she said.

That’s “kind of good news for all of us,” she said. Patients “need this type of good news and solution,” she explained, because they may not tolerate or have access to injectable medications. Atogepant would also give clinicians have another option to offer patients with difficult-to-treat migraine cases, she noted. “It makes life easier for many physicians and many patients for many different reasons,” she said.

Dr. Pozo-Rosich said the likely next step in the research is to conduct the main analysis as well as post hoc analyses with accumulated data from pathology trials “to understand patterns of response, understand the sustainability of the response, [and] adherence to the treatment in the long term.”
 

‘Exciting that it works well’ in difficult-to-treat patients

Commenting on the study, Alan M. Rapoport, MD, clinical professor of neurology at University of California, Los Angeles, and past president of the International Headache Society, agreed that better options in migraine treatment and prevention are needed.

“We needed something that was going to be better than what we had before,” he said.

Dr. Rapoport noted the study was well designed with strongly positive results. “It looks like it’s an effective drug, and it looks really good in that it’s effective for people that have failed all these preventives that have very little hope for the future,” he said.

He specifically praised the inclusion of older participants in the population. “You never see a study on 80-year-olds,” he said, “but I like that, because they felt it would be safe. There are 80-year-old patients – fewer of them than 40-year-old patients – but there are 80-year-old patients who still have migraine, so I’m really glad they put older patients in it,” he said.

For atogepant, he noted that “some patients won’t get the side effects, and some patients will tolerate the side effects because it’s working really well.” While the study was not a head-to-head comparison against other oral migraine preventatives, he pointed out the high rate of constipation among participants in the trial setting may be a warning sign of future issues, as seen with other CGRP receptor agonists.

“I can tell you that with erenumab, the monoclonal antibody that was injected in the double-blind studies, they didn’t find any significant increase in constipation,” he explained. However, some clinicians using erenumab in the real world have reported up to 20% of their patients are constipated. “It’s not good that they’re reporting 10% are constipated” in the study, he said.

Overall, “all you can really say is it does work well,” Dr. Rapoport said. “It’s exciting that it works well in such difficult-to-treat patients, and it does come with some side effects.”

Dr. Pozo-Rosich reports serving as a consultant and developing education materials for AbbVie, Eli Lilly, Novartis, Teva Pharmaceuticals, and Pfizer. Dr. Rapoport is the editor-in-chief of Neurology Reviews; he reports being a consultant for AbbVie, the developer of atogepant. The ELEVATE trial is supported by AbbVie.

*Correction, 5/4/23: An earlier version of this article misstated the percentage of COVID-positive patients in the study population. 

Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.

Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.² A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.

The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.³ A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.

Additional References

1. De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
2. Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
3. Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017

Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.

Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.² A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.

The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.³ A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.

Additional References

1. De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
2. Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
3. Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017

Serrano and colleagues performed a multicenter, double-blind, phase 2b randomized trial investigating various dosing schedules of exemestane (25 mg once daily, three times weekly, or once weekly) for 4-6 weeks before surgery, among 180 postmenopausal women with stage 0-II estrogen receptor–positive breast cancer (BC). Among adherent patients (89% of the population), 25 mg exemestane given three times weekly was noninferior to once-daily dosing in reducing serum estradiol (mean decrease of estradiol, -92% and -91%, respectively; difference in percentage change, 2.0%; P for noninferiority = .02), whereas once-weekly dosing was less effective. Adverse effects were similar, although owing to short exposure in this study, it will be important to explore longer-term differences because aromatase inhibitor–related toxicities may arise later on. These data support further exploration of alternative endocrine therapy schedules in the prevention setting, and also in adjuvant treatment for women who are unable to tolerate the standard dose.

Screening mammography reduces mortality from BC, and advances in techniques, such as digital breast tomosynthesis (DBT), have led to lower recall rates, and higher cancer detection rates compared with digital mammography (DM). Additionally, DBT has demonstrated better cancer detection compared with DM, notably among younger women and those with dense breast tissue.² A retrospective study including over 2.5 million screening mammograms among women 40-79 years of age showed that, compared with DM, DBT had a lower recall rate (10.3% vs 8.9%; adjusted odds ratio [OR] 0.92; P < .001) and higher positive predictive value of recall (4.3% vs 5.9%; adjusted OR 1.33; P < .001), cancer detection rate (4.5 of 1000 vs 5.3 of 1000 screening mammograms; adjusted OR 1.24; P < .001), and biopsy rate (17.6 of 1000 vs 14.5 of 1000 screening mammograms; adjusted OR 1.33, P < .001) (Conant et al). These data add to the growing body of evidence showing superiority in BC screening with DBT vs DM and add support of this technique in routine clinical practice for our patients.

The initial treatment strategy for metastatic hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) BC involves endocrine therapy in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. The three PALOMA trials demonstrated progression-free survival (PFS) benefit with palbociclib plus endocrine therapy, and a pooled analysis of these studies reported consistent improvement in PFS with palbociclib plus endocrine therapy vs endocrine therapy alone in older patients.³ A retrospective study evaluated real-world outcomes of palbociclib plus letrozole vs letrozole alone among 796 women ≥ 65 years of age with HR+/HER- metastatic BC. First-line palbociclib plus letrozole compared with letrozole alone significantly improved median real-world PFS (22.2 vs 15.8 months; adjusted hazard ratio [HR] 0.59; P < .001) and overall survival (not reached vs 43.4 months; adjusted HR 0.55; P < .001). Real-world best tumor response rate was also higher (52.4% vs 22.1%; OR 2.0; P < .001) (Rugo et al). This study highlights the effectiveness of palbociclib plus letrozole in older adults with HR+/HER2- metastatic BC and the benefits of examining a real-world population that adds value to the existing data from randomized clinical trials.

Additional References

1. De Censi A, Lazzeroni M, Puntoni M, et al. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS4-08. https://www.sabcs.org/Portals/SABCS2016/2022%20SABCS/Friday.pdf?ver=2022-11-22-205358-350
2. Conant EF, Barlow WE, Herschorn SD, et al; Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol. 2019;5:635-64 doi: 10.1001/jamaoncol.2018.7078
3. Rugo HS, Turner NC, Finn RS, et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies. Eur J Cancer. 2018;101:123-13 doi: 10.1016/j.ejca.2018.05.017

Torrelo and colleagues described the efficacy and safety of baricitinib in combination with topical corticosteroids in pediatric patients with moderate to severe atopic dermatitis. At the high dose of 4 mg daily, the IGA success rate was about 40%, similar to what we expect for adults treated with dupilumab and less than what we might expect with upadacitinib.

Studies have already been done on efficacy and safety of baricitinib in adults with atopic dermatitis. But baricitinib is indicated for the treatment of adult patients with severe alopecia areata and is not currently indicated as a treatment for anyone with atopic dermatitis, at least not in the United States. At this time, I think the most useful aspect of Torrelo and colleagues' findings is being able to tell our adult patients with alopecia areata that baricitinib was safe enough that they could test it in children as young as 2 years old with eczema.

Perälä and colleagues' report comparing topical tacrolimus and topical corticosteroids (1% hydrocortisone acetate or, if needed, 0.1% hydrocortisone butyrate ointment) in young children with atopic dermatitis is fascinating. They saw patients back at 1 week and followed them for 3 years. In just 1 week, both groups had massive and similar improvement in their atopic dermatitis, and that improvement continued throughout the study. Here are some take-home points:

• Atopic dermatitis responds rapidly to low-to-medium–strength topical steroids.
• Bringing patients back at 1 week may have been a critical aspect of this study, as adherence to topicals can be abysmal; bringing patients back at 1 week probably enables them to use their treatment much better than they would otherwise.
• If we need a nonsteroidal topical, we have an excellent one available at low cost in the form of topical tacrolimus.

Perälä and colleagues also did this study to see whether good treatment of atopic dermatitis in these young children would have long-term benefits on atopic airway issues. Because the researchers didn't have a placebo group (and considered it unethical to have one), we cannot tell whether the topical treatment provided any benefit in that regard.

Yamamoto-Hanada and colleaguesexamined whether "enhanced" topical steroid treatment would prevent food allergy in children with eczema compared with standard topical steroid treatment. Perhaps a better word than "enhanced" would be "aggressive." The enhanced treatment entailed having infants receive alclometasone dipropionate for the whole face and betamethasone valerate for the whole body except face and scalp. While the researchers saw a reduction in egg allergy (from roughly 40% to 30%), they also saw reduced body weight and height. A key take-home message is that with extensive use of topical steroids, we can see systemic effects.

Torrelo and colleagues described the efficacy and safety of baricitinib in combination with topical corticosteroids in pediatric patients with moderate to severe atopic dermatitis. At the high dose of 4 mg daily, the IGA success rate was about 40%, similar to what we expect for adults treated with dupilumab and less than what we might expect with upadacitinib.

Studies have already been done on efficacy and safety of baricitinib in adults with atopic dermatitis. But baricitinib is indicated for the treatment of adult patients with severe alopecia areata and is not currently indicated as a treatment for anyone with atopic dermatitis, at least not in the United States. At this time, I think the most useful aspect of Torrelo and colleagues' findings is being able to tell our adult patients with alopecia areata that baricitinib was safe enough that they could test it in children as young as 2 years old with eczema.

Perälä and colleagues' report comparing topical tacrolimus and topical corticosteroids (1% hydrocortisone acetate or, if needed, 0.1% hydrocortisone butyrate ointment) in young children with atopic dermatitis is fascinating. They saw patients back at 1 week and followed them for 3 years. In just 1 week, both groups had massive and similar improvement in their atopic dermatitis, and that improvement continued throughout the study. Here are some take-home points:

• Atopic dermatitis responds rapidly to low-to-medium–strength topical steroids.
• Bringing patients back at 1 week may have been a critical aspect of this study, as adherence to topicals can be abysmal; bringing patients back at 1 week probably enables them to use their treatment much better than they would otherwise.
• If we need a nonsteroidal topical, we have an excellent one available at low cost in the form of topical tacrolimus.

Perälä and colleagues also did this study to see whether good treatment of atopic dermatitis in these young children would have long-term benefits on atopic airway issues. Because the researchers didn't have a placebo group (and considered it unethical to have one), we cannot tell whether the topical treatment provided any benefit in that regard.

Yamamoto-Hanada and colleaguesexamined whether "enhanced" topical steroid treatment would prevent food allergy in children with eczema compared with standard topical steroid treatment. Perhaps a better word than "enhanced" would be "aggressive." The enhanced treatment entailed having infants receive alclometasone dipropionate for the whole face and betamethasone valerate for the whole body except face and scalp. While the researchers saw a reduction in egg allergy (from roughly 40% to 30%), they also saw reduced body weight and height. A key take-home message is that with extensive use of topical steroids, we can see systemic effects.

Torrelo and colleagues described the efficacy and safety of baricitinib in combination with topical corticosteroids in pediatric patients with moderate to severe atopic dermatitis. At the high dose of 4 mg daily, the IGA success rate was about 40%, similar to what we expect for adults treated with dupilumab and less than what we might expect with upadacitinib.

Studies have already been done on efficacy and safety of baricitinib in adults with atopic dermatitis. But baricitinib is indicated for the treatment of adult patients with severe alopecia areata and is not currently indicated as a treatment for anyone with atopic dermatitis, at least not in the United States. At this time, I think the most useful aspect of Torrelo and colleagues' findings is being able to tell our adult patients with alopecia areata that baricitinib was safe enough that they could test it in children as young as 2 years old with eczema.

Perälä and colleagues' report comparing topical tacrolimus and topical corticosteroids (1% hydrocortisone acetate or, if needed, 0.1% hydrocortisone butyrate ointment) in young children with atopic dermatitis is fascinating. They saw patients back at 1 week and followed them for 3 years. In just 1 week, both groups had massive and similar improvement in their atopic dermatitis, and that improvement continued throughout the study. Here are some take-home points:

• Atopic dermatitis responds rapidly to low-to-medium–strength topical steroids.
• Bringing patients back at 1 week may have been a critical aspect of this study, as adherence to topicals can be abysmal; bringing patients back at 1 week probably enables them to use their treatment much better than they would otherwise.
• If we need a nonsteroidal topical, we have an excellent one available at low cost in the form of topical tacrolimus.

Perälä and colleagues also did this study to see whether good treatment of atopic dermatitis in these young children would have long-term benefits on atopic airway issues. Because the researchers didn't have a placebo group (and considered it unethical to have one), we cannot tell whether the topical treatment provided any benefit in that regard.

Yamamoto-Hanada and colleaguesexamined whether "enhanced" topical steroid treatment would prevent food allergy in children with eczema compared with standard topical steroid treatment. Perhaps a better word than "enhanced" would be "aggressive." The enhanced treatment entailed having infants receive alclometasone dipropionate for the whole face and betamethasone valerate for the whole body except face and scalp. While the researchers saw a reduction in egg allergy (from roughly 40% to 30%), they also saw reduced body weight and height. A key take-home message is that with extensive use of topical steroids, we can see systemic effects.

Abdul Moiz Hafiz, MD, was flabbergasted when he received a phone call from his institution’s credentialing office telling him that he was not certified for interventional cardiology – even though he had passed that exam in 2016.

Dr. Hafiz, who directs the Advanced Structural Heart Disease Program at Southern Illinois University, phoned the American Board of Internal Medicine (ABIM), where he learned that to restore his credentials, he would need to pay $1,225 in maintenance of certification (MOC) fees.

Like Dr. Hafiz, many physicians have been dismayed to learn that the ABIM is now listing as “not certified” physicians who have passed board exams but have not paid annual MOC fees of $220 per year for the first certificate and $120 for each additional certificate.

Even doctors who are participating in mandatory continuing education outside the ABIM’s auspices are finding themselves listed as “not certified.” Some physicians learned of the policy change only after applying for hospital privileges or for jobs that require ABIM certification.

Now that increasing numbers of physicians are employed by hospitals and health care organizations that require ABIM certification, many doctors have no option but to pony up the fees if they want to continue to practice medicine.

“We have no say in the matter,” said Dr. Hafiz, “and there’s no appeal process.”

The change affects nearly 330,000 physicians. Responses to the policy on Twitter included accusations of extortion and denunciations of the ABIM’s “money grab policies.”

Sunil Rao, MD, director of interventional cardiology at NYU Langone Health and president of the Society for Cardiovascular Angiography and Interventions (SCAI), has heard from many SCAI members who had experiences similar to Dr. Hafiz’s. While Dr. Rao describes some of the Twitter outrage as “emotional,” he does acknowledge that the ABIM’s moves appear to be financially motivated.

“The issue here was that as soon as they paid the fee, all of a sudden, ABIM flipped the switch and said they were certified,” he said. “It certainly sounds like a purely financial kind of structure.”

Richard Baron, MD, president and CEO of the ABIM, said doctors are misunderstanding the policy change.

“No doctor loses certification solely for failure to pay fees,” Dr. Baron told this news organization. “What caused them to be reported as not certified was that we didn’t have evidence that they had met program requirements. They could say, ‘But I did meet program requirements, you just didn’t know it.’ To which our answer would be, for us to know it, we have to process them. And our policy is that we don’t process them unless you are current on your fees.”

This is not the first time ABIM policies have alienated physicians.

Last year, the ABIM raised its MOC fees from $165 to $220. That also prompted a wave of outrage. Other grievances go further back. At one time, being board certified was a lifetime credential. However, in 1990 the ABIM made periodic recertification mandatory.

The process, which came to be known as “maintenance of certification,” had to be completed every 10 years, and fees were charged for each certification. At that point, said Dr. Baron, the relationship between the ABIM and physicians changed from a one-time interaction to a career-long relationship. He advises doctors to check in periodically on their portal page at the ABIM or download the app so they will always know their status.

Many physicians would prefer not to be bound to a lifetime relationship with the ABIM. There is an alternative licensing board, the National Board of Physicians and Surgeons (NBPAS), but it is accepted by only a limited number of hospitals.

“Until the NBPAS gains wide recognition,” said Dr. Hafiz, “the ABIM is going to continue to have basically a monopoly over the market.”

The value of MOC itself has been called into question. “There are no direct data supporting the value of the MOC process in either improving care, making patient care safer, or making patient care higher quality,” said Dr. Rao. This feeds frustration in a clinical community already dealing with onerous training requirements and expensive board certification exams and adds to the perception that it is a purely financial transaction, he said. (Studies examining whether the MOC system improves patient care have shown mixed results.)

The true value of the ABIM to physicians, Dr. Baron contends, is that the organization is an independent third party that differentiates those doctors from people who don’t have their skills, training, and expertise. “In these days, where anyone can be an ‘expert’ on the Internet, that’s more valuable than ever before,” he said.
 

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

Abdul Moiz Hafiz, MD, was flabbergasted when he received a phone call from his institution’s credentialing office telling him that he was not certified for interventional cardiology – even though he had passed that exam in 2016.

Dr. Hafiz, who directs the Advanced Structural Heart Disease Program at Southern Illinois University, phoned the American Board of Internal Medicine (ABIM), where he learned that to restore his credentials, he would need to pay $1,225 in maintenance of certification (MOC) fees.

Like Dr. Hafiz, many physicians have been dismayed to learn that the ABIM is now listing as “not certified” physicians who have passed board exams but have not paid annual MOC fees of $220 per year for the first certificate and $120 for each additional certificate.

Even doctors who are participating in mandatory continuing education outside the ABIM’s auspices are finding themselves listed as “not certified.” Some physicians learned of the policy change only after applying for hospital privileges or for jobs that require ABIM certification.

Now that increasing numbers of physicians are employed by hospitals and health care organizations that require ABIM certification, many doctors have no option but to pony up the fees if they want to continue to practice medicine.

“We have no say in the matter,” said Dr. Hafiz, “and there’s no appeal process.”

The change affects nearly 330,000 physicians. Responses to the policy on Twitter included accusations of extortion and denunciations of the ABIM’s “money grab policies.”

Sunil Rao, MD, director of interventional cardiology at NYU Langone Health and president of the Society for Cardiovascular Angiography and Interventions (SCAI), has heard from many SCAI members who had experiences similar to Dr. Hafiz’s. While Dr. Rao describes some of the Twitter outrage as “emotional,” he does acknowledge that the ABIM’s moves appear to be financially motivated.

“The issue here was that as soon as they paid the fee, all of a sudden, ABIM flipped the switch and said they were certified,” he said. “It certainly sounds like a purely financial kind of structure.”

Richard Baron, MD, president and CEO of the ABIM, said doctors are misunderstanding the policy change.

“No doctor loses certification solely for failure to pay fees,” Dr. Baron told this news organization. “What caused them to be reported as not certified was that we didn’t have evidence that they had met program requirements. They could say, ‘But I did meet program requirements, you just didn’t know it.’ To which our answer would be, for us to know it, we have to process them. And our policy is that we don’t process them unless you are current on your fees.”

This is not the first time ABIM policies have alienated physicians.

Last year, the ABIM raised its MOC fees from $165 to $220. That also prompted a wave of outrage. Other grievances go further back. At one time, being board certified was a lifetime credential. However, in 1990 the ABIM made periodic recertification mandatory.

The process, which came to be known as “maintenance of certification,” had to be completed every 10 years, and fees were charged for each certification. At that point, said Dr. Baron, the relationship between the ABIM and physicians changed from a one-time interaction to a career-long relationship. He advises doctors to check in periodically on their portal page at the ABIM or download the app so they will always know their status.

Many physicians would prefer not to be bound to a lifetime relationship with the ABIM. There is an alternative licensing board, the National Board of Physicians and Surgeons (NBPAS), but it is accepted by only a limited number of hospitals.

“Until the NBPAS gains wide recognition,” said Dr. Hafiz, “the ABIM is going to continue to have basically a monopoly over the market.”

The value of MOC itself has been called into question. “There are no direct data supporting the value of the MOC process in either improving care, making patient care safer, or making patient care higher quality,” said Dr. Rao. This feeds frustration in a clinical community already dealing with onerous training requirements and expensive board certification exams and adds to the perception that it is a purely financial transaction, he said. (Studies examining whether the MOC system improves patient care have shown mixed results.)

The true value of the ABIM to physicians, Dr. Baron contends, is that the organization is an independent third party that differentiates those doctors from people who don’t have their skills, training, and expertise. “In these days, where anyone can be an ‘expert’ on the Internet, that’s more valuable than ever before,” he said.
 

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

Abdul Moiz Hafiz, MD, was flabbergasted when he received a phone call from his institution’s credentialing office telling him that he was not certified for interventional cardiology – even though he had passed that exam in 2016.

Dr. Hafiz, who directs the Advanced Structural Heart Disease Program at Southern Illinois University, phoned the American Board of Internal Medicine (ABIM), where he learned that to restore his credentials, he would need to pay $1,225 in maintenance of certification (MOC) fees.

Like Dr. Hafiz, many physicians have been dismayed to learn that the ABIM is now listing as “not certified” physicians who have passed board exams but have not paid annual MOC fees of $220 per year for the first certificate and $120 for each additional certificate.

Even doctors who are participating in mandatory continuing education outside the ABIM’s auspices are finding themselves listed as “not certified.” Some physicians learned of the policy change only after applying for hospital privileges or for jobs that require ABIM certification.

Now that increasing numbers of physicians are employed by hospitals and health care organizations that require ABIM certification, many doctors have no option but to pony up the fees if they want to continue to practice medicine.

“We have no say in the matter,” said Dr. Hafiz, “and there’s no appeal process.”

The change affects nearly 330,000 physicians. Responses to the policy on Twitter included accusations of extortion and denunciations of the ABIM’s “money grab policies.”

Sunil Rao, MD, director of interventional cardiology at NYU Langone Health and president of the Society for Cardiovascular Angiography and Interventions (SCAI), has heard from many SCAI members who had experiences similar to Dr. Hafiz’s. While Dr. Rao describes some of the Twitter outrage as “emotional,” he does acknowledge that the ABIM’s moves appear to be financially motivated.

“The issue here was that as soon as they paid the fee, all of a sudden, ABIM flipped the switch and said they were certified,” he said. “It certainly sounds like a purely financial kind of structure.”

Richard Baron, MD, president and CEO of the ABIM, said doctors are misunderstanding the policy change.

“No doctor loses certification solely for failure to pay fees,” Dr. Baron told this news organization. “What caused them to be reported as not certified was that we didn’t have evidence that they had met program requirements. They could say, ‘But I did meet program requirements, you just didn’t know it.’ To which our answer would be, for us to know it, we have to process them. And our policy is that we don’t process them unless you are current on your fees.”

This is not the first time ABIM policies have alienated physicians.

Last year, the ABIM raised its MOC fees from $165 to $220. That also prompted a wave of outrage. Other grievances go further back. At one time, being board certified was a lifetime credential. However, in 1990 the ABIM made periodic recertification mandatory.

The process, which came to be known as “maintenance of certification,” had to be completed every 10 years, and fees were charged for each certification. At that point, said Dr. Baron, the relationship between the ABIM and physicians changed from a one-time interaction to a career-long relationship. He advises doctors to check in periodically on their portal page at the ABIM or download the app so they will always know their status.

Many physicians would prefer not to be bound to a lifetime relationship with the ABIM. There is an alternative licensing board, the National Board of Physicians and Surgeons (NBPAS), but it is accepted by only a limited number of hospitals.

“Until the NBPAS gains wide recognition,” said Dr. Hafiz, “the ABIM is going to continue to have basically a monopoly over the market.”

The value of MOC itself has been called into question. “There are no direct data supporting the value of the MOC process in either improving care, making patient care safer, or making patient care higher quality,” said Dr. Rao. This feeds frustration in a clinical community already dealing with onerous training requirements and expensive board certification exams and adds to the perception that it is a purely financial transaction, he said. (Studies examining whether the MOC system improves patient care have shown mixed results.)

The true value of the ABIM to physicians, Dr. Baron contends, is that the organization is an independent third party that differentiates those doctors from people who don’t have their skills, training, and expertise. “In these days, where anyone can be an ‘expert’ on the Internet, that’s more valuable than ever before,” he said.
 

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

“BMI is trash. Full stop.” This controversial tweet, which received thousands of likes and retweets, was cited in a recent article by one doctor on when physicians might stop using body mass index (BMI) to diagnose obesity.

BMI has for years been the consensus default method for assessing whether a person is overweight or has obesity, and is still widely used as the gatekeeper metric for treatment eligibility for certain weight-loss agents and bariatric surgery.

But growing appreciation of the limitations of BMI is causing many clinicians to consider alternative measures of obesity that can better assess both the amount of adiposity as well as its body location, an important determinant of the cardiometabolic consequences of fat.

Alternative metrics include waist circumference and/or waist-to-height ratio (WHtR); imaging methods such as CT, MRI, and dual-energy x-ray absorptiometry (DXA); and bioelectrical impedance to assess fat volume and location. All have made some inroads on the tight grip BMI has had on obesity assessment.

Chances are, however, that BMI will not fade away anytime soon given how entrenched it has become in clinical practice and for insurance coverage, as well as its relative simplicity and precision.

“BMI is embedded in a wide range of guidelines on the use of medications and surgery. It’s embedded in Food and Drug Administration regulations and for billing and insurance coverage. It would take extremely strong data and years of work to undo the infrastructure built around BMI and replace it with something else. I don’t see that happening [anytime soon],” commented Daniel H. Bessesen, MD, a professor at the University of Colorado at Denver, Aurora, and chief of endocrinology for Denver Health.

“It would be almost impossible to replace all the studies that have used BMI with investigations using some other measure,” he said.
 

BMI Is ‘imperfect’

The entrenched position of BMI as the go-to metric doesn’t keep detractors from weighing in. As noted in a commentary on current clinical challenges surrounding obesity recently published in Annals of Internal Medicine, the journal’s editor-in-chief, Christine Laine, MD, and senior deputy editor Christina C. Wee, MD, listed six top issues clinicians must deal with, one of which, they say, is the need for a better measure of obesity than BMI.

“Unfortunately, BMI is an imperfect measure of body composition that differs with ethnicity, sex, body frame, and muscle mass,” noted Dr. Laine and Dr. Wee.

BMI is based on a person’s weight in kilograms divided by the square of their height in meters. A “healthy” BMI is between 18.5 and 24.9 kg/m2, overweight is 25-29.9, and 30 or greater is considered to represent obesity. However, certain ethnic groups have lower cutoffs for overweight or obesity because of evidence that such individuals can be at higher risk of obesity-related comorbidities at lower BMIs.

“BMI was chosen as the initial screening tool [for obesity] not because anyone thought it was perfect or the best measure but because of its simplicity. All you need is height, weight, and a calculator,” Dr. Wee said in an interview.

Numerous online calculators are available, including one from the Centers for Disease Control and Prevention where height in feet and inches and weight in pounds can be entered to generate the BMI.

BMI is also inherently limited by being “a proxy for adiposity” and not a direct measure, added Dr. Wee, who is also director of the Obesity Research Program of Beth Israel Deaconess Medical Center, Boston.

As such, BMI can’t distinguish between fat and muscle because it relies on weight only to gauge adiposity, noted Tiffany Powell-Wiley, MD, an obesity researcher at the National Heart, Lung, and Blood Institute in Bethesda, Md. Another shortcoming of BMI is that it “is good for distinguishing population-level risk for cardiovascular disease and other chronic diseases, but it does not help as much for distinguishing risk at an individual level,” she said in an interview.

These and other drawbacks have prompted researchers to look for other useful metrics. WHtR, for example, has recently made headway as a potential BMI alternative or complement.
 

The case for WHtR

Concern about overreliance on BMI despite its limitations is not new. In 2015, an American Heart Association scientific statement from the group’s Obesity Committee concluded that “BMI alone, even with lower thresholds, is a useful but not an ideal tool for identification of obesity or assessment of cardiovascular risk,” especially for people from Asian, Black, Hispanic, and Pacific Islander populations.

The writing panel also recommended that clinicians measure waist circumference annually and use that information along with BMI “to better gauge cardiovascular risk in diverse populations.”

Momentum for moving beyond BMI alone has continued to build following the AHA statement.

In September 2022, the National Institute for Health and Care Excellence, which sets policies for the United Kingdom’s National Health Service, revised its guidancefor assessment and management of people with obesity. The updated guidance recommends that when clinicians assess “adults with BMI below 35 kg/m2, measure and use their WHtR, as well as their BMI, as a practical estimate of central adiposity and use these measurements to help to assess and predict health risks.”

NICE released an extensive literature review with the revision, and based on the evidence, said that “using waist-to-height ratio as well as BMI would help give a practical estimate of central adiposity in adults with BMI under 35 kg/m². This would in turn help professionals assess and predict health risks.”

However, the review added that, “because people with a BMI over 35 kg/m² are always likely to have a high WHtR, the committee recognized that it may not be a useful addition for predicting health risks in this group.” The 2022 NICE review also said that it is “important to estimate central adiposity when assessing future health risks, including for people whose BMI is in the healthy-weight category.”

This new emphasis by NICE on measuring and using WHtR as part of obesity assessment “represents an important change in population health policy,” commented Dr. Powell-Wiley. “I expect more professional organizations will endorse use of waist circumference or waist-to-height ratio now that NICE has taken this step,” she predicted.

Waist circumference and WHtR may become standard measures of adiposity in clinical practice over the next 5-10 years.

The recent move by NICE to highlight a complementary role for WHtR “is another acknowledgment that BMI is an imperfect tool for stratifying cardiometabolic risk in a diverse population, especially in people with lower BMIs” because of its variability, commented Jamie Almandoz, MD, medical director of the weight wellness program at UT Southwestern Medical Center, Dallas.
 

WHtR vs. BMI

Another recent step forward for WHtR came with the publication of a post hoc analysis of data collected in the PARADIGM-HF trial, a study that had the primary purpose of comparing two medications for improving outcomes in more than 8,000 patients with heart failure with reduced ejection fraction.

The new analysis showed that “two indices that incorporate waist circumference and height, but not weight, showed a clearer association between greater adiposity and a higher risk of heart failure hospitalization,” compared with BMI.

WHtR was one of the two indices identified as being a better correlate for the adverse effect of excess adiposity compared with BMI.

The authors of the post hoc analysis did not design their analysis to compare WHtR with BMI. Instead, their goal was to better understand what’s known as the “obesity paradox” in people with heart failure with reduced ejection fraction: The recurring observation that, when these patients with heart failure have lower BMIs they fare worse, with higher rates of mortality and adverse cardiovascular outcomes, compared with patients with higher BMIs.

The new analysis showed that this paradox disappeared when WHtR was substituted for BMI as the obesity metric.

This “provides meaningful data about the superiority of WHtR, compared with BMI, for predicting heart failure outcomes,” said Dr. Powell-Wiley, although she cautioned that the analysis was limited by scant data in diverse populations and did not look at other important cardiovascular disease outcomes. While Dr. Powell-Wiley does not think that WHtR needs assessment in a prospective, controlled trial, she called for analysis of pooled prospective studies with more diverse populations to better document the advantages of WHtR over BMI.

The PARADIGM-HF post hoc analysis shows again how flawed BMI is for health assessment and the relative importance of an individualized understanding of a person’s body composition, Dr. Almandoz said in an interview. “As we collect more data, there is increasing awareness of how imperfect BMI is.”
 

Measuring waist circumference is tricky

Although WHtR looks promising as a substitute for or add-on to BMI, it has its own limitations, particularly the challenge of accurately measuring waist circumference.

Measuring waist circumference “not only takes more time but requires the assessor to be well trained about where to put the tape measure and making sure it’s measured at the same place each time,” even when different people take serial measurements from individual patients, noted Dr. Wee. Determining waist circumference can also be technically difficult when done on larger people, she added, and collectively these challenges make waist circumference “less reproducible from measurement to measurement.”

“It’s relatively clear how to standardize measurement of weight and height, but there is a huge amount of variability when the waist is measured,” agreed Dr. Almandoz. “And waist circumference also differs by ethnicity, race, sex, and body frame. There are significant differences in waist circumference levels that associate with increased health risks” between, for example, White and South Asian people.

Another limitation of waist circumference and WHtR is that they “cannot differentiate between visceral and abdominal subcutaneous adipose tissue, which are vastly different regarding cardiometabolic risk, commented Ian Neeland, MD, director of cardiovascular prevention at the University Hospitals Harrington Heart & Vascular Institute, Cleveland.
 

The imaging option

“Waist-to-height ratio is not the ultimate answer,” Dr. Neeland said in an interview. He instead endorsed “advanced imaging for body fat distribution,” such as CT or MRI scans, as his pick for what should be the standard obesity metric, “given that it is much more specific and actionable for both risk assessment and response to therapy. I expect slow but steady advancements that move away from BMI cutoffs, for example for bariatric surgery, given that BMI is an imprecise and crude tool.”

But although imaging with methods like CT and MRI may provide the best accuracy and precision for tracking the volume of a person’s cardiometabolically dangerous fat, they are also hampered by relatively high cost and, for CT and DXA, the issue of radiation exposure.

“CT, MRI, and DXA scans give more in-depth assessment of body composition, but should we expose people to the radiation and the cost?” Dr. Almandoz wondered.

“Height, weight, and waist circumference cost nothing to obtain,” creating a big relative disadvantage for imaging, said Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow.

“Data would need to show that imaging gives clinicians substantially more information about future risk” to justify its price, Dr. Sattar emphasized.
 

BMI’s limits mean adding on

Regardless of whichever alternatives to BMI end up getting used most, experts generally agree that BMI alone is looking increasingly inadequate.

“Over the next 5 years, BMI will come to be seen as a screening tool that categorizes people into general risk groups” that also needs “other metrics and variables, such as age, race, ethnicity, family history, blood glucose, and blood pressure to better describe health risk in an individual,” predicted Dr. Bessesen.

The endorsement of WHtR by NICE “will lead to more research into how to incorporate WHtR into routine practice. We need more evidence to translate what NICE said into practice,” said Dr. Sattar. “I don’t think we’ll see a shift away from BMI, but we’ll add alternative measures that are particularly useful in certain patients.”

“Because we live in diverse societies, we need to individualize risk assessment and couple that with technology that makes analysis of body composition more accessible,” agreed Dr. Almandoz. He noted that the UT Southwestern weight wellness program where he practices has, for about the past decade, routinely collected waist circumference and bioelectrical impedance data as well as BMI on all people seen in the practice for obesity concerns. Making these additional measurements on a routine basis also helps strengthen patient engagement.

“We get into trouble when we make rigid health policy and clinical decisions based on BMI alone without looking at the patient holistically,” said Dr. Wee. “Patients are more than arbitrary numbers, and clinicians should make clinical decisions based on the totality of evidence for each individual patient.”

Dr. Bessesen, Dr. Wee, Dr. Powell-Wiley, and Dr. Almandoz reported no relevant financial relationships. Dr. Neeland has reported being a consultant for Merck. Dr. Sattar has reported being a consultant or speaker for Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.

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

“BMI is trash. Full stop.” This controversial tweet, which received thousands of likes and retweets, was cited in a recent article by one doctor on when physicians might stop using body mass index (BMI) to diagnose obesity.

BMI has for years been the consensus default method for assessing whether a person is overweight or has obesity, and is still widely used as the gatekeeper metric for treatment eligibility for certain weight-loss agents and bariatric surgery.

But growing appreciation of the limitations of BMI is causing many clinicians to consider alternative measures of obesity that can better assess both the amount of adiposity as well as its body location, an important determinant of the cardiometabolic consequences of fat.

Alternative metrics include waist circumference and/or waist-to-height ratio (WHtR); imaging methods such as CT, MRI, and dual-energy x-ray absorptiometry (DXA); and bioelectrical impedance to assess fat volume and location. All have made some inroads on the tight grip BMI has had on obesity assessment.

Chances are, however, that BMI will not fade away anytime soon given how entrenched it has become in clinical practice and for insurance coverage, as well as its relative simplicity and precision.

“BMI is embedded in a wide range of guidelines on the use of medications and surgery. It’s embedded in Food and Drug Administration regulations and for billing and insurance coverage. It would take extremely strong data and years of work to undo the infrastructure built around BMI and replace it with something else. I don’t see that happening [anytime soon],” commented Daniel H. Bessesen, MD, a professor at the University of Colorado at Denver, Aurora, and chief of endocrinology for Denver Health.

“It would be almost impossible to replace all the studies that have used BMI with investigations using some other measure,” he said.
 

BMI Is ‘imperfect’

The entrenched position of BMI as the go-to metric doesn’t keep detractors from weighing in. As noted in a commentary on current clinical challenges surrounding obesity recently published in Annals of Internal Medicine, the journal’s editor-in-chief, Christine Laine, MD, and senior deputy editor Christina C. Wee, MD, listed six top issues clinicians must deal with, one of which, they say, is the need for a better measure of obesity than BMI.

“Unfortunately, BMI is an imperfect measure of body composition that differs with ethnicity, sex, body frame, and muscle mass,” noted Dr. Laine and Dr. Wee.

BMI is based on a person’s weight in kilograms divided by the square of their height in meters. A “healthy” BMI is between 18.5 and 24.9 kg/m2, overweight is 25-29.9, and 30 or greater is considered to represent obesity. However, certain ethnic groups have lower cutoffs for overweight or obesity because of evidence that such individuals can be at higher risk of obesity-related comorbidities at lower BMIs.

“BMI was chosen as the initial screening tool [for obesity] not because anyone thought it was perfect or the best measure but because of its simplicity. All you need is height, weight, and a calculator,” Dr. Wee said in an interview.

Numerous online calculators are available, including one from the Centers for Disease Control and Prevention where height in feet and inches and weight in pounds can be entered to generate the BMI.

BMI is also inherently limited by being “a proxy for adiposity” and not a direct measure, added Dr. Wee, who is also director of the Obesity Research Program of Beth Israel Deaconess Medical Center, Boston.

As such, BMI can’t distinguish between fat and muscle because it relies on weight only to gauge adiposity, noted Tiffany Powell-Wiley, MD, an obesity researcher at the National Heart, Lung, and Blood Institute in Bethesda, Md. Another shortcoming of BMI is that it “is good for distinguishing population-level risk for cardiovascular disease and other chronic diseases, but it does not help as much for distinguishing risk at an individual level,” she said in an interview.

These and other drawbacks have prompted researchers to look for other useful metrics. WHtR, for example, has recently made headway as a potential BMI alternative or complement.
 

The case for WHtR

Concern about overreliance on BMI despite its limitations is not new. In 2015, an American Heart Association scientific statement from the group’s Obesity Committee concluded that “BMI alone, even with lower thresholds, is a useful but not an ideal tool for identification of obesity or assessment of cardiovascular risk,” especially for people from Asian, Black, Hispanic, and Pacific Islander populations.

The writing panel also recommended that clinicians measure waist circumference annually and use that information along with BMI “to better gauge cardiovascular risk in diverse populations.”

Momentum for moving beyond BMI alone has continued to build following the AHA statement.

In September 2022, the National Institute for Health and Care Excellence, which sets policies for the United Kingdom’s National Health Service, revised its guidancefor assessment and management of people with obesity. The updated guidance recommends that when clinicians assess “adults with BMI below 35 kg/m2, measure and use their WHtR, as well as their BMI, as a practical estimate of central adiposity and use these measurements to help to assess and predict health risks.”

NICE released an extensive literature review with the revision, and based on the evidence, said that “using waist-to-height ratio as well as BMI would help give a practical estimate of central adiposity in adults with BMI under 35 kg/m². This would in turn help professionals assess and predict health risks.”

However, the review added that, “because people with a BMI over 35 kg/m² are always likely to have a high WHtR, the committee recognized that it may not be a useful addition for predicting health risks in this group.” The 2022 NICE review also said that it is “important to estimate central adiposity when assessing future health risks, including for people whose BMI is in the healthy-weight category.”

This new emphasis by NICE on measuring and using WHtR as part of obesity assessment “represents an important change in population health policy,” commented Dr. Powell-Wiley. “I expect more professional organizations will endorse use of waist circumference or waist-to-height ratio now that NICE has taken this step,” she predicted.

Waist circumference and WHtR may become standard measures of adiposity in clinical practice over the next 5-10 years.

The recent move by NICE to highlight a complementary role for WHtR “is another acknowledgment that BMI is an imperfect tool for stratifying cardiometabolic risk in a diverse population, especially in people with lower BMIs” because of its variability, commented Jamie Almandoz, MD, medical director of the weight wellness program at UT Southwestern Medical Center, Dallas.
 

WHtR vs. BMI

Another recent step forward for WHtR came with the publication of a post hoc analysis of data collected in the PARADIGM-HF trial, a study that had the primary purpose of comparing two medications for improving outcomes in more than 8,000 patients with heart failure with reduced ejection fraction.

The new analysis showed that “two indices that incorporate waist circumference and height, but not weight, showed a clearer association between greater adiposity and a higher risk of heart failure hospitalization,” compared with BMI.

WHtR was one of the two indices identified as being a better correlate for the adverse effect of excess adiposity compared with BMI.

The authors of the post hoc analysis did not design their analysis to compare WHtR with BMI. Instead, their goal was to better understand what’s known as the “obesity paradox” in people with heart failure with reduced ejection fraction: The recurring observation that, when these patients with heart failure have lower BMIs they fare worse, with higher rates of mortality and adverse cardiovascular outcomes, compared with patients with higher BMIs.

The new analysis showed that this paradox disappeared when WHtR was substituted for BMI as the obesity metric.

This “provides meaningful data about the superiority of WHtR, compared with BMI, for predicting heart failure outcomes,” said Dr. Powell-Wiley, although she cautioned that the analysis was limited by scant data in diverse populations and did not look at other important cardiovascular disease outcomes. While Dr. Powell-Wiley does not think that WHtR needs assessment in a prospective, controlled trial, she called for analysis of pooled prospective studies with more diverse populations to better document the advantages of WHtR over BMI.

The PARADIGM-HF post hoc analysis shows again how flawed BMI is for health assessment and the relative importance of an individualized understanding of a person’s body composition, Dr. Almandoz said in an interview. “As we collect more data, there is increasing awareness of how imperfect BMI is.”
 

Measuring waist circumference is tricky

Although WHtR looks promising as a substitute for or add-on to BMI, it has its own limitations, particularly the challenge of accurately measuring waist circumference.

Measuring waist circumference “not only takes more time but requires the assessor to be well trained about where to put the tape measure and making sure it’s measured at the same place each time,” even when different people take serial measurements from individual patients, noted Dr. Wee. Determining waist circumference can also be technically difficult when done on larger people, she added, and collectively these challenges make waist circumference “less reproducible from measurement to measurement.”

“It’s relatively clear how to standardize measurement of weight and height, but there is a huge amount of variability when the waist is measured,” agreed Dr. Almandoz. “And waist circumference also differs by ethnicity, race, sex, and body frame. There are significant differences in waist circumference levels that associate with increased health risks” between, for example, White and South Asian people.

Another limitation of waist circumference and WHtR is that they “cannot differentiate between visceral and abdominal subcutaneous adipose tissue, which are vastly different regarding cardiometabolic risk, commented Ian Neeland, MD, director of cardiovascular prevention at the University Hospitals Harrington Heart & Vascular Institute, Cleveland.
 

The imaging option

“Waist-to-height ratio is not the ultimate answer,” Dr. Neeland said in an interview. He instead endorsed “advanced imaging for body fat distribution,” such as CT or MRI scans, as his pick for what should be the standard obesity metric, “given that it is much more specific and actionable for both risk assessment and response to therapy. I expect slow but steady advancements that move away from BMI cutoffs, for example for bariatric surgery, given that BMI is an imprecise and crude tool.”

But although imaging with methods like CT and MRI may provide the best accuracy and precision for tracking the volume of a person’s cardiometabolically dangerous fat, they are also hampered by relatively high cost and, for CT and DXA, the issue of radiation exposure.

“CT, MRI, and DXA scans give more in-depth assessment of body composition, but should we expose people to the radiation and the cost?” Dr. Almandoz wondered.

“Height, weight, and waist circumference cost nothing to obtain,” creating a big relative disadvantage for imaging, said Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow.

“Data would need to show that imaging gives clinicians substantially more information about future risk” to justify its price, Dr. Sattar emphasized.
 

BMI’s limits mean adding on

Regardless of whichever alternatives to BMI end up getting used most, experts generally agree that BMI alone is looking increasingly inadequate.

“Over the next 5 years, BMI will come to be seen as a screening tool that categorizes people into general risk groups” that also needs “other metrics and variables, such as age, race, ethnicity, family history, blood glucose, and blood pressure to better describe health risk in an individual,” predicted Dr. Bessesen.

The endorsement of WHtR by NICE “will lead to more research into how to incorporate WHtR into routine practice. We need more evidence to translate what NICE said into practice,” said Dr. Sattar. “I don’t think we’ll see a shift away from BMI, but we’ll add alternative measures that are particularly useful in certain patients.”

“Because we live in diverse societies, we need to individualize risk assessment and couple that with technology that makes analysis of body composition more accessible,” agreed Dr. Almandoz. He noted that the UT Southwestern weight wellness program where he practices has, for about the past decade, routinely collected waist circumference and bioelectrical impedance data as well as BMI on all people seen in the practice for obesity concerns. Making these additional measurements on a routine basis also helps strengthen patient engagement.

“We get into trouble when we make rigid health policy and clinical decisions based on BMI alone without looking at the patient holistically,” said Dr. Wee. “Patients are more than arbitrary numbers, and clinicians should make clinical decisions based on the totality of evidence for each individual patient.”

Dr. Bessesen, Dr. Wee, Dr. Powell-Wiley, and Dr. Almandoz reported no relevant financial relationships. Dr. Neeland has reported being a consultant for Merck. Dr. Sattar has reported being a consultant or speaker for Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.

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

“BMI is trash. Full stop.” This controversial tweet, which received thousands of likes and retweets, was cited in a recent article by one doctor on when physicians might stop using body mass index (BMI) to diagnose obesity.

BMI has for years been the consensus default method for assessing whether a person is overweight or has obesity, and is still widely used as the gatekeeper metric for treatment eligibility for certain weight-loss agents and bariatric surgery.

But growing appreciation of the limitations of BMI is causing many clinicians to consider alternative measures of obesity that can better assess both the amount of adiposity as well as its body location, an important determinant of the cardiometabolic consequences of fat.

Alternative metrics include waist circumference and/or waist-to-height ratio (WHtR); imaging methods such as CT, MRI, and dual-energy x-ray absorptiometry (DXA); and bioelectrical impedance to assess fat volume and location. All have made some inroads on the tight grip BMI has had on obesity assessment.

Chances are, however, that BMI will not fade away anytime soon given how entrenched it has become in clinical practice and for insurance coverage, as well as its relative simplicity and precision.

“BMI is embedded in a wide range of guidelines on the use of medications and surgery. It’s embedded in Food and Drug Administration regulations and for billing and insurance coverage. It would take extremely strong data and years of work to undo the infrastructure built around BMI and replace it with something else. I don’t see that happening [anytime soon],” commented Daniel H. Bessesen, MD, a professor at the University of Colorado at Denver, Aurora, and chief of endocrinology for Denver Health.

“It would be almost impossible to replace all the studies that have used BMI with investigations using some other measure,” he said.
 

BMI Is ‘imperfect’

The entrenched position of BMI as the go-to metric doesn’t keep detractors from weighing in. As noted in a commentary on current clinical challenges surrounding obesity recently published in Annals of Internal Medicine, the journal’s editor-in-chief, Christine Laine, MD, and senior deputy editor Christina C. Wee, MD, listed six top issues clinicians must deal with, one of which, they say, is the need for a better measure of obesity than BMI.

“Unfortunately, BMI is an imperfect measure of body composition that differs with ethnicity, sex, body frame, and muscle mass,” noted Dr. Laine and Dr. Wee.

BMI is based on a person’s weight in kilograms divided by the square of their height in meters. A “healthy” BMI is between 18.5 and 24.9 kg/m2, overweight is 25-29.9, and 30 or greater is considered to represent obesity. However, certain ethnic groups have lower cutoffs for overweight or obesity because of evidence that such individuals can be at higher risk of obesity-related comorbidities at lower BMIs.

“BMI was chosen as the initial screening tool [for obesity] not because anyone thought it was perfect or the best measure but because of its simplicity. All you need is height, weight, and a calculator,” Dr. Wee said in an interview.

Numerous online calculators are available, including one from the Centers for Disease Control and Prevention where height in feet and inches and weight in pounds can be entered to generate the BMI.

BMI is also inherently limited by being “a proxy for adiposity” and not a direct measure, added Dr. Wee, who is also director of the Obesity Research Program of Beth Israel Deaconess Medical Center, Boston.

As such, BMI can’t distinguish between fat and muscle because it relies on weight only to gauge adiposity, noted Tiffany Powell-Wiley, MD, an obesity researcher at the National Heart, Lung, and Blood Institute in Bethesda, Md. Another shortcoming of BMI is that it “is good for distinguishing population-level risk for cardiovascular disease and other chronic diseases, but it does not help as much for distinguishing risk at an individual level,” she said in an interview.

These and other drawbacks have prompted researchers to look for other useful metrics. WHtR, for example, has recently made headway as a potential BMI alternative or complement.
 

The case for WHtR

Concern about overreliance on BMI despite its limitations is not new. In 2015, an American Heart Association scientific statement from the group’s Obesity Committee concluded that “BMI alone, even with lower thresholds, is a useful but not an ideal tool for identification of obesity or assessment of cardiovascular risk,” especially for people from Asian, Black, Hispanic, and Pacific Islander populations.

The writing panel also recommended that clinicians measure waist circumference annually and use that information along with BMI “to better gauge cardiovascular risk in diverse populations.”

Momentum for moving beyond BMI alone has continued to build following the AHA statement.

In September 2022, the National Institute for Health and Care Excellence, which sets policies for the United Kingdom’s National Health Service, revised its guidancefor assessment and management of people with obesity. The updated guidance recommends that when clinicians assess “adults with BMI below 35 kg/m2, measure and use their WHtR, as well as their BMI, as a practical estimate of central adiposity and use these measurements to help to assess and predict health risks.”

NICE released an extensive literature review with the revision, and based on the evidence, said that “using waist-to-height ratio as well as BMI would help give a practical estimate of central adiposity in adults with BMI under 35 kg/m². This would in turn help professionals assess and predict health risks.”

However, the review added that, “because people with a BMI over 35 kg/m² are always likely to have a high WHtR, the committee recognized that it may not be a useful addition for predicting health risks in this group.” The 2022 NICE review also said that it is “important to estimate central adiposity when assessing future health risks, including for people whose BMI is in the healthy-weight category.”

This new emphasis by NICE on measuring and using WHtR as part of obesity assessment “represents an important change in population health policy,” commented Dr. Powell-Wiley. “I expect more professional organizations will endorse use of waist circumference or waist-to-height ratio now that NICE has taken this step,” she predicted.

Waist circumference and WHtR may become standard measures of adiposity in clinical practice over the next 5-10 years.

The recent move by NICE to highlight a complementary role for WHtR “is another acknowledgment that BMI is an imperfect tool for stratifying cardiometabolic risk in a diverse population, especially in people with lower BMIs” because of its variability, commented Jamie Almandoz, MD, medical director of the weight wellness program at UT Southwestern Medical Center, Dallas.
 

WHtR vs. BMI

Another recent step forward for WHtR came with the publication of a post hoc analysis of data collected in the PARADIGM-HF trial, a study that had the primary purpose of comparing two medications for improving outcomes in more than 8,000 patients with heart failure with reduced ejection fraction.

The new analysis showed that “two indices that incorporate waist circumference and height, but not weight, showed a clearer association between greater adiposity and a higher risk of heart failure hospitalization,” compared with BMI.

WHtR was one of the two indices identified as being a better correlate for the adverse effect of excess adiposity compared with BMI.

The authors of the post hoc analysis did not design their analysis to compare WHtR with BMI. Instead, their goal was to better understand what’s known as the “obesity paradox” in people with heart failure with reduced ejection fraction: The recurring observation that, when these patients with heart failure have lower BMIs they fare worse, with higher rates of mortality and adverse cardiovascular outcomes, compared with patients with higher BMIs.

The new analysis showed that this paradox disappeared when WHtR was substituted for BMI as the obesity metric.

This “provides meaningful data about the superiority of WHtR, compared with BMI, for predicting heart failure outcomes,” said Dr. Powell-Wiley, although she cautioned that the analysis was limited by scant data in diverse populations and did not look at other important cardiovascular disease outcomes. While Dr. Powell-Wiley does not think that WHtR needs assessment in a prospective, controlled trial, she called for analysis of pooled prospective studies with more diverse populations to better document the advantages of WHtR over BMI.

The PARADIGM-HF post hoc analysis shows again how flawed BMI is for health assessment and the relative importance of an individualized understanding of a person’s body composition, Dr. Almandoz said in an interview. “As we collect more data, there is increasing awareness of how imperfect BMI is.”
 

Measuring waist circumference is tricky

Although WHtR looks promising as a substitute for or add-on to BMI, it has its own limitations, particularly the challenge of accurately measuring waist circumference.

Measuring waist circumference “not only takes more time but requires the assessor to be well trained about where to put the tape measure and making sure it’s measured at the same place each time,” even when different people take serial measurements from individual patients, noted Dr. Wee. Determining waist circumference can also be technically difficult when done on larger people, she added, and collectively these challenges make waist circumference “less reproducible from measurement to measurement.”

“It’s relatively clear how to standardize measurement of weight and height, but there is a huge amount of variability when the waist is measured,” agreed Dr. Almandoz. “And waist circumference also differs by ethnicity, race, sex, and body frame. There are significant differences in waist circumference levels that associate with increased health risks” between, for example, White and South Asian people.

Another limitation of waist circumference and WHtR is that they “cannot differentiate between visceral and abdominal subcutaneous adipose tissue, which are vastly different regarding cardiometabolic risk, commented Ian Neeland, MD, director of cardiovascular prevention at the University Hospitals Harrington Heart & Vascular Institute, Cleveland.
 

The imaging option

“Waist-to-height ratio is not the ultimate answer,” Dr. Neeland said in an interview. He instead endorsed “advanced imaging for body fat distribution,” such as CT or MRI scans, as his pick for what should be the standard obesity metric, “given that it is much more specific and actionable for both risk assessment and response to therapy. I expect slow but steady advancements that move away from BMI cutoffs, for example for bariatric surgery, given that BMI is an imprecise and crude tool.”

But although imaging with methods like CT and MRI may provide the best accuracy and precision for tracking the volume of a person’s cardiometabolically dangerous fat, they are also hampered by relatively high cost and, for CT and DXA, the issue of radiation exposure.

“CT, MRI, and DXA scans give more in-depth assessment of body composition, but should we expose people to the radiation and the cost?” Dr. Almandoz wondered.

“Height, weight, and waist circumference cost nothing to obtain,” creating a big relative disadvantage for imaging, said Naveed Sattar, MD, professor of metabolic medicine at the University of Glasgow.

“Data would need to show that imaging gives clinicians substantially more information about future risk” to justify its price, Dr. Sattar emphasized.
 

BMI’s limits mean adding on

Regardless of whichever alternatives to BMI end up getting used most, experts generally agree that BMI alone is looking increasingly inadequate.

“Over the next 5 years, BMI will come to be seen as a screening tool that categorizes people into general risk groups” that also needs “other metrics and variables, such as age, race, ethnicity, family history, blood glucose, and blood pressure to better describe health risk in an individual,” predicted Dr. Bessesen.

The endorsement of WHtR by NICE “will lead to more research into how to incorporate WHtR into routine practice. We need more evidence to translate what NICE said into practice,” said Dr. Sattar. “I don’t think we’ll see a shift away from BMI, but we’ll add alternative measures that are particularly useful in certain patients.”

“Because we live in diverse societies, we need to individualize risk assessment and couple that with technology that makes analysis of body composition more accessible,” agreed Dr. Almandoz. He noted that the UT Southwestern weight wellness program where he practices has, for about the past decade, routinely collected waist circumference and bioelectrical impedance data as well as BMI on all people seen in the practice for obesity concerns. Making these additional measurements on a routine basis also helps strengthen patient engagement.

“We get into trouble when we make rigid health policy and clinical decisions based on BMI alone without looking at the patient holistically,” said Dr. Wee. “Patients are more than arbitrary numbers, and clinicians should make clinical decisions based on the totality of evidence for each individual patient.”

Dr. Bessesen, Dr. Wee, Dr. Powell-Wiley, and Dr. Almandoz reported no relevant financial relationships. Dr. Neeland has reported being a consultant for Merck. Dr. Sattar has reported being a consultant or speaker for Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.

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

Major depressive disorder (MDD) is linked to disruptions in energy and lipid metabolism, possibly caused by the interplay of the gut microbiome and blood metabolome, new research suggests.

Investigators found that MDD had specific metabolic “signatures” consisting of 124 metabolites that spanned energy and lipid pathways, with some involving the tricarboxylic acid cycle in particular. These changes in metabolites were consistent with differences in composition of several gut microbiota.

The researchers found that fatty acids and intermediate and very large lipoproteins changed in association with the depressive disease process. However, high-density lipoproteins and metabolites in the tricarboxylic acid cycle did not.

“As we wait to establish causal influences through clinical trials, clinicians should advise patients suffering from mood disorders to modify their diet by increasing the intake of fresh fruits, vegetables, and whole grains, as these provide the required fuel/fiber to the gut microbiota for their enrichment, and more short-chain fatty acids are produced for the optimal functioning of the body,” study investigator Najaf Amin, PhD, DSc, senior researcher, Nuffield Department of Population Health, Oxford University, England, told this news organization.

“At the same time, patients should be advised to minimize the intake of sugars and processed foods, which are known to have an inverse impact on the gut microbiome and are associated with higher inflammation,” she said.

The study was published online in JAMA Psychiatry.
 

MDD poorly understood

Although most antidepressants target the monoamine pathway, “evidence is increasing for a more complex interplay of multiple pathways involving a wide range of metabolic alterations spanning energy and lipid metabolism,” the authors wrote.

Previous research using the Nightingale proton nuclear magnetic resonance (NMR) metabolomics platform showed a “shift” toward decreased levels of high-density lipoproteins (HDLs) and increased levels of very low-density lipoproteins (VLDLs) and triglycerides among patients with depression.

The gut microbiome, which is primarily modulated by diet, “has been shown to be a major determinant of circulating lipids, specifically triglycerides and HDLs, and to regulate mitochondrial function,” the investigators noted. Patients with MDD are known to have disruptions in the gut microbiome.

The gut microbiome may “explain part of the shift in VLDL and HDL levels observed in patients with depression and if the metabolic signatures of the disease based on Nightingale metabolites can be used as a tool to infer the association between gut microbiome and depression.”

Dr. Amin called depression “one of the most poorly understood diseases, as underlying mechanisms remain elusive.”

Large-scale genetic studies “have shown that the contribution of genetics to depression is modest,” she continued. On the other hand, initial animal studies suggest the gut microbiome “may potentially have a causal influence on depression.”

Several studies have evaluated the influence of gut microbiome on depression, “but, due to small sample sizes and inadequate control for confounding factors, most of their findings were not reproducible.”

Harnessing the power of the UK Biobank, the investigators studied 58,257 individuals who were between the ages of 37 and 73 years at recruitment. They used data on NMR spectroscopy–based plasma metabolites in depression. Individuals who didn’t report depression at baseline served as controls.

Logistic regression analysis was used to test the association of metabolite levels with depression in four models, each with an increasing number of covariates.

To identify patterns of correlation in the “metabolic signatures of MDD and the human gut biome,” they regressed the metabolic signatures of MDD on the metabolic signatures of the gut microbiota and then regressed the metabolic signature of gut microbiota on the metabolic signatures of MDD.

Bidirectional 2-sample Mendelian randomization was used to ascertain the direction of the association observed between metabolites and MDD.

Individuals with lifetime and recurrent MDD were compared with controls (6,811 vs. 51,446 and 4,370 vs. 62,508, respectively).

Participants with lifetime MDD were significantly younger (median [IQR] age, 56 [49-62] years vs. 58 [51-64] years) and were more likely to be female in comparison with controls (54% vs. 35%).
 

‘Novel findings’

In the fully adjusted analysis, metabolic signatures of MDD were found to consist of 124 metabolites that spanned energy and lipid metabolism pathways.

The investigators noted that these “novel findings” included 49 metabolites encompassing those involved in the tricarboxylic acid cycle – citrate and pyruvate.

The findings revealed that fatty acids and intermediate and VLDL changed in association with the disease process. On the other hand, HDL and the metabolites in the tricarboxylic acid cycle did not.

“We observed that the genera Sellimonas, Eggerthella, Hungatella, and Lachnoclostridium were more abundant, while genera Ruminococcaceae ... Coprococcus, Lachnospiraceae ... Eubacterium ventriosum, Subdoligranulum, and family Ruminococcaceae were depleted in the guts of individuals with more symptoms of depression,” said Dr. Amin. “Of these, genus Eggerthella showed statistical evidence of being involved in the causal pathway.”

These microbes are involved in the synthesis of important neurotransmitters, such as gamma aminobutyric acid, butyrate, glutamate, and serotonin, she noted.

Butyrate produced by the gut can cross the blood-brain barrier, enter the brain, and affect transcriptional and translational activity or be used by the cells for generating energy, she added. “So basically, butyrate can influence depression through several routes – i.e., via immune regulation, genomic transcript/translation, and/or affecting energy metabolism.”
 

No causality

Commenting on the study, Emeran Mayer, MD, distinguished research professor of medicine, G. Oppenheimer Center for Neurobiology of Stress and Resilience and UCLA Brain Gut Microbiome Center, called it the “largest, most comprehensive and best validated association study to date providing further evidence for an association between gut microbial taxa, previously identified in patients with MDD, blood metabolites (generated by host and by microbes) and questionnaire data.”

However, “despite its strengths, the study does not allow [us] to identify a causal role of the microbiome alterations in the observed microbial and metabolic changes (fatty acids, Krebs cycle components),” cautioned Dr. Mayer, who was not involved with the study.

Moreover, “causality of gut microbial changes on the behavioral phenotype of depression cannot been inferred,” he concluded.

Metabolomics data were provided by the Alzheimer’s Disease Metabolomics Consortium. The study was funded wholly or in part by grants from the National Institute on Aging and Foundation for the National Institutes of Health. It was further supported by a grant from ZonMW Memorabel. Dr. Amin reports no relevant financial relationships. The other authors’ disclosures are listed oin the original article. Dr. Mayer is a scientific advisory board member of Danone, Axial Therapeutics, Viome, Amare, Mahana Therapeutics, Pendulum, Bloom Biosciences, and APC Microbiome Ireland.
 

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

Major depressive disorder (MDD) is linked to disruptions in energy and lipid metabolism, possibly caused by the interplay of the gut microbiome and blood metabolome, new research suggests.

Investigators found that MDD had specific metabolic “signatures” consisting of 124 metabolites that spanned energy and lipid pathways, with some involving the tricarboxylic acid cycle in particular. These changes in metabolites were consistent with differences in composition of several gut microbiota.

The researchers found that fatty acids and intermediate and very large lipoproteins changed in association with the depressive disease process. However, high-density lipoproteins and metabolites in the tricarboxylic acid cycle did not.

“As we wait to establish causal influences through clinical trials, clinicians should advise patients suffering from mood disorders to modify their diet by increasing the intake of fresh fruits, vegetables, and whole grains, as these provide the required fuel/fiber to the gut microbiota for their enrichment, and more short-chain fatty acids are produced for the optimal functioning of the body,” study investigator Najaf Amin, PhD, DSc, senior researcher, Nuffield Department of Population Health, Oxford University, England, told this news organization.

“At the same time, patients should be advised to minimize the intake of sugars and processed foods, which are known to have an inverse impact on the gut microbiome and are associated with higher inflammation,” she said.

The study was published online in JAMA Psychiatry.
 

MDD poorly understood

Although most antidepressants target the monoamine pathway, “evidence is increasing for a more complex interplay of multiple pathways involving a wide range of metabolic alterations spanning energy and lipid metabolism,” the authors wrote.

Previous research using the Nightingale proton nuclear magnetic resonance (NMR) metabolomics platform showed a “shift” toward decreased levels of high-density lipoproteins (HDLs) and increased levels of very low-density lipoproteins (VLDLs) and triglycerides among patients with depression.

The gut microbiome, which is primarily modulated by diet, “has been shown to be a major determinant of circulating lipids, specifically triglycerides and HDLs, and to regulate mitochondrial function,” the investigators noted. Patients with MDD are known to have disruptions in the gut microbiome.

The gut microbiome may “explain part of the shift in VLDL and HDL levels observed in patients with depression and if the metabolic signatures of the disease based on Nightingale metabolites can be used as a tool to infer the association between gut microbiome and depression.”

Dr. Amin called depression “one of the most poorly understood diseases, as underlying mechanisms remain elusive.”

Large-scale genetic studies “have shown that the contribution of genetics to depression is modest,” she continued. On the other hand, initial animal studies suggest the gut microbiome “may potentially have a causal influence on depression.”

Several studies have evaluated the influence of gut microbiome on depression, “but, due to small sample sizes and inadequate control for confounding factors, most of their findings were not reproducible.”

Harnessing the power of the UK Biobank, the investigators studied 58,257 individuals who were between the ages of 37 and 73 years at recruitment. They used data on NMR spectroscopy–based plasma metabolites in depression. Individuals who didn’t report depression at baseline served as controls.

Logistic regression analysis was used to test the association of metabolite levels with depression in four models, each with an increasing number of covariates.

To identify patterns of correlation in the “metabolic signatures of MDD and the human gut biome,” they regressed the metabolic signatures of MDD on the metabolic signatures of the gut microbiota and then regressed the metabolic signature of gut microbiota on the metabolic signatures of MDD.

Bidirectional 2-sample Mendelian randomization was used to ascertain the direction of the association observed between metabolites and MDD.

Individuals with lifetime and recurrent MDD were compared with controls (6,811 vs. 51,446 and 4,370 vs. 62,508, respectively).

Participants with lifetime MDD were significantly younger (median [IQR] age, 56 [49-62] years vs. 58 [51-64] years) and were more likely to be female in comparison with controls (54% vs. 35%).
 

‘Novel findings’

In the fully adjusted analysis, metabolic signatures of MDD were found to consist of 124 metabolites that spanned energy and lipid metabolism pathways.

The investigators noted that these “novel findings” included 49 metabolites encompassing those involved in the tricarboxylic acid cycle – citrate and pyruvate.

The findings revealed that fatty acids and intermediate and VLDL changed in association with the disease process. On the other hand, HDL and the metabolites in the tricarboxylic acid cycle did not.

“We observed that the genera Sellimonas, Eggerthella, Hungatella, and Lachnoclostridium were more abundant, while genera Ruminococcaceae ... Coprococcus, Lachnospiraceae ... Eubacterium ventriosum, Subdoligranulum, and family Ruminococcaceae were depleted in the guts of individuals with more symptoms of depression,” said Dr. Amin. “Of these, genus Eggerthella showed statistical evidence of being involved in the causal pathway.”

These microbes are involved in the synthesis of important neurotransmitters, such as gamma aminobutyric acid, butyrate, glutamate, and serotonin, she noted.

Butyrate produced by the gut can cross the blood-brain barrier, enter the brain, and affect transcriptional and translational activity or be used by the cells for generating energy, she added. “So basically, butyrate can influence depression through several routes – i.e., via immune regulation, genomic transcript/translation, and/or affecting energy metabolism.”
 

No causality

Commenting on the study, Emeran Mayer, MD, distinguished research professor of medicine, G. Oppenheimer Center for Neurobiology of Stress and Resilience and UCLA Brain Gut Microbiome Center, called it the “largest, most comprehensive and best validated association study to date providing further evidence for an association between gut microbial taxa, previously identified in patients with MDD, blood metabolites (generated by host and by microbes) and questionnaire data.”

However, “despite its strengths, the study does not allow [us] to identify a causal role of the microbiome alterations in the observed microbial and metabolic changes (fatty acids, Krebs cycle components),” cautioned Dr. Mayer, who was not involved with the study.

Moreover, “causality of gut microbial changes on the behavioral phenotype of depression cannot been inferred,” he concluded.

Metabolomics data were provided by the Alzheimer’s Disease Metabolomics Consortium. The study was funded wholly or in part by grants from the National Institute on Aging and Foundation for the National Institutes of Health. It was further supported by a grant from ZonMW Memorabel. Dr. Amin reports no relevant financial relationships. The other authors’ disclosures are listed oin the original article. Dr. Mayer is a scientific advisory board member of Danone, Axial Therapeutics, Viome, Amare, Mahana Therapeutics, Pendulum, Bloom Biosciences, and APC Microbiome Ireland.
 

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

Major depressive disorder (MDD) is linked to disruptions in energy and lipid metabolism, possibly caused by the interplay of the gut microbiome and blood metabolome, new research suggests.

Investigators found that MDD had specific metabolic “signatures” consisting of 124 metabolites that spanned energy and lipid pathways, with some involving the tricarboxylic acid cycle in particular. These changes in metabolites were consistent with differences in composition of several gut microbiota.

The researchers found that fatty acids and intermediate and very large lipoproteins changed in association with the depressive disease process. However, high-density lipoproteins and metabolites in the tricarboxylic acid cycle did not.

“As we wait to establish causal influences through clinical trials, clinicians should advise patients suffering from mood disorders to modify their diet by increasing the intake of fresh fruits, vegetables, and whole grains, as these provide the required fuel/fiber to the gut microbiota for their enrichment, and more short-chain fatty acids are produced for the optimal functioning of the body,” study investigator Najaf Amin, PhD, DSc, senior researcher, Nuffield Department of Population Health, Oxford University, England, told this news organization.

“At the same time, patients should be advised to minimize the intake of sugars and processed foods, which are known to have an inverse impact on the gut microbiome and are associated with higher inflammation,” she said.

The study was published online in JAMA Psychiatry.
 

MDD poorly understood

Although most antidepressants target the monoamine pathway, “evidence is increasing for a more complex interplay of multiple pathways involving a wide range of metabolic alterations spanning energy and lipid metabolism,” the authors wrote.

Previous research using the Nightingale proton nuclear magnetic resonance (NMR) metabolomics platform showed a “shift” toward decreased levels of high-density lipoproteins (HDLs) and increased levels of very low-density lipoproteins (VLDLs) and triglycerides among patients with depression.

The gut microbiome, which is primarily modulated by diet, “has been shown to be a major determinant of circulating lipids, specifically triglycerides and HDLs, and to regulate mitochondrial function,” the investigators noted. Patients with MDD are known to have disruptions in the gut microbiome.

The gut microbiome may “explain part of the shift in VLDL and HDL levels observed in patients with depression and if the metabolic signatures of the disease based on Nightingale metabolites can be used as a tool to infer the association between gut microbiome and depression.”

Dr. Amin called depression “one of the most poorly understood diseases, as underlying mechanisms remain elusive.”

Large-scale genetic studies “have shown that the contribution of genetics to depression is modest,” she continued. On the other hand, initial animal studies suggest the gut microbiome “may potentially have a causal influence on depression.”

Several studies have evaluated the influence of gut microbiome on depression, “but, due to small sample sizes and inadequate control for confounding factors, most of their findings were not reproducible.”

Harnessing the power of the UK Biobank, the investigators studied 58,257 individuals who were between the ages of 37 and 73 years at recruitment. They used data on NMR spectroscopy–based plasma metabolites in depression. Individuals who didn’t report depression at baseline served as controls.

Logistic regression analysis was used to test the association of metabolite levels with depression in four models, each with an increasing number of covariates.

To identify patterns of correlation in the “metabolic signatures of MDD and the human gut biome,” they regressed the metabolic signatures of MDD on the metabolic signatures of the gut microbiota and then regressed the metabolic signature of gut microbiota on the metabolic signatures of MDD.

Bidirectional 2-sample Mendelian randomization was used to ascertain the direction of the association observed between metabolites and MDD.

Individuals with lifetime and recurrent MDD were compared with controls (6,811 vs. 51,446 and 4,370 vs. 62,508, respectively).

Participants with lifetime MDD were significantly younger (median [IQR] age, 56 [49-62] years vs. 58 [51-64] years) and were more likely to be female in comparison with controls (54% vs. 35%).
 

‘Novel findings’

In the fully adjusted analysis, metabolic signatures of MDD were found to consist of 124 metabolites that spanned energy and lipid metabolism pathways.

The investigators noted that these “novel findings” included 49 metabolites encompassing those involved in the tricarboxylic acid cycle – citrate and pyruvate.

The findings revealed that fatty acids and intermediate and VLDL changed in association with the disease process. On the other hand, HDL and the metabolites in the tricarboxylic acid cycle did not.

“We observed that the genera Sellimonas, Eggerthella, Hungatella, and Lachnoclostridium were more abundant, while genera Ruminococcaceae ... Coprococcus, Lachnospiraceae ... Eubacterium ventriosum, Subdoligranulum, and family Ruminococcaceae were depleted in the guts of individuals with more symptoms of depression,” said Dr. Amin. “Of these, genus Eggerthella showed statistical evidence of being involved in the causal pathway.”

These microbes are involved in the synthesis of important neurotransmitters, such as gamma aminobutyric acid, butyrate, glutamate, and serotonin, she noted.

Butyrate produced by the gut can cross the blood-brain barrier, enter the brain, and affect transcriptional and translational activity or be used by the cells for generating energy, she added. “So basically, butyrate can influence depression through several routes – i.e., via immune regulation, genomic transcript/translation, and/or affecting energy metabolism.”
 

No causality

Commenting on the study, Emeran Mayer, MD, distinguished research professor of medicine, G. Oppenheimer Center for Neurobiology of Stress and Resilience and UCLA Brain Gut Microbiome Center, called it the “largest, most comprehensive and best validated association study to date providing further evidence for an association between gut microbial taxa, previously identified in patients with MDD, blood metabolites (generated by host and by microbes) and questionnaire data.”

However, “despite its strengths, the study does not allow [us] to identify a causal role of the microbiome alterations in the observed microbial and metabolic changes (fatty acids, Krebs cycle components),” cautioned Dr. Mayer, who was not involved with the study.

Moreover, “causality of gut microbial changes on the behavioral phenotype of depression cannot been inferred,” he concluded.

Metabolomics data were provided by the Alzheimer’s Disease Metabolomics Consortium. The study was funded wholly or in part by grants from the National Institute on Aging and Foundation for the National Institutes of Health. It was further supported by a grant from ZonMW Memorabel. Dr. Amin reports no relevant financial relationships. The other authors’ disclosures are listed oin the original article. Dr. Mayer is a scientific advisory board member of Danone, Axial Therapeutics, Viome, Amare, Mahana Therapeutics, Pendulum, Bloom Biosciences, and APC Microbiome Ireland.
 

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