Clinical Psychiatry News

An overwhelmingly loud and high-pitched screech rattles against your hip. You startle and groan into the pillow as your thoughts settle into conscious awareness. It is 3 a.m. You are a 2nd-year resident trudging through the night shift, alerted to the presence of a new patient awaiting an emergency assessment. You are the only in-house physician. Walking steadfastly toward the emergency unit, you enter and greet the patient. Immediately, you observe a look of surprise followed immediately by a scowl.

You extend a hand, but your greeting is abruptly cut short with: “I want to see a doctor!” You pace your breaths to quell annoyance and resume your introduction, asserting that you are a doctor and indeed the only doctor on duty. After moments of deep sighs and questions regarding your credentials, you persuade the patient to start the interview.

It is now 8 a.m. The frustration of the night starts to ease as you prepare to leave. While gathering your things, a visitor is overheard inquiring the whereabouts of a hospital unit. Volunteering as a guide, you walk the person toward the opposite end of the hospital. Bleary eyed, muscle laxed, and bone weary, you point out the entrance, then turn to leave. The steady rhythm of your steps suddenly halts as you hear from behind: “Thank you! You speak English really well!” Blankly, you stare. Your voice remains mute while your brain screams: “What is that supposed to mean?” But you do not utter a sound, because intuitively, you know the answer.

While reading this scenario, what did you feel? Pride in knowing that the physician was able to successfully navigate a busy night? Relief in the physician’s ability to maintain a professional demeanor despite belittling microaggressions? Are you angry? Would you replay those moments like reruns of a bad TV show? Can you imagine entering your home and collapsing onto the bed as your tears of fury pool over your rumpled sheets?

The emotional release of that morning is seared into my memory. Over the years, I questioned my reactions. Was I too passive? Should I have schooled them on their ignorance? Had I done so, would I have incurred reprimands? Would standing up for myself cause years of hard work to fall away? Moreover, had I defended myself, would I forever have been viewed as “The Angry Black Woman?”

This story is more than a vignette. For me, it is another reminder that, despite how far we have come, we have much further to go. As a Black woman in a professional sphere, I stand upon the shoulders of those who sacrificed for a dream, a greater purpose. My foremothers and forefathers fought bravely and tirelessly so that we could attain levels of success that were only once but a dream. Despite this progress, a grimace, carelessly spoken words, or a mindless gesture remind me that, no matter how much I toil and what levels of success I achieve, when I meet someone for the first time or encounter someone from my past, I find myself wondering whether I am remembered for me or because I am “The Black One.”
 

Honest look at medicine is imperative

It is important to consider multiple facets of the super-doctor myth. We are dedicated, fearless, authoritative, ambitious individuals. We do not yield to sickness, family obligations, or fatigue. Medicine is a calling, and the patient deserves the utmost respect and professional behavior. Impervious to ethnicity, race, nationality, or creed, we are unbiased and always in service of the greater good. Often, however, I wonder how the expectations of patient-focused, patient-centered care can prevail without an honest look at the vicissitudes facing medicine.

We find ourselves amid a tumultuous year overshadowed by a devastating pandemic that skews heavily toward Black and Brown communities, in addition to political turmoil and racial reckoning that sprang forth from fear, anger, and determination ignited by the murders of Breonna Taylor and George Floyd – communities united in outrage lamenting the cries of Black Lives Matter.

I remember the tears briskly falling upon my blouse as I watched Mr. Floyd’s life violently ripped from this Earth. Shortly thereafter, I remember the phone calls, emails, and texts from close friends, acquaintances, and colleagues offering support, listening ears, pledging to learn and endeavoring to understand the struggle for recognition and the fight for human rights. Even so, the deafening support was clouded by the preternatural silence of some medical organizations. Within the Black physician community, outrage was palpable. We reflected upon years of sacrifice and perseverance despite the challenge of bigotry, ignorance, and racism – not only from patients and their families – but also colleagues and administrators. Yet, in our time of horror and need, in those moments of vulnerability ... silence. Eventually, lengthy proclamations of support were expressed through various media. However, it felt too safe, too corporate, and too generic and inauthentic. As a result, an exodus of Black physicians from leadership positions and academic medicine took hold as the blatant continuation of rhetoric – coupled with ineffective outreach and support – finally took its toll.

Frequently, I question how the obstacles of medical school, residency, and beyond are expected to be traversed while living in a world that consistently affords additional challenges to those who look, act, or speak in a manner that varies from the perceived standard. In a culture where the myth of the super doctor reigns, how do we reconcile attainment of a false and detrimental narrative while the overarching pressure acutely felt by Black physicians magnifies in the setting of stereotypes, sociopolitical turbulence, bigotry, and racism? How can one sacrifice for an entity that is unwilling to acknowledge the psychological implications of that sacrifice?

Throughout my medical career, I encountered, personally and remotely, various incidents that emphasize the unique struggles facing Black physicians. For instance, while in medical school, I transitioned my hair to its natural state but was counseled against doing so because of the risk of losing residency opportunities as a direct result of my “unprofessional” appearance. Throughout residency, multiple incidents come to mind, including frequent demands to see my hospital badge despite the same not being of asked of my White cohorts; denial of entry into physician entrance within the residency building because, despite my professional attire, I was presumed to be a member of the custodial staff; and patients being confused and asking for a doctor despite my long white coat and clear introductions.

Furthermore, the fluency of my speech and the absence of regional dialect or vernacular are quite often lauded by patients. Inquiries to touch my hair as well as hypotheses regarding my nationality or degree of “blackness” with respect to the shape of my nose, eyes, and lips are openly questioned. Unfortunately, those uncomfortable incidents have not been limited to patient encounters.

In one instance, while presenting a patient in the presence of my attending and a 3rd-year medical student, I was sternly admonished for disclosing the race of the patient. I sat still and resolute as this doctor spoke on increased risk of bias in diagnosis and treatment when race is identified. Outwardly, I projected patience but inside, I seethed. In that moment, I realized that I would never have the luxury of ignorance or denial. Although I desire to be valued for my prowess in medicine, the mythical status was not created with my skin color in mind. For is avoidance not but a reflection of denial?

In these chaotic and uncertain times, how can we continue to promote a pathological ideal when the roads traveled are so fundamentally skewed? If a White physician faces a belligerent and argumentative patient, there is opportunity for debriefing both individually and among a larger cohort via classes, conferences, and supervisions. Conversely, when a Black physician is derided with racist sentiment, will they have the same opportunity for reflection and support? Despite identical expectations of professionalism and growth, how can one be successful in a system that either directly or indirectly encourages the opposite?

As we try to shed the super-doctor myth, we must recognize that this unattainable and detrimental persona hinders progress. This myth undermines our ability to understand our fragility, the limitations of our capabilities, and the strength of our vulnerability. We must take an honest look at the manner in which our individual biases and the deeply ingrained (and potentially unconscious) systemic biases are counterintuitive to the success and support of physicians of color.

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

An overwhelmingly loud and high-pitched screech rattles against your hip. You startle and groan into the pillow as your thoughts settle into conscious awareness. It is 3 a.m. You are a 2nd-year resident trudging through the night shift, alerted to the presence of a new patient awaiting an emergency assessment. You are the only in-house physician. Walking steadfastly toward the emergency unit, you enter and greet the patient. Immediately, you observe a look of surprise followed immediately by a scowl.

You extend a hand, but your greeting is abruptly cut short with: “I want to see a doctor!” You pace your breaths to quell annoyance and resume your introduction, asserting that you are a doctor and indeed the only doctor on duty. After moments of deep sighs and questions regarding your credentials, you persuade the patient to start the interview.

It is now 8 a.m. The frustration of the night starts to ease as you prepare to leave. While gathering your things, a visitor is overheard inquiring the whereabouts of a hospital unit. Volunteering as a guide, you walk the person toward the opposite end of the hospital. Bleary eyed, muscle laxed, and bone weary, you point out the entrance, then turn to leave. The steady rhythm of your steps suddenly halts as you hear from behind: “Thank you! You speak English really well!” Blankly, you stare. Your voice remains mute while your brain screams: “What is that supposed to mean?” But you do not utter a sound, because intuitively, you know the answer.

While reading this scenario, what did you feel? Pride in knowing that the physician was able to successfully navigate a busy night? Relief in the physician’s ability to maintain a professional demeanor despite belittling microaggressions? Are you angry? Would you replay those moments like reruns of a bad TV show? Can you imagine entering your home and collapsing onto the bed as your tears of fury pool over your rumpled sheets?

The emotional release of that morning is seared into my memory. Over the years, I questioned my reactions. Was I too passive? Should I have schooled them on their ignorance? Had I done so, would I have incurred reprimands? Would standing up for myself cause years of hard work to fall away? Moreover, had I defended myself, would I forever have been viewed as “The Angry Black Woman?”

This story is more than a vignette. For me, it is another reminder that, despite how far we have come, we have much further to go. As a Black woman in a professional sphere, I stand upon the shoulders of those who sacrificed for a dream, a greater purpose. My foremothers and forefathers fought bravely and tirelessly so that we could attain levels of success that were only once but a dream. Despite this progress, a grimace, carelessly spoken words, or a mindless gesture remind me that, no matter how much I toil and what levels of success I achieve, when I meet someone for the first time or encounter someone from my past, I find myself wondering whether I am remembered for me or because I am “The Black One.”
 

Honest look at medicine is imperative

It is important to consider multiple facets of the super-doctor myth. We are dedicated, fearless, authoritative, ambitious individuals. We do not yield to sickness, family obligations, or fatigue. Medicine is a calling, and the patient deserves the utmost respect and professional behavior. Impervious to ethnicity, race, nationality, or creed, we are unbiased and always in service of the greater good. Often, however, I wonder how the expectations of patient-focused, patient-centered care can prevail without an honest look at the vicissitudes facing medicine.

We find ourselves amid a tumultuous year overshadowed by a devastating pandemic that skews heavily toward Black and Brown communities, in addition to political turmoil and racial reckoning that sprang forth from fear, anger, and determination ignited by the murders of Breonna Taylor and George Floyd – communities united in outrage lamenting the cries of Black Lives Matter.

I remember the tears briskly falling upon my blouse as I watched Mr. Floyd’s life violently ripped from this Earth. Shortly thereafter, I remember the phone calls, emails, and texts from close friends, acquaintances, and colleagues offering support, listening ears, pledging to learn and endeavoring to understand the struggle for recognition and the fight for human rights. Even so, the deafening support was clouded by the preternatural silence of some medical organizations. Within the Black physician community, outrage was palpable. We reflected upon years of sacrifice and perseverance despite the challenge of bigotry, ignorance, and racism – not only from patients and their families – but also colleagues and administrators. Yet, in our time of horror and need, in those moments of vulnerability ... silence. Eventually, lengthy proclamations of support were expressed through various media. However, it felt too safe, too corporate, and too generic and inauthentic. As a result, an exodus of Black physicians from leadership positions and academic medicine took hold as the blatant continuation of rhetoric – coupled with ineffective outreach and support – finally took its toll.

Frequently, I question how the obstacles of medical school, residency, and beyond are expected to be traversed while living in a world that consistently affords additional challenges to those who look, act, or speak in a manner that varies from the perceived standard. In a culture where the myth of the super doctor reigns, how do we reconcile attainment of a false and detrimental narrative while the overarching pressure acutely felt by Black physicians magnifies in the setting of stereotypes, sociopolitical turbulence, bigotry, and racism? How can one sacrifice for an entity that is unwilling to acknowledge the psychological implications of that sacrifice?

Throughout my medical career, I encountered, personally and remotely, various incidents that emphasize the unique struggles facing Black physicians. For instance, while in medical school, I transitioned my hair to its natural state but was counseled against doing so because of the risk of losing residency opportunities as a direct result of my “unprofessional” appearance. Throughout residency, multiple incidents come to mind, including frequent demands to see my hospital badge despite the same not being of asked of my White cohorts; denial of entry into physician entrance within the residency building because, despite my professional attire, I was presumed to be a member of the custodial staff; and patients being confused and asking for a doctor despite my long white coat and clear introductions.

Furthermore, the fluency of my speech and the absence of regional dialect or vernacular are quite often lauded by patients. Inquiries to touch my hair as well as hypotheses regarding my nationality or degree of “blackness” with respect to the shape of my nose, eyes, and lips are openly questioned. Unfortunately, those uncomfortable incidents have not been limited to patient encounters.

In one instance, while presenting a patient in the presence of my attending and a 3rd-year medical student, I was sternly admonished for disclosing the race of the patient. I sat still and resolute as this doctor spoke on increased risk of bias in diagnosis and treatment when race is identified. Outwardly, I projected patience but inside, I seethed. In that moment, I realized that I would never have the luxury of ignorance or denial. Although I desire to be valued for my prowess in medicine, the mythical status was not created with my skin color in mind. For is avoidance not but a reflection of denial?

In these chaotic and uncertain times, how can we continue to promote a pathological ideal when the roads traveled are so fundamentally skewed? If a White physician faces a belligerent and argumentative patient, there is opportunity for debriefing both individually and among a larger cohort via classes, conferences, and supervisions. Conversely, when a Black physician is derided with racist sentiment, will they have the same opportunity for reflection and support? Despite identical expectations of professionalism and growth, how can one be successful in a system that either directly or indirectly encourages the opposite?

As we try to shed the super-doctor myth, we must recognize that this unattainable and detrimental persona hinders progress. This myth undermines our ability to understand our fragility, the limitations of our capabilities, and the strength of our vulnerability. We must take an honest look at the manner in which our individual biases and the deeply ingrained (and potentially unconscious) systemic biases are counterintuitive to the success and support of physicians of color.

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

An overwhelmingly loud and high-pitched screech rattles against your hip. You startle and groan into the pillow as your thoughts settle into conscious awareness. It is 3 a.m. You are a 2nd-year resident trudging through the night shift, alerted to the presence of a new patient awaiting an emergency assessment. You are the only in-house physician. Walking steadfastly toward the emergency unit, you enter and greet the patient. Immediately, you observe a look of surprise followed immediately by a scowl.

You extend a hand, but your greeting is abruptly cut short with: “I want to see a doctor!” You pace your breaths to quell annoyance and resume your introduction, asserting that you are a doctor and indeed the only doctor on duty. After moments of deep sighs and questions regarding your credentials, you persuade the patient to start the interview.

It is now 8 a.m. The frustration of the night starts to ease as you prepare to leave. While gathering your things, a visitor is overheard inquiring the whereabouts of a hospital unit. Volunteering as a guide, you walk the person toward the opposite end of the hospital. Bleary eyed, muscle laxed, and bone weary, you point out the entrance, then turn to leave. The steady rhythm of your steps suddenly halts as you hear from behind: “Thank you! You speak English really well!” Blankly, you stare. Your voice remains mute while your brain screams: “What is that supposed to mean?” But you do not utter a sound, because intuitively, you know the answer.

While reading this scenario, what did you feel? Pride in knowing that the physician was able to successfully navigate a busy night? Relief in the physician’s ability to maintain a professional demeanor despite belittling microaggressions? Are you angry? Would you replay those moments like reruns of a bad TV show? Can you imagine entering your home and collapsing onto the bed as your tears of fury pool over your rumpled sheets?

The emotional release of that morning is seared into my memory. Over the years, I questioned my reactions. Was I too passive? Should I have schooled them on their ignorance? Had I done so, would I have incurred reprimands? Would standing up for myself cause years of hard work to fall away? Moreover, had I defended myself, would I forever have been viewed as “The Angry Black Woman?”

This story is more than a vignette. For me, it is another reminder that, despite how far we have come, we have much further to go. As a Black woman in a professional sphere, I stand upon the shoulders of those who sacrificed for a dream, a greater purpose. My foremothers and forefathers fought bravely and tirelessly so that we could attain levels of success that were only once but a dream. Despite this progress, a grimace, carelessly spoken words, or a mindless gesture remind me that, no matter how much I toil and what levels of success I achieve, when I meet someone for the first time or encounter someone from my past, I find myself wondering whether I am remembered for me or because I am “The Black One.”
 

Honest look at medicine is imperative

It is important to consider multiple facets of the super-doctor myth. We are dedicated, fearless, authoritative, ambitious individuals. We do not yield to sickness, family obligations, or fatigue. Medicine is a calling, and the patient deserves the utmost respect and professional behavior. Impervious to ethnicity, race, nationality, or creed, we are unbiased and always in service of the greater good. Often, however, I wonder how the expectations of patient-focused, patient-centered care can prevail without an honest look at the vicissitudes facing medicine.

We find ourselves amid a tumultuous year overshadowed by a devastating pandemic that skews heavily toward Black and Brown communities, in addition to political turmoil and racial reckoning that sprang forth from fear, anger, and determination ignited by the murders of Breonna Taylor and George Floyd – communities united in outrage lamenting the cries of Black Lives Matter.

I remember the tears briskly falling upon my blouse as I watched Mr. Floyd’s life violently ripped from this Earth. Shortly thereafter, I remember the phone calls, emails, and texts from close friends, acquaintances, and colleagues offering support, listening ears, pledging to learn and endeavoring to understand the struggle for recognition and the fight for human rights. Even so, the deafening support was clouded by the preternatural silence of some medical organizations. Within the Black physician community, outrage was palpable. We reflected upon years of sacrifice and perseverance despite the challenge of bigotry, ignorance, and racism – not only from patients and their families – but also colleagues and administrators. Yet, in our time of horror and need, in those moments of vulnerability ... silence. Eventually, lengthy proclamations of support were expressed through various media. However, it felt too safe, too corporate, and too generic and inauthentic. As a result, an exodus of Black physicians from leadership positions and academic medicine took hold as the blatant continuation of rhetoric – coupled with ineffective outreach and support – finally took its toll.

Frequently, I question how the obstacles of medical school, residency, and beyond are expected to be traversed while living in a world that consistently affords additional challenges to those who look, act, or speak in a manner that varies from the perceived standard. In a culture where the myth of the super doctor reigns, how do we reconcile attainment of a false and detrimental narrative while the overarching pressure acutely felt by Black physicians magnifies in the setting of stereotypes, sociopolitical turbulence, bigotry, and racism? How can one sacrifice for an entity that is unwilling to acknowledge the psychological implications of that sacrifice?

Throughout my medical career, I encountered, personally and remotely, various incidents that emphasize the unique struggles facing Black physicians. For instance, while in medical school, I transitioned my hair to its natural state but was counseled against doing so because of the risk of losing residency opportunities as a direct result of my “unprofessional” appearance. Throughout residency, multiple incidents come to mind, including frequent demands to see my hospital badge despite the same not being of asked of my White cohorts; denial of entry into physician entrance within the residency building because, despite my professional attire, I was presumed to be a member of the custodial staff; and patients being confused and asking for a doctor despite my long white coat and clear introductions.

Furthermore, the fluency of my speech and the absence of regional dialect or vernacular are quite often lauded by patients. Inquiries to touch my hair as well as hypotheses regarding my nationality or degree of “blackness” with respect to the shape of my nose, eyes, and lips are openly questioned. Unfortunately, those uncomfortable incidents have not been limited to patient encounters.

In one instance, while presenting a patient in the presence of my attending and a 3rd-year medical student, I was sternly admonished for disclosing the race of the patient. I sat still and resolute as this doctor spoke on increased risk of bias in diagnosis and treatment when race is identified. Outwardly, I projected patience but inside, I seethed. In that moment, I realized that I would never have the luxury of ignorance or denial. Although I desire to be valued for my prowess in medicine, the mythical status was not created with my skin color in mind. For is avoidance not but a reflection of denial?

In these chaotic and uncertain times, how can we continue to promote a pathological ideal when the roads traveled are so fundamentally skewed? If a White physician faces a belligerent and argumentative patient, there is opportunity for debriefing both individually and among a larger cohort via classes, conferences, and supervisions. Conversely, when a Black physician is derided with racist sentiment, will they have the same opportunity for reflection and support? Despite identical expectations of professionalism and growth, how can one be successful in a system that either directly or indirectly encourages the opposite?

As we try to shed the super-doctor myth, we must recognize that this unattainable and detrimental persona hinders progress. This myth undermines our ability to understand our fragility, the limitations of our capabilities, and the strength of our vulnerability. We must take an honest look at the manner in which our individual biases and the deeply ingrained (and potentially unconscious) systemic biases are counterintuitive to the success and support of physicians of color.

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

There is currently no evidence that newer antiseizure medications increase the risk for suicide among patients with epilepsy, new research shows. “There appears to be no justification for the FDA to label every new antiseizure medication with a warning that it may increase risk of suicidality,” said study investigator Michael R. Sperling, MD, professor of neurology, Thomas Jefferson University, Philadelphia.

“How many patients are afraid of their medication and do not take it because of the warning – and are consequently at risk because of that? We do not know, but have anecdotal experience that this is certainly an issue,” Dr. Sperling, who is director of the Jefferson Comprehensive Epilepsy Center, added.

The study was published online August 2 in JAMA Neurology.
 

Blanket warning

In 2008, the FDA issued an alert stating that antiseizure medications increase suicidality. The alert was based on pooled data from placebo-controlled clinical trials that included 11 antiseizure medications – carbamazepine, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, valproate, and zonisamide.

The meta-analytic review showed that, compared with placebo, antiseizure medications nearly doubled suicide risk among patients treated for epilepsy, psychiatric disorders, and other diseases. As a result of the FDA study, all antiseizure medications that have been approved since 2008 carry a warning for suicidality.

However, subsequent analyses did not show the same results, Dr. Sperling and colleagues noted.

“Pivotal” antiseizure medication epilepsy trials since 2008 have evaluated suicidality prospectively. Since 2011, trials have included the validated Columbia Suicidality Severity Rating Scale, they noted.
 

Meta analysis showed no increased risk

Dr. Sperling and colleagues conducted a meta-analysis of 17 randomized placebo-controlled epilepsy trials of five antiseizure medications approved since 2008. These antiseizure medications were eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate. The trials involved 5,996 patients, including 4,000 who were treated with antiseizure medications and 1,996 who were treated with placebo.

Confining the analysis to epilepsy trials avoids potential confounders, such as possible differences in suicidality risks between different diseases, the researchers noted.

They found no evidence of increased risk for suicidal ideation (overall risk ratio, antiseizure medications vs. placebo: 0.75; 95% confidence interval: 0.35-1.60) or suicide attempt (risk ratio, 0.75; 95% CI: 0.30-1.87) overall or for any individual antiseizure medication.

Suicidal ideation occurred in 12 of 4,000 patients treated with antiseizure medications (0.30%), versus 7 of 1,996 patients treated with placebo (0.35%) (P = .74). Three patients who were treated with antiseizure medications attempted suicide; no patients who were treated with placebo attempted suicide (P = .22). There were no completed suicides.

“There is no current evidence that the five antiseizure medications evaluated in this study increase suicidality in epilepsy and merit a suicidality class warning,” the investigators wrote. When prescribed for epilepsy, “evidence does not support the FDA’s labeling practice of a blanket assumption of increased suicidality,” said Dr. Sperling.

“Our findings indicate the nonspecific suicide warning for all epilepsy drugs is simply not justifiable,” he said. “The results are not surprising. Different drugs affect cells in different ways. So there’s no reason to expect that every drug would increase suicide risk for every patient,” Dr. Sperling said in a statement.

“It’s important to recognize that epilepsy has many causes – perinatal injury, stroke, tumor, head trauma, developmental malformations, genetic causes, and others – and these underlying etiologies may well contribute to the presence of depression and suicidality in this population,” he said in an interview. “Psychodynamic influences also may occur as a consequence of having seizures. This is a complicated area, and drugs are simply one piece of the puzzle,” he added.

Dr. Sperling said the FDA has accomplished “one useful thing with its warning – it highlighted that physicians and other health care providers must pay attention to their patients’ psychological state, ask questions, and treat accordingly.”

The study had no specific funding. Dr. Sperling has received grants from Eisai, Medtronic, Neurelis, SK Life Science, Sunovion, Takeda, Xenon, Cerevel Therapeutics, UCB Pharma, and Engage Pharma; personal fees from Neurelis, Medscape, Neurology Live, International Medical Press, UCB Pharma, Eisai, Oxford University Press, and Projects in Knowledge. He has also consulted for Medtronic outside the submitted work; payments went to Thomas Jefferson University. A complete list of authors’ disclosures is available with the original article.

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

There is currently no evidence that newer antiseizure medications increase the risk for suicide among patients with epilepsy, new research shows. “There appears to be no justification for the FDA to label every new antiseizure medication with a warning that it may increase risk of suicidality,” said study investigator Michael R. Sperling, MD, professor of neurology, Thomas Jefferson University, Philadelphia.

“How many patients are afraid of their medication and do not take it because of the warning – and are consequently at risk because of that? We do not know, but have anecdotal experience that this is certainly an issue,” Dr. Sperling, who is director of the Jefferson Comprehensive Epilepsy Center, added.

The study was published online August 2 in JAMA Neurology.
 

Blanket warning

In 2008, the FDA issued an alert stating that antiseizure medications increase suicidality. The alert was based on pooled data from placebo-controlled clinical trials that included 11 antiseizure medications – carbamazepine, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, valproate, and zonisamide.

The meta-analytic review showed that, compared with placebo, antiseizure medications nearly doubled suicide risk among patients treated for epilepsy, psychiatric disorders, and other diseases. As a result of the FDA study, all antiseizure medications that have been approved since 2008 carry a warning for suicidality.

However, subsequent analyses did not show the same results, Dr. Sperling and colleagues noted.

“Pivotal” antiseizure medication epilepsy trials since 2008 have evaluated suicidality prospectively. Since 2011, trials have included the validated Columbia Suicidality Severity Rating Scale, they noted.
 

Meta analysis showed no increased risk

Dr. Sperling and colleagues conducted a meta-analysis of 17 randomized placebo-controlled epilepsy trials of five antiseizure medications approved since 2008. These antiseizure medications were eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate. The trials involved 5,996 patients, including 4,000 who were treated with antiseizure medications and 1,996 who were treated with placebo.

Confining the analysis to epilepsy trials avoids potential confounders, such as possible differences in suicidality risks between different diseases, the researchers noted.

They found no evidence of increased risk for suicidal ideation (overall risk ratio, antiseizure medications vs. placebo: 0.75; 95% confidence interval: 0.35-1.60) or suicide attempt (risk ratio, 0.75; 95% CI: 0.30-1.87) overall or for any individual antiseizure medication.

Suicidal ideation occurred in 12 of 4,000 patients treated with antiseizure medications (0.30%), versus 7 of 1,996 patients treated with placebo (0.35%) (P = .74). Three patients who were treated with antiseizure medications attempted suicide; no patients who were treated with placebo attempted suicide (P = .22). There were no completed suicides.

“There is no current evidence that the five antiseizure medications evaluated in this study increase suicidality in epilepsy and merit a suicidality class warning,” the investigators wrote. When prescribed for epilepsy, “evidence does not support the FDA’s labeling practice of a blanket assumption of increased suicidality,” said Dr. Sperling.

“Our findings indicate the nonspecific suicide warning for all epilepsy drugs is simply not justifiable,” he said. “The results are not surprising. Different drugs affect cells in different ways. So there’s no reason to expect that every drug would increase suicide risk for every patient,” Dr. Sperling said in a statement.

“It’s important to recognize that epilepsy has many causes – perinatal injury, stroke, tumor, head trauma, developmental malformations, genetic causes, and others – and these underlying etiologies may well contribute to the presence of depression and suicidality in this population,” he said in an interview. “Psychodynamic influences also may occur as a consequence of having seizures. This is a complicated area, and drugs are simply one piece of the puzzle,” he added.

Dr. Sperling said the FDA has accomplished “one useful thing with its warning – it highlighted that physicians and other health care providers must pay attention to their patients’ psychological state, ask questions, and treat accordingly.”

The study had no specific funding. Dr. Sperling has received grants from Eisai, Medtronic, Neurelis, SK Life Science, Sunovion, Takeda, Xenon, Cerevel Therapeutics, UCB Pharma, and Engage Pharma; personal fees from Neurelis, Medscape, Neurology Live, International Medical Press, UCB Pharma, Eisai, Oxford University Press, and Projects in Knowledge. He has also consulted for Medtronic outside the submitted work; payments went to Thomas Jefferson University. A complete list of authors’ disclosures is available with the original article.

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

There is currently no evidence that newer antiseizure medications increase the risk for suicide among patients with epilepsy, new research shows. “There appears to be no justification for the FDA to label every new antiseizure medication with a warning that it may increase risk of suicidality,” said study investigator Michael R. Sperling, MD, professor of neurology, Thomas Jefferson University, Philadelphia.

“How many patients are afraid of their medication and do not take it because of the warning – and are consequently at risk because of that? We do not know, but have anecdotal experience that this is certainly an issue,” Dr. Sperling, who is director of the Jefferson Comprehensive Epilepsy Center, added.

The study was published online August 2 in JAMA Neurology.
 

Blanket warning

In 2008, the FDA issued an alert stating that antiseizure medications increase suicidality. The alert was based on pooled data from placebo-controlled clinical trials that included 11 antiseizure medications – carbamazepine, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, valproate, and zonisamide.

The meta-analytic review showed that, compared with placebo, antiseizure medications nearly doubled suicide risk among patients treated for epilepsy, psychiatric disorders, and other diseases. As a result of the FDA study, all antiseizure medications that have been approved since 2008 carry a warning for suicidality.

However, subsequent analyses did not show the same results, Dr. Sperling and colleagues noted.

“Pivotal” antiseizure medication epilepsy trials since 2008 have evaluated suicidality prospectively. Since 2011, trials have included the validated Columbia Suicidality Severity Rating Scale, they noted.
 

Meta analysis showed no increased risk

Dr. Sperling and colleagues conducted a meta-analysis of 17 randomized placebo-controlled epilepsy trials of five antiseizure medications approved since 2008. These antiseizure medications were eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate. The trials involved 5,996 patients, including 4,000 who were treated with antiseizure medications and 1,996 who were treated with placebo.

Confining the analysis to epilepsy trials avoids potential confounders, such as possible differences in suicidality risks between different diseases, the researchers noted.

They found no evidence of increased risk for suicidal ideation (overall risk ratio, antiseizure medications vs. placebo: 0.75; 95% confidence interval: 0.35-1.60) or suicide attempt (risk ratio, 0.75; 95% CI: 0.30-1.87) overall or for any individual antiseizure medication.

Suicidal ideation occurred in 12 of 4,000 patients treated with antiseizure medications (0.30%), versus 7 of 1,996 patients treated with placebo (0.35%) (P = .74). Three patients who were treated with antiseizure medications attempted suicide; no patients who were treated with placebo attempted suicide (P = .22). There were no completed suicides.

“There is no current evidence that the five antiseizure medications evaluated in this study increase suicidality in epilepsy and merit a suicidality class warning,” the investigators wrote. When prescribed for epilepsy, “evidence does not support the FDA’s labeling practice of a blanket assumption of increased suicidality,” said Dr. Sperling.

“Our findings indicate the nonspecific suicide warning for all epilepsy drugs is simply not justifiable,” he said. “The results are not surprising. Different drugs affect cells in different ways. So there’s no reason to expect that every drug would increase suicide risk for every patient,” Dr. Sperling said in a statement.

“It’s important to recognize that epilepsy has many causes – perinatal injury, stroke, tumor, head trauma, developmental malformations, genetic causes, and others – and these underlying etiologies may well contribute to the presence of depression and suicidality in this population,” he said in an interview. “Psychodynamic influences also may occur as a consequence of having seizures. This is a complicated area, and drugs are simply one piece of the puzzle,” he added.

Dr. Sperling said the FDA has accomplished “one useful thing with its warning – it highlighted that physicians and other health care providers must pay attention to their patients’ psychological state, ask questions, and treat accordingly.”

The study had no specific funding. Dr. Sperling has received grants from Eisai, Medtronic, Neurelis, SK Life Science, Sunovion, Takeda, Xenon, Cerevel Therapeutics, UCB Pharma, and Engage Pharma; personal fees from Neurelis, Medscape, Neurology Live, International Medical Press, UCB Pharma, Eisai, Oxford University Press, and Projects in Knowledge. He has also consulted for Medtronic outside the submitted work; payments went to Thomas Jefferson University. A complete list of authors’ disclosures is available with the original article.

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

Wisdom increases with age, and although this personality trait is regarded as nebulous by many, there is evidence that it has biological and neuropsychiatric underpinnings. It could even hold the key to reducing loneliness and burnout among older people.

Courtesy Dr. Tanya T. Nguyen

Those were some of the key messages delivered by Tanya T. Nguyen, PhD, of the department of psychiatry at the University of California, San Diego, who spoke at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“To many people, wisdom remains a fuzzy concept that’s difficult to operationalize and measure. It’s analogous to the concepts of consciousness, emotions, and cognitions, which at one point were considered nonscientific, but today we accept them as biological and scientific entities,” Dr. Nguyen said during her talk at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Interest in quantifying and studying wisdom has picked up in recent years, and Dr. Nguyen gave a definition with six elements that includes prosocial behaviors such as empathy and compassion, as well as emotional regulation, self-reflection, decisiveness, and social decision-making. She also included a spirituality component, though she conceded that this is controversial.

She noted that there are cultural variations in the definition of wisdom, but it has changed little over time, suggesting that it may be biological rather than cultural in nature, and therefore may have a neuropsychiatric underpinning.

Loss of some or all characteristics of wisdom occurs in some behaviors and disorders, including most markedly in the neurodegenerative disorder frontotemporal dementia (FTD), which is characterized by damage only in the prefrontal cortex and anterior temporal lobes. It usually occurs before age 60, and patients exhibit poor social awareness, impulsivity, antisocial behavior, and a lack of insight and empathy.

This and other lines of evidence have led to the suggestion that wisdom may be governed by processes in the prefrontal cortex and the limbic striatum. The prefrontal cortex controls executive functions such as planning, predicting, and anticipating events, as well as managing emotional reactions and impulses. “Thus, wisdom involves parts of the brain that balance cold, hard analytical reasoning with primitive desires and drives, which ultimately leads to self-regulation, social insight, theory of mind, and empathy,” said Dr. Nguyen.

Wisdom has long been associated with age, but age is also linked to cognitive decline. A recent discovery that the brain does not stop evolving at older age may help explain this contradiction. Brains develop in a back to front order, so that the prefrontal cortex is the last to mature. As we age, neural activity shifts from the occipital lobes to the prefrontal cortex and its executive decision-making power.

“The brain may recruit higher-order networks to the prefrontal cortex that are associated with wisdom development,” said Dr. Nguyen. She also pointed out that asymmetry between the left and right hemisphere is reduced with age, as tasks that relied on circuits from one hemisphere or another more often call upon both. “In order to make up for lost synapses and neurons with aging, active older adults use more neuronal networks from both hemispheres to perform the same mental activity,” Dr. Nguyen said.

Some interventions can improve scores in traits associated with wisdom in older adults, and could be an important contributor to improvements in health and longevity, said Dr. Nguyen. Randomized, controlled trials have demonstrated that psychosocial or behavioral interventions can improve elements of wisdom such as prosocial behaviors and emotional regulation, both in people with mental illness and in the general population, with moderate to large effect sizes. But such studies don’t prove an effect on overall wisdom.

Dr. Nguyen’s group tested a manualized intervention called Raise Your Resilience, which attempts to improve wisdom, resilience, and perceived stress through engagement in value-based activities. The intervention achieved positive results in 89 participants in senior housing communities, though the effect sizes were small, possibly because of high baseline resilience. A subanalysis suggested that reduction in loneliness was mediated by an increase in compassion.

“One of the most striking findings from our research on wisdom is this consistent and very strongly negative correlation between wisdom and loneliness,” Dr. Nguyen said. She highlighted other U.S. nationwide and cross-cultural studies that showed inverse relationships between loneliness and wisdom.

Loneliness is an important topic because it can contribute to burnout and suicide rates.

“Loneliness has a profound effect on how we show up in the workplace, in school, and in our communities. And that leads to anxiety, depression, depersonalization, and emotional fatigue. All are key features of burnout. And together loneliness and burnout have contributed to increased rates of suicide by 30%, and opioid-related deaths almost sixfold since the late 1990s,” Dr. Nguyen said.

Loneliness also is associated with worse physical health, and it may be linked to wisdom. “Loneliness can be conceptualized as being caused and maintained by objective circumstances, such as physical or social distancing, and by thoughts, behaviors, and feelings surrounding those experiences, including biased perceptions of social relations, and a negative assessment of one’s social skills, which then results in a discrepancy between one’s desired and perceived social relationships, which then can contribute to social withdrawal,” Dr. Nguyen said.

Dr. Nguyen highlighted the AARP Foundation’s Experience Corps program, which recruits older adults to act as mentors and tutors for children in kindergarten through third grade. It involves 15 hours per week over an entire school year, with a focus on child literacy, development, and behavioral management skills. A study revealed a significant impact. “It showed improvements in children’s grades and happiness, as well as seniors’ mental and physical health,” Dr. Nguyen said.

Dr. Nguyen concluded that wisdom “may be a vaccine against compassion fatigue and burnout that drive today’s behavioral epidemics of loneliness, opioid abuse, and suicide. It’s a tool for our times. It’s nuanced, flexible, pragmatic, compassionate, and it presents a reasonable framework for getting along in the often messy world that we all share.”
 

Implications for psychiatrists

Henry A. Nasrallah, MD, who organized the conference, suggested that the benefits of wisdom may not be limited to patients. He pointed out that surgeons often retire at age 60 or 65 because of declining physical skills, while psychiatrists continue to practice.

“We develop more wisdom and better skills, and we can practice into our 60s and 70s. I know psychiatrists who practice sometimes into their 80s. It’s really a wonderful thing to know that what you do in life develops or enhances the neuroplasticity of certain brain regions. In our case, in psychiatry, it is the brain regions involved in wisdom,” commented Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.

Dr. Nguyen has no financial disclosures. Dr. Nasrallah has received grants from Abbott, AstraZeneca, Forest, Janssen, Lilly, Pfizer, and Shire, and advises Abbott, AstraZeneca, and Shire.

Wisdom increases with age, and although this personality trait is regarded as nebulous by many, there is evidence that it has biological and neuropsychiatric underpinnings. It could even hold the key to reducing loneliness and burnout among older people.

Courtesy Dr. Tanya T. Nguyen

Those were some of the key messages delivered by Tanya T. Nguyen, PhD, of the department of psychiatry at the University of California, San Diego, who spoke at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“To many people, wisdom remains a fuzzy concept that’s difficult to operationalize and measure. It’s analogous to the concepts of consciousness, emotions, and cognitions, which at one point were considered nonscientific, but today we accept them as biological and scientific entities,” Dr. Nguyen said during her talk at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Interest in quantifying and studying wisdom has picked up in recent years, and Dr. Nguyen gave a definition with six elements that includes prosocial behaviors such as empathy and compassion, as well as emotional regulation, self-reflection, decisiveness, and social decision-making. She also included a spirituality component, though she conceded that this is controversial.

She noted that there are cultural variations in the definition of wisdom, but it has changed little over time, suggesting that it may be biological rather than cultural in nature, and therefore may have a neuropsychiatric underpinning.

Loss of some or all characteristics of wisdom occurs in some behaviors and disorders, including most markedly in the neurodegenerative disorder frontotemporal dementia (FTD), which is characterized by damage only in the prefrontal cortex and anterior temporal lobes. It usually occurs before age 60, and patients exhibit poor social awareness, impulsivity, antisocial behavior, and a lack of insight and empathy.

This and other lines of evidence have led to the suggestion that wisdom may be governed by processes in the prefrontal cortex and the limbic striatum. The prefrontal cortex controls executive functions such as planning, predicting, and anticipating events, as well as managing emotional reactions and impulses. “Thus, wisdom involves parts of the brain that balance cold, hard analytical reasoning with primitive desires and drives, which ultimately leads to self-regulation, social insight, theory of mind, and empathy,” said Dr. Nguyen.

Wisdom has long been associated with age, but age is also linked to cognitive decline. A recent discovery that the brain does not stop evolving at older age may help explain this contradiction. Brains develop in a back to front order, so that the prefrontal cortex is the last to mature. As we age, neural activity shifts from the occipital lobes to the prefrontal cortex and its executive decision-making power.

“The brain may recruit higher-order networks to the prefrontal cortex that are associated with wisdom development,” said Dr. Nguyen. She also pointed out that asymmetry between the left and right hemisphere is reduced with age, as tasks that relied on circuits from one hemisphere or another more often call upon both. “In order to make up for lost synapses and neurons with aging, active older adults use more neuronal networks from both hemispheres to perform the same mental activity,” Dr. Nguyen said.

Some interventions can improve scores in traits associated with wisdom in older adults, and could be an important contributor to improvements in health and longevity, said Dr. Nguyen. Randomized, controlled trials have demonstrated that psychosocial or behavioral interventions can improve elements of wisdom such as prosocial behaviors and emotional regulation, both in people with mental illness and in the general population, with moderate to large effect sizes. But such studies don’t prove an effect on overall wisdom.

Dr. Nguyen’s group tested a manualized intervention called Raise Your Resilience, which attempts to improve wisdom, resilience, and perceived stress through engagement in value-based activities. The intervention achieved positive results in 89 participants in senior housing communities, though the effect sizes were small, possibly because of high baseline resilience. A subanalysis suggested that reduction in loneliness was mediated by an increase in compassion.

“One of the most striking findings from our research on wisdom is this consistent and very strongly negative correlation between wisdom and loneliness,” Dr. Nguyen said. She highlighted other U.S. nationwide and cross-cultural studies that showed inverse relationships between loneliness and wisdom.

Loneliness is an important topic because it can contribute to burnout and suicide rates.

“Loneliness has a profound effect on how we show up in the workplace, in school, and in our communities. And that leads to anxiety, depression, depersonalization, and emotional fatigue. All are key features of burnout. And together loneliness and burnout have contributed to increased rates of suicide by 30%, and opioid-related deaths almost sixfold since the late 1990s,” Dr. Nguyen said.

Loneliness also is associated with worse physical health, and it may be linked to wisdom. “Loneliness can be conceptualized as being caused and maintained by objective circumstances, such as physical or social distancing, and by thoughts, behaviors, and feelings surrounding those experiences, including biased perceptions of social relations, and a negative assessment of one’s social skills, which then results in a discrepancy between one’s desired and perceived social relationships, which then can contribute to social withdrawal,” Dr. Nguyen said.

Dr. Nguyen highlighted the AARP Foundation’s Experience Corps program, which recruits older adults to act as mentors and tutors for children in kindergarten through third grade. It involves 15 hours per week over an entire school year, with a focus on child literacy, development, and behavioral management skills. A study revealed a significant impact. “It showed improvements in children’s grades and happiness, as well as seniors’ mental and physical health,” Dr. Nguyen said.

Dr. Nguyen concluded that wisdom “may be a vaccine against compassion fatigue and burnout that drive today’s behavioral epidemics of loneliness, opioid abuse, and suicide. It’s a tool for our times. It’s nuanced, flexible, pragmatic, compassionate, and it presents a reasonable framework for getting along in the often messy world that we all share.”
 

Implications for psychiatrists

Henry A. Nasrallah, MD, who organized the conference, suggested that the benefits of wisdom may not be limited to patients. He pointed out that surgeons often retire at age 60 or 65 because of declining physical skills, while psychiatrists continue to practice.

“We develop more wisdom and better skills, and we can practice into our 60s and 70s. I know psychiatrists who practice sometimes into their 80s. It’s really a wonderful thing to know that what you do in life develops or enhances the neuroplasticity of certain brain regions. In our case, in psychiatry, it is the brain regions involved in wisdom,” commented Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.

Dr. Nguyen has no financial disclosures. Dr. Nasrallah has received grants from Abbott, AstraZeneca, Forest, Janssen, Lilly, Pfizer, and Shire, and advises Abbott, AstraZeneca, and Shire.

Wisdom increases with age, and although this personality trait is regarded as nebulous by many, there is evidence that it has biological and neuropsychiatric underpinnings. It could even hold the key to reducing loneliness and burnout among older people.

Courtesy Dr. Tanya T. Nguyen

Those were some of the key messages delivered by Tanya T. Nguyen, PhD, of the department of psychiatry at the University of California, San Diego, who spoke at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“To many people, wisdom remains a fuzzy concept that’s difficult to operationalize and measure. It’s analogous to the concepts of consciousness, emotions, and cognitions, which at one point were considered nonscientific, but today we accept them as biological and scientific entities,” Dr. Nguyen said during her talk at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Interest in quantifying and studying wisdom has picked up in recent years, and Dr. Nguyen gave a definition with six elements that includes prosocial behaviors such as empathy and compassion, as well as emotional regulation, self-reflection, decisiveness, and social decision-making. She also included a spirituality component, though she conceded that this is controversial.

She noted that there are cultural variations in the definition of wisdom, but it has changed little over time, suggesting that it may be biological rather than cultural in nature, and therefore may have a neuropsychiatric underpinning.

Loss of some or all characteristics of wisdom occurs in some behaviors and disorders, including most markedly in the neurodegenerative disorder frontotemporal dementia (FTD), which is characterized by damage only in the prefrontal cortex and anterior temporal lobes. It usually occurs before age 60, and patients exhibit poor social awareness, impulsivity, antisocial behavior, and a lack of insight and empathy.

This and other lines of evidence have led to the suggestion that wisdom may be governed by processes in the prefrontal cortex and the limbic striatum. The prefrontal cortex controls executive functions such as planning, predicting, and anticipating events, as well as managing emotional reactions and impulses. “Thus, wisdom involves parts of the brain that balance cold, hard analytical reasoning with primitive desires and drives, which ultimately leads to self-regulation, social insight, theory of mind, and empathy,” said Dr. Nguyen.

Wisdom has long been associated with age, but age is also linked to cognitive decline. A recent discovery that the brain does not stop evolving at older age may help explain this contradiction. Brains develop in a back to front order, so that the prefrontal cortex is the last to mature. As we age, neural activity shifts from the occipital lobes to the prefrontal cortex and its executive decision-making power.

“The brain may recruit higher-order networks to the prefrontal cortex that are associated with wisdom development,” said Dr. Nguyen. She also pointed out that asymmetry between the left and right hemisphere is reduced with age, as tasks that relied on circuits from one hemisphere or another more often call upon both. “In order to make up for lost synapses and neurons with aging, active older adults use more neuronal networks from both hemispheres to perform the same mental activity,” Dr. Nguyen said.

Some interventions can improve scores in traits associated with wisdom in older adults, and could be an important contributor to improvements in health and longevity, said Dr. Nguyen. Randomized, controlled trials have demonstrated that psychosocial or behavioral interventions can improve elements of wisdom such as prosocial behaviors and emotional regulation, both in people with mental illness and in the general population, with moderate to large effect sizes. But such studies don’t prove an effect on overall wisdom.

Dr. Nguyen’s group tested a manualized intervention called Raise Your Resilience, which attempts to improve wisdom, resilience, and perceived stress through engagement in value-based activities. The intervention achieved positive results in 89 participants in senior housing communities, though the effect sizes were small, possibly because of high baseline resilience. A subanalysis suggested that reduction in loneliness was mediated by an increase in compassion.

“One of the most striking findings from our research on wisdom is this consistent and very strongly negative correlation between wisdom and loneliness,” Dr. Nguyen said. She highlighted other U.S. nationwide and cross-cultural studies that showed inverse relationships between loneliness and wisdom.

Loneliness is an important topic because it can contribute to burnout and suicide rates.

“Loneliness has a profound effect on how we show up in the workplace, in school, and in our communities. And that leads to anxiety, depression, depersonalization, and emotional fatigue. All are key features of burnout. And together loneliness and burnout have contributed to increased rates of suicide by 30%, and opioid-related deaths almost sixfold since the late 1990s,” Dr. Nguyen said.

Loneliness also is associated with worse physical health, and it may be linked to wisdom. “Loneliness can be conceptualized as being caused and maintained by objective circumstances, such as physical or social distancing, and by thoughts, behaviors, and feelings surrounding those experiences, including biased perceptions of social relations, and a negative assessment of one’s social skills, which then results in a discrepancy between one’s desired and perceived social relationships, which then can contribute to social withdrawal,” Dr. Nguyen said.

Dr. Nguyen highlighted the AARP Foundation’s Experience Corps program, which recruits older adults to act as mentors and tutors for children in kindergarten through third grade. It involves 15 hours per week over an entire school year, with a focus on child literacy, development, and behavioral management skills. A study revealed a significant impact. “It showed improvements in children’s grades and happiness, as well as seniors’ mental and physical health,” Dr. Nguyen said.

Dr. Nguyen concluded that wisdom “may be a vaccine against compassion fatigue and burnout that drive today’s behavioral epidemics of loneliness, opioid abuse, and suicide. It’s a tool for our times. It’s nuanced, flexible, pragmatic, compassionate, and it presents a reasonable framework for getting along in the often messy world that we all share.”
 

Implications for psychiatrists

Henry A. Nasrallah, MD, who organized the conference, suggested that the benefits of wisdom may not be limited to patients. He pointed out that surgeons often retire at age 60 or 65 because of declining physical skills, while psychiatrists continue to practice.

“We develop more wisdom and better skills, and we can practice into our 60s and 70s. I know psychiatrists who practice sometimes into their 80s. It’s really a wonderful thing to know that what you do in life develops or enhances the neuroplasticity of certain brain regions. In our case, in psychiatry, it is the brain regions involved in wisdom,” commented Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.

Dr. Nguyen has no financial disclosures. Dr. Nasrallah has received grants from Abbott, AstraZeneca, Forest, Janssen, Lilly, Pfizer, and Shire, and advises Abbott, AstraZeneca, and Shire.

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

Rhythmic brain signals that help encode memories also appear to influence blood sugar levels and may regulate the timing of the release of hormones, early, pre-clinical research shows.

“Our study is the first to show how clusters of brain cell firing in the hippocampus may directly regulate metabolism,” senior author György Buzsáki, MD, PhD, professor, department of neuroscience and physiology, NYU Grossman School of Medicine and NYU Langone Health, said in a news release.

“Evidence suggests that the brain evolved, for reasons of efficiency, to use the same signals to achieve two very different functions in terms of memory and hormonal regulation,” added corresponding author David Tingley, PhD, a post-doctoral scholar in Dr. Buzsáki’s lab.

Additional research may also reveal devices or therapies that can adjust the brain signals to lower blood sugar and improve memory, the researchers say.

The study was published online August 11 in Nature.

It’s recently been discovered that populations of hippocampal neurons fire within milliseconds of each other in cycles. This firing pattern is called a “sharp wave ripple” for the shape it takes when captured graphically by electroencephalogram.

In their study, Dr. Buzsáki, Dr. Tingley, and colleagues observed that clusters of sharp wave ripples recorded from the hippocampus of rats were “reliably” and rapidly, followed by decreases in blood sugar concentrations in the animals.

“This correlation was not dependent on circadian, ultradian, or meal-triggered fluctuations; it could be mimicked with optogenetically induced ripples in the hippocampus, but not in the parietal cortex, and was attenuated to chance levels by pharmacogenetically suppressing activity of the lateral septum (LS), the major conduit between the hippocampus and hypothalamus,” the researchers report.

These observations suggest that hippocampal sharp wave ripples may regulate the timing of the release of hormones, possibly including insulin, by the pancreas and liver, as well as other hormones by the pituitary gland, the researchers note.

As sharp wave ripples mostly occur during non-rapid eye movement sleep, the impact of sleep disturbance on sharp wave ripples may provide a mechanistic link between poor sleep and high blood sugar levels seen in type 2 diabetes, they suggest.

“There are a couple of experimental studies showing that if you deprive a young healthy person from sleep [for 48 hours], their glucose tolerance resembles” that of a person with diabetes, Dr. Buzsáki noted in an interview.

Moving forward, the researchers will seek to extend their theory that several hormones could be affected by nightly sharp wave ripples.

The research was funded by National Institutes of Health. The authors have disclosed no relevant financial relationships.

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

Rhythmic brain signals that help encode memories also appear to influence blood sugar levels and may regulate the timing of the release of hormones, early, pre-clinical research shows.

“Our study is the first to show how clusters of brain cell firing in the hippocampus may directly regulate metabolism,” senior author György Buzsáki, MD, PhD, professor, department of neuroscience and physiology, NYU Grossman School of Medicine and NYU Langone Health, said in a news release.

“Evidence suggests that the brain evolved, for reasons of efficiency, to use the same signals to achieve two very different functions in terms of memory and hormonal regulation,” added corresponding author David Tingley, PhD, a post-doctoral scholar in Dr. Buzsáki’s lab.

Additional research may also reveal devices or therapies that can adjust the brain signals to lower blood sugar and improve memory, the researchers say.

The study was published online August 11 in Nature.

It’s recently been discovered that populations of hippocampal neurons fire within milliseconds of each other in cycles. This firing pattern is called a “sharp wave ripple” for the shape it takes when captured graphically by electroencephalogram.

In their study, Dr. Buzsáki, Dr. Tingley, and colleagues observed that clusters of sharp wave ripples recorded from the hippocampus of rats were “reliably” and rapidly, followed by decreases in blood sugar concentrations in the animals.

“This correlation was not dependent on circadian, ultradian, or meal-triggered fluctuations; it could be mimicked with optogenetically induced ripples in the hippocampus, but not in the parietal cortex, and was attenuated to chance levels by pharmacogenetically suppressing activity of the lateral septum (LS), the major conduit between the hippocampus and hypothalamus,” the researchers report.

These observations suggest that hippocampal sharp wave ripples may regulate the timing of the release of hormones, possibly including insulin, by the pancreas and liver, as well as other hormones by the pituitary gland, the researchers note.

As sharp wave ripples mostly occur during non-rapid eye movement sleep, the impact of sleep disturbance on sharp wave ripples may provide a mechanistic link between poor sleep and high blood sugar levels seen in type 2 diabetes, they suggest.

“There are a couple of experimental studies showing that if you deprive a young healthy person from sleep [for 48 hours], their glucose tolerance resembles” that of a person with diabetes, Dr. Buzsáki noted in an interview.

Moving forward, the researchers will seek to extend their theory that several hormones could be affected by nightly sharp wave ripples.

The research was funded by National Institutes of Health. The authors have disclosed no relevant financial relationships.

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

Rhythmic brain signals that help encode memories also appear to influence blood sugar levels and may regulate the timing of the release of hormones, early, pre-clinical research shows.

“Our study is the first to show how clusters of brain cell firing in the hippocampus may directly regulate metabolism,” senior author György Buzsáki, MD, PhD, professor, department of neuroscience and physiology, NYU Grossman School of Medicine and NYU Langone Health, said in a news release.

“Evidence suggests that the brain evolved, for reasons of efficiency, to use the same signals to achieve two very different functions in terms of memory and hormonal regulation,” added corresponding author David Tingley, PhD, a post-doctoral scholar in Dr. Buzsáki’s lab.

Additional research may also reveal devices or therapies that can adjust the brain signals to lower blood sugar and improve memory, the researchers say.

The study was published online August 11 in Nature.

It’s recently been discovered that populations of hippocampal neurons fire within milliseconds of each other in cycles. This firing pattern is called a “sharp wave ripple” for the shape it takes when captured graphically by electroencephalogram.

In their study, Dr. Buzsáki, Dr. Tingley, and colleagues observed that clusters of sharp wave ripples recorded from the hippocampus of rats were “reliably” and rapidly, followed by decreases in blood sugar concentrations in the animals.

“This correlation was not dependent on circadian, ultradian, or meal-triggered fluctuations; it could be mimicked with optogenetically induced ripples in the hippocampus, but not in the parietal cortex, and was attenuated to chance levels by pharmacogenetically suppressing activity of the lateral septum (LS), the major conduit between the hippocampus and hypothalamus,” the researchers report.

These observations suggest that hippocampal sharp wave ripples may regulate the timing of the release of hormones, possibly including insulin, by the pancreas and liver, as well as other hormones by the pituitary gland, the researchers note.

As sharp wave ripples mostly occur during non-rapid eye movement sleep, the impact of sleep disturbance on sharp wave ripples may provide a mechanistic link between poor sleep and high blood sugar levels seen in type 2 diabetes, they suggest.

“There are a couple of experimental studies showing that if you deprive a young healthy person from sleep [for 48 hours], their glucose tolerance resembles” that of a person with diabetes, Dr. Buzsáki noted in an interview.

Moving forward, the researchers will seek to extend their theory that several hormones could be affected by nightly sharp wave ripples.

The research was funded by National Institutes of Health. The authors have disclosed no relevant financial relationships.

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

The Food and Drug Administration has approved an oral solution of calcium, magnesium, potassium, and sodium oxybates (Xywav) for the treatment of idiopathic hypersomnia in adults, the company announced in a news release.

It marks the second approval for Xywav. The FDA approved it last year for the treatment of cataplexy or excessive daytime sleepiness in patients with narcolepsy as young as 7 years of age.

This recent approval is the first for a treatment for idiopathic hypersomnia.

“Idiopathic hypersomnia can have a significant impact on the social, educational, and occupational functioning of people living with the condition,” Diane Powell, board chair and CEO of the Hypersomnia Foundation, noted in the release.

This FDA approval “is a major milestone for the entire idiopathic hypersomnia community as Xywav becomes the first medicine approved to manage this chronic sleep disorder,” said Ms. Powell.

Low sodium oxybate product

Xywav is a novel oxybate product with a unique composition of cations. It contains 92% less sodium than sodium oxybate (Xyrem) at the recommended adult dosage range of 6 to 9 g, the company noted in a news release.

An estimated 37,000 people in the United States have been diagnosed with idiopathic hypersomnia, a neurologic sleep disorder characterized by chronic excessive daytime sleepiness.

Other symptoms of the disorder may include severe sleep inertia or sleep drunkenness (prolonged difficulty waking with frequent re-entries into sleep, confusion, and irritability), as well as prolonged, nonrestorative night-time sleep, cognitive impairment, and long and unrefreshing naps.

The approval was based on findings from a phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal study.

Results showed “statistically significant and clinically meaningful” differences compared with placebo in change in the primary endpoint of Epworth Sleepiness Scale score (P < .0001) and the secondary endpoints of Patient Global Impression of Change (P < .0001) and the Idiopathic Hypersomnia Severity Scale (P < .0001), the company reported.

The most common adverse reactions were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor.

The novel agent can be administered once or twice nightly for the treatment of idiopathic hypersomnia in adults.

“To optimize response, a patient’s health care provider may consider prescribing a twice-nightly regimen in equally or unequally divided doses at bedtime and 2.5 to 4 hours later and gradually titrate Xywav so that a patient may receive an individualized dose and regimen based on efficacy and tolerability,” the company said.

Xywav carries a boxed warning because it is a central nervous system depressant and because there is potential for abuse and misuse. The drug is only available through a risk evaluation and mitigation strategy (REMS) program.

The company plans to make Xywav available to patients with idiopathic hypersomnia later this year following implementation of the REMS program.

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

The Food and Drug Administration has approved an oral solution of calcium, magnesium, potassium, and sodium oxybates (Xywav) for the treatment of idiopathic hypersomnia in adults, the company announced in a news release.

It marks the second approval for Xywav. The FDA approved it last year for the treatment of cataplexy or excessive daytime sleepiness in patients with narcolepsy as young as 7 years of age.

This recent approval is the first for a treatment for idiopathic hypersomnia.

“Idiopathic hypersomnia can have a significant impact on the social, educational, and occupational functioning of people living with the condition,” Diane Powell, board chair and CEO of the Hypersomnia Foundation, noted in the release.

This FDA approval “is a major milestone for the entire idiopathic hypersomnia community as Xywav becomes the first medicine approved to manage this chronic sleep disorder,” said Ms. Powell.

Low sodium oxybate product

Xywav is a novel oxybate product with a unique composition of cations. It contains 92% less sodium than sodium oxybate (Xyrem) at the recommended adult dosage range of 6 to 9 g, the company noted in a news release.

An estimated 37,000 people in the United States have been diagnosed with idiopathic hypersomnia, a neurologic sleep disorder characterized by chronic excessive daytime sleepiness.

Other symptoms of the disorder may include severe sleep inertia or sleep drunkenness (prolonged difficulty waking with frequent re-entries into sleep, confusion, and irritability), as well as prolonged, nonrestorative night-time sleep, cognitive impairment, and long and unrefreshing naps.

The approval was based on findings from a phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal study.

Results showed “statistically significant and clinically meaningful” differences compared with placebo in change in the primary endpoint of Epworth Sleepiness Scale score (P < .0001) and the secondary endpoints of Patient Global Impression of Change (P < .0001) and the Idiopathic Hypersomnia Severity Scale (P < .0001), the company reported.

The most common adverse reactions were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor.

The novel agent can be administered once or twice nightly for the treatment of idiopathic hypersomnia in adults.

“To optimize response, a patient’s health care provider may consider prescribing a twice-nightly regimen in equally or unequally divided doses at bedtime and 2.5 to 4 hours later and gradually titrate Xywav so that a patient may receive an individualized dose and regimen based on efficacy and tolerability,” the company said.

Xywav carries a boxed warning because it is a central nervous system depressant and because there is potential for abuse and misuse. The drug is only available through a risk evaluation and mitigation strategy (REMS) program.

The company plans to make Xywav available to patients with idiopathic hypersomnia later this year following implementation of the REMS program.

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

The Food and Drug Administration has approved an oral solution of calcium, magnesium, potassium, and sodium oxybates (Xywav) for the treatment of idiopathic hypersomnia in adults, the company announced in a news release.

It marks the second approval for Xywav. The FDA approved it last year for the treatment of cataplexy or excessive daytime sleepiness in patients with narcolepsy as young as 7 years of age.

This recent approval is the first for a treatment for idiopathic hypersomnia.

“Idiopathic hypersomnia can have a significant impact on the social, educational, and occupational functioning of people living with the condition,” Diane Powell, board chair and CEO of the Hypersomnia Foundation, noted in the release.

This FDA approval “is a major milestone for the entire idiopathic hypersomnia community as Xywav becomes the first medicine approved to manage this chronic sleep disorder,” said Ms. Powell.

Low sodium oxybate product

Xywav is a novel oxybate product with a unique composition of cations. It contains 92% less sodium than sodium oxybate (Xyrem) at the recommended adult dosage range of 6 to 9 g, the company noted in a news release.

An estimated 37,000 people in the United States have been diagnosed with idiopathic hypersomnia, a neurologic sleep disorder characterized by chronic excessive daytime sleepiness.

Other symptoms of the disorder may include severe sleep inertia or sleep drunkenness (prolonged difficulty waking with frequent re-entries into sleep, confusion, and irritability), as well as prolonged, nonrestorative night-time sleep, cognitive impairment, and long and unrefreshing naps.

The approval was based on findings from a phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal study.

Results showed “statistically significant and clinically meaningful” differences compared with placebo in change in the primary endpoint of Epworth Sleepiness Scale score (P < .0001) and the secondary endpoints of Patient Global Impression of Change (P < .0001) and the Idiopathic Hypersomnia Severity Scale (P < .0001), the company reported.

The most common adverse reactions were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor.

The novel agent can be administered once or twice nightly for the treatment of idiopathic hypersomnia in adults.

“To optimize response, a patient’s health care provider may consider prescribing a twice-nightly regimen in equally or unequally divided doses at bedtime and 2.5 to 4 hours later and gradually titrate Xywav so that a patient may receive an individualized dose and regimen based on efficacy and tolerability,” the company said.

Xywav carries a boxed warning because it is a central nervous system depressant and because there is potential for abuse and misuse. The drug is only available through a risk evaluation and mitigation strategy (REMS) program.

The company plans to make Xywav available to patients with idiopathic hypersomnia later this year following implementation of the REMS program.

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

Therapeutic levels of heparin can have widely varying effects on COVID-19 patients depending on the severity of their disease, according to a multiplatform clinical trial that analyzed patient data from three international trials.

NYU Langone Health

COVID-19 patients in the ICU, or at least receiving ICU-level care, derived no benefit from anticoagulation with heparin, while non–critically ill COVID-19 patients – those who were hospitalized but not receiving ICU-level care – on the same anticoagulation were less likely to progress to need respiratory or cardiovascular organ support despite a slightly heightened risk of bleeding events.

Reporting in two articles published online in the New England Journal of Medicine, authors of three international trials combined their data into one multiplatform trial that makes a strong case for prescribing therapeutic levels of heparin in hospitalized patients not receiving ICU-level care were non–critically ill and critically ill.

“I think this is going to be a game changer,” said Jeffrey S. Berger, MD, ACTIV-4a co–principal investigator and co–first author of the study of non–critically ill patients. “I think that using therapeutic-dose anticoagulation should improve outcomes in the tens of thousands of patients worldwide. I hope our data can have a global impact.”
 

Outcomes based on disease severity

The multiplatform trial analyzed data from the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); and Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

The trial evaluated 2,219 non–critically ill hospitalized patients, 1,181 of whom were randomized to therapeutic-dose anticoagulation; and 1,098 critically ill patients, 534 of whom were prescribed therapeutic levels of heparin.

In the critically ill patients, those on heparin were no more likely to get discharged or spend fewer days on respiratory or CV organ support – oxygen, mechanical ventilation, life support, vasopressors or inotropes – than were those on usual-care thromboprophylaxis. The investigators stopped the trial in both patient populations: in critically ill patients when it became obvious therapeutic-dose anticoagulation was having no impact; and in moderately ill patients when the trial met the prespecified criteria for the superiority of therapeutic-dose anticoagulation.

ICU patients on therapeutic-level heparin spent an average of 1 day free of organ support vs. 4 for patients on usual-care prophylactic antithrombotic drugs. The percentage of patients who survived to hospital discharge was similar in the therapeutic-level and usual-care critically ill patients: 62.7% and 64.5%, respectively. Major bleeding occurred in 3.8% and 2.8%, respectively. Demographic and clinical characteristics were similar between both patient groups.

However, in non–critically ill patients, therapeutic levels of heparin resulted in a marked improvement in outcomes. The researchers estimated that, for every 1,000 hospitalized patients with what they labeled moderate disease, an initial treatment with therapeutic-dose heparin resulted in 40 additional patients surviving compared to usual-care thromboprophylaxis.

The percentages of patients not needing organ support before hospital discharge was 80.2% on therapeutic-dose heparin and 76.4% on usual-care therapy. In terms of adjusted odds ratio, the anticoagulation group had a 27% improved chance of not needing daily organ support.

Those improvements came with an additional seven major bleeding events per 1,000 patients. That broke down to a rate of 1.9% in the therapeutic-dose and 0.9% in the usual-care patients.

As the Delta variant of COVID-19 spreads, Patrick R. Lawler, MD, MPH, principal investigator of the ATTACC trial, said there’s no reason these findings shouldn’t apply for all variants of the disease.

University of Toronto

Dr. Lawler, a physician-scientist at Peter Munk Cardiac Centre at Toronto General Hospital, noted that the multiplatform study did not account for disease variant. “Ongoing clinical trials are tracking the variant patients have or the variants that are most prevalent in an area at that time,” he said. “It may be easier in future trials to look at that question.”
 

Explaining heparin’s varying effects

The study did not specifically sort out why moderately ill patients fared better on heparin than their critically ill counterparts, but Dr. Lawler speculated on possible reasons. “One might be that the extent of illness severity is too extreme in the ICU-level population for heparin to have a beneficial extent,” he said.

He acknowledged that higher rates of macrovascular thrombosis, such as venous thromboembolism, in ICU patients would suggest that heparin would have a greater beneficial effect, but, he added, “it may also suggest how advanced that process is, and perhaps heparin is not adequate to reverse the course at that point given relatively extensive thrombosis and associate organ failure.”

As clinicians have gained experience dealing with COVID-19, they’ve learned that infected patients carry a high burden of macro- and microthrombosis, Dr. Berger said, which may explain why critically ill patients didn’t respond as well to therapeutic levels of heparin. “I think the cat is out of the bag; patients who are severe are too ill to benefit,” he said. “I would think there’s too much microthrombosis that is already in their bodies.”

However, this doesn’t completely rule out therapeutic levels of heparin in critically ill COVID-19 patients. There are some scenarios where it’s needed, said Dr. Berger, associate professor of medicine and surgery and director of the Center for the Prevention of Cardiovascular Disease at New York University Langone Health. “Anyone who has a known clot already, like a known macrothrombosis in their leg or lung, needs to be on full-dose heparin,” he said.

That rationale can help reconcile the different outcomes in the critically and non–critically ill COVID-19 patients, wrote Hugo ten Cate, MD, PhD, of Maastricht University in the Netherlands, wrote in an accompanying editorial. But differences in the study populations may also explain the divergent outcomes, Dr. ten Cate noted.

The studies suggest that critically ill patients may need hon-heparin antithrombotic approaches “or even profibrinolytic strategies,” Dr. Cate wrote, and that the safety and effectiveness of thromboprophylaxis “remains an important question.” Nonetheless, he added, treating physicians must deal with the bleeding risk when using heparin or low-molecular-weight heparin in moderately ill COVID-19 patients.

Deepak L. Bhatt MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview that reconciling the two studies was “a bit challenging,” because effective therapies tend to have a greater impact in sicker patients.

“Of course, with antithrombotic therapies, bleeding side effects can sometimes overwhelm benefits in patients who are at high risk of both bleeding and ischemic complications, though that does not seem to be the explanation here,” Dr. Bhatt said. “I do think we need more data to clarify exactly which COVID patients benefit from various antithrombotic regimens, and fortunately, there are other ongoing studies, some of which will report relatively soon.”

He concurred with Dr. Berger that patients who need anticoagulation should receive it “apart from their COVID status,” Dr. Bhatt said. “Sick, hospitalized patients with or without COVID should receive appropriate prophylactic doses of anticoagulation.” However, he added, “Whether we should routinely go beyond that in COVID-positive inpatients, I think we need more data.”

The ATTACC platform received grants from the Canadian Institutes of Health Research and several other research foundations. The ACTIV-4a platform received funding from the National Heart, Lung, and Blood Institute. REMAP-CAP received funding from the European Union and several international research foundations, as well as Amgen and Eisai.

Dr. Lawler had no relationships to disclose. Dr. Berger disclosed receiving grants from the NHLBI, and financial relationships with AstraZeneca, Janssen, and Amgen outside the submitted work. Dr. ten Cate reported relationships with Alveron, Coagulation Profile, Portola/Alexion, Bayer, Pfizer, Stago, Leo Pharma, Daiichi, and Gilead/Galapagos. Dr. Bhatt is chair of the data safety and monitoring board of the FREEDOM COVID anticoagulation clinical trial.

Therapeutic levels of heparin can have widely varying effects on COVID-19 patients depending on the severity of their disease, according to a multiplatform clinical trial that analyzed patient data from three international trials.

NYU Langone Health

COVID-19 patients in the ICU, or at least receiving ICU-level care, derived no benefit from anticoagulation with heparin, while non–critically ill COVID-19 patients – those who were hospitalized but not receiving ICU-level care – on the same anticoagulation were less likely to progress to need respiratory or cardiovascular organ support despite a slightly heightened risk of bleeding events.

Reporting in two articles published online in the New England Journal of Medicine, authors of three international trials combined their data into one multiplatform trial that makes a strong case for prescribing therapeutic levels of heparin in hospitalized patients not receiving ICU-level care were non–critically ill and critically ill.

“I think this is going to be a game changer,” said Jeffrey S. Berger, MD, ACTIV-4a co–principal investigator and co–first author of the study of non–critically ill patients. “I think that using therapeutic-dose anticoagulation should improve outcomes in the tens of thousands of patients worldwide. I hope our data can have a global impact.”
 

Outcomes based on disease severity

The multiplatform trial analyzed data from the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); and Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

The trial evaluated 2,219 non–critically ill hospitalized patients, 1,181 of whom were randomized to therapeutic-dose anticoagulation; and 1,098 critically ill patients, 534 of whom were prescribed therapeutic levels of heparin.

In the critically ill patients, those on heparin were no more likely to get discharged or spend fewer days on respiratory or CV organ support – oxygen, mechanical ventilation, life support, vasopressors or inotropes – than were those on usual-care thromboprophylaxis. The investigators stopped the trial in both patient populations: in critically ill patients when it became obvious therapeutic-dose anticoagulation was having no impact; and in moderately ill patients when the trial met the prespecified criteria for the superiority of therapeutic-dose anticoagulation.

ICU patients on therapeutic-level heparin spent an average of 1 day free of organ support vs. 4 for patients on usual-care prophylactic antithrombotic drugs. The percentage of patients who survived to hospital discharge was similar in the therapeutic-level and usual-care critically ill patients: 62.7% and 64.5%, respectively. Major bleeding occurred in 3.8% and 2.8%, respectively. Demographic and clinical characteristics were similar between both patient groups.

However, in non–critically ill patients, therapeutic levels of heparin resulted in a marked improvement in outcomes. The researchers estimated that, for every 1,000 hospitalized patients with what they labeled moderate disease, an initial treatment with therapeutic-dose heparin resulted in 40 additional patients surviving compared to usual-care thromboprophylaxis.

The percentages of patients not needing organ support before hospital discharge was 80.2% on therapeutic-dose heparin and 76.4% on usual-care therapy. In terms of adjusted odds ratio, the anticoagulation group had a 27% improved chance of not needing daily organ support.

Those improvements came with an additional seven major bleeding events per 1,000 patients. That broke down to a rate of 1.9% in the therapeutic-dose and 0.9% in the usual-care patients.

As the Delta variant of COVID-19 spreads, Patrick R. Lawler, MD, MPH, principal investigator of the ATTACC trial, said there’s no reason these findings shouldn’t apply for all variants of the disease.

University of Toronto

Dr. Lawler, a physician-scientist at Peter Munk Cardiac Centre at Toronto General Hospital, noted that the multiplatform study did not account for disease variant. “Ongoing clinical trials are tracking the variant patients have or the variants that are most prevalent in an area at that time,” he said. “It may be easier in future trials to look at that question.”
 

Explaining heparin’s varying effects

The study did not specifically sort out why moderately ill patients fared better on heparin than their critically ill counterparts, but Dr. Lawler speculated on possible reasons. “One might be that the extent of illness severity is too extreme in the ICU-level population for heparin to have a beneficial extent,” he said.

He acknowledged that higher rates of macrovascular thrombosis, such as venous thromboembolism, in ICU patients would suggest that heparin would have a greater beneficial effect, but, he added, “it may also suggest how advanced that process is, and perhaps heparin is not adequate to reverse the course at that point given relatively extensive thrombosis and associate organ failure.”

As clinicians have gained experience dealing with COVID-19, they’ve learned that infected patients carry a high burden of macro- and microthrombosis, Dr. Berger said, which may explain why critically ill patients didn’t respond as well to therapeutic levels of heparin. “I think the cat is out of the bag; patients who are severe are too ill to benefit,” he said. “I would think there’s too much microthrombosis that is already in their bodies.”

However, this doesn’t completely rule out therapeutic levels of heparin in critically ill COVID-19 patients. There are some scenarios where it’s needed, said Dr. Berger, associate professor of medicine and surgery and director of the Center for the Prevention of Cardiovascular Disease at New York University Langone Health. “Anyone who has a known clot already, like a known macrothrombosis in their leg or lung, needs to be on full-dose heparin,” he said.

That rationale can help reconcile the different outcomes in the critically and non–critically ill COVID-19 patients, wrote Hugo ten Cate, MD, PhD, of Maastricht University in the Netherlands, wrote in an accompanying editorial. But differences in the study populations may also explain the divergent outcomes, Dr. ten Cate noted.

The studies suggest that critically ill patients may need hon-heparin antithrombotic approaches “or even profibrinolytic strategies,” Dr. Cate wrote, and that the safety and effectiveness of thromboprophylaxis “remains an important question.” Nonetheless, he added, treating physicians must deal with the bleeding risk when using heparin or low-molecular-weight heparin in moderately ill COVID-19 patients.

Deepak L. Bhatt MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview that reconciling the two studies was “a bit challenging,” because effective therapies tend to have a greater impact in sicker patients.

“Of course, with antithrombotic therapies, bleeding side effects can sometimes overwhelm benefits in patients who are at high risk of both bleeding and ischemic complications, though that does not seem to be the explanation here,” Dr. Bhatt said. “I do think we need more data to clarify exactly which COVID patients benefit from various antithrombotic regimens, and fortunately, there are other ongoing studies, some of which will report relatively soon.”

He concurred with Dr. Berger that patients who need anticoagulation should receive it “apart from their COVID status,” Dr. Bhatt said. “Sick, hospitalized patients with or without COVID should receive appropriate prophylactic doses of anticoagulation.” However, he added, “Whether we should routinely go beyond that in COVID-positive inpatients, I think we need more data.”

The ATTACC platform received grants from the Canadian Institutes of Health Research and several other research foundations. The ACTIV-4a platform received funding from the National Heart, Lung, and Blood Institute. REMAP-CAP received funding from the European Union and several international research foundations, as well as Amgen and Eisai.

Dr. Lawler had no relationships to disclose. Dr. Berger disclosed receiving grants from the NHLBI, and financial relationships with AstraZeneca, Janssen, and Amgen outside the submitted work. Dr. ten Cate reported relationships with Alveron, Coagulation Profile, Portola/Alexion, Bayer, Pfizer, Stago, Leo Pharma, Daiichi, and Gilead/Galapagos. Dr. Bhatt is chair of the data safety and monitoring board of the FREEDOM COVID anticoagulation clinical trial.

Therapeutic levels of heparin can have widely varying effects on COVID-19 patients depending on the severity of their disease, according to a multiplatform clinical trial that analyzed patient data from three international trials.

NYU Langone Health

COVID-19 patients in the ICU, or at least receiving ICU-level care, derived no benefit from anticoagulation with heparin, while non–critically ill COVID-19 patients – those who were hospitalized but not receiving ICU-level care – on the same anticoagulation were less likely to progress to need respiratory or cardiovascular organ support despite a slightly heightened risk of bleeding events.

Reporting in two articles published online in the New England Journal of Medicine, authors of three international trials combined their data into one multiplatform trial that makes a strong case for prescribing therapeutic levels of heparin in hospitalized patients not receiving ICU-level care were non–critically ill and critically ill.

“I think this is going to be a game changer,” said Jeffrey S. Berger, MD, ACTIV-4a co–principal investigator and co–first author of the study of non–critically ill patients. “I think that using therapeutic-dose anticoagulation should improve outcomes in the tens of thousands of patients worldwide. I hope our data can have a global impact.”
 

Outcomes based on disease severity

The multiplatform trial analyzed data from the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); and Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

The trial evaluated 2,219 non–critically ill hospitalized patients, 1,181 of whom were randomized to therapeutic-dose anticoagulation; and 1,098 critically ill patients, 534 of whom were prescribed therapeutic levels of heparin.

In the critically ill patients, those on heparin were no more likely to get discharged or spend fewer days on respiratory or CV organ support – oxygen, mechanical ventilation, life support, vasopressors or inotropes – than were those on usual-care thromboprophylaxis. The investigators stopped the trial in both patient populations: in critically ill patients when it became obvious therapeutic-dose anticoagulation was having no impact; and in moderately ill patients when the trial met the prespecified criteria for the superiority of therapeutic-dose anticoagulation.

ICU patients on therapeutic-level heparin spent an average of 1 day free of organ support vs. 4 for patients on usual-care prophylactic antithrombotic drugs. The percentage of patients who survived to hospital discharge was similar in the therapeutic-level and usual-care critically ill patients: 62.7% and 64.5%, respectively. Major bleeding occurred in 3.8% and 2.8%, respectively. Demographic and clinical characteristics were similar between both patient groups.

However, in non–critically ill patients, therapeutic levels of heparin resulted in a marked improvement in outcomes. The researchers estimated that, for every 1,000 hospitalized patients with what they labeled moderate disease, an initial treatment with therapeutic-dose heparin resulted in 40 additional patients surviving compared to usual-care thromboprophylaxis.

The percentages of patients not needing organ support before hospital discharge was 80.2% on therapeutic-dose heparin and 76.4% on usual-care therapy. In terms of adjusted odds ratio, the anticoagulation group had a 27% improved chance of not needing daily organ support.

Those improvements came with an additional seven major bleeding events per 1,000 patients. That broke down to a rate of 1.9% in the therapeutic-dose and 0.9% in the usual-care patients.

As the Delta variant of COVID-19 spreads, Patrick R. Lawler, MD, MPH, principal investigator of the ATTACC trial, said there’s no reason these findings shouldn’t apply for all variants of the disease.

University of Toronto

Dr. Lawler, a physician-scientist at Peter Munk Cardiac Centre at Toronto General Hospital, noted that the multiplatform study did not account for disease variant. “Ongoing clinical trials are tracking the variant patients have or the variants that are most prevalent in an area at that time,” he said. “It may be easier in future trials to look at that question.”
 

Explaining heparin’s varying effects

The study did not specifically sort out why moderately ill patients fared better on heparin than their critically ill counterparts, but Dr. Lawler speculated on possible reasons. “One might be that the extent of illness severity is too extreme in the ICU-level population for heparin to have a beneficial extent,” he said.

He acknowledged that higher rates of macrovascular thrombosis, such as venous thromboembolism, in ICU patients would suggest that heparin would have a greater beneficial effect, but, he added, “it may also suggest how advanced that process is, and perhaps heparin is not adequate to reverse the course at that point given relatively extensive thrombosis and associate organ failure.”

As clinicians have gained experience dealing with COVID-19, they’ve learned that infected patients carry a high burden of macro- and microthrombosis, Dr. Berger said, which may explain why critically ill patients didn’t respond as well to therapeutic levels of heparin. “I think the cat is out of the bag; patients who are severe are too ill to benefit,” he said. “I would think there’s too much microthrombosis that is already in their bodies.”

However, this doesn’t completely rule out therapeutic levels of heparin in critically ill COVID-19 patients. There are some scenarios where it’s needed, said Dr. Berger, associate professor of medicine and surgery and director of the Center for the Prevention of Cardiovascular Disease at New York University Langone Health. “Anyone who has a known clot already, like a known macrothrombosis in their leg or lung, needs to be on full-dose heparin,” he said.

That rationale can help reconcile the different outcomes in the critically and non–critically ill COVID-19 patients, wrote Hugo ten Cate, MD, PhD, of Maastricht University in the Netherlands, wrote in an accompanying editorial. But differences in the study populations may also explain the divergent outcomes, Dr. ten Cate noted.

The studies suggest that critically ill patients may need hon-heparin antithrombotic approaches “or even profibrinolytic strategies,” Dr. Cate wrote, and that the safety and effectiveness of thromboprophylaxis “remains an important question.” Nonetheless, he added, treating physicians must deal with the bleeding risk when using heparin or low-molecular-weight heparin in moderately ill COVID-19 patients.

Deepak L. Bhatt MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview that reconciling the two studies was “a bit challenging,” because effective therapies tend to have a greater impact in sicker patients.

“Of course, with antithrombotic therapies, bleeding side effects can sometimes overwhelm benefits in patients who are at high risk of both bleeding and ischemic complications, though that does not seem to be the explanation here,” Dr. Bhatt said. “I do think we need more data to clarify exactly which COVID patients benefit from various antithrombotic regimens, and fortunately, there are other ongoing studies, some of which will report relatively soon.”

He concurred with Dr. Berger that patients who need anticoagulation should receive it “apart from their COVID status,” Dr. Bhatt said. “Sick, hospitalized patients with or without COVID should receive appropriate prophylactic doses of anticoagulation.” However, he added, “Whether we should routinely go beyond that in COVID-positive inpatients, I think we need more data.”

The ATTACC platform received grants from the Canadian Institutes of Health Research and several other research foundations. The ACTIV-4a platform received funding from the National Heart, Lung, and Blood Institute. REMAP-CAP received funding from the European Union and several international research foundations, as well as Amgen and Eisai.

Dr. Lawler had no relationships to disclose. Dr. Berger disclosed receiving grants from the NHLBI, and financial relationships with AstraZeneca, Janssen, and Amgen outside the submitted work. Dr. ten Cate reported relationships with Alveron, Coagulation Profile, Portola/Alexion, Bayer, Pfizer, Stago, Leo Pharma, Daiichi, and Gilead/Galapagos. Dr. Bhatt is chair of the data safety and monitoring board of the FREEDOM COVID anticoagulation clinical trial.

Case vignette: Laura is a 14-year-old biological girl who presents to your office for a routine well-child visit. She is doing well medically but notes that over the past 3 months she has been having increasing thoughts of suicide and has self-harmed via cutting on her wrists with a blade removed from a shaving razor. You contemplate what the most salient questions are in order to determine the best disposition for your patient.

The case vignette above may sound like one that you have heard before, and if not, you undoubtedly will encounter such a situation moving forward. The rate of suicidal ideation amongst youth ages 10-24 has increased by 57.4% between 2007 and 2018.¹ Furthermore, suicide is the second leading cause of death in those aged 10 through young adulthood.² According to the Centers for Disease Control and Prevention’s 2019 High School Youth Risk Behavior Survey, 18.8% of high school students seriously considered attempting suicide, 15.7% made a plan about how they would attempt suicide, and 8.9% actually attempted suicide, with 2.5% having a suicide attempt that resulted in an injury, poisoning, or overdose that had to be treated by a doctor or nurse during the 12 months before the survey.³ Children often present first to their primary care provider, and they may be the first individual who the child shares their suicidal or self-harm thoughts with. It may be useful to have a standardized approach, while using your own clinical judgment, to determine best next steps. Given the significant recent surge in children presenting to the emergency department for psychiatric needs and that environment having its own limitations (for example, long wait times, nontherapeutic space, etc.), a simple screen and brief assessment may lead to being able to maintain a patient safely outside of the hospital.
 

Screen all appropriate patients for suicide

There are, at minimum, three validated screening tools that can be used as to determine what the best next step should be. They include the Ask Suicide-Screening Questions (ASQ) developed by the National Institute of Mental Health, the Columbia-Suicide Severity Rating Scale (C-SSRS), and the PHQ-9 (modified for adolescents). We can highlight one of the screening tools here as noted below, but the choice of screener may be based on facility and/or clinician preference.

The Ask Suicide-Screening Questions

The ASQ, developed by the National Institute of Mental Health, include the following four binary questions plus a fifth acuity question, as follows:

1. In the past few weeks, have you wished you were dead?

2. In the past few weeks, have you felt that you or your family would be better off if you were dead?

3. In the past week, have you been having thoughts about killing yourself?

4. Have you ever tried to kill yourself?

a. If yes, how?

b. When?

The following acuity question is to be asked if any of the above are answered “yes”:

5. Are you having thoughts of killing yourself right now?

a. If yes, please describe.
 

Assess the level of risk

Once you have screened a patient, you need to assess the level of risk to help determine the level of care required. Returning to our original case vignette, does the patient warrant outpatient management, crisis evaluation, or an emergency psychiatric evaluation? You may have already decided that the patient needs an emergency mental health evaluation from a local crisis clinician evaluation and/or the emergency department. However, you may also find that the screen did not elicit imminent concern, but it does warrant a brief assessment to further elucidate the level of risk and proper disposition. One such instrument that may be helpful is the Brief Suicide Safety Assessment (BSSA) – also developed by the NIMH as a tool linked to the ASQ. There are clear and specific instructions in the BSSA with suggestions on how to ask questions. Important components to the BSSA include:

• A focus on a more thorough clinical history – including frequency of suicidal ideation, suicide plan, past behavior, associated symptoms, and social support/stressors
• Collateral information (e.g., further details from those who know the patient such as family/friends).
• Safety planning.
• Determining disposition.

The BSSA may suggest that a crisis/psychiatric evaluation is warranted or suggest that a safety plan with a mental health referral will likely be sufficient.
 

Triage and safety planning

A safety plan should be created if you determine that a patient can be safely maintained as an outpatient based on your screening, assessment, and triaging. Traditional safety plans come in many different forms and can be found online (Example of a Safety Plan Template). However, most safety plans include some version of the following:

• Increased supervision: 24/7 supervision with doors open/unlocked.
• Reduced access: medications (prescription and OTC) locked away; sharps and firearms secured.
• Adaptive coping strategies (e.g., relaxation techniques such as drawing or listening to music).
• Reliable persons for support (e.g., parent, therapist, school counselor).
• Outpatient mental health provider follow-up and/or referral.
• Provision of local crisis and national hotline contact information.
• Use of a safety plan phone app completed with patient.

Envision a safety plan as a living document that evolves, grows, and changes with your patient/family – one that can be easily reviewed/updated at each visit.
 

Returning to our case vignette

Laura returns to your office for a follow-up after a 10-day stay at a hospital-diversion program or inpatient psychiatric unit. The decision is made to use the primary care NIMH ASQ/BSSA algorithm, and you determine the patient to not be at imminent risk following the screen and assessment. Laura is triaged as appropriate for outpatient care, you collaborate to update the safety plan, regular follow-ups are scheduled, and a mental health referral has been placed. Thus, there are tools to assist with screening, assessing, and triaging pediatric patients with suicidal ideation that provide the patient with appropriate care and treatment and may help alleviate the need to have a patient present to the emergency department.

Dr. Abdul-Karim is a child psychiatrist at the University of Vermont University Children’s Hospital in Burlington.

Additional resources

The American Academy of Child and Adolescent Psychiatry has developed information that can be provided to families about suicide safety precautions that can be taken at home, which can be found here: Facts for Families. Suicide Safety: Precautions at Home.

Screening tools listed above can be found here:

ASQ Toolkit.

C-SSRS.

PHQ-9 Modified for Adolescents (PHQ-A).

References

1. Curtin SC. National Center for Health Statistics. “State Suicide Rates Among Adolescents and Young Adults Aged 10-24: United States, 2000-2018” National Vital Statistics Reports..

2. Centers for Disease Control and Prevention, National Center for Health Statistics. “Underlying Cause of Death 2018-2019” CDC WONDER Online Database. Accessed 2021 Jul 31, 6:57:39 p.m.

3. Centers for Disease Control and Prevention. 1991-2019 High School Youth Risk Behavior Survey Data.

Case vignette: Laura is a 14-year-old biological girl who presents to your office for a routine well-child visit. She is doing well medically but notes that over the past 3 months she has been having increasing thoughts of suicide and has self-harmed via cutting on her wrists with a blade removed from a shaving razor. You contemplate what the most salient questions are in order to determine the best disposition for your patient.

The case vignette above may sound like one that you have heard before, and if not, you undoubtedly will encounter such a situation moving forward. The rate of suicidal ideation amongst youth ages 10-24 has increased by 57.4% between 2007 and 2018.¹ Furthermore, suicide is the second leading cause of death in those aged 10 through young adulthood.² According to the Centers for Disease Control and Prevention’s 2019 High School Youth Risk Behavior Survey, 18.8% of high school students seriously considered attempting suicide, 15.7% made a plan about how they would attempt suicide, and 8.9% actually attempted suicide, with 2.5% having a suicide attempt that resulted in an injury, poisoning, or overdose that had to be treated by a doctor or nurse during the 12 months before the survey.³ Children often present first to their primary care provider, and they may be the first individual who the child shares their suicidal or self-harm thoughts with. It may be useful to have a standardized approach, while using your own clinical judgment, to determine best next steps. Given the significant recent surge in children presenting to the emergency department for psychiatric needs and that environment having its own limitations (for example, long wait times, nontherapeutic space, etc.), a simple screen and brief assessment may lead to being able to maintain a patient safely outside of the hospital.
 

Screen all appropriate patients for suicide

There are, at minimum, three validated screening tools that can be used as to determine what the best next step should be. They include the Ask Suicide-Screening Questions (ASQ) developed by the National Institute of Mental Health, the Columbia-Suicide Severity Rating Scale (C-SSRS), and the PHQ-9 (modified for adolescents). We can highlight one of the screening tools here as noted below, but the choice of screener may be based on facility and/or clinician preference.

The Ask Suicide-Screening Questions

The ASQ, developed by the National Institute of Mental Health, include the following four binary questions plus a fifth acuity question, as follows:

1. In the past few weeks, have you wished you were dead?

2. In the past few weeks, have you felt that you or your family would be better off if you were dead?

3. In the past week, have you been having thoughts about killing yourself?

4. Have you ever tried to kill yourself?

a. If yes, how?

b. When?

The following acuity question is to be asked if any of the above are answered “yes”:

5. Are you having thoughts of killing yourself right now?

a. If yes, please describe.
 

Assess the level of risk

Once you have screened a patient, you need to assess the level of risk to help determine the level of care required. Returning to our original case vignette, does the patient warrant outpatient management, crisis evaluation, or an emergency psychiatric evaluation? You may have already decided that the patient needs an emergency mental health evaluation from a local crisis clinician evaluation and/or the emergency department. However, you may also find that the screen did not elicit imminent concern, but it does warrant a brief assessment to further elucidate the level of risk and proper disposition. One such instrument that may be helpful is the Brief Suicide Safety Assessment (BSSA) – also developed by the NIMH as a tool linked to the ASQ. There are clear and specific instructions in the BSSA with suggestions on how to ask questions. Important components to the BSSA include:

• A focus on a more thorough clinical history – including frequency of suicidal ideation, suicide plan, past behavior, associated symptoms, and social support/stressors
• Collateral information (e.g., further details from those who know the patient such as family/friends).
• Safety planning.
• Determining disposition.

The BSSA may suggest that a crisis/psychiatric evaluation is warranted or suggest that a safety plan with a mental health referral will likely be sufficient.
 

Triage and safety planning

A safety plan should be created if you determine that a patient can be safely maintained as an outpatient based on your screening, assessment, and triaging. Traditional safety plans come in many different forms and can be found online (Example of a Safety Plan Template). However, most safety plans include some version of the following:

• Increased supervision: 24/7 supervision with doors open/unlocked.
• Reduced access: medications (prescription and OTC) locked away; sharps and firearms secured.
• Adaptive coping strategies (e.g., relaxation techniques such as drawing or listening to music).
• Reliable persons for support (e.g., parent, therapist, school counselor).
• Outpatient mental health provider follow-up and/or referral.
• Provision of local crisis and national hotline contact information.
• Use of a safety plan phone app completed with patient.

Envision a safety plan as a living document that evolves, grows, and changes with your patient/family – one that can be easily reviewed/updated at each visit.
 

Returning to our case vignette

Laura returns to your office for a follow-up after a 10-day stay at a hospital-diversion program or inpatient psychiatric unit. The decision is made to use the primary care NIMH ASQ/BSSA algorithm, and you determine the patient to not be at imminent risk following the screen and assessment. Laura is triaged as appropriate for outpatient care, you collaborate to update the safety plan, regular follow-ups are scheduled, and a mental health referral has been placed. Thus, there are tools to assist with screening, assessing, and triaging pediatric patients with suicidal ideation that provide the patient with appropriate care and treatment and may help alleviate the need to have a patient present to the emergency department.

Dr. Abdul-Karim is a child psychiatrist at the University of Vermont University Children’s Hospital in Burlington.

Additional resources

The American Academy of Child and Adolescent Psychiatry has developed information that can be provided to families about suicide safety precautions that can be taken at home, which can be found here: Facts for Families. Suicide Safety: Precautions at Home.

Screening tools listed above can be found here:

ASQ Toolkit.

C-SSRS.

PHQ-9 Modified for Adolescents (PHQ-A).

References

1. Curtin SC. National Center for Health Statistics. “State Suicide Rates Among Adolescents and Young Adults Aged 10-24: United States, 2000-2018” National Vital Statistics Reports..

2. Centers for Disease Control and Prevention, National Center for Health Statistics. “Underlying Cause of Death 2018-2019” CDC WONDER Online Database. Accessed 2021 Jul 31, 6:57:39 p.m.

3. Centers for Disease Control and Prevention. 1991-2019 High School Youth Risk Behavior Survey Data.

Case vignette: Laura is a 14-year-old biological girl who presents to your office for a routine well-child visit. She is doing well medically but notes that over the past 3 months she has been having increasing thoughts of suicide and has self-harmed via cutting on her wrists with a blade removed from a shaving razor. You contemplate what the most salient questions are in order to determine the best disposition for your patient.

The case vignette above may sound like one that you have heard before, and if not, you undoubtedly will encounter such a situation moving forward. The rate of suicidal ideation amongst youth ages 10-24 has increased by 57.4% between 2007 and 2018.¹ Furthermore, suicide is the second leading cause of death in those aged 10 through young adulthood.² According to the Centers for Disease Control and Prevention’s 2019 High School Youth Risk Behavior Survey, 18.8% of high school students seriously considered attempting suicide, 15.7% made a plan about how they would attempt suicide, and 8.9% actually attempted suicide, with 2.5% having a suicide attempt that resulted in an injury, poisoning, or overdose that had to be treated by a doctor or nurse during the 12 months before the survey.³ Children often present first to their primary care provider, and they may be the first individual who the child shares their suicidal or self-harm thoughts with. It may be useful to have a standardized approach, while using your own clinical judgment, to determine best next steps. Given the significant recent surge in children presenting to the emergency department for psychiatric needs and that environment having its own limitations (for example, long wait times, nontherapeutic space, etc.), a simple screen and brief assessment may lead to being able to maintain a patient safely outside of the hospital.
 

Screen all appropriate patients for suicide

There are, at minimum, three validated screening tools that can be used as to determine what the best next step should be. They include the Ask Suicide-Screening Questions (ASQ) developed by the National Institute of Mental Health, the Columbia-Suicide Severity Rating Scale (C-SSRS), and the PHQ-9 (modified for adolescents). We can highlight one of the screening tools here as noted below, but the choice of screener may be based on facility and/or clinician preference.

The Ask Suicide-Screening Questions

The ASQ, developed by the National Institute of Mental Health, include the following four binary questions plus a fifth acuity question, as follows:

1. In the past few weeks, have you wished you were dead?

2. In the past few weeks, have you felt that you or your family would be better off if you were dead?

3. In the past week, have you been having thoughts about killing yourself?

4. Have you ever tried to kill yourself?

a. If yes, how?

b. When?

The following acuity question is to be asked if any of the above are answered “yes”:

5. Are you having thoughts of killing yourself right now?

a. If yes, please describe.
 

Assess the level of risk

Once you have screened a patient, you need to assess the level of risk to help determine the level of care required. Returning to our original case vignette, does the patient warrant outpatient management, crisis evaluation, or an emergency psychiatric evaluation? You may have already decided that the patient needs an emergency mental health evaluation from a local crisis clinician evaluation and/or the emergency department. However, you may also find that the screen did not elicit imminent concern, but it does warrant a brief assessment to further elucidate the level of risk and proper disposition. One such instrument that may be helpful is the Brief Suicide Safety Assessment (BSSA) – also developed by the NIMH as a tool linked to the ASQ. There are clear and specific instructions in the BSSA with suggestions on how to ask questions. Important components to the BSSA include:

• A focus on a more thorough clinical history – including frequency of suicidal ideation, suicide plan, past behavior, associated symptoms, and social support/stressors
• Collateral information (e.g., further details from those who know the patient such as family/friends).
• Safety planning.
• Determining disposition.

The BSSA may suggest that a crisis/psychiatric evaluation is warranted or suggest that a safety plan with a mental health referral will likely be sufficient.
 

Triage and safety planning

A safety plan should be created if you determine that a patient can be safely maintained as an outpatient based on your screening, assessment, and triaging. Traditional safety plans come in many different forms and can be found online (Example of a Safety Plan Template). However, most safety plans include some version of the following:

• Increased supervision: 24/7 supervision with doors open/unlocked.
• Reduced access: medications (prescription and OTC) locked away; sharps and firearms secured.
• Adaptive coping strategies (e.g., relaxation techniques such as drawing or listening to music).
• Reliable persons for support (e.g., parent, therapist, school counselor).
• Outpatient mental health provider follow-up and/or referral.
• Provision of local crisis and national hotline contact information.
• Use of a safety plan phone app completed with patient.

Envision a safety plan as a living document that evolves, grows, and changes with your patient/family – one that can be easily reviewed/updated at each visit.
 

Returning to our case vignette

Laura returns to your office for a follow-up after a 10-day stay at a hospital-diversion program or inpatient psychiatric unit. The decision is made to use the primary care NIMH ASQ/BSSA algorithm, and you determine the patient to not be at imminent risk following the screen and assessment. Laura is triaged as appropriate for outpatient care, you collaborate to update the safety plan, regular follow-ups are scheduled, and a mental health referral has been placed. Thus, there are tools to assist with screening, assessing, and triaging pediatric patients with suicidal ideation that provide the patient with appropriate care and treatment and may help alleviate the need to have a patient present to the emergency department.

Dr. Abdul-Karim is a child psychiatrist at the University of Vermont University Children’s Hospital in Burlington.

Additional resources

The American Academy of Child and Adolescent Psychiatry has developed information that can be provided to families about suicide safety precautions that can be taken at home, which can be found here: Facts for Families. Suicide Safety: Precautions at Home.

Screening tools listed above can be found here:

ASQ Toolkit.

C-SSRS.

PHQ-9 Modified for Adolescents (PHQ-A).

References

1. Curtin SC. National Center for Health Statistics. “State Suicide Rates Among Adolescents and Young Adults Aged 10-24: United States, 2000-2018” National Vital Statistics Reports..

2. Centers for Disease Control and Prevention, National Center for Health Statistics. “Underlying Cause of Death 2018-2019” CDC WONDER Online Database. Accessed 2021 Jul 31, 6:57:39 p.m.

3. Centers for Disease Control and Prevention. 1991-2019 High School Youth Risk Behavior Survey Data.

New research provides further evidence that a high body mass index (BMI) leads to depressed mood and poor well-being via social and physical factors.

Obesity and depression are “major global health challenges; our findings suggest that reducing obesity will lower depression and improve well-being,” co–lead author Jessica O’Loughlin, PhD student, University of Exeter Medical School, United Kingdom, told this news organization.

“Doctors should consider both the biological consequences of having a higher BMI as well as the social implications when treating patients with obesity in order to help reduce the odds of them developing depression,” Ms. O’Loughlin added.

The study was published online July 16 in Human Molecular Genetics.
 

Large body of evidence

A large body of evidence indicates that higher BMI leads to depression.

Ms. O’Loughlin and colleagues leveraged genetic data from more than 145,000 individuals in the UK Biobank and Mendelian randomization to determine whether the causal link between high BMI and depression is the result of psychosocial pathways, physical pathways, or both.

The analysis showed that a genetically determined 1 standard deviation higher BMI (4.6 kg/m²) was associated with higher likelihood of depression (odds ratio, 1.50; 95% confidence interval, 1.15-1.95) and lower well-being (beta, -0.15; 95% CI, -0.26 to -0.04).

Using genetics to distinguish metabolic and psychosocial effects, the results also indicate that, even in the absence of adverse metabolic effects, “higher adiposity remains causal to depression and lowers wellbeing,” the researchers report.

“We showed similar findings when looking at genetically predicted BMI and when using genetic variants that make you fatter but metabolically healthier (favorable adiposity genetic variants),” said Ms. O’Loughlin.

“Although we can’t tell which factor plays a bigger role in the adiposity-depression relationship, our analysis suggests that both physical and social factors (e.g., social stigma) play a role in the relationship between higher BMI and higher odds of depression,” she added.

In contrast, there was little evidence that higher BMI in the presence or absence of adverse metabolic consequences causes generalized anxiety disorder.

“Finding ways to support people to lose weight could benefit their mental health as well as their physical health,” co–lead author Francesco Casanova, PhD, with the University of Exeter, said in a statement.
 

Unexpected finding

Reached for comment, Samoon Ahmad, MD, professor, department of psychiatry, New York University, said that “multiple studies have shown a correlation between stress, obesity, inflammation, overall well-being, and psychiatric disorders, particularly depressive and anxiety disorders.”

He said this new study is important for three reasons.

“The first is the cohort size. There were over 145,000 participants involved in the study, which is significant and serves to make its conclusions stronger,” Dr. Ahmad noted.

“The second point is that the authors found that the correlation between higher adiposity and depression and lower well-being scores occurred even in patients without adverse metabolic effects,” he said in an interview.

“Of note, obesity significantly increases the risk of developing type 2 diabetes, hypertension, and a host of other illnesses as well as inflammatory conditions, which can all have a negative impact on quality of life. Consequently, these can contribute to depression as well as anxiety,” Dr. Ahmad added.

“Interestingly, what this study suggests is that even people without these additional stressors are reporting higher rates of depression and lower scores of well-being, while higher adiposity is the common denominator,” he noted.

“Third, the paper found little to no correlation between higher adiposity and generalized anxiety disorder. This comes as a complete surprise because anxiety and depression are very common comorbidities,” Dr. Ahmad said.

“Moreover, numerous studies as well as clinical data suggest that obesity leads to chronic inflammation, which in turn is associated with less favorable metabolic profiles, and that anxiety and depressive disorders may in some way be psychiatric manifestations of inflammation. To see one but not the other was quite an unexpected finding,” Dr. Ahmad said.

The study was funded by the Academy of Medical Sciences. Ms. O’Loughlin, Dr. Casanova, and Dr. Ahmad have disclosed no relevant conflicts of interest.

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

New research provides further evidence that a high body mass index (BMI) leads to depressed mood and poor well-being via social and physical factors.

Obesity and depression are “major global health challenges; our findings suggest that reducing obesity will lower depression and improve well-being,” co–lead author Jessica O’Loughlin, PhD student, University of Exeter Medical School, United Kingdom, told this news organization.

“Doctors should consider both the biological consequences of having a higher BMI as well as the social implications when treating patients with obesity in order to help reduce the odds of them developing depression,” Ms. O’Loughlin added.

The study was published online July 16 in Human Molecular Genetics.
 

Large body of evidence

A large body of evidence indicates that higher BMI leads to depression.

Ms. O’Loughlin and colleagues leveraged genetic data from more than 145,000 individuals in the UK Biobank and Mendelian randomization to determine whether the causal link between high BMI and depression is the result of psychosocial pathways, physical pathways, or both.

The analysis showed that a genetically determined 1 standard deviation higher BMI (4.6 kg/m²) was associated with higher likelihood of depression (odds ratio, 1.50; 95% confidence interval, 1.15-1.95) and lower well-being (beta, -0.15; 95% CI, -0.26 to -0.04).

Using genetics to distinguish metabolic and psychosocial effects, the results also indicate that, even in the absence of adverse metabolic effects, “higher adiposity remains causal to depression and lowers wellbeing,” the researchers report.

“We showed similar findings when looking at genetically predicted BMI and when using genetic variants that make you fatter but metabolically healthier (favorable adiposity genetic variants),” said Ms. O’Loughlin.

“Although we can’t tell which factor plays a bigger role in the adiposity-depression relationship, our analysis suggests that both physical and social factors (e.g., social stigma) play a role in the relationship between higher BMI and higher odds of depression,” she added.

In contrast, there was little evidence that higher BMI in the presence or absence of adverse metabolic consequences causes generalized anxiety disorder.

“Finding ways to support people to lose weight could benefit their mental health as well as their physical health,” co–lead author Francesco Casanova, PhD, with the University of Exeter, said in a statement.
 

Unexpected finding

Reached for comment, Samoon Ahmad, MD, professor, department of psychiatry, New York University, said that “multiple studies have shown a correlation between stress, obesity, inflammation, overall well-being, and psychiatric disorders, particularly depressive and anxiety disorders.”

He said this new study is important for three reasons.

“The first is the cohort size. There were over 145,000 participants involved in the study, which is significant and serves to make its conclusions stronger,” Dr. Ahmad noted.

“The second point is that the authors found that the correlation between higher adiposity and depression and lower well-being scores occurred even in patients without adverse metabolic effects,” he said in an interview.

“Of note, obesity significantly increases the risk of developing type 2 diabetes, hypertension, and a host of other illnesses as well as inflammatory conditions, which can all have a negative impact on quality of life. Consequently, these can contribute to depression as well as anxiety,” Dr. Ahmad added.

“Interestingly, what this study suggests is that even people without these additional stressors are reporting higher rates of depression and lower scores of well-being, while higher adiposity is the common denominator,” he noted.

“Third, the paper found little to no correlation between higher adiposity and generalized anxiety disorder. This comes as a complete surprise because anxiety and depression are very common comorbidities,” Dr. Ahmad said.

“Moreover, numerous studies as well as clinical data suggest that obesity leads to chronic inflammation, which in turn is associated with less favorable metabolic profiles, and that anxiety and depressive disorders may in some way be psychiatric manifestations of inflammation. To see one but not the other was quite an unexpected finding,” Dr. Ahmad said.

The study was funded by the Academy of Medical Sciences. Ms. O’Loughlin, Dr. Casanova, and Dr. Ahmad have disclosed no relevant conflicts of interest.

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

New research provides further evidence that a high body mass index (BMI) leads to depressed mood and poor well-being via social and physical factors.

Obesity and depression are “major global health challenges; our findings suggest that reducing obesity will lower depression and improve well-being,” co–lead author Jessica O’Loughlin, PhD student, University of Exeter Medical School, United Kingdom, told this news organization.

“Doctors should consider both the biological consequences of having a higher BMI as well as the social implications when treating patients with obesity in order to help reduce the odds of them developing depression,” Ms. O’Loughlin added.

The study was published online July 16 in Human Molecular Genetics.
 

Large body of evidence

A large body of evidence indicates that higher BMI leads to depression.

Ms. O’Loughlin and colleagues leveraged genetic data from more than 145,000 individuals in the UK Biobank and Mendelian randomization to determine whether the causal link between high BMI and depression is the result of psychosocial pathways, physical pathways, or both.

The analysis showed that a genetically determined 1 standard deviation higher BMI (4.6 kg/m²) was associated with higher likelihood of depression (odds ratio, 1.50; 95% confidence interval, 1.15-1.95) and lower well-being (beta, -0.15; 95% CI, -0.26 to -0.04).

Using genetics to distinguish metabolic and psychosocial effects, the results also indicate that, even in the absence of adverse metabolic effects, “higher adiposity remains causal to depression and lowers wellbeing,” the researchers report.

“We showed similar findings when looking at genetically predicted BMI and when using genetic variants that make you fatter but metabolically healthier (favorable adiposity genetic variants),” said Ms. O’Loughlin.

“Although we can’t tell which factor plays a bigger role in the adiposity-depression relationship, our analysis suggests that both physical and social factors (e.g., social stigma) play a role in the relationship between higher BMI and higher odds of depression,” she added.

In contrast, there was little evidence that higher BMI in the presence or absence of adverse metabolic consequences causes generalized anxiety disorder.

“Finding ways to support people to lose weight could benefit their mental health as well as their physical health,” co–lead author Francesco Casanova, PhD, with the University of Exeter, said in a statement.
 

Unexpected finding

Reached for comment, Samoon Ahmad, MD, professor, department of psychiatry, New York University, said that “multiple studies have shown a correlation between stress, obesity, inflammation, overall well-being, and psychiatric disorders, particularly depressive and anxiety disorders.”

He said this new study is important for three reasons.

“The first is the cohort size. There were over 145,000 participants involved in the study, which is significant and serves to make its conclusions stronger,” Dr. Ahmad noted.

“The second point is that the authors found that the correlation between higher adiposity and depression and lower well-being scores occurred even in patients without adverse metabolic effects,” he said in an interview.

“Of note, obesity significantly increases the risk of developing type 2 diabetes, hypertension, and a host of other illnesses as well as inflammatory conditions, which can all have a negative impact on quality of life. Consequently, these can contribute to depression as well as anxiety,” Dr. Ahmad added.

“Interestingly, what this study suggests is that even people without these additional stressors are reporting higher rates of depression and lower scores of well-being, while higher adiposity is the common denominator,” he noted.

“Third, the paper found little to no correlation between higher adiposity and generalized anxiety disorder. This comes as a complete surprise because anxiety and depression are very common comorbidities,” Dr. Ahmad said.

“Moreover, numerous studies as well as clinical data suggest that obesity leads to chronic inflammation, which in turn is associated with less favorable metabolic profiles, and that anxiety and depressive disorders may in some way be psychiatric manifestations of inflammation. To see one but not the other was quite an unexpected finding,” Dr. Ahmad said.

The study was funded by the Academy of Medical Sciences. Ms. O’Loughlin, Dr. Casanova, and Dr. Ahmad have disclosed no relevant conflicts of interest.

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

The FDA has authorized a third dose of either the Pfizer or Moderna COVID-19 vaccines for people with compromised immune systems.

The decision, which came late on Aug. 12, was not unexpected and a Centers for Disease Control and Prevention (CDC) panel meeting Aug. 13 is expected to approve directions to doctors and health care providers on who should receive the booster shot.

“The country has entered yet another wave of the COVID-19 pandemic, and the FDA is especially cognizant that immunocompromised people are particularly at risk for severe disease. After a thorough review of the available data, the FDA determined that this small, vulnerable group may benefit from a third dose of the Pfizer-BioNTech or Moderna Vaccines,” acting FDA Commissioner Janet Woodcock, MD, said in a statement.

Those eligible for a third dose include solid organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.

Meanwhile, White House officials said Aug. 12 they “have supply and are prepared” to give all U.S. residents COVID-19 boosters -- which, as of now, are likely to be authorized first only for immunocompromised people.

“We believe sooner or later you will need a booster,” Anthony Fauci, MD, said at a news briefing Aug. 12. “Right now, we are evaluating this on a day-by-day, week-by-week, month-by-month basis.”

He added: “Right at this moment, apart from the immunocompromised -- elderly or not elderly -- people do not need a booster.” But, he said, “We’re preparing for the eventuality of doing that.”

White House COVID-19 Response Coordinator Jeff Zients said officials “have supply and are prepared” to at some point provide widespread access to boosters.

The immunocompromised population is very small -- less than 3% of adults, said CDC Director Rochelle Walensky, MD.

Meanwhile, COVID-19 rates continue to rise. Dr. Walensky reported that the 7-day average of daily cases is 132,384 -- an increase of 24% from the previous week. Average daily hospitalizations are up 31%, at 9,700, and deaths are up to 452 -- an increase of 22%.

In the past week, Florida has had more COVID-19 cases than the 30 states with the lowest case rates combined, Mr. Zients said. Florida and Texas alone have accounted for nearly 40% of new hospitalizations across the country.


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

The FDA has authorized a third dose of either the Pfizer or Moderna COVID-19 vaccines for people with compromised immune systems.

The decision, which came late on Aug. 12, was not unexpected and a Centers for Disease Control and Prevention (CDC) panel meeting Aug. 13 is expected to approve directions to doctors and health care providers on who should receive the booster shot.

“The country has entered yet another wave of the COVID-19 pandemic, and the FDA is especially cognizant that immunocompromised people are particularly at risk for severe disease. After a thorough review of the available data, the FDA determined that this small, vulnerable group may benefit from a third dose of the Pfizer-BioNTech or Moderna Vaccines,” acting FDA Commissioner Janet Woodcock, MD, said in a statement.

Those eligible for a third dose include solid organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.

Meanwhile, White House officials said Aug. 12 they “have supply and are prepared” to give all U.S. residents COVID-19 boosters -- which, as of now, are likely to be authorized first only for immunocompromised people.

“We believe sooner or later you will need a booster,” Anthony Fauci, MD, said at a news briefing Aug. 12. “Right now, we are evaluating this on a day-by-day, week-by-week, month-by-month basis.”

He added: “Right at this moment, apart from the immunocompromised -- elderly or not elderly -- people do not need a booster.” But, he said, “We’re preparing for the eventuality of doing that.”

White House COVID-19 Response Coordinator Jeff Zients said officials “have supply and are prepared” to at some point provide widespread access to boosters.

The immunocompromised population is very small -- less than 3% of adults, said CDC Director Rochelle Walensky, MD.

Meanwhile, COVID-19 rates continue to rise. Dr. Walensky reported that the 7-day average of daily cases is 132,384 -- an increase of 24% from the previous week. Average daily hospitalizations are up 31%, at 9,700, and deaths are up to 452 -- an increase of 22%.

In the past week, Florida has had more COVID-19 cases than the 30 states with the lowest case rates combined, Mr. Zients said. Florida and Texas alone have accounted for nearly 40% of new hospitalizations across the country.


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

The FDA has authorized a third dose of either the Pfizer or Moderna COVID-19 vaccines for people with compromised immune systems.

The decision, which came late on Aug. 12, was not unexpected and a Centers for Disease Control and Prevention (CDC) panel meeting Aug. 13 is expected to approve directions to doctors and health care providers on who should receive the booster shot.

“The country has entered yet another wave of the COVID-19 pandemic, and the FDA is especially cognizant that immunocompromised people are particularly at risk for severe disease. After a thorough review of the available data, the FDA determined that this small, vulnerable group may benefit from a third dose of the Pfizer-BioNTech or Moderna Vaccines,” acting FDA Commissioner Janet Woodcock, MD, said in a statement.

Those eligible for a third dose include solid organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.

Meanwhile, White House officials said Aug. 12 they “have supply and are prepared” to give all U.S. residents COVID-19 boosters -- which, as of now, are likely to be authorized first only for immunocompromised people.

“We believe sooner or later you will need a booster,” Anthony Fauci, MD, said at a news briefing Aug. 12. “Right now, we are evaluating this on a day-by-day, week-by-week, month-by-month basis.”

He added: “Right at this moment, apart from the immunocompromised -- elderly or not elderly -- people do not need a booster.” But, he said, “We’re preparing for the eventuality of doing that.”

White House COVID-19 Response Coordinator Jeff Zients said officials “have supply and are prepared” to at some point provide widespread access to boosters.

The immunocompromised population is very small -- less than 3% of adults, said CDC Director Rochelle Walensky, MD.

Meanwhile, COVID-19 rates continue to rise. Dr. Walensky reported that the 7-day average of daily cases is 132,384 -- an increase of 24% from the previous week. Average daily hospitalizations are up 31%, at 9,700, and deaths are up to 452 -- an increase of 22%.

In the past week, Florida has had more COVID-19 cases than the 30 states with the lowest case rates combined, Mr. Zients said. Florida and Texas alone have accounted for nearly 40% of new hospitalizations across the country.


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