One of the most inspiring speeches ever made is Rev. Martin Luther King’s “I have a dream” about ending discrimination and achieving social justice. Many of the tenets of that classic speech are relevant to psychiatric patients who have been subjected to discrimination and bias instead of the compassion and support that they deserve, as do patients with other medical disorders.

Like Rev. King, we all have dreams, spoken and unspoken. They may be related to our various goals or objectives as individuals, spouses, parents, professionals, friends, or citizens of the world. Here, I will elaborate on my dream as a psychiatric physician, educator, and researcher, with decades of experience treating thousands of patients, many of whom I followed for a long time. I have come to see the world through the eyes and painful journeys of suffering psychiatric patients.

Vision of a better world for our patients

So, here is my dream, comprised of multiple parts that many clinician-readers may have incorporated in their own dreams about psychiatry. I have a dream:

• that the ugly, stubborn stigma of mental illness evaporates and is replaced with empathy and compassion
• that genuine full parity be implemented for all psychiatric patients
• that the public becomes far more educated about their own mental health, and cognizant of psychiatric symptoms in their family members and friends, so they can urge them to promptly seek medical help. The public should be aware that the success rate of treating psychiatric disorders is similar to that of many general medical conditions, such as heart, lung, kidney, and liver diseases
• that psychiatry continues to evolve into a clinical neuroscience, respected and appreciated like its sister neurology, and emphasizing that all mental illnesses are biologically rooted in various brain circuits
• that neuroscience literacy among psychiatrists increases dramatically, while maintaining our biopsychosocial clinical framework
• that federal funding for research into the causes and treatments of psychiatric disorders increases by an order of magnitude, to help accelerate the discovery of cures for disabling psychiatric disorders, which have a serious personal, societal, and financial toll
• that some of the many fabulously wealthy billionaires in this country (and around the world) adopt psychiatry as their favorite charity, and establish powerful and very well-funded research foundations to explore the brain and solve its mysteries in health and disease
• that effective treatments for and interventions to prevent alcohol and substance use disorders are discovered, including vaccines for alcoholism and other drugs of abuse. This would save countless lives lost to addiction
• that Medicare opens its huge wallet and supports thousands of additional residency training positions to address the serious shortage of psychiatrists
• that pharmaceutical companies, admittedly the only entities with the requisite infrastructure to develop new drugs for psychiatry, be creatively incentivized to discover drugs with new mechanisms of action to effectively treat psychiatric conditions for which there are no FDA-approved medications, such as the negative symptoms and cognitive deficits of schizophrenia, personality disorders (such as borderline personality), autism, and Alzheimer’s disease
• that the jailing, incarceration, and criminalization of patients with serious mental illness ceases immediately and is replaced with hospitalization and dignified medical treatment instead of prison sentences with murders and rapists. Building more hospitals instead of more prisons is the civilized and ethical approach to psychiatric brain disorders
• that the public recognizes that persons suffering from schizophrenia are more likely to be victims of crime rather than perpetrators. Tell that to the misguided media
• that clinicians in primary care specialties, where up to 50% of patients have a diagnosable and treatable psychiatric illness, be much better trained in psychiatry during their residency. Currently, residents in family medicine, general internal medicine, pediatrics, and obstetrics/gynecology receive 0 months to 1 month of psychiatry in their 4 years of training. Many are unable to handle the large number of psychiatric disorders in their patients. In addition, psychiatrists and primary care physicians should be colocalized so psychiatric and primary care patients can both benefit from true collaborative care, because many are dually afflicted
• that the syndemic¹ (ie, multiple epidemics) that often is effectively addressed for the sake of our patients and society at large. The ongoing syndemic includes poverty, child abuse, human trafficking, domestic violence, racism, suicide, gun violence, broken families, and social media addiction across all ages
• that psychiatric practitioners embrace and adopt validated rating scales in their practice to quantify the severity of the patient’s illness and adverse effects at each visit, and to assess the degree of improvement in both. Measurement is at the foundation of science. Psychiatry will be a stronger medical specialty with measurement-based practice
• that licensing boards stop discriminating against physicians who have recovered from a psychiatric disorder or addiction. This form of stigma is destructive to the functioning of highly trained medical professionals who recover with treatment and can return to work
• that the number of psychiatric hospital beds in the country is significantly expanded to accommodate the high demand, and that psychiatric wards in general hospitals not be repurposed for more lucrative, procedure-oriented programs
• that insurance companies stop the absurdity of authorizing only 3 to 4 days for the inpatient treatment of patients who are acutely psychotic, manic, or suicidally depressed. It is impossible for such serious brain disorders to improve rapidly. This leads to discharging patients who are still unstable and who might relapse quickly after discharge, risking harm to themselves, or ending up in jail
• that HIPAA laws are revised to allow psychiatrists to collect or exchange information about ailing adult members of the family. Collateral information is a vital component of psychiatric evaluation, and its prohibition can be harmful to the patient. The family often is the most likely support system for the mentally ill individual, and must be informed about what their family member needs after discharge
• that long-acting antipsychotics are used very early and widely to prevent the tragic consequences of psychotic relapses,² and long-lasting antidepressants are developed to prevent the relapse and risk of suicide in many patients who stop their antidepressant medication once they feel better, and do not recognize that like hypertension or diabetes, depression requires ongoing pharmacotherapy to prevent relapse
• that the time to get a court order for involuntary administration of antipsychotic medication to acutely psychotic patients is reduced to 1 day because a large body of published evidence shows that a longer duration of untreated psychosis has a deleterious neurotoxic effect on the brain, worsening outcomes and prognosis.³ The legal system should catch up with scientific findings.

Just as Martin Luther King’s dream resonated loudly for decades and led to salutary legal and societal changes, I hope that what I dream about will eventually become reality. My dream is shared by all my fellow psychiatrists, and it will come true if we unite, lobby continuously, and advocate vigorously for our patients and our noble profession. I am sure we shall overcome our challenges someday.

One of the most inspiring speeches ever made is Rev. Martin Luther King’s “I have a dream” about ending discrimination and achieving social justice. Many of the tenets of that classic speech are relevant to psychiatric patients who have been subjected to discrimination and bias instead of the compassion and support that they deserve, as do patients with other medical disorders.

Like Rev. King, we all have dreams, spoken and unspoken. They may be related to our various goals or objectives as individuals, spouses, parents, professionals, friends, or citizens of the world. Here, I will elaborate on my dream as a psychiatric physician, educator, and researcher, with decades of experience treating thousands of patients, many of whom I followed for a long time. I have come to see the world through the eyes and painful journeys of suffering psychiatric patients.

Vision of a better world for our patients

So, here is my dream, comprised of multiple parts that many clinician-readers may have incorporated in their own dreams about psychiatry. I have a dream:

• that the ugly, stubborn stigma of mental illness evaporates and is replaced with empathy and compassion
• that genuine full parity be implemented for all psychiatric patients
• that the public becomes far more educated about their own mental health, and cognizant of psychiatric symptoms in their family members and friends, so they can urge them to promptly seek medical help. The public should be aware that the success rate of treating psychiatric disorders is similar to that of many general medical conditions, such as heart, lung, kidney, and liver diseases
• that psychiatry continues to evolve into a clinical neuroscience, respected and appreciated like its sister neurology, and emphasizing that all mental illnesses are biologically rooted in various brain circuits
• that neuroscience literacy among psychiatrists increases dramatically, while maintaining our biopsychosocial clinical framework
• that federal funding for research into the causes and treatments of psychiatric disorders increases by an order of magnitude, to help accelerate the discovery of cures for disabling psychiatric disorders, which have a serious personal, societal, and financial toll
• that some of the many fabulously wealthy billionaires in this country (and around the world) adopt psychiatry as their favorite charity, and establish powerful and very well-funded research foundations to explore the brain and solve its mysteries in health and disease
• that effective treatments for and interventions to prevent alcohol and substance use disorders are discovered, including vaccines for alcoholism and other drugs of abuse. This would save countless lives lost to addiction
• that Medicare opens its huge wallet and supports thousands of additional residency training positions to address the serious shortage of psychiatrists
• that pharmaceutical companies, admittedly the only entities with the requisite infrastructure to develop new drugs for psychiatry, be creatively incentivized to discover drugs with new mechanisms of action to effectively treat psychiatric conditions for which there are no FDA-approved medications, such as the negative symptoms and cognitive deficits of schizophrenia, personality disorders (such as borderline personality), autism, and Alzheimer’s disease
• that the jailing, incarceration, and criminalization of patients with serious mental illness ceases immediately and is replaced with hospitalization and dignified medical treatment instead of prison sentences with murders and rapists. Building more hospitals instead of more prisons is the civilized and ethical approach to psychiatric brain disorders
• that the public recognizes that persons suffering from schizophrenia are more likely to be victims of crime rather than perpetrators. Tell that to the misguided media
• that clinicians in primary care specialties, where up to 50% of patients have a diagnosable and treatable psychiatric illness, be much better trained in psychiatry during their residency. Currently, residents in family medicine, general internal medicine, pediatrics, and obstetrics/gynecology receive 0 months to 1 month of psychiatry in their 4 years of training. Many are unable to handle the large number of psychiatric disorders in their patients. In addition, psychiatrists and primary care physicians should be colocalized so psychiatric and primary care patients can both benefit from true collaborative care, because many are dually afflicted
• that the syndemic¹ (ie, multiple epidemics) that often is effectively addressed for the sake of our patients and society at large. The ongoing syndemic includes poverty, child abuse, human trafficking, domestic violence, racism, suicide, gun violence, broken families, and social media addiction across all ages
• that psychiatric practitioners embrace and adopt validated rating scales in their practice to quantify the severity of the patient’s illness and adverse effects at each visit, and to assess the degree of improvement in both. Measurement is at the foundation of science. Psychiatry will be a stronger medical specialty with measurement-based practice
• that licensing boards stop discriminating against physicians who have recovered from a psychiatric disorder or addiction. This form of stigma is destructive to the functioning of highly trained medical professionals who recover with treatment and can return to work
• that the number of psychiatric hospital beds in the country is significantly expanded to accommodate the high demand, and that psychiatric wards in general hospitals not be repurposed for more lucrative, procedure-oriented programs
• that insurance companies stop the absurdity of authorizing only 3 to 4 days for the inpatient treatment of patients who are acutely psychotic, manic, or suicidally depressed. It is impossible for such serious brain disorders to improve rapidly. This leads to discharging patients who are still unstable and who might relapse quickly after discharge, risking harm to themselves, or ending up in jail
• that HIPAA laws are revised to allow psychiatrists to collect or exchange information about ailing adult members of the family. Collateral information is a vital component of psychiatric evaluation, and its prohibition can be harmful to the patient. The family often is the most likely support system for the mentally ill individual, and must be informed about what their family member needs after discharge
• that long-acting antipsychotics are used very early and widely to prevent the tragic consequences of psychotic relapses,² and long-lasting antidepressants are developed to prevent the relapse and risk of suicide in many patients who stop their antidepressant medication once they feel better, and do not recognize that like hypertension or diabetes, depression requires ongoing pharmacotherapy to prevent relapse
• that the time to get a court order for involuntary administration of antipsychotic medication to acutely psychotic patients is reduced to 1 day because a large body of published evidence shows that a longer duration of untreated psychosis has a deleterious neurotoxic effect on the brain, worsening outcomes and prognosis.³ The legal system should catch up with scientific findings.

Just as Martin Luther King’s dream resonated loudly for decades and led to salutary legal and societal changes, I hope that what I dream about will eventually become reality. My dream is shared by all my fellow psychiatrists, and it will come true if we unite, lobby continuously, and advocate vigorously for our patients and our noble profession. I am sure we shall overcome our challenges someday.

One of the most inspiring speeches ever made is Rev. Martin Luther King’s “I have a dream” about ending discrimination and achieving social justice. Many of the tenets of that classic speech are relevant to psychiatric patients who have been subjected to discrimination and bias instead of the compassion and support that they deserve, as do patients with other medical disorders.

Like Rev. King, we all have dreams, spoken and unspoken. They may be related to our various goals or objectives as individuals, spouses, parents, professionals, friends, or citizens of the world. Here, I will elaborate on my dream as a psychiatric physician, educator, and researcher, with decades of experience treating thousands of patients, many of whom I followed for a long time. I have come to see the world through the eyes and painful journeys of suffering psychiatric patients.

Vision of a better world for our patients

So, here is my dream, comprised of multiple parts that many clinician-readers may have incorporated in their own dreams about psychiatry. I have a dream:

• that the ugly, stubborn stigma of mental illness evaporates and is replaced with empathy and compassion
• that genuine full parity be implemented for all psychiatric patients
• that the public becomes far more educated about their own mental health, and cognizant of psychiatric symptoms in their family members and friends, so they can urge them to promptly seek medical help. The public should be aware that the success rate of treating psychiatric disorders is similar to that of many general medical conditions, such as heart, lung, kidney, and liver diseases
• that psychiatry continues to evolve into a clinical neuroscience, respected and appreciated like its sister neurology, and emphasizing that all mental illnesses are biologically rooted in various brain circuits
• that neuroscience literacy among psychiatrists increases dramatically, while maintaining our biopsychosocial clinical framework
• that federal funding for research into the causes and treatments of psychiatric disorders increases by an order of magnitude, to help accelerate the discovery of cures for disabling psychiatric disorders, which have a serious personal, societal, and financial toll
• that some of the many fabulously wealthy billionaires in this country (and around the world) adopt psychiatry as their favorite charity, and establish powerful and very well-funded research foundations to explore the brain and solve its mysteries in health and disease
• that effective treatments for and interventions to prevent alcohol and substance use disorders are discovered, including vaccines for alcoholism and other drugs of abuse. This would save countless lives lost to addiction
• that Medicare opens its huge wallet and supports thousands of additional residency training positions to address the serious shortage of psychiatrists
• that pharmaceutical companies, admittedly the only entities with the requisite infrastructure to develop new drugs for psychiatry, be creatively incentivized to discover drugs with new mechanisms of action to effectively treat psychiatric conditions for which there are no FDA-approved medications, such as the negative symptoms and cognitive deficits of schizophrenia, personality disorders (such as borderline personality), autism, and Alzheimer’s disease
• that the jailing, incarceration, and criminalization of patients with serious mental illness ceases immediately and is replaced with hospitalization and dignified medical treatment instead of prison sentences with murders and rapists. Building more hospitals instead of more prisons is the civilized and ethical approach to psychiatric brain disorders
• that the public recognizes that persons suffering from schizophrenia are more likely to be victims of crime rather than perpetrators. Tell that to the misguided media
• that clinicians in primary care specialties, where up to 50% of patients have a diagnosable and treatable psychiatric illness, be much better trained in psychiatry during their residency. Currently, residents in family medicine, general internal medicine, pediatrics, and obstetrics/gynecology receive 0 months to 1 month of psychiatry in their 4 years of training. Many are unable to handle the large number of psychiatric disorders in their patients. In addition, psychiatrists and primary care physicians should be colocalized so psychiatric and primary care patients can both benefit from true collaborative care, because many are dually afflicted
• that the syndemic¹ (ie, multiple epidemics) that often is effectively addressed for the sake of our patients and society at large. The ongoing syndemic includes poverty, child abuse, human trafficking, domestic violence, racism, suicide, gun violence, broken families, and social media addiction across all ages
• that psychiatric practitioners embrace and adopt validated rating scales in their practice to quantify the severity of the patient’s illness and adverse effects at each visit, and to assess the degree of improvement in both. Measurement is at the foundation of science. Psychiatry will be a stronger medical specialty with measurement-based practice
• that licensing boards stop discriminating against physicians who have recovered from a psychiatric disorder or addiction. This form of stigma is destructive to the functioning of highly trained medical professionals who recover with treatment and can return to work
• that the number of psychiatric hospital beds in the country is significantly expanded to accommodate the high demand, and that psychiatric wards in general hospitals not be repurposed for more lucrative, procedure-oriented programs
• that insurance companies stop the absurdity of authorizing only 3 to 4 days for the inpatient treatment of patients who are acutely psychotic, manic, or suicidally depressed. It is impossible for such serious brain disorders to improve rapidly. This leads to discharging patients who are still unstable and who might relapse quickly after discharge, risking harm to themselves, or ending up in jail
• that HIPAA laws are revised to allow psychiatrists to collect or exchange information about ailing adult members of the family. Collateral information is a vital component of psychiatric evaluation, and its prohibition can be harmful to the patient. The family often is the most likely support system for the mentally ill individual, and must be informed about what their family member needs after discharge
• that long-acting antipsychotics are used very early and widely to prevent the tragic consequences of psychotic relapses,² and long-lasting antidepressants are developed to prevent the relapse and risk of suicide in many patients who stop their antidepressant medication once they feel better, and do not recognize that like hypertension or diabetes, depression requires ongoing pharmacotherapy to prevent relapse
• that the time to get a court order for involuntary administration of antipsychotic medication to acutely psychotic patients is reduced to 1 day because a large body of published evidence shows that a longer duration of untreated psychosis has a deleterious neurotoxic effect on the brain, worsening outcomes and prognosis.³ The legal system should catch up with scientific findings.

Just as Martin Luther King’s dream resonated loudly for decades and led to salutary legal and societal changes, I hope that what I dream about will eventually become reality. My dream is shared by all my fellow psychiatrists, and it will come true if we unite, lobby continuously, and advocate vigorously for our patients and our noble profession. I am sure we shall overcome our challenges someday.

For this Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Maria A. Oquendo, MD, PhD. Dr. Oquendo is the Ruth Meltzer Professor and Chairman of Psychiatry at University of Pennsylvania and Psychiatrist-in-Chief at the Hospital of the University of Pennsylvania. Until 2016, she was Professor of Psychiatry and Vice Chairman for Education at Columbia University. In 2017, she was elected to the National Academy of Medicine, one of the highest honors in medicine. Dr. Oquendo has used positron emission tomography and magnetic resonance imaging to map brain abnormalities in mood disorders and suicidal behavior. Dr. Oquendo is Past President of the American Psychiatric Association (APA), the International Academy of Suicide Research, and the American College of Neuropsychopharmacology (ACNP). She is President of the American Foundation for Suicide Prevention Board of Directors, Vice President of the College of International Neuropsychopharmacology, and has served on the National Institute of Mental Health’s Advisory Council. A recipient of multiple awards in the US, Europe, and South America, most recently, she received the Virginia Kneeland Award for Distinguished Women in Medicine (Columbia University 2016), the Award for Mood Disorders Research (ACP 2017), the Alexandra Symonds Award (APA 2017), the APA’s Research Award (2018), the Dolores Shockley Award (ACNP 2018), the Alexander Glassman Award (Columbia University 2021), and the Senior Investigator Klerman Award (Depression and Bipolar Support Alliance 2021).

Dr. Aftab: A major focus of your presidential year at APA was on prevention in psychiatry (especially suicide prevention), and working toward prevention through collaboration with colleagues in other medical specialties. What is your perspective on where our field presently stands in this regard?

Dr. Oquendo: There are more and more studies that focus on early childhood or pre-adolescence and the utility of intervening at the first sign of a potential issue. This is quite different from what was the case when I was training. Back then, the idea was that in many cases it was best to wait because kids might “grow out of it.” The implication was that care or intervention were “stigmatizing,” or that it could affect the child’s self-esteem and we wanted to “spare” the child. What we are learning now is that there are advantages of intervening early even if the issues are subtle, potentially preventing development of more serious problems down the line. Still, much work remains to be done. Because so many of the disorders we treat are in fact neurodevelopmental, we desperately need more investigators focused on childhood and adolescent mental health. We also need scientists to identify biomarkers that will permit identification of individuals at risk before the emergence of symptoms. Developing that workforce should be front and center if we are to make a dent in the rising rates of psychiatric disorders.

Dr. Aftab: What do you see as some of the strengths of our profession?


Dr. Oquendo: Our profession’s recognition that the doctor-patient relationship remains a powerful element of healing is one of its greatest strengths. Psychiatry is the only area of medicine in which practitioners are students of the doctor-patient relationship. That provides an unparalleled ability to leverage it for good. Another strength is that many who enter psychiatry are humanists, so as a field, we are collectively engaged in working towards improving conditions for our patients and our community.



Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?


Dr. Oquendo: The most challenging issue that plagues psychiatry is not of our making, but we do have to address it. The ongoing lack of parity in the US and the insurance industry’s approach of using carve-outs and other strategies to keep psychiatry reimbursement low has led many, if not most, to practice on a cash basis only. This hurts our patients, but also our reputation among our medical colleagues. We need to use creative solutions and engage in advocacy to bring about change.



Dr. Aftab: What is your perception of the threats that psychiatry faces or is likely to face in the future?

Dr. Oquendo: An ongoing threat relates to the low reimbursement for psychiatric services, which tends to drive clinicians towards cash-based practices. Advocacy at the state and federal level as well as with large employers may be one strategy to remedy this inequity.


Dr. Aftab: What do you envision for the future of psychiatry? What sort of opportunities lie ahead for us?



Dr. Oquendo: The adoption of the advances in psychiatry that permit greater reach, such as the adoption of integrated mental health services, utilization of physician extenders, etc., has been slow in psychiatry, but I think the pace is accelerating. This is important because of an upcoming opportunity: the burgeoning need for our help. With stigma quickly decreasing and the younger generations being open about their needs and prioritization of mental health and wellness, it will be a new era, one in which we can make a huge difference in the health and quality of life of the population.

For this Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Maria A. Oquendo, MD, PhD. Dr. Oquendo is the Ruth Meltzer Professor and Chairman of Psychiatry at University of Pennsylvania and Psychiatrist-in-Chief at the Hospital of the University of Pennsylvania. Until 2016, she was Professor of Psychiatry and Vice Chairman for Education at Columbia University. In 2017, she was elected to the National Academy of Medicine, one of the highest honors in medicine. Dr. Oquendo has used positron emission tomography and magnetic resonance imaging to map brain abnormalities in mood disorders and suicidal behavior. Dr. Oquendo is Past President of the American Psychiatric Association (APA), the International Academy of Suicide Research, and the American College of Neuropsychopharmacology (ACNP). She is President of the American Foundation for Suicide Prevention Board of Directors, Vice President of the College of International Neuropsychopharmacology, and has served on the National Institute of Mental Health’s Advisory Council. A recipient of multiple awards in the US, Europe, and South America, most recently, she received the Virginia Kneeland Award for Distinguished Women in Medicine (Columbia University 2016), the Award for Mood Disorders Research (ACP 2017), the Alexandra Symonds Award (APA 2017), the APA’s Research Award (2018), the Dolores Shockley Award (ACNP 2018), the Alexander Glassman Award (Columbia University 2021), and the Senior Investigator Klerman Award (Depression and Bipolar Support Alliance 2021).

Dr. Aftab: A major focus of your presidential year at APA was on prevention in psychiatry (especially suicide prevention), and working toward prevention through collaboration with colleagues in other medical specialties. What is your perspective on where our field presently stands in this regard?

Dr. Oquendo: There are more and more studies that focus on early childhood or pre-adolescence and the utility of intervening at the first sign of a potential issue. This is quite different from what was the case when I was training. Back then, the idea was that in many cases it was best to wait because kids might “grow out of it.” The implication was that care or intervention were “stigmatizing,” or that it could affect the child’s self-esteem and we wanted to “spare” the child. What we are learning now is that there are advantages of intervening early even if the issues are subtle, potentially preventing development of more serious problems down the line. Still, much work remains to be done. Because so many of the disorders we treat are in fact neurodevelopmental, we desperately need more investigators focused on childhood and adolescent mental health. We also need scientists to identify biomarkers that will permit identification of individuals at risk before the emergence of symptoms. Developing that workforce should be front and center if we are to make a dent in the rising rates of psychiatric disorders.

Dr. Aftab: What do you see as some of the strengths of our profession?


Dr. Oquendo: Our profession’s recognition that the doctor-patient relationship remains a powerful element of healing is one of its greatest strengths. Psychiatry is the only area of medicine in which practitioners are students of the doctor-patient relationship. That provides an unparalleled ability to leverage it for good. Another strength is that many who enter psychiatry are humanists, so as a field, we are collectively engaged in working towards improving conditions for our patients and our community.



Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?


Dr. Oquendo: The most challenging issue that plagues psychiatry is not of our making, but we do have to address it. The ongoing lack of parity in the US and the insurance industry’s approach of using carve-outs and other strategies to keep psychiatry reimbursement low has led many, if not most, to practice on a cash basis only. This hurts our patients, but also our reputation among our medical colleagues. We need to use creative solutions and engage in advocacy to bring about change.



Dr. Aftab: What is your perception of the threats that psychiatry faces or is likely to face in the future?

Dr. Oquendo: An ongoing threat relates to the low reimbursement for psychiatric services, which tends to drive clinicians towards cash-based practices. Advocacy at the state and federal level as well as with large employers may be one strategy to remedy this inequity.


Dr. Aftab: What do you envision for the future of psychiatry? What sort of opportunities lie ahead for us?



Dr. Oquendo: The adoption of the advances in psychiatry that permit greater reach, such as the adoption of integrated mental health services, utilization of physician extenders, etc., has been slow in psychiatry, but I think the pace is accelerating. This is important because of an upcoming opportunity: the burgeoning need for our help. With stigma quickly decreasing and the younger generations being open about their needs and prioritization of mental health and wellness, it will be a new era, one in which we can make a huge difference in the health and quality of life of the population.

For this Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Maria A. Oquendo, MD, PhD. Dr. Oquendo is the Ruth Meltzer Professor and Chairman of Psychiatry at University of Pennsylvania and Psychiatrist-in-Chief at the Hospital of the University of Pennsylvania. Until 2016, she was Professor of Psychiatry and Vice Chairman for Education at Columbia University. In 2017, she was elected to the National Academy of Medicine, one of the highest honors in medicine. Dr. Oquendo has used positron emission tomography and magnetic resonance imaging to map brain abnormalities in mood disorders and suicidal behavior. Dr. Oquendo is Past President of the American Psychiatric Association (APA), the International Academy of Suicide Research, and the American College of Neuropsychopharmacology (ACNP). She is President of the American Foundation for Suicide Prevention Board of Directors, Vice President of the College of International Neuropsychopharmacology, and has served on the National Institute of Mental Health’s Advisory Council. A recipient of multiple awards in the US, Europe, and South America, most recently, she received the Virginia Kneeland Award for Distinguished Women in Medicine (Columbia University 2016), the Award for Mood Disorders Research (ACP 2017), the Alexandra Symonds Award (APA 2017), the APA’s Research Award (2018), the Dolores Shockley Award (ACNP 2018), the Alexander Glassman Award (Columbia University 2021), and the Senior Investigator Klerman Award (Depression and Bipolar Support Alliance 2021).

Dr. Aftab: A major focus of your presidential year at APA was on prevention in psychiatry (especially suicide prevention), and working toward prevention through collaboration with colleagues in other medical specialties. What is your perspective on where our field presently stands in this regard?

Dr. Oquendo: There are more and more studies that focus on early childhood or pre-adolescence and the utility of intervening at the first sign of a potential issue. This is quite different from what was the case when I was training. Back then, the idea was that in many cases it was best to wait because kids might “grow out of it.” The implication was that care or intervention were “stigmatizing,” or that it could affect the child’s self-esteem and we wanted to “spare” the child. What we are learning now is that there are advantages of intervening early even if the issues are subtle, potentially preventing development of more serious problems down the line. Still, much work remains to be done. Because so many of the disorders we treat are in fact neurodevelopmental, we desperately need more investigators focused on childhood and adolescent mental health. We also need scientists to identify biomarkers that will permit identification of individuals at risk before the emergence of symptoms. Developing that workforce should be front and center if we are to make a dent in the rising rates of psychiatric disorders.

Dr. Aftab: What do you see as some of the strengths of our profession?


Dr. Oquendo: Our profession’s recognition that the doctor-patient relationship remains a powerful element of healing is one of its greatest strengths. Psychiatry is the only area of medicine in which practitioners are students of the doctor-patient relationship. That provides an unparalleled ability to leverage it for good. Another strength is that many who enter psychiatry are humanists, so as a field, we are collectively engaged in working towards improving conditions for our patients and our community.



Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?


Dr. Oquendo: The most challenging issue that plagues psychiatry is not of our making, but we do have to address it. The ongoing lack of parity in the US and the insurance industry’s approach of using carve-outs and other strategies to keep psychiatry reimbursement low has led many, if not most, to practice on a cash basis only. This hurts our patients, but also our reputation among our medical colleagues. We need to use creative solutions and engage in advocacy to bring about change.



Dr. Aftab: What is your perception of the threats that psychiatry faces or is likely to face in the future?

Dr. Oquendo: An ongoing threat relates to the low reimbursement for psychiatric services, which tends to drive clinicians towards cash-based practices. Advocacy at the state and federal level as well as with large employers may be one strategy to remedy this inequity.


Dr. Aftab: What do you envision for the future of psychiatry? What sort of opportunities lie ahead for us?



Dr. Oquendo: The adoption of the advances in psychiatry that permit greater reach, such as the adoption of integrated mental health services, utilization of physician extenders, etc., has been slow in psychiatry, but I think the pace is accelerating. This is important because of an upcoming opportunity: the burgeoning need for our help. With stigma quickly decreasing and the younger generations being open about their needs and prioritization of mental health and wellness, it will be a new era, one in which we can make a huge difference in the health and quality of life of the population.

Mrs. C, age 68, is experiencing worsening paranoid delusions. She believes that because she lied about her income when she was younger, the FBI is tracking her and wants to poison her food and spray dangerous fumes in her house. Her paranoia has made it hard for her to sleep, eat, or feel safe in her home.

Mrs. C’s daughter reports that her mother’s delusions started 3 years ago and have worsened in recent months. Mrs. C has no psychiatric history. Her medical history is signifi­cant for renal transplant in 2015, type 2 diabetes, hyperlipidemia, hypertension, and hypothyroidism. She is currently normotensive. Mrs. C’s home medications include cyclosporine, which is a calcineurin inhibitor, 125 mg twice daily (trough level = 138 mcg/L); mycophenolate mofetil, 500 mg twice daily; cinacalcet, 30 mg 3 times a week; metformin, 500 mg twice daily; amlodipine, 5 mg twice daily; levothyroxine, 112 mcg/d; and atorva­statin, 40 mg at bedtime.

As you review her medications, you wonder if the cyclosporine she began receiving after her kidney transplant could be causing or contributing to her worsening paranoid delusions.

Kidney transplantation has become an ideal treatment for patients with end-stage renal disease. In 2020, 22,817 kidney transplants were performed in the United States.¹ Compared with dialysis, kidney transplant allows patients the chance to return to a satisfactory quality of life.² However, to ensure a successful and long-lasting transplant, patients must be started and maintained on lifelong immunosuppressant agents that have potential adverse effects, including nephrotoxicity and hypertension. Further, immunosuppressant agents—particularly calcineurin inhibitors—are associated with potential adverse effects on mental health. The most commonly documented mental health-related adverse effects include insomnia, anxiety, depression, and confusion.³ In this article, we discuss the risk of severe psychosis associated with the use of calcineurin inhibitors.

Calcineurin inhibitors and psychiatric symptoms

Cyclosporine and tacrolimus are calcineurin inhibitors that are commonly used as immunosuppressant agents after kidney transplantation. They primarily work by specifically and competitively binding to and inhibiting the calcineurin protein to reduce the transcriptional activation of cytokine genes for interleukin-2, tumor necrosis factor-alpha, interleukin-3, interleukin-4, CD40L (CD40 ligand), granulocyte-macrophage colony-stimulating factor, and interferon-gamma.^4,5 The ultimate downstream effect is reduced proliferation of T lymphocytes and thereby an immunosuppressed state that will protect against organ rejection. However, this is not the only downstream effect that can occur from inhibiting calcineurin. Cyclosporine and tacrolimus may modulate the activity of dopamine and N-methyl-D-aspartate (NMDA) via calcineurin.^6-8

An increased effect of dopamine in the mesocortical dopaminergic pathway has long been a suspected cause for psychotic symptoms. A study conducted in rodents suggested that tacrolimus selectively modifies the responsivity and sensitivity of postsynaptic dopamine-2 (D2) and dopamine-3 (D3) receptors.⁹ These receptors are important when discussing psychosis because antipsychotic medications work primarily by blocking dopamine D2, while many also block the D3 receptor. We hypothesize that modifying the responsivity and sensitivity of these 2 receptors could increase the risk of a person developing psychosis. It may also provide insight into how to best treat a psychotic episode.

Tacrolimus has been shown to elicit inhibition of NMDA-induced neurotransmitter release and augmentation of depolarization-induced neurotransmitter release.¹⁰ In theory, this potential inhibition at the NMDA receptors may lead to a compensatory and excessive release of glutamate. Elevated glutamate levels in the brain could lead to psychiatric symptoms, including psychosis. This is supported by the psychosis caused by many NMDA receptor antagonists, such as phencyclidine (PCP) and ketamine. Furthermore, a study examining calcineurin in knockout mice showed that the spectrum of behavioral abnormalities was strikingly similar to those in schizophrenia models.¹¹ These mice displayed impaired working memory, impaired attentional function, social withdrawal, and psychomotor agitation. This further supports the idea that calcineurin inhibition can play a significant role in causing psychiatric symptoms by affecting both dopamine and NMDA receptors.

Continue to: How to address calcineurin inhibitor–induced psychosis...

How to address calcineurin inhibitor–induced psychosis

Here we outline a potential treatment strategy to combat psychosis secondary to calcineurin inhibitors. First, evaluate the patient’s calcineurin inhibitor level (either cyclosporine or tacrolimus). Levels should be drawn as a true trough and doses adjusted if necessary via appropriate consultation with a transplant specialist. Because many of the adverse effects associated with these agents are dose-dependent, we suspect that the risk of psychosis and other mental health–related adverse effects may also follow this trend.

Assuming that the calcineurin inhibitor cannot be stopped, changed to a different agent, or subject to a dose decrease, we recommend initiating an antipsychotic medication to control psychotic symptoms. Given the potential effect of calcineurin inhibitors on dopamine, we suggest trialing a second-generation antipsychotic with relatively high affinity for dopamine D2 receptors, such as risperidone or paliperidone. However, compared with patients with schizophrenia, patients receiving a calcineurin inhibitor may be more likely to develop extrapyramidal symptoms (EPS). Therefore, to avoid potential adverse effects, consider using a lower starting dose or an antipsychotic medication with less dopamine D2 affinity, such as quetiapine, olanzapine, or aripiprazole. Furthermore, because post-transplant patients may be at a higher risk for depression, which may be secondary to medication adverse effects, we suggest avoiding first-generation antipsychotics (FGAs) such as haloperidol because FGAs may worsen depressive symptoms.

We recommend initiating risperidone, 1 mg twice a day, for patients with psychosis secondary to a calcineurin inhibitor. If the patient develops EPS, consider switching to an antipsychotic medication with a less potent dopamine D2 blockade, such as quetiapine, olanzapine, or aripiprazole. We recommend an antipsychotic switch rather than adding benztropine or diphenhydramine to the regimen because many transplant recipients may be older patients, and adding anticholinergic medications can be problematic for this population. However, if the patient is younger or has responded particularly well to risperidone, the benefit of adding an anticholinergic medication may outweigh the risks. This decision should be made on an individual basis and may include other options, such as a switch to quetiapine, olanzapine, or aripiprazole. While these agents may not block the D2 receptor as strongly as risperidone, they all are effective and approved for adjunct therapy in major depressive disorder. We recommend quetiapine and olanzapine as second-line agents because of their potential for sedation and significant weight gain. While aripiprazole has a great metabolic adverse effect profile, its mechanism of action as a partial D2 agonist may make it difficult to control psychotic symptoms in this patient population compared with true D2 antagonists.

Continue to: CASE CONTINUED...

Mrs. C is admitted to the inpatient psychiatric unit and started on risperidone, 1 mg twice daily. Initially, she complains of lightheadedness at night due to the risperidone, so her dose is changed to 2 mg at bedtime. Gradually, she begins to show mild improvement. Previously, she reported feeling frightened of staff members, but after a few days she reports that she feels safe at the hospital. However, her delusions of being monitored by the FBI persist.

After 9 days of hospitalization, Mrs. C is discharged home to the care of her daughter. At first, she does well, but unfortunately she begins to refuse to take her medication and returns to her baseline.

Related Resources

• Gok F, Eroglu MZ. Acute psychotic disorder associated with immunosuppressive agent use after renal transplantation: a case report. Psychiatry and Clinical Psychopharmacology. 2017;3:314-316.
• Bersani G, Marino P, Valerani G, et al. Manic-like psychosis associated with elevated trough tacrolimus blood concentrations 17 years after kidney transplant. Case Rep Psychiatry. 2013;2013:926395. doi: 10.1155/2013/926395

Drug Brand Names

Amlodipine • Norvasc

Aripiprazole • Abilify

Atorvastatin • Lipitor

Benztropine • Cogentin

Cinacalcet • Sensipar

Cyclosporine • Gengraf

Haloperidol • Haldol

Ketamine • Ketalar

Levothyroxine • Synthroid

Metformin • Glucophage

Mycophenolate mofetil • CellCept

Olanzapine • Zyprexa

Quetiapine • Seroquel

Paliperidone • Invega

Risperidone • Risperdal

Tacrolimus • Prograf

Mrs. C, age 68, is experiencing worsening paranoid delusions. She believes that because she lied about her income when she was younger, the FBI is tracking her and wants to poison her food and spray dangerous fumes in her house. Her paranoia has made it hard for her to sleep, eat, or feel safe in her home.

Mrs. C’s daughter reports that her mother’s delusions started 3 years ago and have worsened in recent months. Mrs. C has no psychiatric history. Her medical history is signifi­cant for renal transplant in 2015, type 2 diabetes, hyperlipidemia, hypertension, and hypothyroidism. She is currently normotensive. Mrs. C’s home medications include cyclosporine, which is a calcineurin inhibitor, 125 mg twice daily (trough level = 138 mcg/L); mycophenolate mofetil, 500 mg twice daily; cinacalcet, 30 mg 3 times a week; metformin, 500 mg twice daily; amlodipine, 5 mg twice daily; levothyroxine, 112 mcg/d; and atorva­statin, 40 mg at bedtime.

As you review her medications, you wonder if the cyclosporine she began receiving after her kidney transplant could be causing or contributing to her worsening paranoid delusions.

Kidney transplantation has become an ideal treatment for patients with end-stage renal disease. In 2020, 22,817 kidney transplants were performed in the United States.¹ Compared with dialysis, kidney transplant allows patients the chance to return to a satisfactory quality of life.² However, to ensure a successful and long-lasting transplant, patients must be started and maintained on lifelong immunosuppressant agents that have potential adverse effects, including nephrotoxicity and hypertension. Further, immunosuppressant agents—particularly calcineurin inhibitors—are associated with potential adverse effects on mental health. The most commonly documented mental health-related adverse effects include insomnia, anxiety, depression, and confusion.³ In this article, we discuss the risk of severe psychosis associated with the use of calcineurin inhibitors.

Calcineurin inhibitors and psychiatric symptoms

Cyclosporine and tacrolimus are calcineurin inhibitors that are commonly used as immunosuppressant agents after kidney transplantation. They primarily work by specifically and competitively binding to and inhibiting the calcineurin protein to reduce the transcriptional activation of cytokine genes for interleukin-2, tumor necrosis factor-alpha, interleukin-3, interleukin-4, CD40L (CD40 ligand), granulocyte-macrophage colony-stimulating factor, and interferon-gamma.^4,5 The ultimate downstream effect is reduced proliferation of T lymphocytes and thereby an immunosuppressed state that will protect against organ rejection. However, this is not the only downstream effect that can occur from inhibiting calcineurin. Cyclosporine and tacrolimus may modulate the activity of dopamine and N-methyl-D-aspartate (NMDA) via calcineurin.^6-8

An increased effect of dopamine in the mesocortical dopaminergic pathway has long been a suspected cause for psychotic symptoms. A study conducted in rodents suggested that tacrolimus selectively modifies the responsivity and sensitivity of postsynaptic dopamine-2 (D2) and dopamine-3 (D3) receptors.⁹ These receptors are important when discussing psychosis because antipsychotic medications work primarily by blocking dopamine D2, while many also block the D3 receptor. We hypothesize that modifying the responsivity and sensitivity of these 2 receptors could increase the risk of a person developing psychosis. It may also provide insight into how to best treat a psychotic episode.

Tacrolimus has been shown to elicit inhibition of NMDA-induced neurotransmitter release and augmentation of depolarization-induced neurotransmitter release.¹⁰ In theory, this potential inhibition at the NMDA receptors may lead to a compensatory and excessive release of glutamate. Elevated glutamate levels in the brain could lead to psychiatric symptoms, including psychosis. This is supported by the psychosis caused by many NMDA receptor antagonists, such as phencyclidine (PCP) and ketamine. Furthermore, a study examining calcineurin in knockout mice showed that the spectrum of behavioral abnormalities was strikingly similar to those in schizophrenia models.¹¹ These mice displayed impaired working memory, impaired attentional function, social withdrawal, and psychomotor agitation. This further supports the idea that calcineurin inhibition can play a significant role in causing psychiatric symptoms by affecting both dopamine and NMDA receptors.

Continue to: How to address calcineurin inhibitor–induced psychosis...

How to address calcineurin inhibitor–induced psychosis

Here we outline a potential treatment strategy to combat psychosis secondary to calcineurin inhibitors. First, evaluate the patient’s calcineurin inhibitor level (either cyclosporine or tacrolimus). Levels should be drawn as a true trough and doses adjusted if necessary via appropriate consultation with a transplant specialist. Because many of the adverse effects associated with these agents are dose-dependent, we suspect that the risk of psychosis and other mental health–related adverse effects may also follow this trend.

Assuming that the calcineurin inhibitor cannot be stopped, changed to a different agent, or subject to a dose decrease, we recommend initiating an antipsychotic medication to control psychotic symptoms. Given the potential effect of calcineurin inhibitors on dopamine, we suggest trialing a second-generation antipsychotic with relatively high affinity for dopamine D2 receptors, such as risperidone or paliperidone. However, compared with patients with schizophrenia, patients receiving a calcineurin inhibitor may be more likely to develop extrapyramidal symptoms (EPS). Therefore, to avoid potential adverse effects, consider using a lower starting dose or an antipsychotic medication with less dopamine D2 affinity, such as quetiapine, olanzapine, or aripiprazole. Furthermore, because post-transplant patients may be at a higher risk for depression, which may be secondary to medication adverse effects, we suggest avoiding first-generation antipsychotics (FGAs) such as haloperidol because FGAs may worsen depressive symptoms.

We recommend initiating risperidone, 1 mg twice a day, for patients with psychosis secondary to a calcineurin inhibitor. If the patient develops EPS, consider switching to an antipsychotic medication with a less potent dopamine D2 blockade, such as quetiapine, olanzapine, or aripiprazole. We recommend an antipsychotic switch rather than adding benztropine or diphenhydramine to the regimen because many transplant recipients may be older patients, and adding anticholinergic medications can be problematic for this population. However, if the patient is younger or has responded particularly well to risperidone, the benefit of adding an anticholinergic medication may outweigh the risks. This decision should be made on an individual basis and may include other options, such as a switch to quetiapine, olanzapine, or aripiprazole. While these agents may not block the D2 receptor as strongly as risperidone, they all are effective and approved for adjunct therapy in major depressive disorder. We recommend quetiapine and olanzapine as second-line agents because of their potential for sedation and significant weight gain. While aripiprazole has a great metabolic adverse effect profile, its mechanism of action as a partial D2 agonist may make it difficult to control psychotic symptoms in this patient population compared with true D2 antagonists.

Continue to: CASE CONTINUED...

Mrs. C is admitted to the inpatient psychiatric unit and started on risperidone, 1 mg twice daily. Initially, she complains of lightheadedness at night due to the risperidone, so her dose is changed to 2 mg at bedtime. Gradually, she begins to show mild improvement. Previously, she reported feeling frightened of staff members, but after a few days she reports that she feels safe at the hospital. However, her delusions of being monitored by the FBI persist.

After 9 days of hospitalization, Mrs. C is discharged home to the care of her daughter. At first, she does well, but unfortunately she begins to refuse to take her medication and returns to her baseline.

Related Resources

• Gok F, Eroglu MZ. Acute psychotic disorder associated with immunosuppressive agent use after renal transplantation: a case report. Psychiatry and Clinical Psychopharmacology. 2017;3:314-316.
• Bersani G, Marino P, Valerani G, et al. Manic-like psychosis associated with elevated trough tacrolimus blood concentrations 17 years after kidney transplant. Case Rep Psychiatry. 2013;2013:926395. doi: 10.1155/2013/926395

Drug Brand Names

Amlodipine • Norvasc

Aripiprazole • Abilify

Atorvastatin • Lipitor

Benztropine • Cogentin

Cinacalcet • Sensipar

Cyclosporine • Gengraf

Haloperidol • Haldol

Ketamine • Ketalar

Levothyroxine • Synthroid

Metformin • Glucophage

Mycophenolate mofetil • CellCept

Olanzapine • Zyprexa

Quetiapine • Seroquel

Paliperidone • Invega

Risperidone • Risperdal

Tacrolimus • Prograf

Mrs. C, age 68, is experiencing worsening paranoid delusions. She believes that because she lied about her income when she was younger, the FBI is tracking her and wants to poison her food and spray dangerous fumes in her house. Her paranoia has made it hard for her to sleep, eat, or feel safe in her home.

Mrs. C’s daughter reports that her mother’s delusions started 3 years ago and have worsened in recent months. Mrs. C has no psychiatric history. Her medical history is signifi­cant for renal transplant in 2015, type 2 diabetes, hyperlipidemia, hypertension, and hypothyroidism. She is currently normotensive. Mrs. C’s home medications include cyclosporine, which is a calcineurin inhibitor, 125 mg twice daily (trough level = 138 mcg/L); mycophenolate mofetil, 500 mg twice daily; cinacalcet, 30 mg 3 times a week; metformin, 500 mg twice daily; amlodipine, 5 mg twice daily; levothyroxine, 112 mcg/d; and atorva­statin, 40 mg at bedtime.

As you review her medications, you wonder if the cyclosporine she began receiving after her kidney transplant could be causing or contributing to her worsening paranoid delusions.

Kidney transplantation has become an ideal treatment for patients with end-stage renal disease. In 2020, 22,817 kidney transplants were performed in the United States.¹ Compared with dialysis, kidney transplant allows patients the chance to return to a satisfactory quality of life.² However, to ensure a successful and long-lasting transplant, patients must be started and maintained on lifelong immunosuppressant agents that have potential adverse effects, including nephrotoxicity and hypertension. Further, immunosuppressant agents—particularly calcineurin inhibitors—are associated with potential adverse effects on mental health. The most commonly documented mental health-related adverse effects include insomnia, anxiety, depression, and confusion.³ In this article, we discuss the risk of severe psychosis associated with the use of calcineurin inhibitors.

Calcineurin inhibitors and psychiatric symptoms

Cyclosporine and tacrolimus are calcineurin inhibitors that are commonly used as immunosuppressant agents after kidney transplantation. They primarily work by specifically and competitively binding to and inhibiting the calcineurin protein to reduce the transcriptional activation of cytokine genes for interleukin-2, tumor necrosis factor-alpha, interleukin-3, interleukin-4, CD40L (CD40 ligand), granulocyte-macrophage colony-stimulating factor, and interferon-gamma.^4,5 The ultimate downstream effect is reduced proliferation of T lymphocytes and thereby an immunosuppressed state that will protect against organ rejection. However, this is not the only downstream effect that can occur from inhibiting calcineurin. Cyclosporine and tacrolimus may modulate the activity of dopamine and N-methyl-D-aspartate (NMDA) via calcineurin.^6-8

An increased effect of dopamine in the mesocortical dopaminergic pathway has long been a suspected cause for psychotic symptoms. A study conducted in rodents suggested that tacrolimus selectively modifies the responsivity and sensitivity of postsynaptic dopamine-2 (D2) and dopamine-3 (D3) receptors.⁹ These receptors are important when discussing psychosis because antipsychotic medications work primarily by blocking dopamine D2, while many also block the D3 receptor. We hypothesize that modifying the responsivity and sensitivity of these 2 receptors could increase the risk of a person developing psychosis. It may also provide insight into how to best treat a psychotic episode.

Tacrolimus has been shown to elicit inhibition of NMDA-induced neurotransmitter release and augmentation of depolarization-induced neurotransmitter release.¹⁰ In theory, this potential inhibition at the NMDA receptors may lead to a compensatory and excessive release of glutamate. Elevated glutamate levels in the brain could lead to psychiatric symptoms, including psychosis. This is supported by the psychosis caused by many NMDA receptor antagonists, such as phencyclidine (PCP) and ketamine. Furthermore, a study examining calcineurin in knockout mice showed that the spectrum of behavioral abnormalities was strikingly similar to those in schizophrenia models.¹¹ These mice displayed impaired working memory, impaired attentional function, social withdrawal, and psychomotor agitation. This further supports the idea that calcineurin inhibition can play a significant role in causing psychiatric symptoms by affecting both dopamine and NMDA receptors.

Continue to: How to address calcineurin inhibitor–induced psychosis...

How to address calcineurin inhibitor–induced psychosis

Here we outline a potential treatment strategy to combat psychosis secondary to calcineurin inhibitors. First, evaluate the patient’s calcineurin inhibitor level (either cyclosporine or tacrolimus). Levels should be drawn as a true trough and doses adjusted if necessary via appropriate consultation with a transplant specialist. Because many of the adverse effects associated with these agents are dose-dependent, we suspect that the risk of psychosis and other mental health–related adverse effects may also follow this trend.

Assuming that the calcineurin inhibitor cannot be stopped, changed to a different agent, or subject to a dose decrease, we recommend initiating an antipsychotic medication to control psychotic symptoms. Given the potential effect of calcineurin inhibitors on dopamine, we suggest trialing a second-generation antipsychotic with relatively high affinity for dopamine D2 receptors, such as risperidone or paliperidone. However, compared with patients with schizophrenia, patients receiving a calcineurin inhibitor may be more likely to develop extrapyramidal symptoms (EPS). Therefore, to avoid potential adverse effects, consider using a lower starting dose or an antipsychotic medication with less dopamine D2 affinity, such as quetiapine, olanzapine, or aripiprazole. Furthermore, because post-transplant patients may be at a higher risk for depression, which may be secondary to medication adverse effects, we suggest avoiding first-generation antipsychotics (FGAs) such as haloperidol because FGAs may worsen depressive symptoms.

We recommend initiating risperidone, 1 mg twice a day, for patients with psychosis secondary to a calcineurin inhibitor. If the patient develops EPS, consider switching to an antipsychotic medication with a less potent dopamine D2 blockade, such as quetiapine, olanzapine, or aripiprazole. We recommend an antipsychotic switch rather than adding benztropine or diphenhydramine to the regimen because many transplant recipients may be older patients, and adding anticholinergic medications can be problematic for this population. However, if the patient is younger or has responded particularly well to risperidone, the benefit of adding an anticholinergic medication may outweigh the risks. This decision should be made on an individual basis and may include other options, such as a switch to quetiapine, olanzapine, or aripiprazole. While these agents may not block the D2 receptor as strongly as risperidone, they all are effective and approved for adjunct therapy in major depressive disorder. We recommend quetiapine and olanzapine as second-line agents because of their potential for sedation and significant weight gain. While aripiprazole has a great metabolic adverse effect profile, its mechanism of action as a partial D2 agonist may make it difficult to control psychotic symptoms in this patient population compared with true D2 antagonists.

Continue to: CASE CONTINUED...

Mrs. C is admitted to the inpatient psychiatric unit and started on risperidone, 1 mg twice daily. Initially, she complains of lightheadedness at night due to the risperidone, so her dose is changed to 2 mg at bedtime. Gradually, she begins to show mild improvement. Previously, she reported feeling frightened of staff members, but after a few days she reports that she feels safe at the hospital. However, her delusions of being monitored by the FBI persist.

After 9 days of hospitalization, Mrs. C is discharged home to the care of her daughter. At first, she does well, but unfortunately she begins to refuse to take her medication and returns to her baseline.

Related Resources

• Gok F, Eroglu MZ. Acute psychotic disorder associated with immunosuppressive agent use after renal transplantation: a case report. Psychiatry and Clinical Psychopharmacology. 2017;3:314-316.
• Bersani G, Marino P, Valerani G, et al. Manic-like psychosis associated with elevated trough tacrolimus blood concentrations 17 years after kidney transplant. Case Rep Psychiatry. 2013;2013:926395. doi: 10.1155/2013/926395

Drug Brand Names

Amlodipine • Norvasc

Aripiprazole • Abilify

Atorvastatin • Lipitor

Benztropine • Cogentin

Cinacalcet • Sensipar

Cyclosporine • Gengraf

Haloperidol • Haldol

Ketamine • Ketalar

Levothyroxine • Synthroid

Metformin • Glucophage

Mycophenolate mofetil • CellCept

Olanzapine • Zyprexa

Quetiapine • Seroquel

Paliperidone • Invega

Risperidone • Risperdal

Tacrolimus • Prograf

"Effortless.” “Weightless.” “Limitless.” “Carefree.” In most cases, these are words one would not commonly associate with running. In fact, many people might experience an uptick in anxiety when fathoming the idea of going out for a run. Believe it or not, these words are direct quotes from runners describing the feeling of a “runner’s high”—a well-documented organic euphoria that cannot be purchased or abused. But how is the innately basic and monotonous act of running able to reliably transform something as complex as human emotion? This answer lies in the endocannabinoid system.

For decades, scientists and the public believed the runner’s high was associated with an exercise-induced increase in levels of opioid peptides called beta-endorphins. The problem with this theory is that beta-endorphin, released into the blood by the pituitary gland in response to exercise and stress, has difficulty passing through the blood-brain barrier, rendering central effects of this peripheral opioid unlikely.¹ Only recently have researchers been examining the effects of exercise as it pertains to the endocannabinoid system.² Interest in the study of this system is peaking as use of cannabis and hemp-based products reaches an all-time high.

Exploring the endocannabinoid system

Within the last 25 years, the endocannabinoid system has emerged as a highly relevant and unique neuromodulatory system. As with other neurotransmitter systems, the endocannabinoid system is comprised of the endogenous cannabinoids, their receptors, and an array of enzymes responsible for both synthesis and degradation. Endocannabinoid receptors are ubiquitous in the brain and take effect primarily in the cortex, amygdala, basal ganglia, hippocampus, hypothalamus, and cerebellum. One fascinating feature of endocannabinoids is that their precursors lie embedded within lipid membranes. Nearly on demand, endocannabinoids can be rapidly synthesized and released. This grants them almost immediate availability to get into the action at the synapse.²

One study of mice found that those who were exercised experienced improvements in anxiety behaviors and better tolerance to pain. Further, when the exercised mice were treated with endocannabinoid receptor antagonists, they remained anxious and were more sensitive to pain. Endorphin antagonists had no effect on the outcome of these tests.¹ A similar study conducted in humans found improvement in subjective anxiety scores after 45 minutes of moderate-intensity exercise. This study also showed no change with naltrexone administration vs placebo, again supporting the hypothesis that endorphins play little role in this phenomenon. Interestingly, levels of endogenous cannabinoids were elevated following exercise.³ These findings suggest a possible link between activation of the endogenous endocannabinoid system and the anxiolytic properties of exercise.

For good reason, the endocannabinoid system has attracted substantial interest as a focus for a new class of drugs to treat anxiety and stress-related disorders. It remains unknown how we can best harness its many beneficial effects in a safe and effective manner. With that said, activities such as physical exercise, mindfulness meditation, yoga, and other forms of complementary medicine are immediately available and cost-effective methods that have at least preliminary data revealing their multiple health benefits, including improvement in the symptoms of anxiety and activation of endogenous cannabinoids.^1,3-6

As we are all aware, medical training and practice is full of a variety of stresses and demands. Given these demands, finding a balance between mind, body, and spirit can seem like an impossible task. Besides the obvious physical benefits of regular exercise, running can serve to employ the stress-modifying effects of our endogenous cannabinoid system to reduce perceived anxiety and improve wellness. Indeed, at the start of any bout of exercise—especially running—the transition from rest can be startling. Rest assured that there is good news waiting beyond the first few miles. Your reward for patience and perseverance is a beautiful freedom experienced only by those who have earned it. The best part of it all? It is waiting for you right outside your door.

"Effortless.” “Weightless.” “Limitless.” “Carefree.” In most cases, these are words one would not commonly associate with running. In fact, many people might experience an uptick in anxiety when fathoming the idea of going out for a run. Believe it or not, these words are direct quotes from runners describing the feeling of a “runner’s high”—a well-documented organic euphoria that cannot be purchased or abused. But how is the innately basic and monotonous act of running able to reliably transform something as complex as human emotion? This answer lies in the endocannabinoid system.

For decades, scientists and the public believed the runner’s high was associated with an exercise-induced increase in levels of opioid peptides called beta-endorphins. The problem with this theory is that beta-endorphin, released into the blood by the pituitary gland in response to exercise and stress, has difficulty passing through the blood-brain barrier, rendering central effects of this peripheral opioid unlikely.¹ Only recently have researchers been examining the effects of exercise as it pertains to the endocannabinoid system.² Interest in the study of this system is peaking as use of cannabis and hemp-based products reaches an all-time high.

Exploring the endocannabinoid system

Within the last 25 years, the endocannabinoid system has emerged as a highly relevant and unique neuromodulatory system. As with other neurotransmitter systems, the endocannabinoid system is comprised of the endogenous cannabinoids, their receptors, and an array of enzymes responsible for both synthesis and degradation. Endocannabinoid receptors are ubiquitous in the brain and take effect primarily in the cortex, amygdala, basal ganglia, hippocampus, hypothalamus, and cerebellum. One fascinating feature of endocannabinoids is that their precursors lie embedded within lipid membranes. Nearly on demand, endocannabinoids can be rapidly synthesized and released. This grants them almost immediate availability to get into the action at the synapse.²

One study of mice found that those who were exercised experienced improvements in anxiety behaviors and better tolerance to pain. Further, when the exercised mice were treated with endocannabinoid receptor antagonists, they remained anxious and were more sensitive to pain. Endorphin antagonists had no effect on the outcome of these tests.¹ A similar study conducted in humans found improvement in subjective anxiety scores after 45 minutes of moderate-intensity exercise. This study also showed no change with naltrexone administration vs placebo, again supporting the hypothesis that endorphins play little role in this phenomenon. Interestingly, levels of endogenous cannabinoids were elevated following exercise.³ These findings suggest a possible link between activation of the endogenous endocannabinoid system and the anxiolytic properties of exercise.

For good reason, the endocannabinoid system has attracted substantial interest as a focus for a new class of drugs to treat anxiety and stress-related disorders. It remains unknown how we can best harness its many beneficial effects in a safe and effective manner. With that said, activities such as physical exercise, mindfulness meditation, yoga, and other forms of complementary medicine are immediately available and cost-effective methods that have at least preliminary data revealing their multiple health benefits, including improvement in the symptoms of anxiety and activation of endogenous cannabinoids.^1,3-6

As we are all aware, medical training and practice is full of a variety of stresses and demands. Given these demands, finding a balance between mind, body, and spirit can seem like an impossible task. Besides the obvious physical benefits of regular exercise, running can serve to employ the stress-modifying effects of our endogenous cannabinoid system to reduce perceived anxiety and improve wellness. Indeed, at the start of any bout of exercise—especially running—the transition from rest can be startling. Rest assured that there is good news waiting beyond the first few miles. Your reward for patience and perseverance is a beautiful freedom experienced only by those who have earned it. The best part of it all? It is waiting for you right outside your door.

"Effortless.” “Weightless.” “Limitless.” “Carefree.” In most cases, these are words one would not commonly associate with running. In fact, many people might experience an uptick in anxiety when fathoming the idea of going out for a run. Believe it or not, these words are direct quotes from runners describing the feeling of a “runner’s high”—a well-documented organic euphoria that cannot be purchased or abused. But how is the innately basic and monotonous act of running able to reliably transform something as complex as human emotion? This answer lies in the endocannabinoid system.

For decades, scientists and the public believed the runner’s high was associated with an exercise-induced increase in levels of opioid peptides called beta-endorphins. The problem with this theory is that beta-endorphin, released into the blood by the pituitary gland in response to exercise and stress, has difficulty passing through the blood-brain barrier, rendering central effects of this peripheral opioid unlikely.¹ Only recently have researchers been examining the effects of exercise as it pertains to the endocannabinoid system.² Interest in the study of this system is peaking as use of cannabis and hemp-based products reaches an all-time high.

Exploring the endocannabinoid system

Within the last 25 years, the endocannabinoid system has emerged as a highly relevant and unique neuromodulatory system. As with other neurotransmitter systems, the endocannabinoid system is comprised of the endogenous cannabinoids, their receptors, and an array of enzymes responsible for both synthesis and degradation. Endocannabinoid receptors are ubiquitous in the brain and take effect primarily in the cortex, amygdala, basal ganglia, hippocampus, hypothalamus, and cerebellum. One fascinating feature of endocannabinoids is that their precursors lie embedded within lipid membranes. Nearly on demand, endocannabinoids can be rapidly synthesized and released. This grants them almost immediate availability to get into the action at the synapse.²

One study of mice found that those who were exercised experienced improvements in anxiety behaviors and better tolerance to pain. Further, when the exercised mice were treated with endocannabinoid receptor antagonists, they remained anxious and were more sensitive to pain. Endorphin antagonists had no effect on the outcome of these tests.¹ A similar study conducted in humans found improvement in subjective anxiety scores after 45 minutes of moderate-intensity exercise. This study also showed no change with naltrexone administration vs placebo, again supporting the hypothesis that endorphins play little role in this phenomenon. Interestingly, levels of endogenous cannabinoids were elevated following exercise.³ These findings suggest a possible link between activation of the endogenous endocannabinoid system and the anxiolytic properties of exercise.

For good reason, the endocannabinoid system has attracted substantial interest as a focus for a new class of drugs to treat anxiety and stress-related disorders. It remains unknown how we can best harness its many beneficial effects in a safe and effective manner. With that said, activities such as physical exercise, mindfulness meditation, yoga, and other forms of complementary medicine are immediately available and cost-effective methods that have at least preliminary data revealing their multiple health benefits, including improvement in the symptoms of anxiety and activation of endogenous cannabinoids.^1,3-6

As we are all aware, medical training and practice is full of a variety of stresses and demands. Given these demands, finding a balance between mind, body, and spirit can seem like an impossible task. Besides the obvious physical benefits of regular exercise, running can serve to employ the stress-modifying effects of our endogenous cannabinoid system to reduce perceived anxiety and improve wellness. Indeed, at the start of any bout of exercise—especially running—the transition from rest can be startling. Rest assured that there is good news waiting beyond the first few miles. Your reward for patience and perseverance is a beautiful freedom experienced only by those who have earned it. The best part of it all? It is waiting for you right outside your door.

Disease-modifying antirheumatic drugs (DMARDs) such as biologics may carry an increased risk for preterm birth or cesarean delivery for pregnant women with psoriatic arthritis (PsA), according to a recent study published in Arthritis & Rheumatology.

zoranm/Getty Images

The risk was particularly high for women with PsA who received biologic disease-modifying antirheumatic drugs (bDMARDs), according to Katarina Remaeus, PhD, of the Karolinska Institute in Stockholm and colleagues.

“The results may indicate that a more severe or active PsA disease that requires antirheumatic treatment during pregnancy, especially bDMARDs, is associated with increased risks of adverse pregnancy outcomes compared to non-PsA pregnancies,” Dr. Remaeus and colleagues write in their study. “The risk of preterm birth in PsA pregnancies is further influenced by parity with the most increased risks observed in first pregnancies.”

In a nationwide, register-based cohort study, the researchers evaluated 921 pregnancies of women with PsA between 2007 and 2017, comparing them to the pregnancies of 9,210 women without PsA over the same time frame. The pregnancies for women with PsA were further categorized based on whether the women had not received antirheumatic treatment in the year prior to and/or during pregnancy (495 pregnancies) or had received antirheumatic treatment at any point in the year before and/or during pregnancy (426 pregnancies).

Of the women in the PsA group who were treated in the year prior to pregnancy (170 women), 39.4% received monotherapy with a conventional synthetic DMARD (csDMARD) such as an antimalarial, methotrexate, or sulfasalazine; 24.1% received oral corticosteroids, and 15.9% received a tumor necrosis factor inhibitor (TNFi), whereas about 20% of women received two or more antirheumatic drugs.

In the group of women treated during pregnancy (256 women), 153 did not receive bDMARDs; of these, 41.8% had monotherapy with either a csDMARD or corticosteroids, whereas the group treated with bDMARDs received TNFi monotherapy (43.7%) or TNFi with corticosteroids (35.9%), TNFi with csDMARD (9.7%), or TNFi with csDMARD plus corticosteroids (9.7%).

A majority of women in both groups (70.1%) were between ages 30 and 34 years (37.1%) or older than age 35 years (33%) and had delivered more than one child (63.2%). Women in the PsA group were more likely to be born in a Nordic country (91.8% vs. 82.8%), to have a body mass index between 30.0 and 60.0 kg/m² (19.9% vs. 12.6%), to be a smoker (9.2% vs. 5.3%), to have hypertension (1.4% vs. 0.8%) or diabetes (1.3% vs. 0.5%) prior to pregnancy, and to have a higher level of education (>12 years; 50.1% vs. 43.3%), compared with women in the non-PsA group.

The results showed women in the PsA group were more likely to experience preterm birth (adjusted odds ratio, 1.69; 95% confidence interval, 1.27-2.24) and undergo an elective (aOR, 1.77; 95% CI, 1.43-2.20) or emergency C-section (aOR, 1.42; 95% CI, 1.10-1.84). The group at highest risk for preterm birth with regard to parity was women with PsA having their first child (aOR, 3.95; 95% CI, 1.43-10.95).

Women who received antirheumatic treatment were at greater risk for experiencing preterm birth (aOR, 2.30; 95% CI, 1.49-3.56), and this risk was even higher for treatment with bDMARDs, compared with women without PsA (aOR, 4.49; 95% CI, 2.60-7.79). Use of bDMARDs also was associated with higher risks for spontaneous preterm birth (aOR, 4.73; 95% CI, 2.53-8.87), preterm birth between 32 and 36 weeks’ gestation (aOR, 5.06; 95% CI, 2.91-8.79), elective C-section (aOR, 2.72; 95% CI, 1.61-4.59), emergency C-section (aOR, 2.06; 95% CI, 1.04-4.07), and preeclampsia (aOR, 2.88, 95% CI, 1.35-6.17).

The researchers note that women with PsA should be evaluated for preterm birth particularly if they are having their first child, and “from a clinical point of view, all women with PsA, regardless of antirheumatic treatment, should be counseled about pregnancy outcomes and receive individualized monitoring during pregnancy.”

Are adverse outcomes linked to disease activity or treatment?

Patients in the study had a higher risk of adverse outcomes when they had a PsA diagnosis, and when they received antirheumatic treatment – but were the adverse outcomes associated with a patient’s high disease activity or need for antirheumatic treatment?

“Our interpretation is that a PsA disease that requires continued antirheumatic treatment during pregnancy is more severe than PsA that does not require treatment,” Dr. Remaeus and colleagues write. “Thus, the increased risk of adverse outcomes in pregnancies with maternal antirheumatic treatment is probably attributed to disease severity rather than an effect of the medication itself.”

Anja Strangfeld, MD, PhD, of the German Rheumatism Research Centre in Berlin, told this news organization that the results of the study are important because it is one of the first to report differences in risk in pregnancy outcomes for women with and without PsA.

“The information is relevant to guide rheumatologists in advising patients with PsA when planning the first or subsequent pregnancies,” she said. “The results are reassuring in reporting that the elevated risk for PsA patients for adverse pregnancy outcomes is low in patients not in need of antirheumatic medication, presumably in low-disease activity.”

However, the study is still unclear on whether the association with adverse pregnancy outcomes in patients is the result of higher disease activity or the need for antirheumatic treatment, she explained.

“It was only hypothesized that those patients under bDMARD treatment are/were in high disease activity. There [is] no information on disease activity in the data sources, which limits the results,” she said. “The investigation still does not solve the important question – if adverse pregnancy outcomes are rather related to high disease activity or the medication to treat this situation.”

There was no specific funding for this study. The study authors and Dr. Strangfeld have disclosed no relevant financial relationships.

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

Disease-modifying antirheumatic drugs (DMARDs) such as biologics may carry an increased risk for preterm birth or cesarean delivery for pregnant women with psoriatic arthritis (PsA), according to a recent study published in Arthritis & Rheumatology.

zoranm/Getty Images

The risk was particularly high for women with PsA who received biologic disease-modifying antirheumatic drugs (bDMARDs), according to Katarina Remaeus, PhD, of the Karolinska Institute in Stockholm and colleagues.

“The results may indicate that a more severe or active PsA disease that requires antirheumatic treatment during pregnancy, especially bDMARDs, is associated with increased risks of adverse pregnancy outcomes compared to non-PsA pregnancies,” Dr. Remaeus and colleagues write in their study. “The risk of preterm birth in PsA pregnancies is further influenced by parity with the most increased risks observed in first pregnancies.”

In a nationwide, register-based cohort study, the researchers evaluated 921 pregnancies of women with PsA between 2007 and 2017, comparing them to the pregnancies of 9,210 women without PsA over the same time frame. The pregnancies for women with PsA were further categorized based on whether the women had not received antirheumatic treatment in the year prior to and/or during pregnancy (495 pregnancies) or had received antirheumatic treatment at any point in the year before and/or during pregnancy (426 pregnancies).

Of the women in the PsA group who were treated in the year prior to pregnancy (170 women), 39.4% received monotherapy with a conventional synthetic DMARD (csDMARD) such as an antimalarial, methotrexate, or sulfasalazine; 24.1% received oral corticosteroids, and 15.9% received a tumor necrosis factor inhibitor (TNFi), whereas about 20% of women received two or more antirheumatic drugs.

In the group of women treated during pregnancy (256 women), 153 did not receive bDMARDs; of these, 41.8% had monotherapy with either a csDMARD or corticosteroids, whereas the group treated with bDMARDs received TNFi monotherapy (43.7%) or TNFi with corticosteroids (35.9%), TNFi with csDMARD (9.7%), or TNFi with csDMARD plus corticosteroids (9.7%).

A majority of women in both groups (70.1%) were between ages 30 and 34 years (37.1%) or older than age 35 years (33%) and had delivered more than one child (63.2%). Women in the PsA group were more likely to be born in a Nordic country (91.8% vs. 82.8%), to have a body mass index between 30.0 and 60.0 kg/m² (19.9% vs. 12.6%), to be a smoker (9.2% vs. 5.3%), to have hypertension (1.4% vs. 0.8%) or diabetes (1.3% vs. 0.5%) prior to pregnancy, and to have a higher level of education (>12 years; 50.1% vs. 43.3%), compared with women in the non-PsA group.

The results showed women in the PsA group were more likely to experience preterm birth (adjusted odds ratio, 1.69; 95% confidence interval, 1.27-2.24) and undergo an elective (aOR, 1.77; 95% CI, 1.43-2.20) or emergency C-section (aOR, 1.42; 95% CI, 1.10-1.84). The group at highest risk for preterm birth with regard to parity was women with PsA having their first child (aOR, 3.95; 95% CI, 1.43-10.95).

Women who received antirheumatic treatment were at greater risk for experiencing preterm birth (aOR, 2.30; 95% CI, 1.49-3.56), and this risk was even higher for treatment with bDMARDs, compared with women without PsA (aOR, 4.49; 95% CI, 2.60-7.79). Use of bDMARDs also was associated with higher risks for spontaneous preterm birth (aOR, 4.73; 95% CI, 2.53-8.87), preterm birth between 32 and 36 weeks’ gestation (aOR, 5.06; 95% CI, 2.91-8.79), elective C-section (aOR, 2.72; 95% CI, 1.61-4.59), emergency C-section (aOR, 2.06; 95% CI, 1.04-4.07), and preeclampsia (aOR, 2.88, 95% CI, 1.35-6.17).

The researchers note that women with PsA should be evaluated for preterm birth particularly if they are having their first child, and “from a clinical point of view, all women with PsA, regardless of antirheumatic treatment, should be counseled about pregnancy outcomes and receive individualized monitoring during pregnancy.”

Are adverse outcomes linked to disease activity or treatment?

Patients in the study had a higher risk of adverse outcomes when they had a PsA diagnosis, and when they received antirheumatic treatment – but were the adverse outcomes associated with a patient’s high disease activity or need for antirheumatic treatment?

“Our interpretation is that a PsA disease that requires continued antirheumatic treatment during pregnancy is more severe than PsA that does not require treatment,” Dr. Remaeus and colleagues write. “Thus, the increased risk of adverse outcomes in pregnancies with maternal antirheumatic treatment is probably attributed to disease severity rather than an effect of the medication itself.”

Anja Strangfeld, MD, PhD, of the German Rheumatism Research Centre in Berlin, told this news organization that the results of the study are important because it is one of the first to report differences in risk in pregnancy outcomes for women with and without PsA.

“The information is relevant to guide rheumatologists in advising patients with PsA when planning the first or subsequent pregnancies,” she said. “The results are reassuring in reporting that the elevated risk for PsA patients for adverse pregnancy outcomes is low in patients not in need of antirheumatic medication, presumably in low-disease activity.”

However, the study is still unclear on whether the association with adverse pregnancy outcomes in patients is the result of higher disease activity or the need for antirheumatic treatment, she explained.

“It was only hypothesized that those patients under bDMARD treatment are/were in high disease activity. There [is] no information on disease activity in the data sources, which limits the results,” she said. “The investigation still does not solve the important question – if adverse pregnancy outcomes are rather related to high disease activity or the medication to treat this situation.”

There was no specific funding for this study. The study authors and Dr. Strangfeld have disclosed no relevant financial relationships.

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

Disease-modifying antirheumatic drugs (DMARDs) such as biologics may carry an increased risk for preterm birth or cesarean delivery for pregnant women with psoriatic arthritis (PsA), according to a recent study published in Arthritis & Rheumatology.

zoranm/Getty Images

The risk was particularly high for women with PsA who received biologic disease-modifying antirheumatic drugs (bDMARDs), according to Katarina Remaeus, PhD, of the Karolinska Institute in Stockholm and colleagues.

“The results may indicate that a more severe or active PsA disease that requires antirheumatic treatment during pregnancy, especially bDMARDs, is associated with increased risks of adverse pregnancy outcomes compared to non-PsA pregnancies,” Dr. Remaeus and colleagues write in their study. “The risk of preterm birth in PsA pregnancies is further influenced by parity with the most increased risks observed in first pregnancies.”

In a nationwide, register-based cohort study, the researchers evaluated 921 pregnancies of women with PsA between 2007 and 2017, comparing them to the pregnancies of 9,210 women without PsA over the same time frame. The pregnancies for women with PsA were further categorized based on whether the women had not received antirheumatic treatment in the year prior to and/or during pregnancy (495 pregnancies) or had received antirheumatic treatment at any point in the year before and/or during pregnancy (426 pregnancies).

Of the women in the PsA group who were treated in the year prior to pregnancy (170 women), 39.4% received monotherapy with a conventional synthetic DMARD (csDMARD) such as an antimalarial, methotrexate, or sulfasalazine; 24.1% received oral corticosteroids, and 15.9% received a tumor necrosis factor inhibitor (TNFi), whereas about 20% of women received two or more antirheumatic drugs.

In the group of women treated during pregnancy (256 women), 153 did not receive bDMARDs; of these, 41.8% had monotherapy with either a csDMARD or corticosteroids, whereas the group treated with bDMARDs received TNFi monotherapy (43.7%) or TNFi with corticosteroids (35.9%), TNFi with csDMARD (9.7%), or TNFi with csDMARD plus corticosteroids (9.7%).

A majority of women in both groups (70.1%) were between ages 30 and 34 years (37.1%) or older than age 35 years (33%) and had delivered more than one child (63.2%). Women in the PsA group were more likely to be born in a Nordic country (91.8% vs. 82.8%), to have a body mass index between 30.0 and 60.0 kg/m² (19.9% vs. 12.6%), to be a smoker (9.2% vs. 5.3%), to have hypertension (1.4% vs. 0.8%) or diabetes (1.3% vs. 0.5%) prior to pregnancy, and to have a higher level of education (>12 years; 50.1% vs. 43.3%), compared with women in the non-PsA group.

The results showed women in the PsA group were more likely to experience preterm birth (adjusted odds ratio, 1.69; 95% confidence interval, 1.27-2.24) and undergo an elective (aOR, 1.77; 95% CI, 1.43-2.20) or emergency C-section (aOR, 1.42; 95% CI, 1.10-1.84). The group at highest risk for preterm birth with regard to parity was women with PsA having their first child (aOR, 3.95; 95% CI, 1.43-10.95).

Women who received antirheumatic treatment were at greater risk for experiencing preterm birth (aOR, 2.30; 95% CI, 1.49-3.56), and this risk was even higher for treatment with bDMARDs, compared with women without PsA (aOR, 4.49; 95% CI, 2.60-7.79). Use of bDMARDs also was associated with higher risks for spontaneous preterm birth (aOR, 4.73; 95% CI, 2.53-8.87), preterm birth between 32 and 36 weeks’ gestation (aOR, 5.06; 95% CI, 2.91-8.79), elective C-section (aOR, 2.72; 95% CI, 1.61-4.59), emergency C-section (aOR, 2.06; 95% CI, 1.04-4.07), and preeclampsia (aOR, 2.88, 95% CI, 1.35-6.17).

The researchers note that women with PsA should be evaluated for preterm birth particularly if they are having their first child, and “from a clinical point of view, all women with PsA, regardless of antirheumatic treatment, should be counseled about pregnancy outcomes and receive individualized monitoring during pregnancy.”

Are adverse outcomes linked to disease activity or treatment?

Patients in the study had a higher risk of adverse outcomes when they had a PsA diagnosis, and when they received antirheumatic treatment – but were the adverse outcomes associated with a patient’s high disease activity or need for antirheumatic treatment?

“Our interpretation is that a PsA disease that requires continued antirheumatic treatment during pregnancy is more severe than PsA that does not require treatment,” Dr. Remaeus and colleagues write. “Thus, the increased risk of adverse outcomes in pregnancies with maternal antirheumatic treatment is probably attributed to disease severity rather than an effect of the medication itself.”

Anja Strangfeld, MD, PhD, of the German Rheumatism Research Centre in Berlin, told this news organization that the results of the study are important because it is one of the first to report differences in risk in pregnancy outcomes for women with and without PsA.

“The information is relevant to guide rheumatologists in advising patients with PsA when planning the first or subsequent pregnancies,” she said. “The results are reassuring in reporting that the elevated risk for PsA patients for adverse pregnancy outcomes is low in patients not in need of antirheumatic medication, presumably in low-disease activity.”

However, the study is still unclear on whether the association with adverse pregnancy outcomes in patients is the result of higher disease activity or the need for antirheumatic treatment, she explained.

“It was only hypothesized that those patients under bDMARD treatment are/were in high disease activity. There [is] no information on disease activity in the data sources, which limits the results,” she said. “The investigation still does not solve the important question – if adverse pregnancy outcomes are rather related to high disease activity or the medication to treat this situation.”

There was no specific funding for this study. The study authors and Dr. Strangfeld have disclosed no relevant financial relationships.

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

LAS VEGAS – In the treatment of Helicobacter pylori infection, combination therapies using the oral potassium-competitive acid blocker vonoprazan were superior to standard proton pump inhibitor (PPI)–based triple therapy, producing higher eradication rates, according to combined data from a U.S. and a European phase 3 randomized, controlled trial.

Vonoprazan has been submitted to the Food and Drug Administration for approval with a Fast Track designation in combination with amoxicillin and clarithromycin (triple therapy) or amoxicillin alone (dual therapy) for treating H. pylori infection. It has already been approved in Japan for the treatment of gastric and duodenal ulcers, reflux esophagitis, secondary prevention of low-dose aspirin– or nonsteroidal anti-inflammatory drug–induced gastric mucosal damage, and for first and second-line H. pylori eradication therapy.

Study details

The study included 1,046 treatment-naive patients who had dyspepsia, a recent or new diagnosis of a nonbleeding peptic ulcer, a history of a peptic ulcer, or long-term stable use of an NSAID. Patients were randomized to PPI-based triple therapy (lansoprazole, amoxicillin, clarithromycin), vonoprazan triple therapy (plus amoxicillin, clarithromycin), or vonoprazan dual therapy (amoxicillin). The treatment period was 14 days, followed by 13C urea breath test (UBT) 4 weeks after treatment.

The researchers conducted several analyses, including: Modified intention-to-treat analyses, which included all enrollees; per protocol analyses, which included patients who took at least 75% of each study medication and underwent 13C UBT in the expected time frame; and a safety population of all patients who took at least one study drug.

Among patients with H. pylori strains that were not resistant to clarithromycin, the PPI-based triple-therapy group had an eradication rate of 78.8%, compared with 84.7% in the vonoprazan triple-therapy group (P < .0001), and 78.5% in the vonoprazan dual-therapy group (P = .0037). In the per protocol analysis, PPI-based triple therapy eradicated H. pylori 82.1% of the time, compared with 90.4% in the vonoprazan triple-therapy group (P < .0001) and 81.2% in the vonoprazan dual-therapy group (P = .0077). Both vonoprazan treatment groups were noninferior to PPI-based triple therapy.

A prespecified exploratory analysis found that vonoprazan triple therapy outperformed PPI-based triple therapy in the modified intention-to-treat population (P = .0408) and the per protocol population (P = .0059).

Among patients with clarithromycin-resistant strains of H. pylori, in the modified intention-to-treat population, 31.9% achieved eradication with PPI triple therapy, compared with 65.8% in the vonoprazan triple-therapy group, and 69.6% in the vonoprazan dual-therapy group. In the per protocol population, the numbers were 29.0% versus 67.2% and 79.5%, respectively (P < .0001 for both versus PPI triple therapy).

Among all patients, in the modified intention-to-treat population, 68.5% achieved eradication with PPI triple therapy, 80.8% with vonoprazan triple therapy (P =. 0001), and 77.2% with vonoprazan dual therapy (P = .0063)*. In the per protocol population, the numbers were 70.0%, 85.7% (P < .0001), and 81.1% (P = .0013), respectively.

Safety outcomes were similar among the three groups, with treatment-emergent adverse events occurring in 34.5% of the PPI triple-therapy group (1.2% discontinued), 34.1% of the vonoprazan triple-therapy group (2.3% discontinued), and 29.9% in the vonoprazan dual-therapy group (0.9% discontinued).

Fighting against resistance

The efficacy of PPI-based clarithromycin-based triple therapy has fallen below 80% in the United States and Europe over the past few decades, largely because of antibiotic resistance, said William Chey, MD, during a presentation of the results at the annual meeting of the American College of Gastroenterology. Dr. Chey is a professor of medicine and director of the GI physiology laboratory at Michigan Medicine.

Vonoprazan is more stable in acid than are PPIs, and produces greater and more durable acid reduction, according to Dr. Chey. That’s important for two reasons: One is that some antibiotics are acid-labile, and so may have their efficacy directly impacted in a more acidic environment. The other factor is that most antibiotics work better on bacteria that are actively replicating, and H. pylori reproduces better in a more neutral environment. “So, you increase the replication, you increase the bioavailability of the antibiotics. And therefore, hopefully, that underlies why we see it working better in the patients with [antibiotic] resistance,” Dr. Chey said in an interview.

It remains to be seen whether or not the drug will receive FDA approval, but he pointed to other regimens like bismuth quadruple therapy and rifabutin-based triple therapy that are already available. “If I had the choice, I would never use a PPI-based triple therapy again. People should not be doing that,” said Dr. Chey.

“More successful H. pylori eradication regimens are certainly needed, and these results are particularly relevant and interesting given the increasing failure of initial treatment regimens,” said Kimberly Harer, MD, who moderated the session. She noted that the secondary analysis of patients with clarithromycin-resistant infections was particularly relevant. “The superiority analysis indicating vonoprazan triple therapy resulted in increased H. pylori eradication compared to lanzoprazole triple therapy was especially interesting,” said Dr. Harer, who is a clinical lecturer at University of Michigan Health, Ann Arbor.

One downside to the study is that it didn’t compare vonoprazan combinations to quadruple therapy of a PPI, bismuth, tetracycline, and a nitroimidazole, said Joseph Jennings, MD, who was asked to comment on the study. Other treatment approaches include sequential antibiotics and other combinations. Dr. Jennings also highlighted the findings that the vonoprazan regimens were superior against clarithromycin-resistant strains. “The more different regimens we can add to the armamentarium, the better chance we have because the resistant patterns fluctuate all throughout the world,” said Dr. Jennings, who is an assistant professor of medicine at Georgetown University and director of the center for GI bleeding at MedStar Georgetown University Hospital, both in Washington.

He also pointed out that physicians can face a conundrum when patients fail multiple lines of therapy and have testing done that shows high levels of resistance. Some have allergies that prevent them from turning to other antibiotics. “That’s a market where lots of doctors struggle. Something like this would be a nice add-on,” said Dr. Jennings.

The study was funded by Phathom Pharmaceuticals.** Dr. Chey has consulted and/or received research support from Abbvie, Alfasigma, Allakos, Alnylam, Bayer, Bioamerica, Cosmo, Intrinsic Medicine, Ironwood, Modify Health, My GI Health, My Nutrition Health, Nestle, Phathom Pharmaceuticals, QOL Medical, Redhill, Salix/Valeant, Takeda, Urovant, and Vibrant. Dr. Harer and Dr. Jennings have no relevant financial disclosures.

*Correction, 10/29/21: An earlier version of this article misstated the percentage of patients in the modified intention-to-treat population who achieved eradication with vonoprazan triple therapy.

**Correction, 10/29/21: An earlier version of this article misstated the name of Phathom Pharmaceuticals.

LAS VEGAS – In the treatment of Helicobacter pylori infection, combination therapies using the oral potassium-competitive acid blocker vonoprazan were superior to standard proton pump inhibitor (PPI)–based triple therapy, producing higher eradication rates, according to combined data from a U.S. and a European phase 3 randomized, controlled trial.

Vonoprazan has been submitted to the Food and Drug Administration for approval with a Fast Track designation in combination with amoxicillin and clarithromycin (triple therapy) or amoxicillin alone (dual therapy) for treating H. pylori infection. It has already been approved in Japan for the treatment of gastric and duodenal ulcers, reflux esophagitis, secondary prevention of low-dose aspirin– or nonsteroidal anti-inflammatory drug–induced gastric mucosal damage, and for first and second-line H. pylori eradication therapy.

Study details

The study included 1,046 treatment-naive patients who had dyspepsia, a recent or new diagnosis of a nonbleeding peptic ulcer, a history of a peptic ulcer, or long-term stable use of an NSAID. Patients were randomized to PPI-based triple therapy (lansoprazole, amoxicillin, clarithromycin), vonoprazan triple therapy (plus amoxicillin, clarithromycin), or vonoprazan dual therapy (amoxicillin). The treatment period was 14 days, followed by 13C urea breath test (UBT) 4 weeks after treatment.

The researchers conducted several analyses, including: Modified intention-to-treat analyses, which included all enrollees; per protocol analyses, which included patients who took at least 75% of each study medication and underwent 13C UBT in the expected time frame; and a safety population of all patients who took at least one study drug.

Among patients with H. pylori strains that were not resistant to clarithromycin, the PPI-based triple-therapy group had an eradication rate of 78.8%, compared with 84.7% in the vonoprazan triple-therapy group (P < .0001), and 78.5% in the vonoprazan dual-therapy group (P = .0037). In the per protocol analysis, PPI-based triple therapy eradicated H. pylori 82.1% of the time, compared with 90.4% in the vonoprazan triple-therapy group (P < .0001) and 81.2% in the vonoprazan dual-therapy group (P = .0077). Both vonoprazan treatment groups were noninferior to PPI-based triple therapy.

A prespecified exploratory analysis found that vonoprazan triple therapy outperformed PPI-based triple therapy in the modified intention-to-treat population (P = .0408) and the per protocol population (P = .0059).

Among patients with clarithromycin-resistant strains of H. pylori, in the modified intention-to-treat population, 31.9% achieved eradication with PPI triple therapy, compared with 65.8% in the vonoprazan triple-therapy group, and 69.6% in the vonoprazan dual-therapy group. In the per protocol population, the numbers were 29.0% versus 67.2% and 79.5%, respectively (P < .0001 for both versus PPI triple therapy).

Among all patients, in the modified intention-to-treat population, 68.5% achieved eradication with PPI triple therapy, 80.8% with vonoprazan triple therapy (P =. 0001), and 77.2% with vonoprazan dual therapy (P = .0063)*. In the per protocol population, the numbers were 70.0%, 85.7% (P < .0001), and 81.1% (P = .0013), respectively.

Safety outcomes were similar among the three groups, with treatment-emergent adverse events occurring in 34.5% of the PPI triple-therapy group (1.2% discontinued), 34.1% of the vonoprazan triple-therapy group (2.3% discontinued), and 29.9% in the vonoprazan dual-therapy group (0.9% discontinued).

Fighting against resistance

The efficacy of PPI-based clarithromycin-based triple therapy has fallen below 80% in the United States and Europe over the past few decades, largely because of antibiotic resistance, said William Chey, MD, during a presentation of the results at the annual meeting of the American College of Gastroenterology. Dr. Chey is a professor of medicine and director of the GI physiology laboratory at Michigan Medicine.

Vonoprazan is more stable in acid than are PPIs, and produces greater and more durable acid reduction, according to Dr. Chey. That’s important for two reasons: One is that some antibiotics are acid-labile, and so may have their efficacy directly impacted in a more acidic environment. The other factor is that most antibiotics work better on bacteria that are actively replicating, and H. pylori reproduces better in a more neutral environment. “So, you increase the replication, you increase the bioavailability of the antibiotics. And therefore, hopefully, that underlies why we see it working better in the patients with [antibiotic] resistance,” Dr. Chey said in an interview.

It remains to be seen whether or not the drug will receive FDA approval, but he pointed to other regimens like bismuth quadruple therapy and rifabutin-based triple therapy that are already available. “If I had the choice, I would never use a PPI-based triple therapy again. People should not be doing that,” said Dr. Chey.

“More successful H. pylori eradication regimens are certainly needed, and these results are particularly relevant and interesting given the increasing failure of initial treatment regimens,” said Kimberly Harer, MD, who moderated the session. She noted that the secondary analysis of patients with clarithromycin-resistant infections was particularly relevant. “The superiority analysis indicating vonoprazan triple therapy resulted in increased H. pylori eradication compared to lanzoprazole triple therapy was especially interesting,” said Dr. Harer, who is a clinical lecturer at University of Michigan Health, Ann Arbor.

One downside to the study is that it didn’t compare vonoprazan combinations to quadruple therapy of a PPI, bismuth, tetracycline, and a nitroimidazole, said Joseph Jennings, MD, who was asked to comment on the study. Other treatment approaches include sequential antibiotics and other combinations. Dr. Jennings also highlighted the findings that the vonoprazan regimens were superior against clarithromycin-resistant strains. “The more different regimens we can add to the armamentarium, the better chance we have because the resistant patterns fluctuate all throughout the world,” said Dr. Jennings, who is an assistant professor of medicine at Georgetown University and director of the center for GI bleeding at MedStar Georgetown University Hospital, both in Washington.

He also pointed out that physicians can face a conundrum when patients fail multiple lines of therapy and have testing done that shows high levels of resistance. Some have allergies that prevent them from turning to other antibiotics. “That’s a market where lots of doctors struggle. Something like this would be a nice add-on,” said Dr. Jennings.

The study was funded by Phathom Pharmaceuticals.** Dr. Chey has consulted and/or received research support from Abbvie, Alfasigma, Allakos, Alnylam, Bayer, Bioamerica, Cosmo, Intrinsic Medicine, Ironwood, Modify Health, My GI Health, My Nutrition Health, Nestle, Phathom Pharmaceuticals, QOL Medical, Redhill, Salix/Valeant, Takeda, Urovant, and Vibrant. Dr. Harer and Dr. Jennings have no relevant financial disclosures.

*Correction, 10/29/21: An earlier version of this article misstated the percentage of patients in the modified intention-to-treat population who achieved eradication with vonoprazan triple therapy.

**Correction, 10/29/21: An earlier version of this article misstated the name of Phathom Pharmaceuticals.

LAS VEGAS – In the treatment of Helicobacter pylori infection, combination therapies using the oral potassium-competitive acid blocker vonoprazan were superior to standard proton pump inhibitor (PPI)–based triple therapy, producing higher eradication rates, according to combined data from a U.S. and a European phase 3 randomized, controlled trial.

Vonoprazan has been submitted to the Food and Drug Administration for approval with a Fast Track designation in combination with amoxicillin and clarithromycin (triple therapy) or amoxicillin alone (dual therapy) for treating H. pylori infection. It has already been approved in Japan for the treatment of gastric and duodenal ulcers, reflux esophagitis, secondary prevention of low-dose aspirin– or nonsteroidal anti-inflammatory drug–induced gastric mucosal damage, and for first and second-line H. pylori eradication therapy.

Study details

The study included 1,046 treatment-naive patients who had dyspepsia, a recent or new diagnosis of a nonbleeding peptic ulcer, a history of a peptic ulcer, or long-term stable use of an NSAID. Patients were randomized to PPI-based triple therapy (lansoprazole, amoxicillin, clarithromycin), vonoprazan triple therapy (plus amoxicillin, clarithromycin), or vonoprazan dual therapy (amoxicillin). The treatment period was 14 days, followed by 13C urea breath test (UBT) 4 weeks after treatment.

The researchers conducted several analyses, including: Modified intention-to-treat analyses, which included all enrollees; per protocol analyses, which included patients who took at least 75% of each study medication and underwent 13C UBT in the expected time frame; and a safety population of all patients who took at least one study drug.

Among patients with H. pylori strains that were not resistant to clarithromycin, the PPI-based triple-therapy group had an eradication rate of 78.8%, compared with 84.7% in the vonoprazan triple-therapy group (P < .0001), and 78.5% in the vonoprazan dual-therapy group (P = .0037). In the per protocol analysis, PPI-based triple therapy eradicated H. pylori 82.1% of the time, compared with 90.4% in the vonoprazan triple-therapy group (P < .0001) and 81.2% in the vonoprazan dual-therapy group (P = .0077). Both vonoprazan treatment groups were noninferior to PPI-based triple therapy.

A prespecified exploratory analysis found that vonoprazan triple therapy outperformed PPI-based triple therapy in the modified intention-to-treat population (P = .0408) and the per protocol population (P = .0059).

Among patients with clarithromycin-resistant strains of H. pylori, in the modified intention-to-treat population, 31.9% achieved eradication with PPI triple therapy, compared with 65.8% in the vonoprazan triple-therapy group, and 69.6% in the vonoprazan dual-therapy group. In the per protocol population, the numbers were 29.0% versus 67.2% and 79.5%, respectively (P < .0001 for both versus PPI triple therapy).

Among all patients, in the modified intention-to-treat population, 68.5% achieved eradication with PPI triple therapy, 80.8% with vonoprazan triple therapy (P =. 0001), and 77.2% with vonoprazan dual therapy (P = .0063)*. In the per protocol population, the numbers were 70.0%, 85.7% (P < .0001), and 81.1% (P = .0013), respectively.

Safety outcomes were similar among the three groups, with treatment-emergent adverse events occurring in 34.5% of the PPI triple-therapy group (1.2% discontinued), 34.1% of the vonoprazan triple-therapy group (2.3% discontinued), and 29.9% in the vonoprazan dual-therapy group (0.9% discontinued).

Fighting against resistance

The efficacy of PPI-based clarithromycin-based triple therapy has fallen below 80% in the United States and Europe over the past few decades, largely because of antibiotic resistance, said William Chey, MD, during a presentation of the results at the annual meeting of the American College of Gastroenterology. Dr. Chey is a professor of medicine and director of the GI physiology laboratory at Michigan Medicine.

Vonoprazan is more stable in acid than are PPIs, and produces greater and more durable acid reduction, according to Dr. Chey. That’s important for two reasons: One is that some antibiotics are acid-labile, and so may have their efficacy directly impacted in a more acidic environment. The other factor is that most antibiotics work better on bacteria that are actively replicating, and H. pylori reproduces better in a more neutral environment. “So, you increase the replication, you increase the bioavailability of the antibiotics. And therefore, hopefully, that underlies why we see it working better in the patients with [antibiotic] resistance,” Dr. Chey said in an interview.

It remains to be seen whether or not the drug will receive FDA approval, but he pointed to other regimens like bismuth quadruple therapy and rifabutin-based triple therapy that are already available. “If I had the choice, I would never use a PPI-based triple therapy again. People should not be doing that,” said Dr. Chey.

“More successful H. pylori eradication regimens are certainly needed, and these results are particularly relevant and interesting given the increasing failure of initial treatment regimens,” said Kimberly Harer, MD, who moderated the session. She noted that the secondary analysis of patients with clarithromycin-resistant infections was particularly relevant. “The superiority analysis indicating vonoprazan triple therapy resulted in increased H. pylori eradication compared to lanzoprazole triple therapy was especially interesting,” said Dr. Harer, who is a clinical lecturer at University of Michigan Health, Ann Arbor.

One downside to the study is that it didn’t compare vonoprazan combinations to quadruple therapy of a PPI, bismuth, tetracycline, and a nitroimidazole, said Joseph Jennings, MD, who was asked to comment on the study. Other treatment approaches include sequential antibiotics and other combinations. Dr. Jennings also highlighted the findings that the vonoprazan regimens were superior against clarithromycin-resistant strains. “The more different regimens we can add to the armamentarium, the better chance we have because the resistant patterns fluctuate all throughout the world,” said Dr. Jennings, who is an assistant professor of medicine at Georgetown University and director of the center for GI bleeding at MedStar Georgetown University Hospital, both in Washington.

He also pointed out that physicians can face a conundrum when patients fail multiple lines of therapy and have testing done that shows high levels of resistance. Some have allergies that prevent them from turning to other antibiotics. “That’s a market where lots of doctors struggle. Something like this would be a nice add-on,” said Dr. Jennings.

The study was funded by Phathom Pharmaceuticals.** Dr. Chey has consulted and/or received research support from Abbvie, Alfasigma, Allakos, Alnylam, Bayer, Bioamerica, Cosmo, Intrinsic Medicine, Ironwood, Modify Health, My GI Health, My Nutrition Health, Nestle, Phathom Pharmaceuticals, QOL Medical, Redhill, Salix/Valeant, Takeda, Urovant, and Vibrant. Dr. Harer and Dr. Jennings have no relevant financial disclosures.

*Correction, 10/29/21: An earlier version of this article misstated the percentage of patients in the modified intention-to-treat population who achieved eradication with vonoprazan triple therapy.

**Correction, 10/29/21: An earlier version of this article misstated the name of Phathom Pharmaceuticals.

Fundraising walks for multiple sclerosis (MS) should be familiar to everyone nationwide. They serve to raise money for MS, bolster public awareness of the disease, and build a sense of community. But such in-person events took a big hit during the pandemic.

Recently, this news organization spoke with Kristin Gibbs, vice president of Walk MS for the National MS Society. She described the challenges posed by the COVID pandemic on the National MS Society’s efforts to fundraise on behalf of the MS community.
 

How has the National MS Society raised money before the pandemic?

We are a peer-to-peer fundraising event. That means our registered participants ask their family, friends and coworkers to support them by donating. More than 90% of our participants are friends-and-family teams, and nearly everyone who participates in Walk MS has a connection to MS. We do also have corporate and national teams that fundraise, as well as national and local sponsors that provide monetary support of Walk MS.



About how many Walk MS events were held nationally in an average prepandemic year?

Going back to 2019, we held almost 400 Walk MS events. Next year, the Society will host 234 events, with at least one in each state. The reduction in the number of events reflects a prepandemic strategy of focusing our limited resources in areas where we can have the biggest impact.



How has the pandemic impacted fundraising and community building/outreach?

Fewer people registered and participated in our virtual events in 2020 and 2021, and the pandemic made it challenging for participants to fundraise. While normally we might see more than 200,000 participants nationally, in 2021 we attracted 40,000. Our fundraising decreased from nearly $40 million in prepandemic years to around $20 million in 2021. Our experience is similar to that of most nonprofit peer-to-peer events. However, we were encouraged by the individuals who did support Walk MS during the pandemic, as their fundraising averages were higher than prepandemic campaigns.



What kinds of ‘virtual events’ were held during the pandemic lockdowns?

When it comes to building community, during the pandemic we innovatively utilized online gathering technology, especially Teams, to bring our Walk MS participants together. We held numerous meetings for Team Captains and conducted pre-event pep rallies online to help share information and generate excitement. We produced Facebook Live broadcasts and launched a cutting-edge online version of a Walk MS event called Walk MS On Demand. On Demand visitors could create a virtual bib, learn about the Society, watch inspirational videos, and secure information from national and local sponsors.

 

How is fundraising handled nationally and locally?

In 2022 we will have 234 Walk MS events spread across the country. We are anticipating 100,000 participants will register and our goal is to raise $24 million. Our fundraising will come from individuals, teams, and corporations who contribute at the local and national levels. We are hopeful the excitement surrounding safely being back in person will allow the Walk MS campaign to quickly regain its financial and community-building impact.



Has the pandemic impacted corporate contributions?

We were extremely lucky to maintain support of our national sponsors, and to engage a strong number of local partners. Because we offered the Walk MS On Demand online experience where sponsors could showcase their companies in innovative ways, even though we were virtual we could provide our important partners with a unique way to connect to our constituents. That made a tremendous difference. Also, our partners are strongly committed to the mission and knew their continued support during the pandemic was critical to our organization.



How is the money distributed? Who benefits and how? 

Walk MS is the United States’ 7^th-largest nonprofit walk series, and the 12^th-largest nonprofit event overall. Our Walk MS funds help provide support, programming, and research for individuals diagnosed with MS. Over the history of Walk MS, participants and sponsors have generated more than $1 billion to support those who live with MS.

Courtesy of National MS Society

Fundraising walks for multiple sclerosis (MS) should be familiar to everyone nationwide. They serve to raise money for MS, bolster public awareness of the disease, and build a sense of community. But such in-person events took a big hit during the pandemic.

Recently, this news organization spoke with Kristin Gibbs, vice president of Walk MS for the National MS Society. She described the challenges posed by the COVID pandemic on the National MS Society’s efforts to fundraise on behalf of the MS community.
 

How has the National MS Society raised money before the pandemic?

We are a peer-to-peer fundraising event. That means our registered participants ask their family, friends and coworkers to support them by donating. More than 90% of our participants are friends-and-family teams, and nearly everyone who participates in Walk MS has a connection to MS. We do also have corporate and national teams that fundraise, as well as national and local sponsors that provide monetary support of Walk MS.



About how many Walk MS events were held nationally in an average prepandemic year?

Going back to 2019, we held almost 400 Walk MS events. Next year, the Society will host 234 events, with at least one in each state. The reduction in the number of events reflects a prepandemic strategy of focusing our limited resources in areas where we can have the biggest impact.



How has the pandemic impacted fundraising and community building/outreach?

Fewer people registered and participated in our virtual events in 2020 and 2021, and the pandemic made it challenging for participants to fundraise. While normally we might see more than 200,000 participants nationally, in 2021 we attracted 40,000. Our fundraising decreased from nearly $40 million in prepandemic years to around $20 million in 2021. Our experience is similar to that of most nonprofit peer-to-peer events. However, we were encouraged by the individuals who did support Walk MS during the pandemic, as their fundraising averages were higher than prepandemic campaigns.



What kinds of ‘virtual events’ were held during the pandemic lockdowns?

When it comes to building community, during the pandemic we innovatively utilized online gathering technology, especially Teams, to bring our Walk MS participants together. We held numerous meetings for Team Captains and conducted pre-event pep rallies online to help share information and generate excitement. We produced Facebook Live broadcasts and launched a cutting-edge online version of a Walk MS event called Walk MS On Demand. On Demand visitors could create a virtual bib, learn about the Society, watch inspirational videos, and secure information from national and local sponsors.

 

How is fundraising handled nationally and locally?

In 2022 we will have 234 Walk MS events spread across the country. We are anticipating 100,000 participants will register and our goal is to raise $24 million. Our fundraising will come from individuals, teams, and corporations who contribute at the local and national levels. We are hopeful the excitement surrounding safely being back in person will allow the Walk MS campaign to quickly regain its financial and community-building impact.



Has the pandemic impacted corporate contributions?

We were extremely lucky to maintain support of our national sponsors, and to engage a strong number of local partners. Because we offered the Walk MS On Demand online experience where sponsors could showcase their companies in innovative ways, even though we were virtual we could provide our important partners with a unique way to connect to our constituents. That made a tremendous difference. Also, our partners are strongly committed to the mission and knew their continued support during the pandemic was critical to our organization.



How is the money distributed? Who benefits and how? 

Walk MS is the United States’ 7^th-largest nonprofit walk series, and the 12^th-largest nonprofit event overall. Our Walk MS funds help provide support, programming, and research for individuals diagnosed with MS. Over the history of Walk MS, participants and sponsors have generated more than $1 billion to support those who live with MS.

Courtesy of National MS Society

Fundraising walks for multiple sclerosis (MS) should be familiar to everyone nationwide. They serve to raise money for MS, bolster public awareness of the disease, and build a sense of community. But such in-person events took a big hit during the pandemic.

Recently, this news organization spoke with Kristin Gibbs, vice president of Walk MS for the National MS Society. She described the challenges posed by the COVID pandemic on the National MS Society’s efforts to fundraise on behalf of the MS community.
 

How has the National MS Society raised money before the pandemic?

We are a peer-to-peer fundraising event. That means our registered participants ask their family, friends and coworkers to support them by donating. More than 90% of our participants are friends-and-family teams, and nearly everyone who participates in Walk MS has a connection to MS. We do also have corporate and national teams that fundraise, as well as national and local sponsors that provide monetary support of Walk MS.



About how many Walk MS events were held nationally in an average prepandemic year?

Going back to 2019, we held almost 400 Walk MS events. Next year, the Society will host 234 events, with at least one in each state. The reduction in the number of events reflects a prepandemic strategy of focusing our limited resources in areas where we can have the biggest impact.



How has the pandemic impacted fundraising and community building/outreach?

Fewer people registered and participated in our virtual events in 2020 and 2021, and the pandemic made it challenging for participants to fundraise. While normally we might see more than 200,000 participants nationally, in 2021 we attracted 40,000. Our fundraising decreased from nearly $40 million in prepandemic years to around $20 million in 2021. Our experience is similar to that of most nonprofit peer-to-peer events. However, we were encouraged by the individuals who did support Walk MS during the pandemic, as their fundraising averages were higher than prepandemic campaigns.



What kinds of ‘virtual events’ were held during the pandemic lockdowns?

When it comes to building community, during the pandemic we innovatively utilized online gathering technology, especially Teams, to bring our Walk MS participants together. We held numerous meetings for Team Captains and conducted pre-event pep rallies online to help share information and generate excitement. We produced Facebook Live broadcasts and launched a cutting-edge online version of a Walk MS event called Walk MS On Demand. On Demand visitors could create a virtual bib, learn about the Society, watch inspirational videos, and secure information from national and local sponsors.

 

How is fundraising handled nationally and locally?

In 2022 we will have 234 Walk MS events spread across the country. We are anticipating 100,000 participants will register and our goal is to raise $24 million. Our fundraising will come from individuals, teams, and corporations who contribute at the local and national levels. We are hopeful the excitement surrounding safely being back in person will allow the Walk MS campaign to quickly regain its financial and community-building impact.



Has the pandemic impacted corporate contributions?

We were extremely lucky to maintain support of our national sponsors, and to engage a strong number of local partners. Because we offered the Walk MS On Demand online experience where sponsors could showcase their companies in innovative ways, even though we were virtual we could provide our important partners with a unique way to connect to our constituents. That made a tremendous difference. Also, our partners are strongly committed to the mission and knew their continued support during the pandemic was critical to our organization.



How is the money distributed? Who benefits and how? 

Walk MS is the United States’ 7^th-largest nonprofit walk series, and the 12^th-largest nonprofit event overall. Our Walk MS funds help provide support, programming, and research for individuals diagnosed with MS. Over the history of Walk MS, participants and sponsors have generated more than $1 billion to support those who live with MS.

Courtesy of National MS Society

LAS VEGAS – The G-EYE colonoscope facilitates detection of adenomas more so than does the Endocuff Vision, researchers say.

In the first head-to-head comparison of two mechanical enhancement colonoscopy devices, “the G-EYE demonstrated a meaningful increase in adenoma detection rate [ADR] over Endocuff, particularly for advanced adenomas,” said Seth Gross, MD, a professor of medicine at New York University.

Previous studies have shown that mechanical enhancements are more effective than optical enhancements, Dr. Gross said. “To take it a step further, when you look at mechanical devices, especially these two, in past studies, the G-EYE has been sort of the leader in adenoma detection,” he told this news organization.

But until now, no studies had compared them head to head, said Dr. Gross, who presented the finding here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

The two devices work differently. The Endocuff Vision fits onto the colonoscope tip. During withdrawal, it expands radially, and its arms flatten the folds within the colon. The G-EYE balloon is deflated at insertion, then is inflated at the cecum, smoothing the colon wall while centering the colonoscopic view.

To compare the two, Dr. Gross and colleagues randomly assigned 363 patients to undergo colonoscopy with G-EYE and 364 patients to undergo colonoscopy with Endocuff Vision. The two groups were similar in demographics.

Withdrawal times were >6 minutes in both groups. The researchers detected adenomas in a higher percentage of patients with the G-EYE than with the Endocuff Vision. The same was true for advanced adenomas.

When using the G-EYE, the researchers also found more adenomas per patient, more sessile serrated adenomas per patient, more large adenomas per patient, and more right colon adenomas per patient.

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

LAS VEGAS – The G-EYE colonoscope facilitates detection of adenomas more so than does the Endocuff Vision, researchers say.

In the first head-to-head comparison of two mechanical enhancement colonoscopy devices, “the G-EYE demonstrated a meaningful increase in adenoma detection rate [ADR] over Endocuff, particularly for advanced adenomas,” said Seth Gross, MD, a professor of medicine at New York University.

Previous studies have shown that mechanical enhancements are more effective than optical enhancements, Dr. Gross said. “To take it a step further, when you look at mechanical devices, especially these two, in past studies, the G-EYE has been sort of the leader in adenoma detection,” he told this news organization.

But until now, no studies had compared them head to head, said Dr. Gross, who presented the finding here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

The two devices work differently. The Endocuff Vision fits onto the colonoscope tip. During withdrawal, it expands radially, and its arms flatten the folds within the colon. The G-EYE balloon is deflated at insertion, then is inflated at the cecum, smoothing the colon wall while centering the colonoscopic view.

To compare the two, Dr. Gross and colleagues randomly assigned 363 patients to undergo colonoscopy with G-EYE and 364 patients to undergo colonoscopy with Endocuff Vision. The two groups were similar in demographics.

Withdrawal times were >6 minutes in both groups. The researchers detected adenomas in a higher percentage of patients with the G-EYE than with the Endocuff Vision. The same was true for advanced adenomas.

When using the G-EYE, the researchers also found more adenomas per patient, more sessile serrated adenomas per patient, more large adenomas per patient, and more right colon adenomas per patient.

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

LAS VEGAS – The G-EYE colonoscope facilitates detection of adenomas more so than does the Endocuff Vision, researchers say.

In the first head-to-head comparison of two mechanical enhancement colonoscopy devices, “the G-EYE demonstrated a meaningful increase in adenoma detection rate [ADR] over Endocuff, particularly for advanced adenomas,” said Seth Gross, MD, a professor of medicine at New York University.

Previous studies have shown that mechanical enhancements are more effective than optical enhancements, Dr. Gross said. “To take it a step further, when you look at mechanical devices, especially these two, in past studies, the G-EYE has been sort of the leader in adenoma detection,” he told this news organization.

But until now, no studies had compared them head to head, said Dr. Gross, who presented the finding here at the American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting.

The two devices work differently. The Endocuff Vision fits onto the colonoscope tip. During withdrawal, it expands radially, and its arms flatten the folds within the colon. The G-EYE balloon is deflated at insertion, then is inflated at the cecum, smoothing the colon wall while centering the colonoscopic view.

To compare the two, Dr. Gross and colleagues randomly assigned 363 patients to undergo colonoscopy with G-EYE and 364 patients to undergo colonoscopy with Endocuff Vision. The two groups were similar in demographics.

Withdrawal times were >6 minutes in both groups. The researchers detected adenomas in a higher percentage of patients with the G-EYE than with the Endocuff Vision. The same was true for advanced adenomas.

When using the G-EYE, the researchers also found more adenomas per patient, more sessile serrated adenomas per patient, more large adenomas per patient, and more right colon adenomas per patient.

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

A “green” adaptation to the traditional Mediterranean diet could help improve insulin sensitivity and reduce visceral fat by increasing levels of ghrelin, the “hunger hormone,” new research suggests.

The current study is a new analysis of data from the randomized DIRECT-PLUS trial, which showed that the addition of green tea and substitution of red meat for a plant-based (Mankai) protein shake at dinner – dubbed the “green Mediterranean diet” – resulted in further improved cardiometabolic benefits compared with the traditional Mediterranean diet among people with baseline abdominal obesity and/or dyslipidemia, according to the researchers.

They specifically looked at ghrelin, nicknamed the “hunger hormone,” a neuropeptide mainly secreted by the gastric epithelium. It acts on the pituitary gland to release growth hormone. Ghrelin concentrations increase during fasting and decrease after eating. Lower levels are associated with insulin resistance and obesity.

Fasting ghrelin levels were elevated with weight loss, but those increases were associated with improved insulin sensitivity and regression of visceral adipose tissue even beyond weight loss.

Although the caloric restriction and weight loss were comparable with the two Mediterranean diets, the green Mediterranean diet group had double the increase in fasting ghrelin as the traditional Mediterranean diet group, the researchers point out in their report .
 

‘Hypothesis-generating’ study pushes many hot topic buttons

“This specific study is the first to show that ghrelin levels play an important role in metabolic adaptation to a dietary or lifestyle intervention and that ghrelin is an important player in the axis of adiposity, insulin resistance, and metabolic health,” lead researcher Gal Tsaban, MD, told this news organization.

The data partially explain some of the prior beneficial effects seen with the Green Mediterranean diet, even after adjustment for weight loss, he explained, noting that the revised version of the diet “could be considered as an alternative lifestyle intervention with possible metabolic benefits even beyond the Mediterranean diet, which is what we currently recommend for patients.”

Asked for comment, Christopher Gardner, PhD, was not as enthusiastic.

He took issue with the fact that ghrelin wasn’t a primary or even a prespecified secondary outcome of the DIRECT-PLUS trial and because the specific plant-based ingredients of the green Mediterranean diet used in the study may not be widely available or desirable and therefore limit the study’s generalizability.

Dr. Gardner, who is director of nutrition studies at the Stanford Prevention Research Center, California, also said: “They’re tying lots of interesting things together. The Mediterranean diet is a cool thing, ghrelin is a cool thing, and insulin resistance is hugely important in this day and age, even though we don’t all agree on how to measure it.”

“But it gets tough as you try to link them all together for an exploratory outcome. ... To me it’s an interesting hypothesis-generating study that pushes a lot of interesting buttons that are hot topics in the field.”
 

Green Mediterranean diet led to higher ghrelin, metabolic benefits

In DIRECT-PLUS, a total of 294 adults (88% men) older than 30 years of age with abdominal obesity (waist circumference >102 cm for men or >88 cm for women), or dyslipidemia (triglycerides >150 mg/dL and HDL-cholesterol ≤40 mg/dL for men or ≤50 mg/dL for women) were included. Half had prediabetes or type 2 diabetes.

They were randomized to one of three diets: a diet based on standard healthy dietary guidelines; a traditional Mediterranean diet low in simple carbohydrates, rich in vegetables, with poultry and fish replacing beef and lamb and 28 g/day of walnuts; or the Green-Mediterranean diet, including 3-4 cups/day of green tea and 100 g/day of a green shake made from the Mankai strain of Wolffia globosa (also known as duckweed) replacing dinner, and 28 g/day of walnuts.

The Green Mediterranean diet included 800 mg more polyphenols than the traditional Mediterranean diet. Both were equally calorie-restricted, at about 1,500-1,800 kcal/day for men and 1,200-1,400 kcal/day for women. All three groups were instructed to engage in regular physical activity and were given free gym memberships.

The retention rate was 98.3% after 6 months and 89.8% after 18 months.

Weight loss was similar between the two Mediterranean diet groups (2.9% and 3.9% for the traditional and green versions, respectively) compared with the standard healthy diet (0.6%) (P < .05 for both Mediterranean diet groups vs. control).

After 6 months, fasting ghrelin increased in the traditional (8.0%; P = .015) and green (10.5%; P = 0.031) Mediterranean groups versus baseline, with no significant change in the control group.

By 18 months, fasting ghrelin was significantly greater compared with baseline only in the green Mediterranean group (P = .012).

Because the differences in fasting ghrelin trajectories were only significant in men – likely due to the small sample size of women – a subsequent 18-month analysis was limited to the men. In a multivariate model adjusted for age, intervention group, baseline biomarker values, and 18-month weight changes, the 18-month change in fasting ghrelin remained a significant predictor for changes in A1c and homeostatic model of insulin resistance (HOMA-IR; P = .022).

Because weight loss remained the most significant predictor of improved insulin resistance, a further analysis examined the association between changes in fasting ghrelin levels with changes in the fraction of insulin resistance marker that were not attributed to weight loss, per se. With the other adjustments, fasting ghrelin was associated with residual reductions in A1c (P = .003), HOMA-IR (P = .021), increased HDL-cholesterol (P = .024), and relative visceral adipose tissue loss (P = .003).  
 

No specific product needed to push Mediterranean diet towards vegan

Dr. Tsaban, a nutritional researcher and cardiologist at Ben-Gurion University and Soroka University Medical Center, Be’er-Sheva, Israel, said the Mankai shake is commonly consumed in Israel but is also available worldwide. The study participants, all employees at an isolated nuclear research facility in the Negev, were particularly motivated. “They didn’t have a satiety problem with the drink. It made them very full,” he said. The manufacturer supplied the shakes but didn’t fund the study, he added.

However, Dr. Tsaban said that the “green Mediterranean diet” doesn’t depend on specific products.

Rather, “the concept is to push the Mediterranean diet a bit further and to replace the animal-based protein with vegetable-based protein, to shift your dietary habits towards a more vegan lifestyle. It’s not completely vegan, but it’s trending there. ... Our main goal was to increase the polyphenol intake, the antioxidant intake from vegetables. ... I think it can be replicated.”

Dr. Gardner said, “At the end of the day, it’s an exploratory study. ... It raises some interesting points that give the rest of us room to follow-up on.”

The study was funded by grants from the German Research Foundation, the Israel Ministry of Health, the Israel Ministry of Science and Technology, and the California Walnut Commission. Dr. Tsaban has reported no further relevant financial relationships. Dr. Gardner has reported receiving study funding from Beyond Meat.

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

A “green” adaptation to the traditional Mediterranean diet could help improve insulin sensitivity and reduce visceral fat by increasing levels of ghrelin, the “hunger hormone,” new research suggests.

The current study is a new analysis of data from the randomized DIRECT-PLUS trial, which showed that the addition of green tea and substitution of red meat for a plant-based (Mankai) protein shake at dinner – dubbed the “green Mediterranean diet” – resulted in further improved cardiometabolic benefits compared with the traditional Mediterranean diet among people with baseline abdominal obesity and/or dyslipidemia, according to the researchers.

They specifically looked at ghrelin, nicknamed the “hunger hormone,” a neuropeptide mainly secreted by the gastric epithelium. It acts on the pituitary gland to release growth hormone. Ghrelin concentrations increase during fasting and decrease after eating. Lower levels are associated with insulin resistance and obesity.

Fasting ghrelin levels were elevated with weight loss, but those increases were associated with improved insulin sensitivity and regression of visceral adipose tissue even beyond weight loss.

Although the caloric restriction and weight loss were comparable with the two Mediterranean diets, the green Mediterranean diet group had double the increase in fasting ghrelin as the traditional Mediterranean diet group, the researchers point out in their report .
 

‘Hypothesis-generating’ study pushes many hot topic buttons

“This specific study is the first to show that ghrelin levels play an important role in metabolic adaptation to a dietary or lifestyle intervention and that ghrelin is an important player in the axis of adiposity, insulin resistance, and metabolic health,” lead researcher Gal Tsaban, MD, told this news organization.

The data partially explain some of the prior beneficial effects seen with the Green Mediterranean diet, even after adjustment for weight loss, he explained, noting that the revised version of the diet “could be considered as an alternative lifestyle intervention with possible metabolic benefits even beyond the Mediterranean diet, which is what we currently recommend for patients.”

Asked for comment, Christopher Gardner, PhD, was not as enthusiastic.

He took issue with the fact that ghrelin wasn’t a primary or even a prespecified secondary outcome of the DIRECT-PLUS trial and because the specific plant-based ingredients of the green Mediterranean diet used in the study may not be widely available or desirable and therefore limit the study’s generalizability.

Dr. Gardner, who is director of nutrition studies at the Stanford Prevention Research Center, California, also said: “They’re tying lots of interesting things together. The Mediterranean diet is a cool thing, ghrelin is a cool thing, and insulin resistance is hugely important in this day and age, even though we don’t all agree on how to measure it.”

“But it gets tough as you try to link them all together for an exploratory outcome. ... To me it’s an interesting hypothesis-generating study that pushes a lot of interesting buttons that are hot topics in the field.”
 

Green Mediterranean diet led to higher ghrelin, metabolic benefits

In DIRECT-PLUS, a total of 294 adults (88% men) older than 30 years of age with abdominal obesity (waist circumference >102 cm for men or >88 cm for women), or dyslipidemia (triglycerides >150 mg/dL and HDL-cholesterol ≤40 mg/dL for men or ≤50 mg/dL for women) were included. Half had prediabetes or type 2 diabetes.

They were randomized to one of three diets: a diet based on standard healthy dietary guidelines; a traditional Mediterranean diet low in simple carbohydrates, rich in vegetables, with poultry and fish replacing beef and lamb and 28 g/day of walnuts; or the Green-Mediterranean diet, including 3-4 cups/day of green tea and 100 g/day of a green shake made from the Mankai strain of Wolffia globosa (also known as duckweed) replacing dinner, and 28 g/day of walnuts.

The Green Mediterranean diet included 800 mg more polyphenols than the traditional Mediterranean diet. Both were equally calorie-restricted, at about 1,500-1,800 kcal/day for men and 1,200-1,400 kcal/day for women. All three groups were instructed to engage in regular physical activity and were given free gym memberships.

The retention rate was 98.3% after 6 months and 89.8% after 18 months.

Weight loss was similar between the two Mediterranean diet groups (2.9% and 3.9% for the traditional and green versions, respectively) compared with the standard healthy diet (0.6%) (P < .05 for both Mediterranean diet groups vs. control).

After 6 months, fasting ghrelin increased in the traditional (8.0%; P = .015) and green (10.5%; P = 0.031) Mediterranean groups versus baseline, with no significant change in the control group.

By 18 months, fasting ghrelin was significantly greater compared with baseline only in the green Mediterranean group (P = .012).

Because the differences in fasting ghrelin trajectories were only significant in men – likely due to the small sample size of women – a subsequent 18-month analysis was limited to the men. In a multivariate model adjusted for age, intervention group, baseline biomarker values, and 18-month weight changes, the 18-month change in fasting ghrelin remained a significant predictor for changes in A1c and homeostatic model of insulin resistance (HOMA-IR; P = .022).

Because weight loss remained the most significant predictor of improved insulin resistance, a further analysis examined the association between changes in fasting ghrelin levels with changes in the fraction of insulin resistance marker that were not attributed to weight loss, per se. With the other adjustments, fasting ghrelin was associated with residual reductions in A1c (P = .003), HOMA-IR (P = .021), increased HDL-cholesterol (P = .024), and relative visceral adipose tissue loss (P = .003).  
 

No specific product needed to push Mediterranean diet towards vegan

Dr. Tsaban, a nutritional researcher and cardiologist at Ben-Gurion University and Soroka University Medical Center, Be’er-Sheva, Israel, said the Mankai shake is commonly consumed in Israel but is also available worldwide. The study participants, all employees at an isolated nuclear research facility in the Negev, were particularly motivated. “They didn’t have a satiety problem with the drink. It made them very full,” he said. The manufacturer supplied the shakes but didn’t fund the study, he added.

However, Dr. Tsaban said that the “green Mediterranean diet” doesn’t depend on specific products.

Rather, “the concept is to push the Mediterranean diet a bit further and to replace the animal-based protein with vegetable-based protein, to shift your dietary habits towards a more vegan lifestyle. It’s not completely vegan, but it’s trending there. ... Our main goal was to increase the polyphenol intake, the antioxidant intake from vegetables. ... I think it can be replicated.”

Dr. Gardner said, “At the end of the day, it’s an exploratory study. ... It raises some interesting points that give the rest of us room to follow-up on.”

The study was funded by grants from the German Research Foundation, the Israel Ministry of Health, the Israel Ministry of Science and Technology, and the California Walnut Commission. Dr. Tsaban has reported no further relevant financial relationships. Dr. Gardner has reported receiving study funding from Beyond Meat.

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

A “green” adaptation to the traditional Mediterranean diet could help improve insulin sensitivity and reduce visceral fat by increasing levels of ghrelin, the “hunger hormone,” new research suggests.

The current study is a new analysis of data from the randomized DIRECT-PLUS trial, which showed that the addition of green tea and substitution of red meat for a plant-based (Mankai) protein shake at dinner – dubbed the “green Mediterranean diet” – resulted in further improved cardiometabolic benefits compared with the traditional Mediterranean diet among people with baseline abdominal obesity and/or dyslipidemia, according to the researchers.

They specifically looked at ghrelin, nicknamed the “hunger hormone,” a neuropeptide mainly secreted by the gastric epithelium. It acts on the pituitary gland to release growth hormone. Ghrelin concentrations increase during fasting and decrease after eating. Lower levels are associated with insulin resistance and obesity.

Fasting ghrelin levels were elevated with weight loss, but those increases were associated with improved insulin sensitivity and regression of visceral adipose tissue even beyond weight loss.

Although the caloric restriction and weight loss were comparable with the two Mediterranean diets, the green Mediterranean diet group had double the increase in fasting ghrelin as the traditional Mediterranean diet group, the researchers point out in their report .
 

‘Hypothesis-generating’ study pushes many hot topic buttons

“This specific study is the first to show that ghrelin levels play an important role in metabolic adaptation to a dietary or lifestyle intervention and that ghrelin is an important player in the axis of adiposity, insulin resistance, and metabolic health,” lead researcher Gal Tsaban, MD, told this news organization.

The data partially explain some of the prior beneficial effects seen with the Green Mediterranean diet, even after adjustment for weight loss, he explained, noting that the revised version of the diet “could be considered as an alternative lifestyle intervention with possible metabolic benefits even beyond the Mediterranean diet, which is what we currently recommend for patients.”

Asked for comment, Christopher Gardner, PhD, was not as enthusiastic.

He took issue with the fact that ghrelin wasn’t a primary or even a prespecified secondary outcome of the DIRECT-PLUS trial and because the specific plant-based ingredients of the green Mediterranean diet used in the study may not be widely available or desirable and therefore limit the study’s generalizability.

Dr. Gardner, who is director of nutrition studies at the Stanford Prevention Research Center, California, also said: “They’re tying lots of interesting things together. The Mediterranean diet is a cool thing, ghrelin is a cool thing, and insulin resistance is hugely important in this day and age, even though we don’t all agree on how to measure it.”

“But it gets tough as you try to link them all together for an exploratory outcome. ... To me it’s an interesting hypothesis-generating study that pushes a lot of interesting buttons that are hot topics in the field.”
 

Green Mediterranean diet led to higher ghrelin, metabolic benefits

In DIRECT-PLUS, a total of 294 adults (88% men) older than 30 years of age with abdominal obesity (waist circumference >102 cm for men or >88 cm for women), or dyslipidemia (triglycerides >150 mg/dL and HDL-cholesterol ≤40 mg/dL for men or ≤50 mg/dL for women) were included. Half had prediabetes or type 2 diabetes.

They were randomized to one of three diets: a diet based on standard healthy dietary guidelines; a traditional Mediterranean diet low in simple carbohydrates, rich in vegetables, with poultry and fish replacing beef and lamb and 28 g/day of walnuts; or the Green-Mediterranean diet, including 3-4 cups/day of green tea and 100 g/day of a green shake made from the Mankai strain of Wolffia globosa (also known as duckweed) replacing dinner, and 28 g/day of walnuts.

The Green Mediterranean diet included 800 mg more polyphenols than the traditional Mediterranean diet. Both were equally calorie-restricted, at about 1,500-1,800 kcal/day for men and 1,200-1,400 kcal/day for women. All three groups were instructed to engage in regular physical activity and were given free gym memberships.

The retention rate was 98.3% after 6 months and 89.8% after 18 months.

Weight loss was similar between the two Mediterranean diet groups (2.9% and 3.9% for the traditional and green versions, respectively) compared with the standard healthy diet (0.6%) (P < .05 for both Mediterranean diet groups vs. control).

After 6 months, fasting ghrelin increased in the traditional (8.0%; P = .015) and green (10.5%; P = 0.031) Mediterranean groups versus baseline, with no significant change in the control group.

By 18 months, fasting ghrelin was significantly greater compared with baseline only in the green Mediterranean group (P = .012).

Because the differences in fasting ghrelin trajectories were only significant in men – likely due to the small sample size of women – a subsequent 18-month analysis was limited to the men. In a multivariate model adjusted for age, intervention group, baseline biomarker values, and 18-month weight changes, the 18-month change in fasting ghrelin remained a significant predictor for changes in A1c and homeostatic model of insulin resistance (HOMA-IR; P = .022).

Because weight loss remained the most significant predictor of improved insulin resistance, a further analysis examined the association between changes in fasting ghrelin levels with changes in the fraction of insulin resistance marker that were not attributed to weight loss, per se. With the other adjustments, fasting ghrelin was associated with residual reductions in A1c (P = .003), HOMA-IR (P = .021), increased HDL-cholesterol (P = .024), and relative visceral adipose tissue loss (P = .003).  
 

No specific product needed to push Mediterranean diet towards vegan

Dr. Tsaban, a nutritional researcher and cardiologist at Ben-Gurion University and Soroka University Medical Center, Be’er-Sheva, Israel, said the Mankai shake is commonly consumed in Israel but is also available worldwide. The study participants, all employees at an isolated nuclear research facility in the Negev, were particularly motivated. “They didn’t have a satiety problem with the drink. It made them very full,” he said. The manufacturer supplied the shakes but didn’t fund the study, he added.

However, Dr. Tsaban said that the “green Mediterranean diet” doesn’t depend on specific products.

Rather, “the concept is to push the Mediterranean diet a bit further and to replace the animal-based protein with vegetable-based protein, to shift your dietary habits towards a more vegan lifestyle. It’s not completely vegan, but it’s trending there. ... Our main goal was to increase the polyphenol intake, the antioxidant intake from vegetables. ... I think it can be replicated.”

Dr. Gardner said, “At the end of the day, it’s an exploratory study. ... It raises some interesting points that give the rest of us room to follow-up on.”

The study was funded by grants from the German Research Foundation, the Israel Ministry of Health, the Israel Ministry of Science and Technology, and the California Walnut Commission. Dr. Tsaban has reported no further relevant financial relationships. Dr. Gardner has reported receiving study funding from Beyond Meat.

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

The CDC is urging parents and guardians to vaccinate children ages 5-11 against COVID-19 once the shot is fully approved, despite questions from FDA advisers about the urgency given falling national case rates.

On Oct. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee voted to recommend a 10-microgram shot for children. Though 17 of the 18 panelists voted in favor of it, some members said it was a hard decision and questioned the need for it now that cases and hospitalizations are down.

“There’s urgency because we’re seeing disease in children, we’ve seen deaths in children, we’ve seen long COVID,” CDC Director Rochelle Walensky, MD, said at a White House briefing on Oct. 27. “Certainly we’ve seen cases come down before, and the way to prevent surges again is to get more and more people vaccinated.”

CDC data presented at an Oct. 26 advisory committee meeting show that among children 5-11, COVID-19 was one of top 10 causes of death over last year, Dr. Walensky said. There have been more than 8,300 hospitalizations and 745 deaths in children under 18.

As of yesterday, the 7-day average of daily COVID-19 cases was 65,900, a 16% decrease from the prior week. Hospitalizations are down 54% from the week of Aug. 28, Dr. Walensky said.

“If the trends continue the way they are going, the emergency for children is not what we might think it would be. That was my concern,” James Hildreth, MD, president and CEO at Meharry Medical College in Nashville, said at the advisory committee meeting on Oct. 26.

But according to one CDC study, hospitalization rates for adolescents were 10 times higher in those who were unvaccinated. Another study found that COVID-related emergency room visits and hospital admissions among children were more than 3 times as high in states with the lowest vaccination rates.

“We are down from our peak in early September, and we are now heading in the right direction, but with cases still high, we must remain vigilant heading into the colder, drier winter months,” Dr. Walensky said, noting that the 7-day average of daily deaths still exceeds 1,000.

Meanwhile, the booster program is off to a “very strong start,” said White House COVID-19 Response Coordinator Jeff Zients.

In the 5 days since authorizations, about 15 million people have received an additional dose of the Pfizer, Moderna, and Johnson & Johnson vaccines.

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

The CDC is urging parents and guardians to vaccinate children ages 5-11 against COVID-19 once the shot is fully approved, despite questions from FDA advisers about the urgency given falling national case rates.

On Oct. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee voted to recommend a 10-microgram shot for children. Though 17 of the 18 panelists voted in favor of it, some members said it was a hard decision and questioned the need for it now that cases and hospitalizations are down.

“There’s urgency because we’re seeing disease in children, we’ve seen deaths in children, we’ve seen long COVID,” CDC Director Rochelle Walensky, MD, said at a White House briefing on Oct. 27. “Certainly we’ve seen cases come down before, and the way to prevent surges again is to get more and more people vaccinated.”

CDC data presented at an Oct. 26 advisory committee meeting show that among children 5-11, COVID-19 was one of top 10 causes of death over last year, Dr. Walensky said. There have been more than 8,300 hospitalizations and 745 deaths in children under 18.

As of yesterday, the 7-day average of daily COVID-19 cases was 65,900, a 16% decrease from the prior week. Hospitalizations are down 54% from the week of Aug. 28, Dr. Walensky said.

“If the trends continue the way they are going, the emergency for children is not what we might think it would be. That was my concern,” James Hildreth, MD, president and CEO at Meharry Medical College in Nashville, said at the advisory committee meeting on Oct. 26.

But according to one CDC study, hospitalization rates for adolescents were 10 times higher in those who were unvaccinated. Another study found that COVID-related emergency room visits and hospital admissions among children were more than 3 times as high in states with the lowest vaccination rates.

“We are down from our peak in early September, and we are now heading in the right direction, but with cases still high, we must remain vigilant heading into the colder, drier winter months,” Dr. Walensky said, noting that the 7-day average of daily deaths still exceeds 1,000.

Meanwhile, the booster program is off to a “very strong start,” said White House COVID-19 Response Coordinator Jeff Zients.

In the 5 days since authorizations, about 15 million people have received an additional dose of the Pfizer, Moderna, and Johnson & Johnson vaccines.

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

The CDC is urging parents and guardians to vaccinate children ages 5-11 against COVID-19 once the shot is fully approved, despite questions from FDA advisers about the urgency given falling national case rates.

On Oct. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee voted to recommend a 10-microgram shot for children. Though 17 of the 18 panelists voted in favor of it, some members said it was a hard decision and questioned the need for it now that cases and hospitalizations are down.

“There’s urgency because we’re seeing disease in children, we’ve seen deaths in children, we’ve seen long COVID,” CDC Director Rochelle Walensky, MD, said at a White House briefing on Oct. 27. “Certainly we’ve seen cases come down before, and the way to prevent surges again is to get more and more people vaccinated.”

CDC data presented at an Oct. 26 advisory committee meeting show that among children 5-11, COVID-19 was one of top 10 causes of death over last year, Dr. Walensky said. There have been more than 8,300 hospitalizations and 745 deaths in children under 18.

As of yesterday, the 7-day average of daily COVID-19 cases was 65,900, a 16% decrease from the prior week. Hospitalizations are down 54% from the week of Aug. 28, Dr. Walensky said.

“If the trends continue the way they are going, the emergency for children is not what we might think it would be. That was my concern,” James Hildreth, MD, president and CEO at Meharry Medical College in Nashville, said at the advisory committee meeting on Oct. 26.

But according to one CDC study, hospitalization rates for adolescents were 10 times higher in those who were unvaccinated. Another study found that COVID-related emergency room visits and hospital admissions among children were more than 3 times as high in states with the lowest vaccination rates.

“We are down from our peak in early September, and we are now heading in the right direction, but with cases still high, we must remain vigilant heading into the colder, drier winter months,” Dr. Walensky said, noting that the 7-day average of daily deaths still exceeds 1,000.

Meanwhile, the booster program is off to a “very strong start,” said White House COVID-19 Response Coordinator Jeff Zients.

In the 5 days since authorizations, about 15 million people have received an additional dose of the Pfizer, Moderna, and Johnson & Johnson vaccines.

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