Clinical Psychiatry News

A new study provides real-world evidence to support the potential repurposing of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), used to treat type 2 diabetes and obesity, for prevention of Alzheimer’s disease.

Adults with type 2 diabetes who were prescribed the GLP-1 RA semaglutide had a significantly lower risk for Alzheimer’s disease compared with their peers who were prescribed any of seven other antidiabetic medications, including other types of GLP-1 receptor–targeting medications. 

“These findings support further clinical trials to assess semaglutide’s potential in delaying or preventing Alzheimer’s disease,” wrote the investigators, led by Rong Xu, PhD, with Case Western Reserve School of Medicine, Cleveland, Ohio. 

The study was published online on October 24 in Alzheimer’s & Dementia.
 

Real-World Data

Semaglutide has shown neuroprotective effects in animal models of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. In animal models of Alzheimer’s disease, the drug reduced beta-amyloid deposition and improved spatial learning and memory, as well as glucose metabolism in the brain. 

In a real-world analysis, Xu and colleagues used electronic health record data to identify 17,104 new users of semaglutide and 1,077,657 new users of seven other antidiabetic medications, including other GLP-1 RAs, insulin, metformin, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, sulfonylurea, and thiazolidinedione.

Over 3 years, treatment with semaglutide was associated with significantly reduced risk of developing Alzheimer’s disease, most strongly compared with insulin (hazard ratio [HR], 0.33) and most weakly compared with other GLP-1 RAs (HR, 0.59). 

Compared with the other medications, semaglutide was associated with a 40%-70% reduced risk for first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes, with similar reductions seen across obesity status and gender and age groups, the authors reported. 

The findings align with recent evidence suggesting GLP-1 RAs may protect cognitive function. 

For example, as previously reported, in the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 RA liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months compared with placebo. 
 

Promising, but Preliminary 

Reached for comment, Courtney Kloske, PhD, Alzheimer’s Association director of scientific engagement, noted that diabetes is a known risk factor for AD and managing diabetes with drugs such as semaglutide “could benefit brain health simply by managing diabetes.”

“However, we still need large clinical trials in representative populations to determine if semaglutide specifically lowers the risk of Alzheimer’s, so it is too early to recommend it for prevention,” Kloske said. 

She noted that some research suggests that GLP-1 RAs “may help reduce inflammation and positively impact brain energy use. However, more research is needed to fully understand how these processes might contribute to preventing cognitive decline or Alzheimer’s,” Kloske cautioned. 

The Alzheimer’s Association’s “Part the Cloud” initiative has invested more than $68 million to advance 65 clinical trials targeting a variety of compounds, including repurposed drugs that may address known and potential new aspects of the disease, Kloske said. 

The study was supported by grants from the National Institute on Aging and the National Center for Advancing Translational Sciences. Xu and Kloske have no relevant conflicts.
 

A version of this article appeared on Medscape.com.

A new study provides real-world evidence to support the potential repurposing of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), used to treat type 2 diabetes and obesity, for prevention of Alzheimer’s disease.

Adults with type 2 diabetes who were prescribed the GLP-1 RA semaglutide had a significantly lower risk for Alzheimer’s disease compared with their peers who were prescribed any of seven other antidiabetic medications, including other types of GLP-1 receptor–targeting medications. 

“These findings support further clinical trials to assess semaglutide’s potential in delaying or preventing Alzheimer’s disease,” wrote the investigators, led by Rong Xu, PhD, with Case Western Reserve School of Medicine, Cleveland, Ohio. 

The study was published online on October 24 in Alzheimer’s & Dementia.
 

Real-World Data

Semaglutide has shown neuroprotective effects in animal models of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. In animal models of Alzheimer’s disease, the drug reduced beta-amyloid deposition and improved spatial learning and memory, as well as glucose metabolism in the brain. 

In a real-world analysis, Xu and colleagues used electronic health record data to identify 17,104 new users of semaglutide and 1,077,657 new users of seven other antidiabetic medications, including other GLP-1 RAs, insulin, metformin, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, sulfonylurea, and thiazolidinedione.

Over 3 years, treatment with semaglutide was associated with significantly reduced risk of developing Alzheimer’s disease, most strongly compared with insulin (hazard ratio [HR], 0.33) and most weakly compared with other GLP-1 RAs (HR, 0.59). 

Compared with the other medications, semaglutide was associated with a 40%-70% reduced risk for first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes, with similar reductions seen across obesity status and gender and age groups, the authors reported. 

The findings align with recent evidence suggesting GLP-1 RAs may protect cognitive function. 

For example, as previously reported, in the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 RA liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months compared with placebo. 
 

Promising, but Preliminary 

Reached for comment, Courtney Kloske, PhD, Alzheimer’s Association director of scientific engagement, noted that diabetes is a known risk factor for AD and managing diabetes with drugs such as semaglutide “could benefit brain health simply by managing diabetes.”

“However, we still need large clinical trials in representative populations to determine if semaglutide specifically lowers the risk of Alzheimer’s, so it is too early to recommend it for prevention,” Kloske said. 

She noted that some research suggests that GLP-1 RAs “may help reduce inflammation and positively impact brain energy use. However, more research is needed to fully understand how these processes might contribute to preventing cognitive decline or Alzheimer’s,” Kloske cautioned. 

The Alzheimer’s Association’s “Part the Cloud” initiative has invested more than $68 million to advance 65 clinical trials targeting a variety of compounds, including repurposed drugs that may address known and potential new aspects of the disease, Kloske said. 

The study was supported by grants from the National Institute on Aging and the National Center for Advancing Translational Sciences. Xu and Kloske have no relevant conflicts.
 

A version of this article appeared on Medscape.com.

A new study provides real-world evidence to support the potential repurposing of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), used to treat type 2 diabetes and obesity, for prevention of Alzheimer’s disease.

Adults with type 2 diabetes who were prescribed the GLP-1 RA semaglutide had a significantly lower risk for Alzheimer’s disease compared with their peers who were prescribed any of seven other antidiabetic medications, including other types of GLP-1 receptor–targeting medications. 

“These findings support further clinical trials to assess semaglutide’s potential in delaying or preventing Alzheimer’s disease,” wrote the investigators, led by Rong Xu, PhD, with Case Western Reserve School of Medicine, Cleveland, Ohio. 

The study was published online on October 24 in Alzheimer’s & Dementia.
 

Real-World Data

Semaglutide has shown neuroprotective effects in animal models of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. In animal models of Alzheimer’s disease, the drug reduced beta-amyloid deposition and improved spatial learning and memory, as well as glucose metabolism in the brain. 

In a real-world analysis, Xu and colleagues used electronic health record data to identify 17,104 new users of semaglutide and 1,077,657 new users of seven other antidiabetic medications, including other GLP-1 RAs, insulin, metformin, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, sulfonylurea, and thiazolidinedione.

Over 3 years, treatment with semaglutide was associated with significantly reduced risk of developing Alzheimer’s disease, most strongly compared with insulin (hazard ratio [HR], 0.33) and most weakly compared with other GLP-1 RAs (HR, 0.59). 

Compared with the other medications, semaglutide was associated with a 40%-70% reduced risk for first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes, with similar reductions seen across obesity status and gender and age groups, the authors reported. 

The findings align with recent evidence suggesting GLP-1 RAs may protect cognitive function. 

For example, as previously reported, in the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 RA liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months compared with placebo. 
 

Promising, but Preliminary 

Reached for comment, Courtney Kloske, PhD, Alzheimer’s Association director of scientific engagement, noted that diabetes is a known risk factor for AD and managing diabetes with drugs such as semaglutide “could benefit brain health simply by managing diabetes.”

“However, we still need large clinical trials in representative populations to determine if semaglutide specifically lowers the risk of Alzheimer’s, so it is too early to recommend it for prevention,” Kloske said. 

She noted that some research suggests that GLP-1 RAs “may help reduce inflammation and positively impact brain energy use. However, more research is needed to fully understand how these processes might contribute to preventing cognitive decline or Alzheimer’s,” Kloske cautioned. 

The Alzheimer’s Association’s “Part the Cloud” initiative has invested more than $68 million to advance 65 clinical trials targeting a variety of compounds, including repurposed drugs that may address known and potential new aspects of the disease, Kloske said. 

The study was supported by grants from the National Institute on Aging and the National Center for Advancing Translational Sciences. Xu and Kloske have no relevant conflicts.
 

A version of this article appeared on Medscape.com.

With the approval of anti-amyloid monoclonal antibodies to treat early-stage Alzheimer’s disease, the need for accurate and early diagnosis is crucial.

Blood-based biomarkers offer a promising alternative to amyloid PET scans and cerebrospinal fluid (CSF) analysis and are being increasingly used in clinical practice to support an Alzheimer’s disease diagnosis.

Recently, an expert workgroup convened by the Global CEO Initiative on Alzheimer’s Disease published recommendations for the clinical implementation of Alzheimer’s disease blood-based biomarkers.

“Our hope was to provide some recommendations that clinicians could use to develop the best pathways for their clinical practice,” said workgroup co-chair Michelle M. Mielke, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina.
 

Triage and Confirmatory Pathways

The group recommends two implementation pathways for Alzheimer’s disease blood biomarkers — one for current use for triaging and another for future use to confirm amyloid pathology once blood biomarker tests have reached sufficient performance for this purpose.

In the triage pathway, a negative blood biomarker test would flag individuals unlikely to have detectable brain amyloid pathology. This outcome would prompt clinicians to focus on evaluating non–Alzheimer’s disease-related causes of cognitive impairment, which may streamline the diagnosis of other causes of cognitive impairment, the authors said.

A positive triage blood test would suggest a higher likelihood of amyloid pathology and prompt referral to secondary care for further assessment and consideration for a second, more accurate test, such as amyloid PET or CSF for amyloid confirmation.

In the confirmatory pathway, a positive blood biomarker test result would identify amyloid pathology without the need for a second test, providing a faster route to diagnosis, the authors noted.

Mielke emphasized that these recommendations represent a “first step” and will need to be updated as experiences with the Alzheimer’s disease blood biomarkers in clinical care increase and additional barriers and facilitators are identified.

“These updates will likely include community-informed approaches that incorporate feedback from patients as well as healthcare providers, alongside results from validation in diverse real-world settings,” said workgroup co-chair Chi Udeh-Momoh, PhD, MSc, with Wake Forest University School of Medicine and the Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.

The Alzheimer’s Association published “appropriate use” recommendations for blood biomarkers in 2022.

“Currently, the Alzheimer’s Association is building an updated library of clinical guidance that distills the scientific evidence using de novo systematic reviews and translates them into clear and actionable recommendations for clinical practice,” said Rebecca M. Edelmayer, PhD, vice president of scientific engagement, Alzheimer’s Association.

“The first major effort with our new process will be the upcoming Evidence-based Clinical Practice Guideline on the Use of Blood-based Biomarkers (BBMs) in Specialty Care Settings. This guideline’s recommendations will be published in early 2025,” Edelmayer said.
 

Availability and Accuracy

Research has shown that amyloid beta and tau protein blood biomarkers — especially a high plasma phosphorylated (p)–tau217 levels — are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics.

Several tests targeting plasma p-tau217 are now available for use. They include the PrecivityAD2 blood test from C2N Diagnostics and the Simoa p-Tau 217 Planar Kit and LucentAD p-Tau 217 — both from Quanterix.

In a recent head-to-head comparison of seven leading blood tests for AD pathology, measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with Alzheimer’s disease outcomes.

A recent Swedish study showed that the PrecivityAD2 test had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.

“We’ve been using these blood biomarkers in research for a long time and we’re now taking the jump to start using them in clinic to risk stratify patients,” said Fanny Elahi, MD, PhD, director of fluid biomarker research for the Barbara and Maurice Deane Center for Wellness and Cognitive Health at Icahn Mount Sinai in New York City.

New York’s Mount Sinai Health System is among the first in the northeast to offer blood tests across primary and specialty care settings for early diagnosis of AD and related dementias.

Edelmayer cautioned, “There is no single, stand-alone test to diagnose Alzheimer’s disease today. Blood testing is one piece of the diagnostic process.”

“Currently, physicians use well-established diagnostic tools combined with medical history and other information, including neurological exams, cognitive and functional assessments as well as brain imaging and spinal fluid analysis and blood to make an accurate diagnosis and to understand which patients are eligible for approved treatments,” she said.

There are also emerging biomarkers in the research pipeline, Edelmayer said.

“For example, some researchers think retinal imaging has the potential to detect biological signs of Alzheimer’s disease within certain areas of the eye,” she explained.

“Other emerging biomarkers include examining components in saliva and the skin for signals that may indicate early biological changes in the brain. These biomarkers are still very exploratory, and more research is needed before these tests or biomarkers can be used more routinely to study risk or aid in diagnosis,” Edelmayer said.
 

Ideal Candidates for Alzheimer’s Disease Blood Testing?

Experts agree that blood tests represent a convenient and scalable option to address the anticipated surge in demand for biomarker testing with the availability of disease-modifying treatments. For now, however, they are not for all older adults worried about their memory.

“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid,” the authors of a recent JAMA editorial noted.

At Mount Sinai, “we’re not starting with stone-cold asymptomatic individuals. But ultimately, this is what the blood tests are intended for — screening,” Elahi noted.

She also noted that Mount Sinai has a “very diverse population” — some with young onset cognitive symptoms, so the entry criteria for testing are “very wide.”

“Anyone above age 40 with symptoms can qualify to get a blood test. We do ask at this stage that either the individual report symptoms or someone in their life or their clinician be worried about their cognition or their brain function,” Elahi said.
 

Ethical Considerations, Counseling

Elahi emphasized the importance of counseling patients who come to the clinic seeking an Alzheimer’s disease blood test. This should include how the diagnostic process will unfold and what the next steps are with a given result.

Elahi said patients need to be informed that Alzheimer’s disease blood biomarkers are still “relatively new,” and a test can help a patient “know the likelihood of having the disease, but it won’t be 100% definitive.”

To ensure the ethical principle of “do no harm,” counseling should ensure that patients are fully prepared for the implications of the test results and ensure that the decision to test aligns with the patient’s readiness and well-being, Elahi said.

Edelmayer said the forthcoming clinical practice guidelines will provide “evidence-based recommendations for physicians to help guide them through the decision-making process around who should be tested and when. In the meantime, the Alzheimer’s Association urges providers to refer to the 2022 appropriate use recommendations for blood tests in clinical practice and trial settings.”

Mielke has served on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio. Edelmayer and Elahi had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

With the approval of anti-amyloid monoclonal antibodies to treat early-stage Alzheimer’s disease, the need for accurate and early diagnosis is crucial.

Blood-based biomarkers offer a promising alternative to amyloid PET scans and cerebrospinal fluid (CSF) analysis and are being increasingly used in clinical practice to support an Alzheimer’s disease diagnosis.

Recently, an expert workgroup convened by the Global CEO Initiative on Alzheimer’s Disease published recommendations for the clinical implementation of Alzheimer’s disease blood-based biomarkers.

“Our hope was to provide some recommendations that clinicians could use to develop the best pathways for their clinical practice,” said workgroup co-chair Michelle M. Mielke, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina.
 

Triage and Confirmatory Pathways

The group recommends two implementation pathways for Alzheimer’s disease blood biomarkers — one for current use for triaging and another for future use to confirm amyloid pathology once blood biomarker tests have reached sufficient performance for this purpose.

In the triage pathway, a negative blood biomarker test would flag individuals unlikely to have detectable brain amyloid pathology. This outcome would prompt clinicians to focus on evaluating non–Alzheimer’s disease-related causes of cognitive impairment, which may streamline the diagnosis of other causes of cognitive impairment, the authors said.

A positive triage blood test would suggest a higher likelihood of amyloid pathology and prompt referral to secondary care for further assessment and consideration for a second, more accurate test, such as amyloid PET or CSF for amyloid confirmation.

In the confirmatory pathway, a positive blood biomarker test result would identify amyloid pathology without the need for a second test, providing a faster route to diagnosis, the authors noted.

Mielke emphasized that these recommendations represent a “first step” and will need to be updated as experiences with the Alzheimer’s disease blood biomarkers in clinical care increase and additional barriers and facilitators are identified.

“These updates will likely include community-informed approaches that incorporate feedback from patients as well as healthcare providers, alongside results from validation in diverse real-world settings,” said workgroup co-chair Chi Udeh-Momoh, PhD, MSc, with Wake Forest University School of Medicine and the Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.

The Alzheimer’s Association published “appropriate use” recommendations for blood biomarkers in 2022.

“Currently, the Alzheimer’s Association is building an updated library of clinical guidance that distills the scientific evidence using de novo systematic reviews and translates them into clear and actionable recommendations for clinical practice,” said Rebecca M. Edelmayer, PhD, vice president of scientific engagement, Alzheimer’s Association.

“The first major effort with our new process will be the upcoming Evidence-based Clinical Practice Guideline on the Use of Blood-based Biomarkers (BBMs) in Specialty Care Settings. This guideline’s recommendations will be published in early 2025,” Edelmayer said.
 

Availability and Accuracy

Research has shown that amyloid beta and tau protein blood biomarkers — especially a high plasma phosphorylated (p)–tau217 levels — are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics.

Several tests targeting plasma p-tau217 are now available for use. They include the PrecivityAD2 blood test from C2N Diagnostics and the Simoa p-Tau 217 Planar Kit and LucentAD p-Tau 217 — both from Quanterix.

In a recent head-to-head comparison of seven leading blood tests for AD pathology, measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with Alzheimer’s disease outcomes.

A recent Swedish study showed that the PrecivityAD2 test had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.

“We’ve been using these blood biomarkers in research for a long time and we’re now taking the jump to start using them in clinic to risk stratify patients,” said Fanny Elahi, MD, PhD, director of fluid biomarker research for the Barbara and Maurice Deane Center for Wellness and Cognitive Health at Icahn Mount Sinai in New York City.

New York’s Mount Sinai Health System is among the first in the northeast to offer blood tests across primary and specialty care settings for early diagnosis of AD and related dementias.

Edelmayer cautioned, “There is no single, stand-alone test to diagnose Alzheimer’s disease today. Blood testing is one piece of the diagnostic process.”

“Currently, physicians use well-established diagnostic tools combined with medical history and other information, including neurological exams, cognitive and functional assessments as well as brain imaging and spinal fluid analysis and blood to make an accurate diagnosis and to understand which patients are eligible for approved treatments,” she said.

There are also emerging biomarkers in the research pipeline, Edelmayer said.

“For example, some researchers think retinal imaging has the potential to detect biological signs of Alzheimer’s disease within certain areas of the eye,” she explained.

“Other emerging biomarkers include examining components in saliva and the skin for signals that may indicate early biological changes in the brain. These biomarkers are still very exploratory, and more research is needed before these tests or biomarkers can be used more routinely to study risk or aid in diagnosis,” Edelmayer said.
 

Ideal Candidates for Alzheimer’s Disease Blood Testing?

Experts agree that blood tests represent a convenient and scalable option to address the anticipated surge in demand for biomarker testing with the availability of disease-modifying treatments. For now, however, they are not for all older adults worried about their memory.

“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid,” the authors of a recent JAMA editorial noted.

At Mount Sinai, “we’re not starting with stone-cold asymptomatic individuals. But ultimately, this is what the blood tests are intended for — screening,” Elahi noted.

She also noted that Mount Sinai has a “very diverse population” — some with young onset cognitive symptoms, so the entry criteria for testing are “very wide.”

“Anyone above age 40 with symptoms can qualify to get a blood test. We do ask at this stage that either the individual report symptoms or someone in their life or their clinician be worried about their cognition or their brain function,” Elahi said.
 

Ethical Considerations, Counseling

Elahi emphasized the importance of counseling patients who come to the clinic seeking an Alzheimer’s disease blood test. This should include how the diagnostic process will unfold and what the next steps are with a given result.

Elahi said patients need to be informed that Alzheimer’s disease blood biomarkers are still “relatively new,” and a test can help a patient “know the likelihood of having the disease, but it won’t be 100% definitive.”

To ensure the ethical principle of “do no harm,” counseling should ensure that patients are fully prepared for the implications of the test results and ensure that the decision to test aligns with the patient’s readiness and well-being, Elahi said.

Edelmayer said the forthcoming clinical practice guidelines will provide “evidence-based recommendations for physicians to help guide them through the decision-making process around who should be tested and when. In the meantime, the Alzheimer’s Association urges providers to refer to the 2022 appropriate use recommendations for blood tests in clinical practice and trial settings.”

Mielke has served on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio. Edelmayer and Elahi had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

With the approval of anti-amyloid monoclonal antibodies to treat early-stage Alzheimer’s disease, the need for accurate and early diagnosis is crucial.

Blood-based biomarkers offer a promising alternative to amyloid PET scans and cerebrospinal fluid (CSF) analysis and are being increasingly used in clinical practice to support an Alzheimer’s disease diagnosis.

Recently, an expert workgroup convened by the Global CEO Initiative on Alzheimer’s Disease published recommendations for the clinical implementation of Alzheimer’s disease blood-based biomarkers.

“Our hope was to provide some recommendations that clinicians could use to develop the best pathways for their clinical practice,” said workgroup co-chair Michelle M. Mielke, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina.
 

Triage and Confirmatory Pathways

The group recommends two implementation pathways for Alzheimer’s disease blood biomarkers — one for current use for triaging and another for future use to confirm amyloid pathology once blood biomarker tests have reached sufficient performance for this purpose.

In the triage pathway, a negative blood biomarker test would flag individuals unlikely to have detectable brain amyloid pathology. This outcome would prompt clinicians to focus on evaluating non–Alzheimer’s disease-related causes of cognitive impairment, which may streamline the diagnosis of other causes of cognitive impairment, the authors said.

A positive triage blood test would suggest a higher likelihood of amyloid pathology and prompt referral to secondary care for further assessment and consideration for a second, more accurate test, such as amyloid PET or CSF for amyloid confirmation.

In the confirmatory pathway, a positive blood biomarker test result would identify amyloid pathology without the need for a second test, providing a faster route to diagnosis, the authors noted.

Mielke emphasized that these recommendations represent a “first step” and will need to be updated as experiences with the Alzheimer’s disease blood biomarkers in clinical care increase and additional barriers and facilitators are identified.

“These updates will likely include community-informed approaches that incorporate feedback from patients as well as healthcare providers, alongside results from validation in diverse real-world settings,” said workgroup co-chair Chi Udeh-Momoh, PhD, MSc, with Wake Forest University School of Medicine and the Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.

The Alzheimer’s Association published “appropriate use” recommendations for blood biomarkers in 2022.

“Currently, the Alzheimer’s Association is building an updated library of clinical guidance that distills the scientific evidence using de novo systematic reviews and translates them into clear and actionable recommendations for clinical practice,” said Rebecca M. Edelmayer, PhD, vice president of scientific engagement, Alzheimer’s Association.

“The first major effort with our new process will be the upcoming Evidence-based Clinical Practice Guideline on the Use of Blood-based Biomarkers (BBMs) in Specialty Care Settings. This guideline’s recommendations will be published in early 2025,” Edelmayer said.
 

Availability and Accuracy

Research has shown that amyloid beta and tau protein blood biomarkers — especially a high plasma phosphorylated (p)–tau217 levels — are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics.

Several tests targeting plasma p-tau217 are now available for use. They include the PrecivityAD2 blood test from C2N Diagnostics and the Simoa p-Tau 217 Planar Kit and LucentAD p-Tau 217 — both from Quanterix.

In a recent head-to-head comparison of seven leading blood tests for AD pathology, measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with Alzheimer’s disease outcomes.

A recent Swedish study showed that the PrecivityAD2 test had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.

“We’ve been using these blood biomarkers in research for a long time and we’re now taking the jump to start using them in clinic to risk stratify patients,” said Fanny Elahi, MD, PhD, director of fluid biomarker research for the Barbara and Maurice Deane Center for Wellness and Cognitive Health at Icahn Mount Sinai in New York City.

New York’s Mount Sinai Health System is among the first in the northeast to offer blood tests across primary and specialty care settings for early diagnosis of AD and related dementias.

Edelmayer cautioned, “There is no single, stand-alone test to diagnose Alzheimer’s disease today. Blood testing is one piece of the diagnostic process.”

“Currently, physicians use well-established diagnostic tools combined with medical history and other information, including neurological exams, cognitive and functional assessments as well as brain imaging and spinal fluid analysis and blood to make an accurate diagnosis and to understand which patients are eligible for approved treatments,” she said.

There are also emerging biomarkers in the research pipeline, Edelmayer said.

“For example, some researchers think retinal imaging has the potential to detect biological signs of Alzheimer’s disease within certain areas of the eye,” she explained.

“Other emerging biomarkers include examining components in saliva and the skin for signals that may indicate early biological changes in the brain. These biomarkers are still very exploratory, and more research is needed before these tests or biomarkers can be used more routinely to study risk or aid in diagnosis,” Edelmayer said.
 

Ideal Candidates for Alzheimer’s Disease Blood Testing?

Experts agree that blood tests represent a convenient and scalable option to address the anticipated surge in demand for biomarker testing with the availability of disease-modifying treatments. For now, however, they are not for all older adults worried about their memory.

“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid,” the authors of a recent JAMA editorial noted.

At Mount Sinai, “we’re not starting with stone-cold asymptomatic individuals. But ultimately, this is what the blood tests are intended for — screening,” Elahi noted.

She also noted that Mount Sinai has a “very diverse population” — some with young onset cognitive symptoms, so the entry criteria for testing are “very wide.”

“Anyone above age 40 with symptoms can qualify to get a blood test. We do ask at this stage that either the individual report symptoms or someone in their life or their clinician be worried about their cognition or their brain function,” Elahi said.
 

Ethical Considerations, Counseling

Elahi emphasized the importance of counseling patients who come to the clinic seeking an Alzheimer’s disease blood test. This should include how the diagnostic process will unfold and what the next steps are with a given result.

Elahi said patients need to be informed that Alzheimer’s disease blood biomarkers are still “relatively new,” and a test can help a patient “know the likelihood of having the disease, but it won’t be 100% definitive.”

To ensure the ethical principle of “do no harm,” counseling should ensure that patients are fully prepared for the implications of the test results and ensure that the decision to test aligns with the patient’s readiness and well-being, Elahi said.

Edelmayer said the forthcoming clinical practice guidelines will provide “evidence-based recommendations for physicians to help guide them through the decision-making process around who should be tested and when. In the meantime, the Alzheimer’s Association urges providers to refer to the 2022 appropriate use recommendations for blood tests in clinical practice and trial settings.”

Mielke has served on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio. Edelmayer and Elahi had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE: 

More than half of the US peer reviewers for four major medical journals received industry payments between 2020-2022, new research shows. Altogether they received more than $64 million in general, non-research payments, with a median payment per physician of $7614. Research payments — including money paid directly to physicians as well as funds related to research for which a physician was registered as a principal investigator — exceeded $1 billion.

METHODOLOGY:

• Researchers identified peer reviewers in 2022 for The BMJ, JAMA, The Lancet, and The New England Journal of Medicine using each journal’s list of reviewers for that year. They included 1962 US-based physicians in their analysis.
• General and research payments made to the peer reviewers between 2020-2022 were extracted from the Open Payments database.

TAKEAWAY:

• Nearly 59% of the peer reviewers received industry payments between 2020-2022.
• Payments included $34.31 million in consulting fees and $11.8 million for speaking compensation unrelated to continuing medical education programs.
• Male reviewers received a significantly higher median total payment than did female reviewers ($38,959 vs $19,586). General payments were higher for men as well ($8663 vs $4183).
• For comparison, the median general payment to all physicians in 2018 was $216, the researchers noted.

IN PRACTICE:

“Additional research and transparency regarding industry payments in the peer review process are needed,” the authors of the study wrote.

SOURCE:

Christopher J. D. Wallis, MD, PhD, with the division of urology at the University of Toronto, Canada, was the corresponding author for the study. The article was published online October 10 in JAMA.

LIMITATIONS: 

Whether the financial ties were relevant to any of the papers that the peer reviewers critiqued is not known. Some reviewers might have received additional payments from insurance and technology companies that were not captured in this study. The findings might not apply to other journals, the researchers noted. 

DISCLOSURES:

Wallis disclosed personal fees from Janssen Oncology, Nanostics, Precision Point Specialty, Sesen Bio, AbbVie, Astellas, AstraZeneca, Bayer, EMD Serono, Knight Therapeutics, Merck, Science and Medicine Canada, TerSera, and Tolmar. He and some coauthors also disclosed support and grants from foundations and government institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE: 

More than half of the US peer reviewers for four major medical journals received industry payments between 2020-2022, new research shows. Altogether they received more than $64 million in general, non-research payments, with a median payment per physician of $7614. Research payments — including money paid directly to physicians as well as funds related to research for which a physician was registered as a principal investigator — exceeded $1 billion.

METHODOLOGY:

• Researchers identified peer reviewers in 2022 for The BMJ, JAMA, The Lancet, and The New England Journal of Medicine using each journal’s list of reviewers for that year. They included 1962 US-based physicians in their analysis.
• General and research payments made to the peer reviewers between 2020-2022 were extracted from the Open Payments database.

TAKEAWAY:

• Nearly 59% of the peer reviewers received industry payments between 2020-2022.
• Payments included $34.31 million in consulting fees and $11.8 million for speaking compensation unrelated to continuing medical education programs.
• Male reviewers received a significantly higher median total payment than did female reviewers ($38,959 vs $19,586). General payments were higher for men as well ($8663 vs $4183).
• For comparison, the median general payment to all physicians in 2018 was $216, the researchers noted.

IN PRACTICE:

“Additional research and transparency regarding industry payments in the peer review process are needed,” the authors of the study wrote.

SOURCE:

Christopher J. D. Wallis, MD, PhD, with the division of urology at the University of Toronto, Canada, was the corresponding author for the study. The article was published online October 10 in JAMA.

LIMITATIONS: 

Whether the financial ties were relevant to any of the papers that the peer reviewers critiqued is not known. Some reviewers might have received additional payments from insurance and technology companies that were not captured in this study. The findings might not apply to other journals, the researchers noted. 

DISCLOSURES:

Wallis disclosed personal fees from Janssen Oncology, Nanostics, Precision Point Specialty, Sesen Bio, AbbVie, Astellas, AstraZeneca, Bayer, EMD Serono, Knight Therapeutics, Merck, Science and Medicine Canada, TerSera, and Tolmar. He and some coauthors also disclosed support and grants from foundations and government institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE: 

More than half of the US peer reviewers for four major medical journals received industry payments between 2020-2022, new research shows. Altogether they received more than $64 million in general, non-research payments, with a median payment per physician of $7614. Research payments — including money paid directly to physicians as well as funds related to research for which a physician was registered as a principal investigator — exceeded $1 billion.

METHODOLOGY:

• Researchers identified peer reviewers in 2022 for The BMJ, JAMA, The Lancet, and The New England Journal of Medicine using each journal’s list of reviewers for that year. They included 1962 US-based physicians in their analysis.
• General and research payments made to the peer reviewers between 2020-2022 were extracted from the Open Payments database.

TAKEAWAY:

• Nearly 59% of the peer reviewers received industry payments between 2020-2022.
• Payments included $34.31 million in consulting fees and $11.8 million for speaking compensation unrelated to continuing medical education programs.
• Male reviewers received a significantly higher median total payment than did female reviewers ($38,959 vs $19,586). General payments were higher for men as well ($8663 vs $4183).
• For comparison, the median general payment to all physicians in 2018 was $216, the researchers noted.

IN PRACTICE:

“Additional research and transparency regarding industry payments in the peer review process are needed,” the authors of the study wrote.

SOURCE:

Christopher J. D. Wallis, MD, PhD, with the division of urology at the University of Toronto, Canada, was the corresponding author for the study. The article was published online October 10 in JAMA.

LIMITATIONS: 

Whether the financial ties were relevant to any of the papers that the peer reviewers critiqued is not known. Some reviewers might have received additional payments from insurance and technology companies that were not captured in this study. The findings might not apply to other journals, the researchers noted. 

DISCLOSURES:

Wallis disclosed personal fees from Janssen Oncology, Nanostics, Precision Point Specialty, Sesen Bio, AbbVie, Astellas, AstraZeneca, Bayer, EMD Serono, Knight Therapeutics, Merck, Science and Medicine Canada, TerSera, and Tolmar. He and some coauthors also disclosed support and grants from foundations and government institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Words do have power. Names have power. Words are events, they do things, change things. They transform both speaker and hearer ... They feed understanding or emotion back and forth and amplify it. — Ursula K. Le Guin
 

Every medical student should have a class in linguistics. I’m just unsure what it might replace. Maybe physiology? (When was the last time you used Fick’s or Fourier’s Laws anyway?). Even if we don’t supplant any core curriculum, it’s worth noting that we spend more time in our daily work calculating how to communicate things than calculating cardiac outputs. That we can convey so much so consistently and without specific training is a marvel. Making the diagnosis or a plan is often the easy part. The difficulty comes in trying to communicate what we know to patients such that they understand and can act on it.

Linguistics is a broad field. At its essence, it studies how we communicate. It’s fascinating how we use tone, word choice, gestures, syntax, and grammar to explain, reassure, instruct or implore patients. Medical appointments are sometimes high stakes and occur within a huge variety of circumstances. In a single day of clinic, I had a patient with dementia, and one pursuing a PhD in P-Chem. I had English speakers, second language English speakers, and a Vietnamese patient who knew no English. In just one day, I explained things to toddlers and adults, a Black woman from Oklahoma and a Jewish woman from New York. For a brief few minutes, each of them was my partner in a game of medical charades. For each one, I had to figure out how to get them to know what I’m thinking.

Dr. Benabio

I learned of this game of charades concept from a podcast featuring Morten Christiansen, professor of psychology at Cornell University, and professor in Cognitive Science of Language, at Aarhus University, Denmark. The idea is that language can be thought of as a game where speakers constantly improvise based on the topic, each one’s expertise, and the shared understanding. I found this intriguing. In his explanation, grammar and definitions are less important than the mutual understanding of what is being communicated. It helps explain the wide variations of speech even among those speaking the same language. It also flips the idea that brains are designed for language, a concept proposed by linguistic greats such as Noam Chomsky and Steven Pinker. Rather, what we call language is just the best solution our brains could create to convey information.

I thought about how each of us instinctively varies the complexity of sentences and tone of voice based on the ability of each patient to understand. Gestures, storytelling and analogies are linguistic tools we use without thinking about them. We’ve a unique communications conundrum in that we often need patients to understand a complex idea, but only have minutes to get them there. We don’t want them to panic. We also don’t want them to be so dispassionate as to not act. To speed things up, we often use a technique known as chunking, short phrases that capture an idea in one bite. For example, “soak and smear” to get atopic patients to moisturize or “scrape and burn” to describe a curettage and electrodesiccation of a basal cell carcinoma or “a stick and a burn” before injecting them (I never liked that one). These are pithy, efficient. But they don’t always work.

One afternoon I had a 93-year-old woman with glossodynia. She had dementia and her 96-year-old husband was helping. When I explained how she’d “swish and spit” her magic mouthwash, he looked perplexed. Is she swishing a wand or something? I shook my head, “No” and gestured with my hands palms down, waving back and forth. It is just a mouthwash. She should rinse, then spit it out. I lost that round.

Then a 64-year-old woman whom I had to advise that the pink bump on her arm was a cutaneous neuroendocrine tumor. Do I call it a Merkel cell carcinoma? Do I say, “You know, like the one Jimmy Buffett had?” (Nope, not a good use of storytelling). She wanted to know how she got it. Sun exposure, we think. Or, perhaps a virus. Just how does one explain a virus called MCPyV that is ubiquitous but somehow caused cancer just for you? How do you convey, “This is serious, but you might not die like Jimmy Buffett?” I had to use all my language skills to get this right.

Then there is the Henderson-Hasselbalch problem of linguistics: communicating through a translator. When doing so, I’m cognizant of choosing short, simple sentences. Subject, verb, object. First this, then that. This mitigates what’s lost in translation and reduces waiting for translations (especially when your patient is storytelling in paragraphs). But try doing this with an emotionally wrought condition like alopecia. Finding the fewest words to convey that your FSH and estrogen levels are irrelevant to your telogen effluvium to a Vietnamese speaker is tricky. “Yes, I see your primary care physician ordered these tests. No, the numbers do not matter.” Did that translate as they are normal? Or that they don’t matter because she is 54? Or that they don’t matter to me because I didn’t order them?

When you find yourself exhausted at the day’s end, perhaps you’ll better appreciate how it was not only the graduate level medicine you did today; you’ve practically got a PhD in linguistics as well. You just didn’t realize it.

Dr. Benabio is chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].

Words do have power. Names have power. Words are events, they do things, change things. They transform both speaker and hearer ... They feed understanding or emotion back and forth and amplify it. — Ursula K. Le Guin
 

Every medical student should have a class in linguistics. I’m just unsure what it might replace. Maybe physiology? (When was the last time you used Fick’s or Fourier’s Laws anyway?). Even if we don’t supplant any core curriculum, it’s worth noting that we spend more time in our daily work calculating how to communicate things than calculating cardiac outputs. That we can convey so much so consistently and without specific training is a marvel. Making the diagnosis or a plan is often the easy part. The difficulty comes in trying to communicate what we know to patients such that they understand and can act on it.

Linguistics is a broad field. At its essence, it studies how we communicate. It’s fascinating how we use tone, word choice, gestures, syntax, and grammar to explain, reassure, instruct or implore patients. Medical appointments are sometimes high stakes and occur within a huge variety of circumstances. In a single day of clinic, I had a patient with dementia, and one pursuing a PhD in P-Chem. I had English speakers, second language English speakers, and a Vietnamese patient who knew no English. In just one day, I explained things to toddlers and adults, a Black woman from Oklahoma and a Jewish woman from New York. For a brief few minutes, each of them was my partner in a game of medical charades. For each one, I had to figure out how to get them to know what I’m thinking.

Dr. Benabio

I learned of this game of charades concept from a podcast featuring Morten Christiansen, professor of psychology at Cornell University, and professor in Cognitive Science of Language, at Aarhus University, Denmark. The idea is that language can be thought of as a game where speakers constantly improvise based on the topic, each one’s expertise, and the shared understanding. I found this intriguing. In his explanation, grammar and definitions are less important than the mutual understanding of what is being communicated. It helps explain the wide variations of speech even among those speaking the same language. It also flips the idea that brains are designed for language, a concept proposed by linguistic greats such as Noam Chomsky and Steven Pinker. Rather, what we call language is just the best solution our brains could create to convey information.

I thought about how each of us instinctively varies the complexity of sentences and tone of voice based on the ability of each patient to understand. Gestures, storytelling and analogies are linguistic tools we use without thinking about them. We’ve a unique communications conundrum in that we often need patients to understand a complex idea, but only have minutes to get them there. We don’t want them to panic. We also don’t want them to be so dispassionate as to not act. To speed things up, we often use a technique known as chunking, short phrases that capture an idea in one bite. For example, “soak and smear” to get atopic patients to moisturize or “scrape and burn” to describe a curettage and electrodesiccation of a basal cell carcinoma or “a stick and a burn” before injecting them (I never liked that one). These are pithy, efficient. But they don’t always work.

One afternoon I had a 93-year-old woman with glossodynia. She had dementia and her 96-year-old husband was helping. When I explained how she’d “swish and spit” her magic mouthwash, he looked perplexed. Is she swishing a wand or something? I shook my head, “No” and gestured with my hands palms down, waving back and forth. It is just a mouthwash. She should rinse, then spit it out. I lost that round.

Then a 64-year-old woman whom I had to advise that the pink bump on her arm was a cutaneous neuroendocrine tumor. Do I call it a Merkel cell carcinoma? Do I say, “You know, like the one Jimmy Buffett had?” (Nope, not a good use of storytelling). She wanted to know how she got it. Sun exposure, we think. Or, perhaps a virus. Just how does one explain a virus called MCPyV that is ubiquitous but somehow caused cancer just for you? How do you convey, “This is serious, but you might not die like Jimmy Buffett?” I had to use all my language skills to get this right.

Then there is the Henderson-Hasselbalch problem of linguistics: communicating through a translator. When doing so, I’m cognizant of choosing short, simple sentences. Subject, verb, object. First this, then that. This mitigates what’s lost in translation and reduces waiting for translations (especially when your patient is storytelling in paragraphs). But try doing this with an emotionally wrought condition like alopecia. Finding the fewest words to convey that your FSH and estrogen levels are irrelevant to your telogen effluvium to a Vietnamese speaker is tricky. “Yes, I see your primary care physician ordered these tests. No, the numbers do not matter.” Did that translate as they are normal? Or that they don’t matter because she is 54? Or that they don’t matter to me because I didn’t order them?

When you find yourself exhausted at the day’s end, perhaps you’ll better appreciate how it was not only the graduate level medicine you did today; you’ve practically got a PhD in linguistics as well. You just didn’t realize it.

Dr. Benabio is chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].

Words do have power. Names have power. Words are events, they do things, change things. They transform both speaker and hearer ... They feed understanding or emotion back and forth and amplify it. — Ursula K. Le Guin
 

Every medical student should have a class in linguistics. I’m just unsure what it might replace. Maybe physiology? (When was the last time you used Fick’s or Fourier’s Laws anyway?). Even if we don’t supplant any core curriculum, it’s worth noting that we spend more time in our daily work calculating how to communicate things than calculating cardiac outputs. That we can convey so much so consistently and without specific training is a marvel. Making the diagnosis or a plan is often the easy part. The difficulty comes in trying to communicate what we know to patients such that they understand and can act on it.

Linguistics is a broad field. At its essence, it studies how we communicate. It’s fascinating how we use tone, word choice, gestures, syntax, and grammar to explain, reassure, instruct or implore patients. Medical appointments are sometimes high stakes and occur within a huge variety of circumstances. In a single day of clinic, I had a patient with dementia, and one pursuing a PhD in P-Chem. I had English speakers, second language English speakers, and a Vietnamese patient who knew no English. In just one day, I explained things to toddlers and adults, a Black woman from Oklahoma and a Jewish woman from New York. For a brief few minutes, each of them was my partner in a game of medical charades. For each one, I had to figure out how to get them to know what I’m thinking.

Dr. Benabio

I learned of this game of charades concept from a podcast featuring Morten Christiansen, professor of psychology at Cornell University, and professor in Cognitive Science of Language, at Aarhus University, Denmark. The idea is that language can be thought of as a game where speakers constantly improvise based on the topic, each one’s expertise, and the shared understanding. I found this intriguing. In his explanation, grammar and definitions are less important than the mutual understanding of what is being communicated. It helps explain the wide variations of speech even among those speaking the same language. It also flips the idea that brains are designed for language, a concept proposed by linguistic greats such as Noam Chomsky and Steven Pinker. Rather, what we call language is just the best solution our brains could create to convey information.

I thought about how each of us instinctively varies the complexity of sentences and tone of voice based on the ability of each patient to understand. Gestures, storytelling and analogies are linguistic tools we use without thinking about them. We’ve a unique communications conundrum in that we often need patients to understand a complex idea, but only have minutes to get them there. We don’t want them to panic. We also don’t want them to be so dispassionate as to not act. To speed things up, we often use a technique known as chunking, short phrases that capture an idea in one bite. For example, “soak and smear” to get atopic patients to moisturize or “scrape and burn” to describe a curettage and electrodesiccation of a basal cell carcinoma or “a stick and a burn” before injecting them (I never liked that one). These are pithy, efficient. But they don’t always work.

One afternoon I had a 93-year-old woman with glossodynia. She had dementia and her 96-year-old husband was helping. When I explained how she’d “swish and spit” her magic mouthwash, he looked perplexed. Is she swishing a wand or something? I shook my head, “No” and gestured with my hands palms down, waving back and forth. It is just a mouthwash. She should rinse, then spit it out. I lost that round.

Then a 64-year-old woman whom I had to advise that the pink bump on her arm was a cutaneous neuroendocrine tumor. Do I call it a Merkel cell carcinoma? Do I say, “You know, like the one Jimmy Buffett had?” (Nope, not a good use of storytelling). She wanted to know how she got it. Sun exposure, we think. Or, perhaps a virus. Just how does one explain a virus called MCPyV that is ubiquitous but somehow caused cancer just for you? How do you convey, “This is serious, but you might not die like Jimmy Buffett?” I had to use all my language skills to get this right.

Then there is the Henderson-Hasselbalch problem of linguistics: communicating through a translator. When doing so, I’m cognizant of choosing short, simple sentences. Subject, verb, object. First this, then that. This mitigates what’s lost in translation and reduces waiting for translations (especially when your patient is storytelling in paragraphs). But try doing this with an emotionally wrought condition like alopecia. Finding the fewest words to convey that your FSH and estrogen levels are irrelevant to your telogen effluvium to a Vietnamese speaker is tricky. “Yes, I see your primary care physician ordered these tests. No, the numbers do not matter.” Did that translate as they are normal? Or that they don’t matter because she is 54? Or that they don’t matter to me because I didn’t order them?

When you find yourself exhausted at the day’s end, perhaps you’ll better appreciate how it was not only the graduate level medicine you did today; you’ve practically got a PhD in linguistics as well. You just didn’t realize it.

Dr. Benabio is chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X. Write to him at [email protected].

Emergencies happen anywhere, anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. Is There a Doctor in the House? is a Medscape Medical News series telling these stories.

I sincerely believe that what goes around comes around. Good things come to good people. And sometimes that saves lives.

My 10-year-old son was in the semifinals of the Little League district championship. And we were losing. My son is an excellent pitcher, and he had started the game. But that night, he was struggling. He just couldn’t find where to throw the ball. Needless to say, he was frustrated.

He was changed to shortstop in the second inning, and the home plate umpire walked over to him. This umpire is well known in the area for his kindness and commitment, how he encourages the kids and helps make baseball fun even when it’s stressful.

We didn’t know him well, but he was really supportive of my kid in that moment, talking to him about how baseball is a team sport and we’re here to have fun. Just being really positive.

As the game continued, I saw the umpire suddenly walk to the side of the field. I hadn’t seen it, but he had been hit by a wild pitch on the side of his neck. He was wearing protective gear, but the ball managed to bounce up the side and caught bare neck. I knew something wasn’t right.

I went down to talk to him, and my medical assistant (MA), who was also at the game, came with me. I could tell the umpire was injured, but he didn’t want to leave the game. I suggested going to the hospital, but he wouldn’t consider it. So I sat there with my arms crossed, watching him.

His symptoms got worse. I could see he was in pain, and it was getting harder for him to speak. My concern was that there was a tracheal injury, a carotid injury, or something of that nature that was expanding.

Again, I strongly urged him to go to the hospital, but again, he said no.

In the sixth inning, things got bad enough that the umpire finally agreed to leave the game. As I was figuring out how to get him to the hospital, he disappeared on me. He had walked up to the second floor of the snack shack. My MA and I got him back downstairs and sat him on a bench behind home plate.

We were in the process of calling 911 ... when he arrested.

Luckily, when he lost vital signs, my MA and I were standing right next to him. We were able to activate ACLS protocol and start CPR within seconds.

Many times in these critical situations — especially if people are scared or have never seen an emergency like this — there’s the potential for chaos. Well, that was the polar opposite of what happened.

As soon as I started to run the code, there was this sense of order. People were keeping their composure and following directions. My MA and I would say, “this is what we need,” and the task would immediately be assigned to someone. It was quiet. There was no yelling. Everyone trusted me, even though some of them had never met me before. It was so surprising. I remember thinking, we’re running an arrest, but it’s so calm.

We were an organized team, and it really worked like clockwork, which was remarkable given where we were. It’s one thing to be in the hospital for an event like that. But to be on a baseball field where you have nothing is a completely different scenario.

Meanwhile, the game went on.

I had requested that all the kids be placed in the dugout when they weren’t on the field. So they saw the umpire walk off, but none of them saw him arrest. Some parents were really helpful with making sure the kids were okay.

The president of Oxford Little League ran across the street to a fire station to get an AED. But the fire department personnel were out on a call. He had to break down the door.

By the time he got back, the umpire’s vital signs were returning. And then EMS arrived.

They loaded him in the ambulance, and I called ahead to the trauma team, so they knew exactly what was happening.

I was pretty worried. My hypothesis was that there was probably compression on the vasculature, which had caused him to lose his vital signs. I thought he probably had an impending airway loss. I wasn’t sure if he was going to make it through the night.

What I didn’t know was that while I was giving CPR, my son stole home, and we won the game. As the ambulance was leaving, the celebration was going on in the outfield.

The umpire was in the hospital for several days. Early on, I got permission from his family to visit him. The first time I saw him, I felt this incredible gratitude and peace.

My dad was an ER doctor, and growing up, it seemed like every time we went on a family vacation, there was an emergency. We would be near a car accident or something, and my father would fly in and save the day. I remember being on the Autobahn somewhere in Europe, and there was a devastating accident between a car and a motorcycle. My father stabilized the guy, had him airlifted out, and apparently, he did fine. I grew up watching things like this and thinking, wow, that’s incredible.

Fast forward to 2 years ago, my father was diagnosed with a lung cancer he never should have had. He never smoked. As a cancer surgeon, I know we did everything in our power to save him. But it didn’t happen. He passed away.

I realize this is superstitious, but seeing the umpire alive, I had this feeling that somehow my dad was there. It was bittersweet but also a joyful moment — like I could breathe again.

I met the umpire’s family that first time, and it was like meeting family that you didn’t know you had but now you have forever. Even though the event was traumatic — I’m still trying not to be on high alert every time I go to a game — it felt like a gift to be part of this journey with them.

Little League’s mission is to teach kids about teamwork, leadership, and making good choices so communities are stronger. Our umpire is a guy who does that every day. He’s not a Little League umpire because he makes any money. He shows up at every single game to support these kids and engage them, to model respect, gratitude, and kindness.

I think our obligation as people is to live with intentionality. We all need to make sure we leave the world a better place, even when we are called upon to do uncomfortable things. Our umpire showed our kids what that looks like, and in that moment when he could have died, we were able to do the same for him.

Jennifer LaFemina, MD, is a surgical oncologist at UMass Memorial Medical Center in Massachusetts.
 

Are you a medical professional with a dramatic story outside the clinic? Medscape Medical News would love to consider your story for Is There a Doctor in the House? Please email your contact information and a short summary to [email protected].

A version of this article appeared on Medscape.com.

Emergencies happen anywhere, anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. Is There a Doctor in the House? is a Medscape Medical News series telling these stories.

I sincerely believe that what goes around comes around. Good things come to good people. And sometimes that saves lives.

My 10-year-old son was in the semifinals of the Little League district championship. And we were losing. My son is an excellent pitcher, and he had started the game. But that night, he was struggling. He just couldn’t find where to throw the ball. Needless to say, he was frustrated.

He was changed to shortstop in the second inning, and the home plate umpire walked over to him. This umpire is well known in the area for his kindness and commitment, how he encourages the kids and helps make baseball fun even when it’s stressful.

We didn’t know him well, but he was really supportive of my kid in that moment, talking to him about how baseball is a team sport and we’re here to have fun. Just being really positive.

As the game continued, I saw the umpire suddenly walk to the side of the field. I hadn’t seen it, but he had been hit by a wild pitch on the side of his neck. He was wearing protective gear, but the ball managed to bounce up the side and caught bare neck. I knew something wasn’t right.

I went down to talk to him, and my medical assistant (MA), who was also at the game, came with me. I could tell the umpire was injured, but he didn’t want to leave the game. I suggested going to the hospital, but he wouldn’t consider it. So I sat there with my arms crossed, watching him.

His symptoms got worse. I could see he was in pain, and it was getting harder for him to speak. My concern was that there was a tracheal injury, a carotid injury, or something of that nature that was expanding.

Again, I strongly urged him to go to the hospital, but again, he said no.

In the sixth inning, things got bad enough that the umpire finally agreed to leave the game. As I was figuring out how to get him to the hospital, he disappeared on me. He had walked up to the second floor of the snack shack. My MA and I got him back downstairs and sat him on a bench behind home plate.

We were in the process of calling 911 ... when he arrested.

Luckily, when he lost vital signs, my MA and I were standing right next to him. We were able to activate ACLS protocol and start CPR within seconds.

Many times in these critical situations — especially if people are scared or have never seen an emergency like this — there’s the potential for chaos. Well, that was the polar opposite of what happened.

As soon as I started to run the code, there was this sense of order. People were keeping their composure and following directions. My MA and I would say, “this is what we need,” and the task would immediately be assigned to someone. It was quiet. There was no yelling. Everyone trusted me, even though some of them had never met me before. It was so surprising. I remember thinking, we’re running an arrest, but it’s so calm.

We were an organized team, and it really worked like clockwork, which was remarkable given where we were. It’s one thing to be in the hospital for an event like that. But to be on a baseball field where you have nothing is a completely different scenario.

Meanwhile, the game went on.

I had requested that all the kids be placed in the dugout when they weren’t on the field. So they saw the umpire walk off, but none of them saw him arrest. Some parents were really helpful with making sure the kids were okay.

The president of Oxford Little League ran across the street to a fire station to get an AED. But the fire department personnel were out on a call. He had to break down the door.

By the time he got back, the umpire’s vital signs were returning. And then EMS arrived.

They loaded him in the ambulance, and I called ahead to the trauma team, so they knew exactly what was happening.

I was pretty worried. My hypothesis was that there was probably compression on the vasculature, which had caused him to lose his vital signs. I thought he probably had an impending airway loss. I wasn’t sure if he was going to make it through the night.

What I didn’t know was that while I was giving CPR, my son stole home, and we won the game. As the ambulance was leaving, the celebration was going on in the outfield.

The umpire was in the hospital for several days. Early on, I got permission from his family to visit him. The first time I saw him, I felt this incredible gratitude and peace.

My dad was an ER doctor, and growing up, it seemed like every time we went on a family vacation, there was an emergency. We would be near a car accident or something, and my father would fly in and save the day. I remember being on the Autobahn somewhere in Europe, and there was a devastating accident between a car and a motorcycle. My father stabilized the guy, had him airlifted out, and apparently, he did fine. I grew up watching things like this and thinking, wow, that’s incredible.

Fast forward to 2 years ago, my father was diagnosed with a lung cancer he never should have had. He never smoked. As a cancer surgeon, I know we did everything in our power to save him. But it didn’t happen. He passed away.

I realize this is superstitious, but seeing the umpire alive, I had this feeling that somehow my dad was there. It was bittersweet but also a joyful moment — like I could breathe again.

I met the umpire’s family that first time, and it was like meeting family that you didn’t know you had but now you have forever. Even though the event was traumatic — I’m still trying not to be on high alert every time I go to a game — it felt like a gift to be part of this journey with them.

Little League’s mission is to teach kids about teamwork, leadership, and making good choices so communities are stronger. Our umpire is a guy who does that every day. He’s not a Little League umpire because he makes any money. He shows up at every single game to support these kids and engage them, to model respect, gratitude, and kindness.

I think our obligation as people is to live with intentionality. We all need to make sure we leave the world a better place, even when we are called upon to do uncomfortable things. Our umpire showed our kids what that looks like, and in that moment when he could have died, we were able to do the same for him.

Jennifer LaFemina, MD, is a surgical oncologist at UMass Memorial Medical Center in Massachusetts.
 

Are you a medical professional with a dramatic story outside the clinic? Medscape Medical News would love to consider your story for Is There a Doctor in the House? Please email your contact information and a short summary to [email protected].

A version of this article appeared on Medscape.com.

Emergencies happen anywhere, anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. Is There a Doctor in the House? is a Medscape Medical News series telling these stories.

I sincerely believe that what goes around comes around. Good things come to good people. And sometimes that saves lives.

My 10-year-old son was in the semifinals of the Little League district championship. And we were losing. My son is an excellent pitcher, and he had started the game. But that night, he was struggling. He just couldn’t find where to throw the ball. Needless to say, he was frustrated.

He was changed to shortstop in the second inning, and the home plate umpire walked over to him. This umpire is well known in the area for his kindness and commitment, how he encourages the kids and helps make baseball fun even when it’s stressful.

We didn’t know him well, but he was really supportive of my kid in that moment, talking to him about how baseball is a team sport and we’re here to have fun. Just being really positive.

As the game continued, I saw the umpire suddenly walk to the side of the field. I hadn’t seen it, but he had been hit by a wild pitch on the side of his neck. He was wearing protective gear, but the ball managed to bounce up the side and caught bare neck. I knew something wasn’t right.

I went down to talk to him, and my medical assistant (MA), who was also at the game, came with me. I could tell the umpire was injured, but he didn’t want to leave the game. I suggested going to the hospital, but he wouldn’t consider it. So I sat there with my arms crossed, watching him.

His symptoms got worse. I could see he was in pain, and it was getting harder for him to speak. My concern was that there was a tracheal injury, a carotid injury, or something of that nature that was expanding.

Again, I strongly urged him to go to the hospital, but again, he said no.

In the sixth inning, things got bad enough that the umpire finally agreed to leave the game. As I was figuring out how to get him to the hospital, he disappeared on me. He had walked up to the second floor of the snack shack. My MA and I got him back downstairs and sat him on a bench behind home plate.

We were in the process of calling 911 ... when he arrested.

Luckily, when he lost vital signs, my MA and I were standing right next to him. We were able to activate ACLS protocol and start CPR within seconds.

Many times in these critical situations — especially if people are scared or have never seen an emergency like this — there’s the potential for chaos. Well, that was the polar opposite of what happened.

As soon as I started to run the code, there was this sense of order. People were keeping their composure and following directions. My MA and I would say, “this is what we need,” and the task would immediately be assigned to someone. It was quiet. There was no yelling. Everyone trusted me, even though some of them had never met me before. It was so surprising. I remember thinking, we’re running an arrest, but it’s so calm.

We were an organized team, and it really worked like clockwork, which was remarkable given where we were. It’s one thing to be in the hospital for an event like that. But to be on a baseball field where you have nothing is a completely different scenario.

Meanwhile, the game went on.

I had requested that all the kids be placed in the dugout when they weren’t on the field. So they saw the umpire walk off, but none of them saw him arrest. Some parents were really helpful with making sure the kids were okay.

The president of Oxford Little League ran across the street to a fire station to get an AED. But the fire department personnel were out on a call. He had to break down the door.

By the time he got back, the umpire’s vital signs were returning. And then EMS arrived.

They loaded him in the ambulance, and I called ahead to the trauma team, so they knew exactly what was happening.

I was pretty worried. My hypothesis was that there was probably compression on the vasculature, which had caused him to lose his vital signs. I thought he probably had an impending airway loss. I wasn’t sure if he was going to make it through the night.

What I didn’t know was that while I was giving CPR, my son stole home, and we won the game. As the ambulance was leaving, the celebration was going on in the outfield.

The umpire was in the hospital for several days. Early on, I got permission from his family to visit him. The first time I saw him, I felt this incredible gratitude and peace.

My dad was an ER doctor, and growing up, it seemed like every time we went on a family vacation, there was an emergency. We would be near a car accident or something, and my father would fly in and save the day. I remember being on the Autobahn somewhere in Europe, and there was a devastating accident between a car and a motorcycle. My father stabilized the guy, had him airlifted out, and apparently, he did fine. I grew up watching things like this and thinking, wow, that’s incredible.

Fast forward to 2 years ago, my father was diagnosed with a lung cancer he never should have had. He never smoked. As a cancer surgeon, I know we did everything in our power to save him. But it didn’t happen. He passed away.

I realize this is superstitious, but seeing the umpire alive, I had this feeling that somehow my dad was there. It was bittersweet but also a joyful moment — like I could breathe again.

I met the umpire’s family that first time, and it was like meeting family that you didn’t know you had but now you have forever. Even though the event was traumatic — I’m still trying not to be on high alert every time I go to a game — it felt like a gift to be part of this journey with them.

Little League’s mission is to teach kids about teamwork, leadership, and making good choices so communities are stronger. Our umpire is a guy who does that every day. He’s not a Little League umpire because he makes any money. He shows up at every single game to support these kids and engage them, to model respect, gratitude, and kindness.

I think our obligation as people is to live with intentionality. We all need to make sure we leave the world a better place, even when we are called upon to do uncomfortable things. Our umpire showed our kids what that looks like, and in that moment when he could have died, we were able to do the same for him.

Jennifer LaFemina, MD, is a surgical oncologist at UMass Memorial Medical Center in Massachusetts.
 

Are you a medical professional with a dramatic story outside the clinic? Medscape Medical News would love to consider your story for Is There a Doctor in the House? Please email your contact information and a short summary to [email protected].

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with dry eye disease are more than three times as likely to have mental health conditions, such as depression and anxiety, as those without the condition.

METHODOLOGY:

• Researchers used a database from the National Institutes of Health to investigate the association between dry eye disease and mental health disorders in a large and diverse nationwide population of American adults.
• They identified 18,257 patients (mean age, 64.9 years; 67% women) with dry eye disease who were propensity score–matched with 54,765 participants without the condition.
• The cases of dry eye disease were identified using Systematized Nomenclature of Medicine codes for dry eyes, meibomian gland dysfunction, and tear film insufficiency.
• The outcome measures for mental health conditions were clinical diagnoses of depressive disorders, anxiety-related disorders, bipolar disorder, and schizophrenia spectrum disorders.

TAKEAWAY:

• Patients with dry eye disease had more than triple the risk for mental health conditions than participants without the condition (adjusted odds ratio [aOR], 3.21; P < .001).
• Patients with dry eye disease had a higher risk for a depressive disorder (aOR, 3.47), anxiety-related disorder (aOR, 2.74), bipolar disorder (aOR, 2.23), and schizophrenia spectrum disorder (aOR, 2.48; P < .001 for all) than participants without the condition.
• The associations between dry eye disease and mental health conditions were significantly stronger among Black individuals than among White individuals, except for bipolar disorder.
• Dry eye disease was associated with two- to threefold higher odds of depressive disorders, anxiety-related disorders, bipolar disorder, and schizophrenia spectrum disorders even in participants who never used medications for mental health (P < .001 for all).

IN PRACTICE:

“Greater efforts should be undertaken to screen patients with DED [dry eye disease] for mental health conditions, particularly in historically medically underserved populations,” the authors of the study wrote.

SOURCE:

This study was led by Aaron T. Zhao, of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and was published online on October 15, 2024, in the American Journal of Ophthalmology.

LIMITATIONS:

This study relied on electronic health record data, which may have led to the inclusion of participants with undiagnosed dry eye disease as control participants. Moreover, the study did not evaluate the severity of dry eye disease or the severity and duration of mental health conditions, which may have affected the results. The database analyzed in this study may not have fully captured the complete demographic profile of the nationwide population, which may have affected the generalizability of the findings.

DISCLOSURES:

This study was supported by funding from the National Institutes of Health and Research to Prevent Blindness. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with dry eye disease are more than three times as likely to have mental health conditions, such as depression and anxiety, as those without the condition.

METHODOLOGY:

• Researchers used a database from the National Institutes of Health to investigate the association between dry eye disease and mental health disorders in a large and diverse nationwide population of American adults.
• They identified 18,257 patients (mean age, 64.9 years; 67% women) with dry eye disease who were propensity score–matched with 54,765 participants without the condition.
• The cases of dry eye disease were identified using Systematized Nomenclature of Medicine codes for dry eyes, meibomian gland dysfunction, and tear film insufficiency.
• The outcome measures for mental health conditions were clinical diagnoses of depressive disorders, anxiety-related disorders, bipolar disorder, and schizophrenia spectrum disorders.

TAKEAWAY:

• Patients with dry eye disease had more than triple the risk for mental health conditions than participants without the condition (adjusted odds ratio [aOR], 3.21; P < .001).
• Patients with dry eye disease had a higher risk for a depressive disorder (aOR, 3.47), anxiety-related disorder (aOR, 2.74), bipolar disorder (aOR, 2.23), and schizophrenia spectrum disorder (aOR, 2.48; P < .001 for all) than participants without the condition.
• The associations between dry eye disease and mental health conditions were significantly stronger among Black individuals than among White individuals, except for bipolar disorder.
• Dry eye disease was associated with two- to threefold higher odds of depressive disorders, anxiety-related disorders, bipolar disorder, and schizophrenia spectrum disorders even in participants who never used medications for mental health (P < .001 for all).

IN PRACTICE:

“Greater efforts should be undertaken to screen patients with DED [dry eye disease] for mental health conditions, particularly in historically medically underserved populations,” the authors of the study wrote.

SOURCE:

This study was led by Aaron T. Zhao, of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and was published online on October 15, 2024, in the American Journal of Ophthalmology.

LIMITATIONS:

This study relied on electronic health record data, which may have led to the inclusion of participants with undiagnosed dry eye disease as control participants. Moreover, the study did not evaluate the severity of dry eye disease or the severity and duration of mental health conditions, which may have affected the results. The database analyzed in this study may not have fully captured the complete demographic profile of the nationwide population, which may have affected the generalizability of the findings.

DISCLOSURES:

This study was supported by funding from the National Institutes of Health and Research to Prevent Blindness. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with dry eye disease are more than three times as likely to have mental health conditions, such as depression and anxiety, as those without the condition.

METHODOLOGY:

• Researchers used a database from the National Institutes of Health to investigate the association between dry eye disease and mental health disorders in a large and diverse nationwide population of American adults.
• They identified 18,257 patients (mean age, 64.9 years; 67% women) with dry eye disease who were propensity score–matched with 54,765 participants without the condition.
• The cases of dry eye disease were identified using Systematized Nomenclature of Medicine codes for dry eyes, meibomian gland dysfunction, and tear film insufficiency.
• The outcome measures for mental health conditions were clinical diagnoses of depressive disorders, anxiety-related disorders, bipolar disorder, and schizophrenia spectrum disorders.

TAKEAWAY:

• Patients with dry eye disease had more than triple the risk for mental health conditions than participants without the condition (adjusted odds ratio [aOR], 3.21; P < .001).
• Patients with dry eye disease had a higher risk for a depressive disorder (aOR, 3.47), anxiety-related disorder (aOR, 2.74), bipolar disorder (aOR, 2.23), and schizophrenia spectrum disorder (aOR, 2.48; P < .001 for all) than participants without the condition.
• The associations between dry eye disease and mental health conditions were significantly stronger among Black individuals than among White individuals, except for bipolar disorder.
• Dry eye disease was associated with two- to threefold higher odds of depressive disorders, anxiety-related disorders, bipolar disorder, and schizophrenia spectrum disorders even in participants who never used medications for mental health (P < .001 for all).

IN PRACTICE:

“Greater efforts should be undertaken to screen patients with DED [dry eye disease] for mental health conditions, particularly in historically medically underserved populations,” the authors of the study wrote.

SOURCE:

This study was led by Aaron T. Zhao, of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and was published online on October 15, 2024, in the American Journal of Ophthalmology.

LIMITATIONS:

This study relied on electronic health record data, which may have led to the inclusion of participants with undiagnosed dry eye disease as control participants. Moreover, the study did not evaluate the severity of dry eye disease or the severity and duration of mental health conditions, which may have affected the results. The database analyzed in this study may not have fully captured the complete demographic profile of the nationwide population, which may have affected the generalizability of the findings.

DISCLOSURES:

This study was supported by funding from the National Institutes of Health and Research to Prevent Blindness. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

What do we do if we don’t like patients? We take the Hippocratic Oath as young students in Glasgow. We do that just before our graduation ceremony; we hold our hands up and repeat the Hippocratic Oath: “First, do no harm,” and so on.

What happens if we intensely dislike a patient? Is it possible to offer them the very best care? I was thinking back over a long career. I’ve been a cancer doctor for 40 years and I quite like saying that.

I can only think genuinely over a couple of times in which I’ve acted reflexively when a patient has done something awful. The couple of times it happened, it was just terrible racist comments to junior doctors who were with me. Extraordinarily dreadful things such as, “I don’t want to be touched by ...” or something of that sort.

Without really thinking about it, you react as a normal citizen and say, “That’s absolutely awful. Apologize immediately or leave the consultation room, and never ever come back again.” 

I remember that it happened once in Glasgow and once when I was a young professor in Birmingham, and it’s just an automatic gut reaction. The patient got a fright, and I immediately apologized and groveled around. In that relationship, we hold all the power, don’t we? Rather than being gentle about it, I was genuinely angry because of these ridiculous comments. 

Otherwise, I think most of the doctor-patient relationships are predicated on nonromantic love. I think patients want us to love them as one would a son, mother, father, or daughter, because if we do, then we will do better for them and we’ll pull out all the stops. “Placebo” means “I will please.” I think in the vast majority of cases, at least in our National Health Service (NHS), patients come with trust and a sense of wanting to build that relationship. That may be changing, but not for me. 

What about putting the boot on the other foot? What if the patients don’t like us rather than vice versa? As part of our accreditation appraisal process, from time to time we have to take patient surveys as to whether the patients felt that, after they had been seen in a consultation, they were treated with dignity, the quality of information given was appropriate, and they were treated with kindness. 

It’s an excellent exercise. Without bragging about it, patients objectively, according to these measures, appreciate the service that I give. It’s like getting five-star reviews on Trustpilot, or whatever these things are, that allow you to review car salesmen and so on. I have always had five-star reviews across the board. 

That, again, I thought was just a feature of that relationship, of patients wanting to please. These are patients who had been treated, who were in the outpatient department, who were in the midst of battle. Still, the scores are very high. I speak to my colleagues and that’s not uniformly the case. Patients actually do use these feedback forms, I think in a positive rather than negative way, reflecting back on the way that they were treated.

It has caused some of my colleagues to think quite hard about their personal style and approach to patients. That sense of feedback is important. 

What about losing trust? If that’s at the heart of everything that we do, then what would be an objective measure of losing trust? Again, in our healthcare system, it has been exceedingly unusual for a patient to request a second opinion. Now, that’s changing. The government is trying to change it. Leaders of the NHS are trying to change it so that patients feel assured that they can seek second opinions.

Again, in all the years I’ve been a cancer doctor, it has been incredibly infrequent that somebody has sought a second opinion after I’ve said something. That may be a measure of trust. Again, I’ve lived through an NHS in which seeking second opinions was something of a rarity. 

I’d be really interested to see what you think. In your own sphere of healthcare practice, is it possible for us to look after patients that we don’t like, or should we be honest and say, “I don’t like you. Our relationship has broken down. I want you to be seen by a colleague,” or “I want you to be nursed by somebody else”?

Has that happened? Is that something that you think is common or may become more common? What about when trust breaks down the other way? Can you think of instances in which the relationship, for whatever reason, just didn’t work and the patient had to move on because of that loss of trust and what underpinned it? I’d be really interested to know. 

I seek to be informed rather than the other way around. Can we truly look after patients that we don’t like or can we rise above it as Hippocrates might have done? 

Thanks for listening, as always. For the time being, over and out.

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, and Roche.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

What do we do if we don’t like patients? We take the Hippocratic Oath as young students in Glasgow. We do that just before our graduation ceremony; we hold our hands up and repeat the Hippocratic Oath: “First, do no harm,” and so on.

What happens if we intensely dislike a patient? Is it possible to offer them the very best care? I was thinking back over a long career. I’ve been a cancer doctor for 40 years and I quite like saying that.

I can only think genuinely over a couple of times in which I’ve acted reflexively when a patient has done something awful. The couple of times it happened, it was just terrible racist comments to junior doctors who were with me. Extraordinarily dreadful things such as, “I don’t want to be touched by ...” or something of that sort.

Without really thinking about it, you react as a normal citizen and say, “That’s absolutely awful. Apologize immediately or leave the consultation room, and never ever come back again.” 

I remember that it happened once in Glasgow and once when I was a young professor in Birmingham, and it’s just an automatic gut reaction. The patient got a fright, and I immediately apologized and groveled around. In that relationship, we hold all the power, don’t we? Rather than being gentle about it, I was genuinely angry because of these ridiculous comments. 

Otherwise, I think most of the doctor-patient relationships are predicated on nonromantic love. I think patients want us to love them as one would a son, mother, father, or daughter, because if we do, then we will do better for them and we’ll pull out all the stops. “Placebo” means “I will please.” I think in the vast majority of cases, at least in our National Health Service (NHS), patients come with trust and a sense of wanting to build that relationship. That may be changing, but not for me. 

What about putting the boot on the other foot? What if the patients don’t like us rather than vice versa? As part of our accreditation appraisal process, from time to time we have to take patient surveys as to whether the patients felt that, after they had been seen in a consultation, they were treated with dignity, the quality of information given was appropriate, and they were treated with kindness. 

It’s an excellent exercise. Without bragging about it, patients objectively, according to these measures, appreciate the service that I give. It’s like getting five-star reviews on Trustpilot, or whatever these things are, that allow you to review car salesmen and so on. I have always had five-star reviews across the board. 

That, again, I thought was just a feature of that relationship, of patients wanting to please. These are patients who had been treated, who were in the outpatient department, who were in the midst of battle. Still, the scores are very high. I speak to my colleagues and that’s not uniformly the case. Patients actually do use these feedback forms, I think in a positive rather than negative way, reflecting back on the way that they were treated.

It has caused some of my colleagues to think quite hard about their personal style and approach to patients. That sense of feedback is important. 

What about losing trust? If that’s at the heart of everything that we do, then what would be an objective measure of losing trust? Again, in our healthcare system, it has been exceedingly unusual for a patient to request a second opinion. Now, that’s changing. The government is trying to change it. Leaders of the NHS are trying to change it so that patients feel assured that they can seek second opinions.

Again, in all the years I’ve been a cancer doctor, it has been incredibly infrequent that somebody has sought a second opinion after I’ve said something. That may be a measure of trust. Again, I’ve lived through an NHS in which seeking second opinions was something of a rarity. 

I’d be really interested to see what you think. In your own sphere of healthcare practice, is it possible for us to look after patients that we don’t like, or should we be honest and say, “I don’t like you. Our relationship has broken down. I want you to be seen by a colleague,” or “I want you to be nursed by somebody else”?

Has that happened? Is that something that you think is common or may become more common? What about when trust breaks down the other way? Can you think of instances in which the relationship, for whatever reason, just didn’t work and the patient had to move on because of that loss of trust and what underpinned it? I’d be really interested to know. 

I seek to be informed rather than the other way around. Can we truly look after patients that we don’t like or can we rise above it as Hippocrates might have done? 

Thanks for listening, as always. For the time being, over and out.

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, and Roche.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

What do we do if we don’t like patients? We take the Hippocratic Oath as young students in Glasgow. We do that just before our graduation ceremony; we hold our hands up and repeat the Hippocratic Oath: “First, do no harm,” and so on.

What happens if we intensely dislike a patient? Is it possible to offer them the very best care? I was thinking back over a long career. I’ve been a cancer doctor for 40 years and I quite like saying that.

I can only think genuinely over a couple of times in which I’ve acted reflexively when a patient has done something awful. The couple of times it happened, it was just terrible racist comments to junior doctors who were with me. Extraordinarily dreadful things such as, “I don’t want to be touched by ...” or something of that sort.

Without really thinking about it, you react as a normal citizen and say, “That’s absolutely awful. Apologize immediately or leave the consultation room, and never ever come back again.” 

I remember that it happened once in Glasgow and once when I was a young professor in Birmingham, and it’s just an automatic gut reaction. The patient got a fright, and I immediately apologized and groveled around. In that relationship, we hold all the power, don’t we? Rather than being gentle about it, I was genuinely angry because of these ridiculous comments. 

Otherwise, I think most of the doctor-patient relationships are predicated on nonromantic love. I think patients want us to love them as one would a son, mother, father, or daughter, because if we do, then we will do better for them and we’ll pull out all the stops. “Placebo” means “I will please.” I think in the vast majority of cases, at least in our National Health Service (NHS), patients come with trust and a sense of wanting to build that relationship. That may be changing, but not for me. 

What about putting the boot on the other foot? What if the patients don’t like us rather than vice versa? As part of our accreditation appraisal process, from time to time we have to take patient surveys as to whether the patients felt that, after they had been seen in a consultation, they were treated with dignity, the quality of information given was appropriate, and they were treated with kindness. 

It’s an excellent exercise. Without bragging about it, patients objectively, according to these measures, appreciate the service that I give. It’s like getting five-star reviews on Trustpilot, or whatever these things are, that allow you to review car salesmen and so on. I have always had five-star reviews across the board. 

That, again, I thought was just a feature of that relationship, of patients wanting to please. These are patients who had been treated, who were in the outpatient department, who were in the midst of battle. Still, the scores are very high. I speak to my colleagues and that’s not uniformly the case. Patients actually do use these feedback forms, I think in a positive rather than negative way, reflecting back on the way that they were treated.

It has caused some of my colleagues to think quite hard about their personal style and approach to patients. That sense of feedback is important. 

What about losing trust? If that’s at the heart of everything that we do, then what would be an objective measure of losing trust? Again, in our healthcare system, it has been exceedingly unusual for a patient to request a second opinion. Now, that’s changing. The government is trying to change it. Leaders of the NHS are trying to change it so that patients feel assured that they can seek second opinions.

Again, in all the years I’ve been a cancer doctor, it has been incredibly infrequent that somebody has sought a second opinion after I’ve said something. That may be a measure of trust. Again, I’ve lived through an NHS in which seeking second opinions was something of a rarity. 

I’d be really interested to see what you think. In your own sphere of healthcare practice, is it possible for us to look after patients that we don’t like, or should we be honest and say, “I don’t like you. Our relationship has broken down. I want you to be seen by a colleague,” or “I want you to be nursed by somebody else”?

Has that happened? Is that something that you think is common or may become more common? What about when trust breaks down the other way? Can you think of instances in which the relationship, for whatever reason, just didn’t work and the patient had to move on because of that loss of trust and what underpinned it? I’d be really interested to know. 

I seek to be informed rather than the other way around. Can we truly look after patients that we don’t like or can we rise above it as Hippocrates might have done? 

Thanks for listening, as always. For the time being, over and out.

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, and Roche.

A version of this article appeared on Medscape.com.

A new study provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) used to treat diabetes and obesity could be repurposed for opioid use disorder (OUD) and alcohol use disorder (AUD).

Researchers found that patients with OUD or AUD who were taking semaglutide (Ozempic, Novo Nordisk) or similar medications for diabetes or weight-related conditions had a 40% lower rate of opioid overdose and a 50% lower rate of alcohol intoxication than their peers with OUD or AUD who were not taking these medications.

Their real-world study of more than 1 million adults with a history of OUD or AUD provide “foundational” estimates of the association between glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA prescriptions and opioid overdose/alcohol intoxication “and introduce the idea that GLP-1 RA and other related drugs should be investigated as a novel pharmacotherapy treatment option for individuals with OUD or AUD,” wrote the investigators, led by Fares Qeadan, PhD, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, Illinois.

The study was published online in the journal Addiction.
 

Protective Effect?

As previously reported by Medscape Medical News, earlier studies have pointed to a link between weight loss drugs and reduced overdose risk in people with OUD and decreased alcohol intake in people with AUD.

Until now, most studies on GLP-1 RAs and GIP agonists like tirzepatide (Mounjaro) to treat substance use disorders consisted of animal studies and small-scale clinical trials, investigators noted.

This new retrospective cohort study analyzed de-identified electronic health record data from the Oracle Health Real-World Data.

Participants, all aged 18 years or older, included 503,747 patients with a history of OUD, of whom 8103 had a GLP-1 RA or GIP prescription, and 817,309 patients with a history of AUD, of whom 5621 had a GLP-1 RA or GIP prescription.

Patients with OUD who were prescribed GLP-1 RAs had a 40% lower rate of opioid overdose than those without such prescriptions (adjusted incidence rate ratio [aIRR], 0.60; 95% CI, 0.43-0.83), the study team found.

In addition, patients with AUD and a GLP-1 RA prescription exhibited a 50% lower rate of alcohol intoxication (aIRR, 0.50; 95% CI, 0.40-0.63).

The protective effect of GLP-1 RA on opioid overdose and alcohol intoxication was maintained across patients with comorbid conditions, such as type 2 diabetes and obesity.

“Future research should focus on prospective clinical trials to validate these findings, explore the underlying mechanisms, and determine the long-term efficacy and safety of GIP/GLP-1 RA medications in diverse populations,” Qeadan and colleagues concluded.

“Additionally, the study highlights the importance of interdisciplinary research in understanding the neurobiological links between metabolic disorders and problematic substance use, potentially leading to more effective treatment strategies within healthcare systems,” they added.
 

Questions Remain

In a statement from the UK nonprofit Science Media Centre, Matt Field, DPhil, professor of psychology, The University of Sheffield, in England, noted that the findings “add to those from other studies, particularly animal research, which suggest that this and similar drugs might one day be prescribed to help people with addiction.”

However, “a note of caution is that the outcomes are very extreme instances of substance intoxication,” added Field, who wasn’t involved in the study.

“Those outcomes are very different from the outcomes used when researchers test new treatments for addiction, in which case we might look at whether the treatment helps people to stop taking the substance altogether (complete abstinence), or if it helps people to reduce the amount of substance they consume, or how often they consume it. Those things could not be measured in this study,” he continued.

“This leaves open the possibility that while Ozempic may — for reasons currently unknown — prevent people from taking so much alcohol or heroin that they overdose and end up in hospital, it may not actually help them to reduce their substance use, or to abstain altogether,” Field said.

The study had no specific funding. The study authors and Field declared no relevant conflicts of interest.
 

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

A new study provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) used to treat diabetes and obesity could be repurposed for opioid use disorder (OUD) and alcohol use disorder (AUD).

Researchers found that patients with OUD or AUD who were taking semaglutide (Ozempic, Novo Nordisk) or similar medications for diabetes or weight-related conditions had a 40% lower rate of opioid overdose and a 50% lower rate of alcohol intoxication than their peers with OUD or AUD who were not taking these medications.

Their real-world study of more than 1 million adults with a history of OUD or AUD provide “foundational” estimates of the association between glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA prescriptions and opioid overdose/alcohol intoxication “and introduce the idea that GLP-1 RA and other related drugs should be investigated as a novel pharmacotherapy treatment option for individuals with OUD or AUD,” wrote the investigators, led by Fares Qeadan, PhD, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, Illinois.

The study was published online in the journal Addiction.
 

Protective Effect?

As previously reported by Medscape Medical News, earlier studies have pointed to a link between weight loss drugs and reduced overdose risk in people with OUD and decreased alcohol intake in people with AUD.

Until now, most studies on GLP-1 RAs and GIP agonists like tirzepatide (Mounjaro) to treat substance use disorders consisted of animal studies and small-scale clinical trials, investigators noted.

This new retrospective cohort study analyzed de-identified electronic health record data from the Oracle Health Real-World Data.

Participants, all aged 18 years or older, included 503,747 patients with a history of OUD, of whom 8103 had a GLP-1 RA or GIP prescription, and 817,309 patients with a history of AUD, of whom 5621 had a GLP-1 RA or GIP prescription.

Patients with OUD who were prescribed GLP-1 RAs had a 40% lower rate of opioid overdose than those without such prescriptions (adjusted incidence rate ratio [aIRR], 0.60; 95% CI, 0.43-0.83), the study team found.

In addition, patients with AUD and a GLP-1 RA prescription exhibited a 50% lower rate of alcohol intoxication (aIRR, 0.50; 95% CI, 0.40-0.63).

The protective effect of GLP-1 RA on opioid overdose and alcohol intoxication was maintained across patients with comorbid conditions, such as type 2 diabetes and obesity.

“Future research should focus on prospective clinical trials to validate these findings, explore the underlying mechanisms, and determine the long-term efficacy and safety of GIP/GLP-1 RA medications in diverse populations,” Qeadan and colleagues concluded.

“Additionally, the study highlights the importance of interdisciplinary research in understanding the neurobiological links between metabolic disorders and problematic substance use, potentially leading to more effective treatment strategies within healthcare systems,” they added.
 

Questions Remain

In a statement from the UK nonprofit Science Media Centre, Matt Field, DPhil, professor of psychology, The University of Sheffield, in England, noted that the findings “add to those from other studies, particularly animal research, which suggest that this and similar drugs might one day be prescribed to help people with addiction.”

However, “a note of caution is that the outcomes are very extreme instances of substance intoxication,” added Field, who wasn’t involved in the study.

“Those outcomes are very different from the outcomes used when researchers test new treatments for addiction, in which case we might look at whether the treatment helps people to stop taking the substance altogether (complete abstinence), or if it helps people to reduce the amount of substance they consume, or how often they consume it. Those things could not be measured in this study,” he continued.

“This leaves open the possibility that while Ozempic may — for reasons currently unknown — prevent people from taking so much alcohol or heroin that they overdose and end up in hospital, it may not actually help them to reduce their substance use, or to abstain altogether,” Field said.

The study had no specific funding. The study authors and Field declared no relevant conflicts of interest.
 

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

A new study provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) used to treat diabetes and obesity could be repurposed for opioid use disorder (OUD) and alcohol use disorder (AUD).

Researchers found that patients with OUD or AUD who were taking semaglutide (Ozempic, Novo Nordisk) or similar medications for diabetes or weight-related conditions had a 40% lower rate of opioid overdose and a 50% lower rate of alcohol intoxication than their peers with OUD or AUD who were not taking these medications.

Their real-world study of more than 1 million adults with a history of OUD or AUD provide “foundational” estimates of the association between glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA prescriptions and opioid overdose/alcohol intoxication “and introduce the idea that GLP-1 RA and other related drugs should be investigated as a novel pharmacotherapy treatment option for individuals with OUD or AUD,” wrote the investigators, led by Fares Qeadan, PhD, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, Illinois.

The study was published online in the journal Addiction.
 

Protective Effect?

As previously reported by Medscape Medical News, earlier studies have pointed to a link between weight loss drugs and reduced overdose risk in people with OUD and decreased alcohol intake in people with AUD.

Until now, most studies on GLP-1 RAs and GIP agonists like tirzepatide (Mounjaro) to treat substance use disorders consisted of animal studies and small-scale clinical trials, investigators noted.

This new retrospective cohort study analyzed de-identified electronic health record data from the Oracle Health Real-World Data.

Participants, all aged 18 years or older, included 503,747 patients with a history of OUD, of whom 8103 had a GLP-1 RA or GIP prescription, and 817,309 patients with a history of AUD, of whom 5621 had a GLP-1 RA or GIP prescription.

Patients with OUD who were prescribed GLP-1 RAs had a 40% lower rate of opioid overdose than those without such prescriptions (adjusted incidence rate ratio [aIRR], 0.60; 95% CI, 0.43-0.83), the study team found.

In addition, patients with AUD and a GLP-1 RA prescription exhibited a 50% lower rate of alcohol intoxication (aIRR, 0.50; 95% CI, 0.40-0.63).

The protective effect of GLP-1 RA on opioid overdose and alcohol intoxication was maintained across patients with comorbid conditions, such as type 2 diabetes and obesity.

“Future research should focus on prospective clinical trials to validate these findings, explore the underlying mechanisms, and determine the long-term efficacy and safety of GIP/GLP-1 RA medications in diverse populations,” Qeadan and colleagues concluded.

“Additionally, the study highlights the importance of interdisciplinary research in understanding the neurobiological links between metabolic disorders and problematic substance use, potentially leading to more effective treatment strategies within healthcare systems,” they added.
 

Questions Remain

In a statement from the UK nonprofit Science Media Centre, Matt Field, DPhil, professor of psychology, The University of Sheffield, in England, noted that the findings “add to those from other studies, particularly animal research, which suggest that this and similar drugs might one day be prescribed to help people with addiction.”

However, “a note of caution is that the outcomes are very extreme instances of substance intoxication,” added Field, who wasn’t involved in the study.

“Those outcomes are very different from the outcomes used when researchers test new treatments for addiction, in which case we might look at whether the treatment helps people to stop taking the substance altogether (complete abstinence), or if it helps people to reduce the amount of substance they consume, or how often they consume it. Those things could not be measured in this study,” he continued.

“This leaves open the possibility that while Ozempic may — for reasons currently unknown — prevent people from taking so much alcohol or heroin that they overdose and end up in hospital, it may not actually help them to reduce their substance use, or to abstain altogether,” Field said.

The study had no specific funding. The study authors and Field declared no relevant conflicts of interest.
 

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

Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.

Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.

The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.

“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”

Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.

Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
 

Etiology

Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.

Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
 

Risk Factors

These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.

A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.

Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
 

Diagnosis

Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.

Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.

Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.

“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”

PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.

In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
 

Treatments

In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.

Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.

Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.

“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.

Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.

If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.

Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.

Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.

Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.

Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.

Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.

Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.

Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.

A small study suggested that supplemental zinc may improve both physical and psychological symptoms.

Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.

Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.

The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”

Ireland and Haque had no competing interests with regard to their comments.
 

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

Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.

Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.

The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.

“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”

Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.

Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
 

Etiology

Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.

Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
 

Risk Factors

These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.

A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.

Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
 

Diagnosis

Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.

Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.

Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.

“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”

PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.

In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
 

Treatments

In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.

Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.

Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.

“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.

Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.

If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.

Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.

Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.

Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.

Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.

Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.

Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.

Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.

A small study suggested that supplemental zinc may improve both physical and psychological symptoms.

Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.

Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.

The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”

Ireland and Haque had no competing interests with regard to their comments.
 

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

Premenstrual disorders (PMDs), including premenstrual dysphoric disorder (PMDD), adversely affect the lives of millions of women worldwide. Most girls and women — as many as 80%-90%— will experience some premenstrual discomfort such as irritability, depressed mood, food or alcohol cravings, bloating, body aches, breast pain, constipation, or fatigue.

Diagnosable menstrual disorders include, collectively, premenstrual syndrome (PMS); PMDD, formerly called late luteal phase dysphoric disorder; and premenstrual worsening of another medical condition.

The most debilitating of these is PMDD, which has an estimated prevalence of about 4%-8% in women of reproductive age, according to obstetrician/gynecologist Hoosna Haque, MD, assistant professor of medicine at Columbia University Irving Medical Center in New York City.

“It’s difficult to be sure because this condition is underreported,” said Luu D. Ireland, MD, MPH, assistant professor of obstetrics and gynecology at UMass Memorial Medical Center in Worcester, Massachusetts. “But more women are coming forward, and there’s more discussion and media coverage of this condition.”

Occurring in the same post-follicular timeframe as PMS, PMDD takes cyclical discomfort to a more intense level, with a trifecta of affective comorbidities, somatic manifestations, and behavioral changes, all of which can seriously impair daily functioning, including work, physical activities, and personal relationships. Romantic and marital relationships can be particularly impaired.

Although recent cost figures are lacking, PMDs exact a considerable economic toll with increased direct healthcare costs from doctor visits and pharmaceuticals. A 2010 study found that US women with PMS were more likely to accrue in excess of $500 in healthcare visit costs over 2 years, and the figure would likely be higher today. PMDs also increase work/school absenteeism and reduce productivity.
 

Etiology

Brain areas that regulate emotion and behavior contain receptors for estrogen, progesterone, and other sex hormones, which affect the functioning of neurotransmitter systems influencing mood and thinking. Although the precise pathophysiology remains unclear, PMDD is likely multifactorial and results in a heightened sensitivity to normal fluctuations in estrogen and progesterone during the luteal phase of the menstrual cycle and dysfunction of the serotonin and gamma-aminobutyric acid neurotransmitter systems.

Patients with PMDD have lower levels of cortisol and beta-endorphins during both the follicular and luteal phases, suggesting abnormalities in the hypothalamic-pituitary-gonadal axis (HPGA), which is consistent with dysregulation in mood disorders.
 

Risk Factors

These include family history, past traumatic events, smoking, chronic pain syndrome, and obesity. There may be a genetic component as recent studies have suggested the involvement of the gene that codes for the serotonergic 5HT1A receptor and allelic variants of ESR1 in the development of PMS/PMDD.

A particularly concerning aspect of PMDs of any sort is their possible association with a higher risk for death from non-natural causes. In a recent Swedish study, which did not distinguish between PMDs in general and PMDD in particular, patients had an almost 60% greater risk for death from non-natural causes and nearly twice the risk for death by suicide compared with women without PMDs.

Those diagnosed with a PMD at an early age showed excess mortality, and the risk for suicide was elevated regardless of age. “These findings support the need for careful follow-up for young women with PMDs and the need for suicide prevention strategies,” wrote lead author Marion Opatowski, PhD, a medical epidemiologist at Karolinska Institutet in Stockholm, Sweden. “Women with severe PMDD should definitely be monitored for suicidal thoughts or behavior and they should have an emergency outreach plan in place,” Haque added.
 

Diagnosis

Although the somatic manifestations of PMDD resemble those of PMS, they are more severe and associated psychological symptoms are greater. “In my experience, PMDD symptoms can last the whole 2 weeks of the luteal phase, whereas PMS might occur a couple of days before menstruation,” said Ireland.

Symptoms include labile mood, nervousness, hopelessness, anger and aggressiveness, as well as tension and irritability. Those affected may have suicidal thoughts or even behaviors. In addition to a lethargic loss of interest in normal activities, patients with PMDD may feel paranoid, confused, exhausted, or out of control and experience insomnia or hypersomnia. They may have trouble concentrating or remembering. Some patients with PMDD may already be prone to attention-deficit/hyperactivity disorder and non–cycle-related depression, anxiety, and panic attacks.

Diagnosis is based on the presence of any five of the typical affective, somatic, or behavioral symptoms outlined above in the week before onset of menses.

“It’s important to do a careful diagnosis for PMDD and rule out other underlying conditions such as existing depressive or anxiety disorders,” said Haque. “Symptoms tend to be more intense in periods of high hormonal fluctuation such as in the postpartum and perimenopause periods. Women with PMDD should be monitored for postpartum depression.”

PMDD is considered both a gynecologic-genitourinary disorder and an affective condition.

In 2013, it was controversially included as a depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Strongly advocated by some patients, psychiatrists, and pharmaceutical companies, its inclusion was criticized by psychologists and generalists, who feared it would lead to overdiagnosis and pathologization of normal female hormonal changes. Women’s advocates protested that this inclusion would stigmatize female biology and harm their advance in society and the workplace, while some doctors continued to dismiss PMDD as not a serious concern.
 

Treatments

In its latest clinical practice guideline on PMDs, the American College of Obstetricians and Gynecologists (ACOG), for which Ireland served as the lead author, recommends that most patients with PMDD get medical treatment and outlines the following therapies, based on varying degrees of evidence strength.

Antidepressants. These may benefit patients with strong affective symptoms. Selective serotonin reuptake inhibitors such as sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), or fluoxetine (Prozac) are first choices.

Antidepressants may interrupt aberrant signaling in the HPGA, the circuit linking brain and ovaries and regulating the reproductive cycle. Serotonin norepinephrine reuptake inhibitor venlafaxine (Effexor) may also improve symptoms, but other types of antidepressants have not proven effective.

“The response to these well-tolerated drugs is rapid and can happen in the first 2 days,” said Ireland. The drugs may be taken either just in the luteal period or over the month, especially by patients with chronic depression or anxiety.

Hormonal therapy. ACOG recommends the use of combined oral contraceptives (COCs), gonadotropin-releasing hormone (GnRH) agonists to induce anovulation (with combined add-back hormones), progestin-only methods, and noncontraceptive continuous estrogen formulations. It notes, however, that COCs have not been more effective than placebo in reducing depressive symptom scores.

If symptoms do not improve over two to three cycles, an alternate therapy should be considered. Haque recommends an assessment after three cycles and then yearly.

Some women in her practice take both antidepressant and hormone therapy. “Unfortunately, there are no new pharmaceutical treatments on the horizon, but we have good ones already and we would love for patients to utilize them more often,” Ireland said.

Nonsteroidal anti-inflammatory drugs. Limited evidence shows these may reduce physical symptoms such as abdominal cramps, headaches, and general body aches, as well as some mood-related symptoms, which may be an indirect effect of pain alleviation.

Surgery. For women with the most severe intractable symptoms, bilateral oophorectomy with or without hysterectomy may be a last-resort option when medical management has failed. A trial period of GnRH agonist therapy (with or without adjunctive estrogen add-back treatment) is advised before surgery to predict a patient’s response to surgical management.

Acupuncture. ACOG suggests that acupuncture may help manage physical and affective premenstrual symptoms.

Diet. The usual dietary advice for premenstrual symptoms — such as consuming less caffeine, sugar, or alcohol and eating smaller, more frequent meals — is unlikely to help women with PMDD.

Exercise. Although it has not been well studied for PMDD, aerobic exercises such as walking, swimming, and biking tend to improve mood and energy levels in general. Exercise may reduce symptoms through several pathways, including effects on beta-endorphin, cortisol, and ovarian hormone levels.

Supplements. Vitamin B6, calcium and magnesium supplements, and herbal remedies are not supported by consistent or compelling evidence of efficacy. ACOG conditionally recommends calcium supplementation of 100-200 mg/d in adults to help manage physical and affective symptoms.

A small study suggested that supplemental zinc may improve both physical and psychological symptoms.

Cognitive-behavioral therapy. This treatment aims to interrupt negative and irrational thought patterns and may include awareness and education, as well as relaxation techniques, problem-solving and coping skills, and stress management. It has been associated with small to moderate improvement in anxiety and depression, said Ireland.

Peer support. Patients should consider joining a support group. The International Association for Premenstrual Disorders can help patients connect and develop coping skills.

The bottom line is that people with strong symptomatic evidence of PMDD should have medical intervention — to the benefit of their health and quality of life. Screening for PMDD should be part of women’s wellness examinations, said Ireland. “The impact of PMDD should not be minimized or dismissed,” said Haque. “And patients need to know there are very effective treatments.”

Ireland and Haque had no competing interests with regard to their comments.
 

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

It has been 24 years since a pharmaceutical was last approved for posttraumatic stress disorder (PTSD). The condition is notoriously difficult to treat, with up to 40% patients finding no relief from symptoms through psychotherapy or current medications.

Many clinicians, advocates, and patients had pinned their hopes on the psychedelic drug midomafetamine with assisted therapy (MDMA-AT). However, in August, the US Food and Drug Administration (FDA) rejected it. At this point, it’s unclear when the therapy will be available, if ever.

“Not getting the FDA approval of any drug at this point is a setback for the field,” Lori Davis, MD, a senior research psychiatrist at the Birmingham Veterans Affairs (VA) Health Care System in Birmingham, Alabama, told Medscape Medical News.

Having an FDA-approved product would have helped increase public awareness of PTSD and driven interest in developing new therapies, said Davis, who is also adjunct professor of psychiatry at the Heersink School of Medicine, University of Alabama at Birmingham.
 

A Treatable Condition

So with MDMA-AT off the table, where does the field go next? 

A public meeting in September hosted by the Reagan-Udall Foundation for the FDA in sought to answer that question. Agency officials joined representatives from the Department of Defense (DoD) and VA, patients, advocates, and industry representatives to discuss the current treatment landscape and what can be done to accelerate development of PTSD treatment.

Despite the common belief that PTSD is intractable, it “is a treatable condition,” Paula P. Schnurr, PhD, executive director of the VA National Center for PTSD, said at the meeting.

“There are effective treatments that work well for a lot of people, although not everyone has a satisfactory response,” she added.

The most effective psychotherapies are “trauma-focused,” and include cognitive processing therapy, eye movement desensitization and reprocessing, and prolonged exposure, according to the VA National Center for PTSD.

Three drugs have been approved by the FDA for PTSD: Venlafaxine (Effexor) in 1993, sertraline (Zoloft) in 1999, and paroxetine (Paxil) in 2000.

However, as the September meeting demonstrated, more therapies are needed.

“It’s clear to FDA and the federal government at large that there is an unmet need for safe and effective therapies to treat PTSD,” Bernard Fischer, MD, deputy director of the Division of Psychiatry in the Office of New Drugs at FDA’s Center for Drug Evaluation and Research, said at the meeting.

There is no shortage of research, Fischer added. Nearly 500 trials focused on PTSD are listed on clinicaltrials.gov are recruiting participants now or plan to soon.

Unsurprisingly, one of the primary drivers of PTSD therapeutics research is the VA. About 14% of the 5.7 million veterans who received care through the VA in 2023 had a diagnosis of PTSD.

“The US military is currently losing thousands of service members each year to PTSD- related disability discharges,” US Army Maj. Aaron Wolfgang, MD, a psychiatrist at the Walter Reed National Military Medical Center, said at the meeting. Only about 12%-20% of patients achieve remission with conventional therapies, added Wolfgang, who also is an assistant professor at the Uniformed Services University.

“For these reasons, establishing better treatments for PTSD is not only a matter of humanitarianism but also a pressing matter of national security,” he said.

The VA has committed at least $230 million to more than 140 active research projects in PTSD, Miriam J. Smyth, PhD, acting director of the clinical science, research and development service at the VA, said at the Reagan-Udall meeting.

One of the VA projects is the PTSD psychopharmacology initiative, which began in 2017 and now has 14 active clinical trials, said Smyth, who is also acting director for brain behavior and mental health at the VA. The first study should be finished by 2025.

The Million Veteran Program, with more than 1 million enrollees, has led to the discovery of genes related to re-experiencing traumatic memories and has confirmed that both PTSD and traumatic brain injury are risk factors for dementia, Smyth said.

The DoD has created a novel platform that establishes a common infrastructure for testing multiple drugs, called M-PACT. The platform allows sharing of placebo data across treatment arms. Drugs cycle off the platform if evidence indicates probability of success or failure.

Four trials are actively recruiting veterans and current service members. One is looking at vilazodone, approved in 2011 for major depressive disorder. It is being compared with placebo and fluoxetine in a trial that is currently recruiting.

Another trial will study daridorexant (sold as Quviviq), an orexin receptor antagonist, against placebo. The FDA approved daridorexant in 2022 as an insomnia treatment. A core issue in PTSD is sleep disruption, noted Davis.
 

New Therapies on the Way

Separately, Davis and colleagues are also studying methylphenidate, the stimulant used for attention-deficit/hyperactivity disorder. It may help with neurocognitive complaints and reduce PTSD symptoms, said Davis.

Because it is generic, few pharmaceutical manufacturers are likely to test it for PTSD, she said. But eventually, their work may lead a company to test newer stimulants for PTSD, she said.

Another potential therapeutic, BNC210, received Fast Track designation for PTSD from the FDA in 2019. Bionomics Limited in Australia will soon launch phase 3 trials of the investigational oral drug, which is a negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor. In late July, the company announced “ favorable feedback” from the agency on its phase 2 study, which led to the decision to move forward with larger trials.

Researchers at Brigham and Women’s Hospital have just reported that they may have found a target within the brain that will allow for transcranial magnetic stimulation (TMS) to ameliorate PTSD symptoms. They published results of a mapping effort in Nature Neuroscience and reported on one patient who had improved symptoms after receiving TMS for severe PTSD.

But perhaps one of the most promising treatments is a combination of sertraline and the new psychiatric medication brexpiprazole.

Brexpiprazole was developed by Otsuka Pharmaceutical and approved in the United States in 2015 as an adjunctive therapy to antidepressants for major depressive disorder and as a treatment for schizophrenia. In 2023, the FDA approved it for Alzheimer’s-related agitation. However, according to Otsuka, its mechanism of action is unknown.

Its efficacy may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, antagonist activity at serotonin 5-HT2A receptors, as well as antagonism of alpha-1B/2C receptors, said the company.

“It is the combination, rather than either alone, that’s going to have that broad synergistic pharmacology that is obviously potent for ameliorating the symptoms of PTSD,” said Davis, who has received consulting fees from Otsuka. “That’s an exciting development.”

Otsuka and partner Lundbeck Pharmaceuticals reported results in May from the companies’ phase 2 and 3 randomized clinical trials. The therapy achieved a statistically significant reduction (P <.05) in PTSD symptoms compared with sertraline plus placebo. This was without any supplemental psychotherapy.

The FDA accepted the companies’ new drug application in June and is expected to make a decision on approval in February 2025.
 

The Potential of Psychedelics

Though Lykos Therapeutics may have to go back to the drawing board on its MDMA-AT, psychedelics still have potential as PTSD therapies, Smyth said, who added that the VA is continuing to encourage study of MDMA and other psychedelic agents.

The VA issued a call for proposals for research on psychedelics in January, focused on MDMA or psilocybin in combination with psychotherapy. The administration received the first wave of applications early in the summer.

Scientific peer review panels made up of research experts from within and outside the VA have reviewed the applications and funding announcements are expected this fall, Smyth said.

Wolfgang, the Army psychiatrist, said, “Under the psychedelic treatment research clinical trial award, we welcome investigators to apply to what we anticipate will usher in a new era of innovation and hope for service members and their families who need it the most.”

Psychedelic studies are also proceeding without VA funding, as they have for years, when most of the trials were backed by universities or foundations or other private money. Johns Hopkins University is recruiting for a study in which patients would receive psilocybin along with trauma-focused psychotherapy, as is Ohio State University.

London-based Compass Pathways said in May that it successfully completed a phase 2 trial of Comp360, its synthetic psilocybin, in PTSD. The company has started a phase 3 study in treatment-resistant depression but has not given any further updates on PTSD.

Davis said that she believes that the FDA’s rejection of Lykos won’t lead to a shutdown of exploration of psychedelics.

“I think it informs these designs going forward, but it doesn’t eliminate that whole field of research,” she said.

Davis reported receiving consulting fees from Boehringer Ingelheim and Otsuka and research funding from Alkermes, the Patient-Centered Outcomes Research Institute, and the VA. Schnurr, Fischer, Smyth, and Wolfgang reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

It has been 24 years since a pharmaceutical was last approved for posttraumatic stress disorder (PTSD). The condition is notoriously difficult to treat, with up to 40% patients finding no relief from symptoms through psychotherapy or current medications.

Many clinicians, advocates, and patients had pinned their hopes on the psychedelic drug midomafetamine with assisted therapy (MDMA-AT). However, in August, the US Food and Drug Administration (FDA) rejected it. At this point, it’s unclear when the therapy will be available, if ever.

“Not getting the FDA approval of any drug at this point is a setback for the field,” Lori Davis, MD, a senior research psychiatrist at the Birmingham Veterans Affairs (VA) Health Care System in Birmingham, Alabama, told Medscape Medical News.

Having an FDA-approved product would have helped increase public awareness of PTSD and driven interest in developing new therapies, said Davis, who is also adjunct professor of psychiatry at the Heersink School of Medicine, University of Alabama at Birmingham.
 

A Treatable Condition

So with MDMA-AT off the table, where does the field go next? 

A public meeting in September hosted by the Reagan-Udall Foundation for the FDA in sought to answer that question. Agency officials joined representatives from the Department of Defense (DoD) and VA, patients, advocates, and industry representatives to discuss the current treatment landscape and what can be done to accelerate development of PTSD treatment.

Despite the common belief that PTSD is intractable, it “is a treatable condition,” Paula P. Schnurr, PhD, executive director of the VA National Center for PTSD, said at the meeting.

“There are effective treatments that work well for a lot of people, although not everyone has a satisfactory response,” she added.

The most effective psychotherapies are “trauma-focused,” and include cognitive processing therapy, eye movement desensitization and reprocessing, and prolonged exposure, according to the VA National Center for PTSD.

Three drugs have been approved by the FDA for PTSD: Venlafaxine (Effexor) in 1993, sertraline (Zoloft) in 1999, and paroxetine (Paxil) in 2000.

However, as the September meeting demonstrated, more therapies are needed.

“It’s clear to FDA and the federal government at large that there is an unmet need for safe and effective therapies to treat PTSD,” Bernard Fischer, MD, deputy director of the Division of Psychiatry in the Office of New Drugs at FDA’s Center for Drug Evaluation and Research, said at the meeting.

There is no shortage of research, Fischer added. Nearly 500 trials focused on PTSD are listed on clinicaltrials.gov are recruiting participants now or plan to soon.

Unsurprisingly, one of the primary drivers of PTSD therapeutics research is the VA. About 14% of the 5.7 million veterans who received care through the VA in 2023 had a diagnosis of PTSD.

“The US military is currently losing thousands of service members each year to PTSD- related disability discharges,” US Army Maj. Aaron Wolfgang, MD, a psychiatrist at the Walter Reed National Military Medical Center, said at the meeting. Only about 12%-20% of patients achieve remission with conventional therapies, added Wolfgang, who also is an assistant professor at the Uniformed Services University.

“For these reasons, establishing better treatments for PTSD is not only a matter of humanitarianism but also a pressing matter of national security,” he said.

The VA has committed at least $230 million to more than 140 active research projects in PTSD, Miriam J. Smyth, PhD, acting director of the clinical science, research and development service at the VA, said at the Reagan-Udall meeting.

One of the VA projects is the PTSD psychopharmacology initiative, which began in 2017 and now has 14 active clinical trials, said Smyth, who is also acting director for brain behavior and mental health at the VA. The first study should be finished by 2025.

The Million Veteran Program, with more than 1 million enrollees, has led to the discovery of genes related to re-experiencing traumatic memories and has confirmed that both PTSD and traumatic brain injury are risk factors for dementia, Smyth said.

The DoD has created a novel platform that establishes a common infrastructure for testing multiple drugs, called M-PACT. The platform allows sharing of placebo data across treatment arms. Drugs cycle off the platform if evidence indicates probability of success or failure.

Four trials are actively recruiting veterans and current service members. One is looking at vilazodone, approved in 2011 for major depressive disorder. It is being compared with placebo and fluoxetine in a trial that is currently recruiting.

Another trial will study daridorexant (sold as Quviviq), an orexin receptor antagonist, against placebo. The FDA approved daridorexant in 2022 as an insomnia treatment. A core issue in PTSD is sleep disruption, noted Davis.
 

New Therapies on the Way

Separately, Davis and colleagues are also studying methylphenidate, the stimulant used for attention-deficit/hyperactivity disorder. It may help with neurocognitive complaints and reduce PTSD symptoms, said Davis.

Because it is generic, few pharmaceutical manufacturers are likely to test it for PTSD, she said. But eventually, their work may lead a company to test newer stimulants for PTSD, she said.

Another potential therapeutic, BNC210, received Fast Track designation for PTSD from the FDA in 2019. Bionomics Limited in Australia will soon launch phase 3 trials of the investigational oral drug, which is a negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor. In late July, the company announced “ favorable feedback” from the agency on its phase 2 study, which led to the decision to move forward with larger trials.

Researchers at Brigham and Women’s Hospital have just reported that they may have found a target within the brain that will allow for transcranial magnetic stimulation (TMS) to ameliorate PTSD symptoms. They published results of a mapping effort in Nature Neuroscience and reported on one patient who had improved symptoms after receiving TMS for severe PTSD.

But perhaps one of the most promising treatments is a combination of sertraline and the new psychiatric medication brexpiprazole.

Brexpiprazole was developed by Otsuka Pharmaceutical and approved in the United States in 2015 as an adjunctive therapy to antidepressants for major depressive disorder and as a treatment for schizophrenia. In 2023, the FDA approved it for Alzheimer’s-related agitation. However, according to Otsuka, its mechanism of action is unknown.

Its efficacy may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, antagonist activity at serotonin 5-HT2A receptors, as well as antagonism of alpha-1B/2C receptors, said the company.

“It is the combination, rather than either alone, that’s going to have that broad synergistic pharmacology that is obviously potent for ameliorating the symptoms of PTSD,” said Davis, who has received consulting fees from Otsuka. “That’s an exciting development.”

Otsuka and partner Lundbeck Pharmaceuticals reported results in May from the companies’ phase 2 and 3 randomized clinical trials. The therapy achieved a statistically significant reduction (P <.05) in PTSD symptoms compared with sertraline plus placebo. This was without any supplemental psychotherapy.

The FDA accepted the companies’ new drug application in June and is expected to make a decision on approval in February 2025.
 

The Potential of Psychedelics

Though Lykos Therapeutics may have to go back to the drawing board on its MDMA-AT, psychedelics still have potential as PTSD therapies, Smyth said, who added that the VA is continuing to encourage study of MDMA and other psychedelic agents.

The VA issued a call for proposals for research on psychedelics in January, focused on MDMA or psilocybin in combination with psychotherapy. The administration received the first wave of applications early in the summer.

Scientific peer review panels made up of research experts from within and outside the VA have reviewed the applications and funding announcements are expected this fall, Smyth said.

Wolfgang, the Army psychiatrist, said, “Under the psychedelic treatment research clinical trial award, we welcome investigators to apply to what we anticipate will usher in a new era of innovation and hope for service members and their families who need it the most.”

Psychedelic studies are also proceeding without VA funding, as they have for years, when most of the trials were backed by universities or foundations or other private money. Johns Hopkins University is recruiting for a study in which patients would receive psilocybin along with trauma-focused psychotherapy, as is Ohio State University.

London-based Compass Pathways said in May that it successfully completed a phase 2 trial of Comp360, its synthetic psilocybin, in PTSD. The company has started a phase 3 study in treatment-resistant depression but has not given any further updates on PTSD.

Davis said that she believes that the FDA’s rejection of Lykos won’t lead to a shutdown of exploration of psychedelics.

“I think it informs these designs going forward, but it doesn’t eliminate that whole field of research,” she said.

Davis reported receiving consulting fees from Boehringer Ingelheim and Otsuka and research funding from Alkermes, the Patient-Centered Outcomes Research Institute, and the VA. Schnurr, Fischer, Smyth, and Wolfgang reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

It has been 24 years since a pharmaceutical was last approved for posttraumatic stress disorder (PTSD). The condition is notoriously difficult to treat, with up to 40% patients finding no relief from symptoms through psychotherapy or current medications.

Many clinicians, advocates, and patients had pinned their hopes on the psychedelic drug midomafetamine with assisted therapy (MDMA-AT). However, in August, the US Food and Drug Administration (FDA) rejected it. At this point, it’s unclear when the therapy will be available, if ever.

“Not getting the FDA approval of any drug at this point is a setback for the field,” Lori Davis, MD, a senior research psychiatrist at the Birmingham Veterans Affairs (VA) Health Care System in Birmingham, Alabama, told Medscape Medical News.

Having an FDA-approved product would have helped increase public awareness of PTSD and driven interest in developing new therapies, said Davis, who is also adjunct professor of psychiatry at the Heersink School of Medicine, University of Alabama at Birmingham.
 

A Treatable Condition

So with MDMA-AT off the table, where does the field go next? 

A public meeting in September hosted by the Reagan-Udall Foundation for the FDA in sought to answer that question. Agency officials joined representatives from the Department of Defense (DoD) and VA, patients, advocates, and industry representatives to discuss the current treatment landscape and what can be done to accelerate development of PTSD treatment.

Despite the common belief that PTSD is intractable, it “is a treatable condition,” Paula P. Schnurr, PhD, executive director of the VA National Center for PTSD, said at the meeting.

“There are effective treatments that work well for a lot of people, although not everyone has a satisfactory response,” she added.

The most effective psychotherapies are “trauma-focused,” and include cognitive processing therapy, eye movement desensitization and reprocessing, and prolonged exposure, according to the VA National Center for PTSD.

Three drugs have been approved by the FDA for PTSD: Venlafaxine (Effexor) in 1993, sertraline (Zoloft) in 1999, and paroxetine (Paxil) in 2000.

However, as the September meeting demonstrated, more therapies are needed.

“It’s clear to FDA and the federal government at large that there is an unmet need for safe and effective therapies to treat PTSD,” Bernard Fischer, MD, deputy director of the Division of Psychiatry in the Office of New Drugs at FDA’s Center for Drug Evaluation and Research, said at the meeting.

There is no shortage of research, Fischer added. Nearly 500 trials focused on PTSD are listed on clinicaltrials.gov are recruiting participants now or plan to soon.

Unsurprisingly, one of the primary drivers of PTSD therapeutics research is the VA. About 14% of the 5.7 million veterans who received care through the VA in 2023 had a diagnosis of PTSD.

“The US military is currently losing thousands of service members each year to PTSD- related disability discharges,” US Army Maj. Aaron Wolfgang, MD, a psychiatrist at the Walter Reed National Military Medical Center, said at the meeting. Only about 12%-20% of patients achieve remission with conventional therapies, added Wolfgang, who also is an assistant professor at the Uniformed Services University.

“For these reasons, establishing better treatments for PTSD is not only a matter of humanitarianism but also a pressing matter of national security,” he said.

The VA has committed at least $230 million to more than 140 active research projects in PTSD, Miriam J. Smyth, PhD, acting director of the clinical science, research and development service at the VA, said at the Reagan-Udall meeting.

One of the VA projects is the PTSD psychopharmacology initiative, which began in 2017 and now has 14 active clinical trials, said Smyth, who is also acting director for brain behavior and mental health at the VA. The first study should be finished by 2025.

The Million Veteran Program, with more than 1 million enrollees, has led to the discovery of genes related to re-experiencing traumatic memories and has confirmed that both PTSD and traumatic brain injury are risk factors for dementia, Smyth said.

The DoD has created a novel platform that establishes a common infrastructure for testing multiple drugs, called M-PACT. The platform allows sharing of placebo data across treatment arms. Drugs cycle off the platform if evidence indicates probability of success or failure.

Four trials are actively recruiting veterans and current service members. One is looking at vilazodone, approved in 2011 for major depressive disorder. It is being compared with placebo and fluoxetine in a trial that is currently recruiting.

Another trial will study daridorexant (sold as Quviviq), an orexin receptor antagonist, against placebo. The FDA approved daridorexant in 2022 as an insomnia treatment. A core issue in PTSD is sleep disruption, noted Davis.
 

New Therapies on the Way

Separately, Davis and colleagues are also studying methylphenidate, the stimulant used for attention-deficit/hyperactivity disorder. It may help with neurocognitive complaints and reduce PTSD symptoms, said Davis.

Because it is generic, few pharmaceutical manufacturers are likely to test it for PTSD, she said. But eventually, their work may lead a company to test newer stimulants for PTSD, she said.

Another potential therapeutic, BNC210, received Fast Track designation for PTSD from the FDA in 2019. Bionomics Limited in Australia will soon launch phase 3 trials of the investigational oral drug, which is a negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor. In late July, the company announced “ favorable feedback” from the agency on its phase 2 study, which led to the decision to move forward with larger trials.

Researchers at Brigham and Women’s Hospital have just reported that they may have found a target within the brain that will allow for transcranial magnetic stimulation (TMS) to ameliorate PTSD symptoms. They published results of a mapping effort in Nature Neuroscience and reported on one patient who had improved symptoms after receiving TMS for severe PTSD.

But perhaps one of the most promising treatments is a combination of sertraline and the new psychiatric medication brexpiprazole.

Brexpiprazole was developed by Otsuka Pharmaceutical and approved in the United States in 2015 as an adjunctive therapy to antidepressants for major depressive disorder and as a treatment for schizophrenia. In 2023, the FDA approved it for Alzheimer’s-related agitation. However, according to Otsuka, its mechanism of action is unknown.

Its efficacy may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, antagonist activity at serotonin 5-HT2A receptors, as well as antagonism of alpha-1B/2C receptors, said the company.

“It is the combination, rather than either alone, that’s going to have that broad synergistic pharmacology that is obviously potent for ameliorating the symptoms of PTSD,” said Davis, who has received consulting fees from Otsuka. “That’s an exciting development.”

Otsuka and partner Lundbeck Pharmaceuticals reported results in May from the companies’ phase 2 and 3 randomized clinical trials. The therapy achieved a statistically significant reduction (P <.05) in PTSD symptoms compared with sertraline plus placebo. This was without any supplemental psychotherapy.

The FDA accepted the companies’ new drug application in June and is expected to make a decision on approval in February 2025.
 

The Potential of Psychedelics

Though Lykos Therapeutics may have to go back to the drawing board on its MDMA-AT, psychedelics still have potential as PTSD therapies, Smyth said, who added that the VA is continuing to encourage study of MDMA and other psychedelic agents.

The VA issued a call for proposals for research on psychedelics in January, focused on MDMA or psilocybin in combination with psychotherapy. The administration received the first wave of applications early in the summer.

Scientific peer review panels made up of research experts from within and outside the VA have reviewed the applications and funding announcements are expected this fall, Smyth said.

Wolfgang, the Army psychiatrist, said, “Under the psychedelic treatment research clinical trial award, we welcome investigators to apply to what we anticipate will usher in a new era of innovation and hope for service members and their families who need it the most.”

Psychedelic studies are also proceeding without VA funding, as they have for years, when most of the trials were backed by universities or foundations or other private money. Johns Hopkins University is recruiting for a study in which patients would receive psilocybin along with trauma-focused psychotherapy, as is Ohio State University.

London-based Compass Pathways said in May that it successfully completed a phase 2 trial of Comp360, its synthetic psilocybin, in PTSD. The company has started a phase 3 study in treatment-resistant depression but has not given any further updates on PTSD.

Davis said that she believes that the FDA’s rejection of Lykos won’t lead to a shutdown of exploration of psychedelics.

“I think it informs these designs going forward, but it doesn’t eliminate that whole field of research,” she said.

Davis reported receiving consulting fees from Boehringer Ingelheim and Otsuka and research funding from Alkermes, the Patient-Centered Outcomes Research Institute, and the VA. Schnurr, Fischer, Smyth, and Wolfgang reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.