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Oral Microbiome Dysbiosis: Biomarker for Upper GI Disorders?
TOPLINE:
Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.
METHODOLOGY:
- Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
- In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
- Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
- UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.
TAKEAWAY:
- Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
- In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
- Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.
IN PRACTICE:
“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”
SOURCE:
The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.
LIMITATIONS:
The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.
DISCLOSURES:
The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.
A version of this article first appeared on Medscape.com.
TOPLINE:
Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.
METHODOLOGY:
- Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
- In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
- Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
- UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.
TAKEAWAY:
- Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
- In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
- Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.
IN PRACTICE:
“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”
SOURCE:
The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.
LIMITATIONS:
The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.
DISCLOSURES:
The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.
A version of this article first appeared on Medscape.com.
TOPLINE:
Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.
METHODOLOGY:
- Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
- In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
- Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
- UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.
TAKEAWAY:
- Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
- In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
- Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.
IN PRACTICE:
“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”
SOURCE:
The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.
LIMITATIONS:
The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.
DISCLOSURES:
The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.
A version of this article first appeared on Medscape.com.
Updated Alzheimer’s Guidelines Chart the Full Diagnostic Journey
This is the first update since 2001 for specialists and the first guideline for primary care physicians. Executive summaries of the guidelines were published in three articles online on December 23 in a special issue of Alzheimer’s & Dementia.
What’s New?
“With this guideline, we expand the scope of prior guidelines by providing recommendations for practicing clinicians on the process from start to finish,” coauthor Brad Dickerson, MD, director of the Massachusetts General Hospital Frontotemporal Disorders Unit and professor of neurology at Harvard Medical School, Boston, said in a statement.
“If clinicians adopt these recommendations and healthcare systems provide adequate resources, outcomes should improve in most patients in most practice settings,” Dickerson added in an interview.
Through a modified-Delphi approach and guideline-development process, an expert workgroup representing primary and specialty care reviewed 7374 publications, of which 133 met inclusion criteria.
Based on the information, the workgroup outlined a three-step patient-centered evaluation process, which includes assessing cognitive functional status, identifying the cognitive-behavioral syndrome based on specific symptoms, and determining the likely brain diseases or conditions causing the symptoms.
What Are the Key Recommendations?
The guidelines include 19 “practical” recommendations that are applicable to any practice setting. They capture the core elements of a high-quality evaluation and disclosure process, the author said. Here is a brief summary of the recommendations:
Initial evaluation: Perform a multitiered evaluation for patients who self-report or whose care partner or clinician reports cognitive, behavioral, or functional changes.
Patient-centered communication: Partner with the patient and/or care partner to establish shared goals for the evaluation process; assess the patient’s capacity to engage in goal setting.
Diagnostic formulation: Use a tiered approach to assessments and tests based on individual presentation, risk factors, and profile, aiming to determine the level of impairment, cognitive-behavioral syndrome, and likely causes and contributing factors.
History taking: Gather reliable information from informants about changes in cognition, activities of daily living, mood, neuropsychiatric symptoms, and sensory/motor functions. Document individualized risk factors for cognitive decline.
Examination: Conduct a comprehensive examination of cognition, mood, behavior, and a dementia-focused neurologic evaluation using validated tools.
Laboratory tests: Perform tiered, individualized laboratory evaluations, starting with routine tests for all patients.
Structural imaging: Obtain structural brain imaging (MRI preferred, CT as an alternative) to help establish a cause.
Ongoing communication: Engage in ongoing dialogue with patient/care partner to guide them throughout the diagnostic process.
Diagnostic disclosure: Share findings honestly and compassionately, explaining the syndrome, its severity, probable cause, prognosis, treatment options and support resources.
Specialist referral: Refer patients with atypical, uncertain, early-onset, or rapidly progressing symptoms to a dementia subspecialist.
Neuropsychological testing: Use in instances of diagnostic uncertainty or patients with complex clinical profiles. At a minimum, the neuropsychological evaluation should include normed neuropsychological testing of the domains of learning and memory (in particular delayed free and cued recall/recognition), attention, executive function, visuospatial function, and language.
Advanced diagnostic testing: When diagnostic uncertainty remains, obtain additional laboratory tests tailored to individual patient profiles.
Molecular imaging: In a patient with an established cognitive-behavioral syndrome in whom there is continued diagnostic uncertainty regarding cause(s) after structural imaging, a dementia specialist can obtain molecular imaging with fluorodeoxyglucose PET to improve diagnostic accuracy.
Cerebrospinal fluid (CSF) analysis: Utilize CSF biomarkers to evaluate amyloid beta and tau profiles in cases with unresolved diagnostic uncertainty.
Amyloid PET imaging: Perform amyloid PET scans for patients with persistent diagnostic uncertainty after other assessments.
Genetic counseling and testing: Consider genetic testing for patients with strong autosomal dominant family histories and involve a genetic counselor.
Future Directions?
Maria C. Carrillo, PhD, chief science officer and medical affairs lead for the Alzheimer’s Association, encourages clinicians to incorporate these guidelines into their practice.
“These guidelines are important because they guide clinicians in the evaluation of memory complaints, which could have many underlying causes. That is the necessary start for an early and accurate Alzheimer’s diagnosis,” Carrillo said in a statement.
Dickerson said the new guidelines do not address blood-based biomarkers “because nobody really feels that they are ready for prime time yet, even though they’re getting rolled out as clinical products.”
However, the recommendations will be revised as needed. “That’s one of the values of setting this up as a process; whenever any new development occurs, it will be easy to update the guidelines to show where that new test or new biomarker fits in the overall process,” he said.
New Appropriate Use Guidance
A separate workgroup, jointly convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, has revised appropriate use criteria (AUC) for amyloid PET imaging and developed AUC for tau PET imaging.
They were simultaneously published online in Alzheimer’s & Dementia and The Journal of Nuclear Medicine. They are the first revision since the initial AUC for amyloid PET was introduced in 2013.
“The updated amyloid/tau appropriate use criteria will help ensure these tracers are used in a cost-effective manner and the scan results will be used appropriately to add value to the diagnosis and management of dementia,” said workgroup members Kevin Donohoe, MD, with Beth Israel Deaconess Medical Center, Boston, and Phillip Kuo, MD, with City of Hope National Medical Center, Duarte, California.
The AUC include 17 real-world scenarios in which amyloid or tau PET may be considered, with the two tests considered separately and given their own rating for each scenario.
Overall, the strongest evidence for their use includes assessment and prognosis for people with mild cognitive impairment; assessment of people with dementia when the cause is not clearly known; and determining eligibility for treatment with new disease-modifying therapies, and monitoring response to these treatments, the workgroup said.
“Whereas the prior AUC was written at a time when only the deposition of amyloid could be documented, the new therapeutic agents allow us to demonstrate the actual clearance of amyloid during therapy,” Donohoe and Kuo explained.
“These new therapeutic agents are expensive and, as with most medications, may cause unwanted side effects. The most recent version of the AUC includes information about the appropriate use of amyloid imaging for both documenting the presence of amyloid deposits in the brain, making anti-amyloid therapy an option, as well as documenting the effectiveness of the therapeutic agents as amyloid is (or is not) cleared from the brain,” Donahoe and Kuo noted.
The revised AUC also state that, in most cases, amyloid and tau PET tests should not be used for people who do not have cognitive impairment, even if they carry the APOE4 risk-related gene for Alzheimer’s disease; nonmedical use such as for legal concerns, insurance coverage, or employment screening; and in place of genetic testing in patients suspected of carrying a disease-causing genetic mutation.
In a statement, lead author Gil D. Rabinovici, MD, with University of California, San Francisco, emphasized that the AUC “should be considered guidelines for clinicians, not a substitute for careful clinical judgment that considers the full clinical context for each patient with cognitive complaints.”
This research was funded by the Alzheimer’s Association. Disclosures for guideline authors are available with the original articles.
A version of this article first appeared on Medscape.com.
This is the first update since 2001 for specialists and the first guideline for primary care physicians. Executive summaries of the guidelines were published in three articles online on December 23 in a special issue of Alzheimer’s & Dementia.
What’s New?
“With this guideline, we expand the scope of prior guidelines by providing recommendations for practicing clinicians on the process from start to finish,” coauthor Brad Dickerson, MD, director of the Massachusetts General Hospital Frontotemporal Disorders Unit and professor of neurology at Harvard Medical School, Boston, said in a statement.
“If clinicians adopt these recommendations and healthcare systems provide adequate resources, outcomes should improve in most patients in most practice settings,” Dickerson added in an interview.
Through a modified-Delphi approach and guideline-development process, an expert workgroup representing primary and specialty care reviewed 7374 publications, of which 133 met inclusion criteria.
Based on the information, the workgroup outlined a three-step patient-centered evaluation process, which includes assessing cognitive functional status, identifying the cognitive-behavioral syndrome based on specific symptoms, and determining the likely brain diseases or conditions causing the symptoms.
What Are the Key Recommendations?
The guidelines include 19 “practical” recommendations that are applicable to any practice setting. They capture the core elements of a high-quality evaluation and disclosure process, the author said. Here is a brief summary of the recommendations:
Initial evaluation: Perform a multitiered evaluation for patients who self-report or whose care partner or clinician reports cognitive, behavioral, or functional changes.
Patient-centered communication: Partner with the patient and/or care partner to establish shared goals for the evaluation process; assess the patient’s capacity to engage in goal setting.
Diagnostic formulation: Use a tiered approach to assessments and tests based on individual presentation, risk factors, and profile, aiming to determine the level of impairment, cognitive-behavioral syndrome, and likely causes and contributing factors.
History taking: Gather reliable information from informants about changes in cognition, activities of daily living, mood, neuropsychiatric symptoms, and sensory/motor functions. Document individualized risk factors for cognitive decline.
Examination: Conduct a comprehensive examination of cognition, mood, behavior, and a dementia-focused neurologic evaluation using validated tools.
Laboratory tests: Perform tiered, individualized laboratory evaluations, starting with routine tests for all patients.
Structural imaging: Obtain structural brain imaging (MRI preferred, CT as an alternative) to help establish a cause.
Ongoing communication: Engage in ongoing dialogue with patient/care partner to guide them throughout the diagnostic process.
Diagnostic disclosure: Share findings honestly and compassionately, explaining the syndrome, its severity, probable cause, prognosis, treatment options and support resources.
Specialist referral: Refer patients with atypical, uncertain, early-onset, or rapidly progressing symptoms to a dementia subspecialist.
Neuropsychological testing: Use in instances of diagnostic uncertainty or patients with complex clinical profiles. At a minimum, the neuropsychological evaluation should include normed neuropsychological testing of the domains of learning and memory (in particular delayed free and cued recall/recognition), attention, executive function, visuospatial function, and language.
Advanced diagnostic testing: When diagnostic uncertainty remains, obtain additional laboratory tests tailored to individual patient profiles.
Molecular imaging: In a patient with an established cognitive-behavioral syndrome in whom there is continued diagnostic uncertainty regarding cause(s) after structural imaging, a dementia specialist can obtain molecular imaging with fluorodeoxyglucose PET to improve diagnostic accuracy.
Cerebrospinal fluid (CSF) analysis: Utilize CSF biomarkers to evaluate amyloid beta and tau profiles in cases with unresolved diagnostic uncertainty.
Amyloid PET imaging: Perform amyloid PET scans for patients with persistent diagnostic uncertainty after other assessments.
Genetic counseling and testing: Consider genetic testing for patients with strong autosomal dominant family histories and involve a genetic counselor.
Future Directions?
Maria C. Carrillo, PhD, chief science officer and medical affairs lead for the Alzheimer’s Association, encourages clinicians to incorporate these guidelines into their practice.
“These guidelines are important because they guide clinicians in the evaluation of memory complaints, which could have many underlying causes. That is the necessary start for an early and accurate Alzheimer’s diagnosis,” Carrillo said in a statement.
Dickerson said the new guidelines do not address blood-based biomarkers “because nobody really feels that they are ready for prime time yet, even though they’re getting rolled out as clinical products.”
However, the recommendations will be revised as needed. “That’s one of the values of setting this up as a process; whenever any new development occurs, it will be easy to update the guidelines to show where that new test or new biomarker fits in the overall process,” he said.
New Appropriate Use Guidance
A separate workgroup, jointly convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, has revised appropriate use criteria (AUC) for amyloid PET imaging and developed AUC for tau PET imaging.
They were simultaneously published online in Alzheimer’s & Dementia and The Journal of Nuclear Medicine. They are the first revision since the initial AUC for amyloid PET was introduced in 2013.
“The updated amyloid/tau appropriate use criteria will help ensure these tracers are used in a cost-effective manner and the scan results will be used appropriately to add value to the diagnosis and management of dementia,” said workgroup members Kevin Donohoe, MD, with Beth Israel Deaconess Medical Center, Boston, and Phillip Kuo, MD, with City of Hope National Medical Center, Duarte, California.
The AUC include 17 real-world scenarios in which amyloid or tau PET may be considered, with the two tests considered separately and given their own rating for each scenario.
Overall, the strongest evidence for their use includes assessment and prognosis for people with mild cognitive impairment; assessment of people with dementia when the cause is not clearly known; and determining eligibility for treatment with new disease-modifying therapies, and monitoring response to these treatments, the workgroup said.
“Whereas the prior AUC was written at a time when only the deposition of amyloid could be documented, the new therapeutic agents allow us to demonstrate the actual clearance of amyloid during therapy,” Donohoe and Kuo explained.
“These new therapeutic agents are expensive and, as with most medications, may cause unwanted side effects. The most recent version of the AUC includes information about the appropriate use of amyloid imaging for both documenting the presence of amyloid deposits in the brain, making anti-amyloid therapy an option, as well as documenting the effectiveness of the therapeutic agents as amyloid is (or is not) cleared from the brain,” Donahoe and Kuo noted.
The revised AUC also state that, in most cases, amyloid and tau PET tests should not be used for people who do not have cognitive impairment, even if they carry the APOE4 risk-related gene for Alzheimer’s disease; nonmedical use such as for legal concerns, insurance coverage, or employment screening; and in place of genetic testing in patients suspected of carrying a disease-causing genetic mutation.
In a statement, lead author Gil D. Rabinovici, MD, with University of California, San Francisco, emphasized that the AUC “should be considered guidelines for clinicians, not a substitute for careful clinical judgment that considers the full clinical context for each patient with cognitive complaints.”
This research was funded by the Alzheimer’s Association. Disclosures for guideline authors are available with the original articles.
A version of this article first appeared on Medscape.com.
This is the first update since 2001 for specialists and the first guideline for primary care physicians. Executive summaries of the guidelines were published in three articles online on December 23 in a special issue of Alzheimer’s & Dementia.
What’s New?
“With this guideline, we expand the scope of prior guidelines by providing recommendations for practicing clinicians on the process from start to finish,” coauthor Brad Dickerson, MD, director of the Massachusetts General Hospital Frontotemporal Disorders Unit and professor of neurology at Harvard Medical School, Boston, said in a statement.
“If clinicians adopt these recommendations and healthcare systems provide adequate resources, outcomes should improve in most patients in most practice settings,” Dickerson added in an interview.
Through a modified-Delphi approach and guideline-development process, an expert workgroup representing primary and specialty care reviewed 7374 publications, of which 133 met inclusion criteria.
Based on the information, the workgroup outlined a three-step patient-centered evaluation process, which includes assessing cognitive functional status, identifying the cognitive-behavioral syndrome based on specific symptoms, and determining the likely brain diseases or conditions causing the symptoms.
What Are the Key Recommendations?
The guidelines include 19 “practical” recommendations that are applicable to any practice setting. They capture the core elements of a high-quality evaluation and disclosure process, the author said. Here is a brief summary of the recommendations:
Initial evaluation: Perform a multitiered evaluation for patients who self-report or whose care partner or clinician reports cognitive, behavioral, or functional changes.
Patient-centered communication: Partner with the patient and/or care partner to establish shared goals for the evaluation process; assess the patient’s capacity to engage in goal setting.
Diagnostic formulation: Use a tiered approach to assessments and tests based on individual presentation, risk factors, and profile, aiming to determine the level of impairment, cognitive-behavioral syndrome, and likely causes and contributing factors.
History taking: Gather reliable information from informants about changes in cognition, activities of daily living, mood, neuropsychiatric symptoms, and sensory/motor functions. Document individualized risk factors for cognitive decline.
Examination: Conduct a comprehensive examination of cognition, mood, behavior, and a dementia-focused neurologic evaluation using validated tools.
Laboratory tests: Perform tiered, individualized laboratory evaluations, starting with routine tests for all patients.
Structural imaging: Obtain structural brain imaging (MRI preferred, CT as an alternative) to help establish a cause.
Ongoing communication: Engage in ongoing dialogue with patient/care partner to guide them throughout the diagnostic process.
Diagnostic disclosure: Share findings honestly and compassionately, explaining the syndrome, its severity, probable cause, prognosis, treatment options and support resources.
Specialist referral: Refer patients with atypical, uncertain, early-onset, or rapidly progressing symptoms to a dementia subspecialist.
Neuropsychological testing: Use in instances of diagnostic uncertainty or patients with complex clinical profiles. At a minimum, the neuropsychological evaluation should include normed neuropsychological testing of the domains of learning and memory (in particular delayed free and cued recall/recognition), attention, executive function, visuospatial function, and language.
Advanced diagnostic testing: When diagnostic uncertainty remains, obtain additional laboratory tests tailored to individual patient profiles.
Molecular imaging: In a patient with an established cognitive-behavioral syndrome in whom there is continued diagnostic uncertainty regarding cause(s) after structural imaging, a dementia specialist can obtain molecular imaging with fluorodeoxyglucose PET to improve diagnostic accuracy.
Cerebrospinal fluid (CSF) analysis: Utilize CSF biomarkers to evaluate amyloid beta and tau profiles in cases with unresolved diagnostic uncertainty.
Amyloid PET imaging: Perform amyloid PET scans for patients with persistent diagnostic uncertainty after other assessments.
Genetic counseling and testing: Consider genetic testing for patients with strong autosomal dominant family histories and involve a genetic counselor.
Future Directions?
Maria C. Carrillo, PhD, chief science officer and medical affairs lead for the Alzheimer’s Association, encourages clinicians to incorporate these guidelines into their practice.
“These guidelines are important because they guide clinicians in the evaluation of memory complaints, which could have many underlying causes. That is the necessary start for an early and accurate Alzheimer’s diagnosis,” Carrillo said in a statement.
Dickerson said the new guidelines do not address blood-based biomarkers “because nobody really feels that they are ready for prime time yet, even though they’re getting rolled out as clinical products.”
However, the recommendations will be revised as needed. “That’s one of the values of setting this up as a process; whenever any new development occurs, it will be easy to update the guidelines to show where that new test or new biomarker fits in the overall process,” he said.
New Appropriate Use Guidance
A separate workgroup, jointly convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, has revised appropriate use criteria (AUC) for amyloid PET imaging and developed AUC for tau PET imaging.
They were simultaneously published online in Alzheimer’s & Dementia and The Journal of Nuclear Medicine. They are the first revision since the initial AUC for amyloid PET was introduced in 2013.
“The updated amyloid/tau appropriate use criteria will help ensure these tracers are used in a cost-effective manner and the scan results will be used appropriately to add value to the diagnosis and management of dementia,” said workgroup members Kevin Donohoe, MD, with Beth Israel Deaconess Medical Center, Boston, and Phillip Kuo, MD, with City of Hope National Medical Center, Duarte, California.
The AUC include 17 real-world scenarios in which amyloid or tau PET may be considered, with the two tests considered separately and given their own rating for each scenario.
Overall, the strongest evidence for their use includes assessment and prognosis for people with mild cognitive impairment; assessment of people with dementia when the cause is not clearly known; and determining eligibility for treatment with new disease-modifying therapies, and monitoring response to these treatments, the workgroup said.
“Whereas the prior AUC was written at a time when only the deposition of amyloid could be documented, the new therapeutic agents allow us to demonstrate the actual clearance of amyloid during therapy,” Donohoe and Kuo explained.
“These new therapeutic agents are expensive and, as with most medications, may cause unwanted side effects. The most recent version of the AUC includes information about the appropriate use of amyloid imaging for both documenting the presence of amyloid deposits in the brain, making anti-amyloid therapy an option, as well as documenting the effectiveness of the therapeutic agents as amyloid is (or is not) cleared from the brain,” Donahoe and Kuo noted.
The revised AUC also state that, in most cases, amyloid and tau PET tests should not be used for people who do not have cognitive impairment, even if they carry the APOE4 risk-related gene for Alzheimer’s disease; nonmedical use such as for legal concerns, insurance coverage, or employment screening; and in place of genetic testing in patients suspected of carrying a disease-causing genetic mutation.
In a statement, lead author Gil D. Rabinovici, MD, with University of California, San Francisco, emphasized that the AUC “should be considered guidelines for clinicians, not a substitute for careful clinical judgment that considers the full clinical context for each patient with cognitive complaints.”
This research was funded by the Alzheimer’s Association. Disclosures for guideline authors are available with the original articles.
A version of this article first appeared on Medscape.com.
FROM ALZHEIMER’S & DEMENTIA
Traumatic Brain Injury May Reactivate Herpes Virus Leading to Neurodegeneration
a new study suggested.
Using a three-dimensional (3D) human brain tissue model, researchers observed that quiescent HSV-1 can be reactivated by a mechanical jolt mimicking concussion, leading to signature markers of Alzheimer’s disease, including neuroinflammation and production of amyloid beta and phosphorylated tau (p-tau) and gliosis — a phenotype made worse by repeated head injury.
“This opens the question as to whether antiviral drugs or anti-inflammatory agents might be useful as early preventive treatments after head trauma to stop HSV-1 activation in its tracks and lower the risk of Alzheimer’s disease,” lead investigator Dana Cairns, PhD, with the Department of Biomedical Engineering at Tufts University, Medford, Massachusetts, said in a statement.
But outside experts urged caution in drawing any firm conclusions, pending further study.
The study was published online in the journal Science Signaling.
HSV-1: A Major Alzheimer’s Disease Risk Factor?
TBI is a major risk factor for Alzheimer’s disease and dementia, but the pathways in the brain leading from TBI to dementia are unknown.
HSV-1 is found in over 80% of people; varicella zoster virus (VZV) is found in about 95%. Both viruses are known to enter the brain and lay dormant in neurons and glial cells. Prior evidence indicates that HSV-1 in the brain of APOE-ε4 carriers confers a strong risk for Alzheimer’s disease.
A number of years ago, the team created a 3D model of human brain tissue to study the link between TBI, the viruses, and dementia. The model is 6 mm wide, shaped like a donut, and made of a spongy material of silk protein and collagen saturated with neural stem cells. The cells mature into neurons, communicate with each other, and form a network that mimics the brain environment.
In an earlier study using the model quiescently infected with HSV-1, Cairns and colleagues found that subsequent exposure to VZV created the inflammatory conditions that led to reactivation of HSV-1.
This led them to wonder what would happen if they subjected the brain tissue model to a physical disruption akin to a concussion. Would HSV-1 wake up and start the process of neurodegeneration?
To investigate, they examined the effects of one or more controlled blows to the 3D human brain tissue model in the absence or presence of quiescent HSV-1 infection.
After repeated, mild controlled blows, researchers found that the latently infected 3D brain tissue displayed reactivated HSV-1 and the production and accumulation of amyloid beta and p-tau — which promotes neurodegeneration. The blows also activated gliosis, which is associated with destructive neuroinflammation.
These effects are collectively associated with Alzheimer’s disease, dementia, and chronic traumatic encephalopathy, they pointed out, and were increased with additional injury but were absent in tissue not infected with HSV-1.
“These data suggest that HSV-1 in the brain is pivotal in increasing the risk of Alzheimer’s disease, as other recent studies using cerebral organoids have suggested,” the researchers wrote.
They propose that following brain injury, “whether by infection or mechanical damage, the resulting inflammation induces HSV-1 reactivation in the brain leading to the development of Alzheimer’s disease/dementia and that HSV-1 is a major cause of the disease, especially in APOE4 carriers.”
Future studies should investigate “possible ways of mitigating or stopping the damage caused by head injury, thereby reducing subsequent development of Alzheimer’s disease by implementing efforts to prevent the reactivation of virus in brain such as anti-inflammatory and/or antiviral treatment post-injury,” researchers suggested.
Outside Experts Weigh in
Several outside experts offered perspective on the study in a statement from the UK nonprofit Science Media Centre.
Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, London, England, said that, while the study is interesting, there are limitations.
“The increase in Alzheimer’s-like brain changes in these latent virus-containing cells subjected to injury does not resemble the pathology that is found in the brain of people with Alzheimer’s disease,” Spires-Jones noted.
“These experiments were also in cells grown in artificial conditions without important Alzheimer’s-related factors such as age and blood vessel changes. Finally, these experiments were repeated in a small number of experimental replicates (three times per experiment), so these results will need to be confirmed in more relevant biological systems with larger studies to be sure there is a biological link between latent herpes simplex virus type 1, brain injury, and Alzheimer’s pathology,” Spires-Jones cautioned.
Robert Howard, MD, MRCPsych, University College London (UCL) Division of Psychiatry, said the study suggests a possible mechanism for the association between HSV-1, brain injury, and Alzheimer’s disease.
“However, as so often in science, it is very important to bear in mind that association does not mean causation. Much more research will be needed before this can be seriously considered a plausible mechanism for the development of dementia,” Howard cautioned.
“Avoidance of brain injuries, such as those encountered in some contact sports, is already known to be an important way to prevent dementia, and I’m unconvinced that this reflects anything more complicated than mechanical damage causing death of brain cells,” he added.
Jennifer Pocock, PhD, with UCL Queen Square Institute of Neurology, noted the role of microglia, which are activated by mild and repetitive TBI, isn’t addressed in the study.
“This paper seems to suggest that only astrocytes contribute to the reported neuroinflammation in brain tissue. Also, the inclusion of APOE3/4 is not clearly defined. Because of this, the findings are likely to represent an over interpretation for the ‘real world’ as the inclusion of microglia may negate or accentuate them, depending on the severity of the TBI,” Pocock said.
The study was funded by the US Army Research Office and Department of Defense. The authors have declared no relevant conflicts of interest. Spires-Jones and Howard had no relevant disclosures related to this study. Pocock has received research funding from AstraZeneca and Daiichi Sankyo.
A version of this article appeared on Medscape.com.
a new study suggested.
Using a three-dimensional (3D) human brain tissue model, researchers observed that quiescent HSV-1 can be reactivated by a mechanical jolt mimicking concussion, leading to signature markers of Alzheimer’s disease, including neuroinflammation and production of amyloid beta and phosphorylated tau (p-tau) and gliosis — a phenotype made worse by repeated head injury.
“This opens the question as to whether antiviral drugs or anti-inflammatory agents might be useful as early preventive treatments after head trauma to stop HSV-1 activation in its tracks and lower the risk of Alzheimer’s disease,” lead investigator Dana Cairns, PhD, with the Department of Biomedical Engineering at Tufts University, Medford, Massachusetts, said in a statement.
But outside experts urged caution in drawing any firm conclusions, pending further study.
The study was published online in the journal Science Signaling.
HSV-1: A Major Alzheimer’s Disease Risk Factor?
TBI is a major risk factor for Alzheimer’s disease and dementia, but the pathways in the brain leading from TBI to dementia are unknown.
HSV-1 is found in over 80% of people; varicella zoster virus (VZV) is found in about 95%. Both viruses are known to enter the brain and lay dormant in neurons and glial cells. Prior evidence indicates that HSV-1 in the brain of APOE-ε4 carriers confers a strong risk for Alzheimer’s disease.
A number of years ago, the team created a 3D model of human brain tissue to study the link between TBI, the viruses, and dementia. The model is 6 mm wide, shaped like a donut, and made of a spongy material of silk protein and collagen saturated with neural stem cells. The cells mature into neurons, communicate with each other, and form a network that mimics the brain environment.
In an earlier study using the model quiescently infected with HSV-1, Cairns and colleagues found that subsequent exposure to VZV created the inflammatory conditions that led to reactivation of HSV-1.
This led them to wonder what would happen if they subjected the brain tissue model to a physical disruption akin to a concussion. Would HSV-1 wake up and start the process of neurodegeneration?
To investigate, they examined the effects of one or more controlled blows to the 3D human brain tissue model in the absence or presence of quiescent HSV-1 infection.
After repeated, mild controlled blows, researchers found that the latently infected 3D brain tissue displayed reactivated HSV-1 and the production and accumulation of amyloid beta and p-tau — which promotes neurodegeneration. The blows also activated gliosis, which is associated with destructive neuroinflammation.
These effects are collectively associated with Alzheimer’s disease, dementia, and chronic traumatic encephalopathy, they pointed out, and were increased with additional injury but were absent in tissue not infected with HSV-1.
“These data suggest that HSV-1 in the brain is pivotal in increasing the risk of Alzheimer’s disease, as other recent studies using cerebral organoids have suggested,” the researchers wrote.
They propose that following brain injury, “whether by infection or mechanical damage, the resulting inflammation induces HSV-1 reactivation in the brain leading to the development of Alzheimer’s disease/dementia and that HSV-1 is a major cause of the disease, especially in APOE4 carriers.”
Future studies should investigate “possible ways of mitigating or stopping the damage caused by head injury, thereby reducing subsequent development of Alzheimer’s disease by implementing efforts to prevent the reactivation of virus in brain such as anti-inflammatory and/or antiviral treatment post-injury,” researchers suggested.
Outside Experts Weigh in
Several outside experts offered perspective on the study in a statement from the UK nonprofit Science Media Centre.
Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, London, England, said that, while the study is interesting, there are limitations.
“The increase in Alzheimer’s-like brain changes in these latent virus-containing cells subjected to injury does not resemble the pathology that is found in the brain of people with Alzheimer’s disease,” Spires-Jones noted.
“These experiments were also in cells grown in artificial conditions without important Alzheimer’s-related factors such as age and blood vessel changes. Finally, these experiments were repeated in a small number of experimental replicates (three times per experiment), so these results will need to be confirmed in more relevant biological systems with larger studies to be sure there is a biological link between latent herpes simplex virus type 1, brain injury, and Alzheimer’s pathology,” Spires-Jones cautioned.
Robert Howard, MD, MRCPsych, University College London (UCL) Division of Psychiatry, said the study suggests a possible mechanism for the association between HSV-1, brain injury, and Alzheimer’s disease.
“However, as so often in science, it is very important to bear in mind that association does not mean causation. Much more research will be needed before this can be seriously considered a plausible mechanism for the development of dementia,” Howard cautioned.
“Avoidance of brain injuries, such as those encountered in some contact sports, is already known to be an important way to prevent dementia, and I’m unconvinced that this reflects anything more complicated than mechanical damage causing death of brain cells,” he added.
Jennifer Pocock, PhD, with UCL Queen Square Institute of Neurology, noted the role of microglia, which are activated by mild and repetitive TBI, isn’t addressed in the study.
“This paper seems to suggest that only astrocytes contribute to the reported neuroinflammation in brain tissue. Also, the inclusion of APOE3/4 is not clearly defined. Because of this, the findings are likely to represent an over interpretation for the ‘real world’ as the inclusion of microglia may negate or accentuate them, depending on the severity of the TBI,” Pocock said.
The study was funded by the US Army Research Office and Department of Defense. The authors have declared no relevant conflicts of interest. Spires-Jones and Howard had no relevant disclosures related to this study. Pocock has received research funding from AstraZeneca and Daiichi Sankyo.
A version of this article appeared on Medscape.com.
a new study suggested.
Using a three-dimensional (3D) human brain tissue model, researchers observed that quiescent HSV-1 can be reactivated by a mechanical jolt mimicking concussion, leading to signature markers of Alzheimer’s disease, including neuroinflammation and production of amyloid beta and phosphorylated tau (p-tau) and gliosis — a phenotype made worse by repeated head injury.
“This opens the question as to whether antiviral drugs or anti-inflammatory agents might be useful as early preventive treatments after head trauma to stop HSV-1 activation in its tracks and lower the risk of Alzheimer’s disease,” lead investigator Dana Cairns, PhD, with the Department of Biomedical Engineering at Tufts University, Medford, Massachusetts, said in a statement.
But outside experts urged caution in drawing any firm conclusions, pending further study.
The study was published online in the journal Science Signaling.
HSV-1: A Major Alzheimer’s Disease Risk Factor?
TBI is a major risk factor for Alzheimer’s disease and dementia, but the pathways in the brain leading from TBI to dementia are unknown.
HSV-1 is found in over 80% of people; varicella zoster virus (VZV) is found in about 95%. Both viruses are known to enter the brain and lay dormant in neurons and glial cells. Prior evidence indicates that HSV-1 in the brain of APOE-ε4 carriers confers a strong risk for Alzheimer’s disease.
A number of years ago, the team created a 3D model of human brain tissue to study the link between TBI, the viruses, and dementia. The model is 6 mm wide, shaped like a donut, and made of a spongy material of silk protein and collagen saturated with neural stem cells. The cells mature into neurons, communicate with each other, and form a network that mimics the brain environment.
In an earlier study using the model quiescently infected with HSV-1, Cairns and colleagues found that subsequent exposure to VZV created the inflammatory conditions that led to reactivation of HSV-1.
This led them to wonder what would happen if they subjected the brain tissue model to a physical disruption akin to a concussion. Would HSV-1 wake up and start the process of neurodegeneration?
To investigate, they examined the effects of one or more controlled blows to the 3D human brain tissue model in the absence or presence of quiescent HSV-1 infection.
After repeated, mild controlled blows, researchers found that the latently infected 3D brain tissue displayed reactivated HSV-1 and the production and accumulation of amyloid beta and p-tau — which promotes neurodegeneration. The blows also activated gliosis, which is associated with destructive neuroinflammation.
These effects are collectively associated with Alzheimer’s disease, dementia, and chronic traumatic encephalopathy, they pointed out, and were increased with additional injury but were absent in tissue not infected with HSV-1.
“These data suggest that HSV-1 in the brain is pivotal in increasing the risk of Alzheimer’s disease, as other recent studies using cerebral organoids have suggested,” the researchers wrote.
They propose that following brain injury, “whether by infection or mechanical damage, the resulting inflammation induces HSV-1 reactivation in the brain leading to the development of Alzheimer’s disease/dementia and that HSV-1 is a major cause of the disease, especially in APOE4 carriers.”
Future studies should investigate “possible ways of mitigating or stopping the damage caused by head injury, thereby reducing subsequent development of Alzheimer’s disease by implementing efforts to prevent the reactivation of virus in brain such as anti-inflammatory and/or antiviral treatment post-injury,” researchers suggested.
Outside Experts Weigh in
Several outside experts offered perspective on the study in a statement from the UK nonprofit Science Media Centre.
Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, London, England, said that, while the study is interesting, there are limitations.
“The increase in Alzheimer’s-like brain changes in these latent virus-containing cells subjected to injury does not resemble the pathology that is found in the brain of people with Alzheimer’s disease,” Spires-Jones noted.
“These experiments were also in cells grown in artificial conditions without important Alzheimer’s-related factors such as age and blood vessel changes. Finally, these experiments were repeated in a small number of experimental replicates (three times per experiment), so these results will need to be confirmed in more relevant biological systems with larger studies to be sure there is a biological link between latent herpes simplex virus type 1, brain injury, and Alzheimer’s pathology,” Spires-Jones cautioned.
Robert Howard, MD, MRCPsych, University College London (UCL) Division of Psychiatry, said the study suggests a possible mechanism for the association between HSV-1, brain injury, and Alzheimer’s disease.
“However, as so often in science, it is very important to bear in mind that association does not mean causation. Much more research will be needed before this can be seriously considered a plausible mechanism for the development of dementia,” Howard cautioned.
“Avoidance of brain injuries, such as those encountered in some contact sports, is already known to be an important way to prevent dementia, and I’m unconvinced that this reflects anything more complicated than mechanical damage causing death of brain cells,” he added.
Jennifer Pocock, PhD, with UCL Queen Square Institute of Neurology, noted the role of microglia, which are activated by mild and repetitive TBI, isn’t addressed in the study.
“This paper seems to suggest that only astrocytes contribute to the reported neuroinflammation in brain tissue. Also, the inclusion of APOE3/4 is not clearly defined. Because of this, the findings are likely to represent an over interpretation for the ‘real world’ as the inclusion of microglia may negate or accentuate them, depending on the severity of the TBI,” Pocock said.
The study was funded by the US Army Research Office and Department of Defense. The authors have declared no relevant conflicts of interest. Spires-Jones and Howard had no relevant disclosures related to this study. Pocock has received research funding from AstraZeneca and Daiichi Sankyo.
A version of this article appeared on Medscape.com.
FROM SCIENCE SIGNALING
Major Depression in Older Adults Tied to Risky Driving Behaviors
Older adults with major depressive disorder (MDD) exhibit riskier driving behaviors, compared with their nondepressed peers, including hard braking, cornering, and unpredictable driving patterns, new research showed.
Data for the study came from commercial vehicle data trackers installed in participants’ vehicles. After about a year of follow-up, the investigators found that MDD was associated with an increase in the amount and severity of risking driving, even after they controlled for antidepressant use.
Late-life depression often goes undiagnosed, and the new findings highlight the importance of routine depression screening and targeted interventions to ensure driving safety among older adults, the study team said.
“By using longitudinal, real-world driving data rather than controlled settings or self-reports, the study provides robust evidence of how MDD influences driving behaviors in day-to-day contexts,” first author Ganesh M. Babulal, PhD, OTD, with the Department of Neurology, Washington University School of Medicine in St Louis, Missouri, said in an interview.
“By analyzing the influence of antidepressant use and overall medication load, the study disentangles the effects of MDD from those of driver-impairing medications, further clarifying the unique contributions of depression to driving behaviors,” Babulal noted.
The study was published online in JAMA Network Open.
Road Risks
As the number of older adults grows, safe driving practices in this age group become increasingly crucial. By 2050, one quarter of drivers in the United States will be older than 65 years. MDD affects about 8% of US adults and is linked to cognitive impairments that may compromise driving safety.
Prior studies revealed a link between depression and increased car crash risk, regardless of age. And earlier research by Babulal and colleagues showed that older adults with depression were three times more likely to receive a marginal or failing score on a standardized road test.
To further study the issue, Babulal and colleagues examined the impact of MDD on naturalistic driving behaviors among older adults using longitudinal data.
Participants were recruited from the Driving Real-World In-Vehicle Evaluation System Project, where their daily driving behaviors were recorded using commercial vehicle data loggers installed in their personal vehicles.
The cohort included 85 adults with MDD (mean age, 69 years; 71% women) and 310 adults without MDD (mean age, 70 years; 49% women). The majority of participants in both groups were non-Hispanic White individuals.
Based on intercepts, adults with MDD had a propensity toward riskier driving habits with a higher frequency of speeding events and spending more time on the road than those without MDD, they found.
During a mean of 1.1 years of follow-up, compared with older adults without MDD, those with MDD exhibited significantly more hard braking (P < .001) and hard cornering events per trip (P = .04) over time. They also traveled farther from home and visited more unique destinations (P < .001 for both).
Over time, older adults also displayed increased entropy in driving patterns (P < .001), indicated less predictable driving routes.
“Driving unpredictability, as evidenced by increased random entropy, highlights the unique challenges posed by MDD in maintaining safe driving practices,” the researchers wrote.
Adjustment for antidepressant use, which could impair driving, or total medication burden did not change the findings, suggesting MDD independently affects driving.
“Most importantly, our findings demonstrate that MDD — a common and treatable illness in older adults — was associated with an increase in both the amount and magnitude of risky driving behaviors over time,” the researchers wrote.
The researchers noted that the study did not account for changes in depression severity over time and other psychiatric conditions co-occurring with MDD were not adjusted for. Also, situational factors like weather or traffic conditions were not assessed.
Clear Clinical Implications
There is a “pressing need” for targeted interventions to manage and mitigate the driving risks associated with late-life depression, the researchers wrote.
“The study emphasizes the need for interventions tailored to the mental health and driving behaviors of older adults. These could include cognitive retraining, driver rehabilitation programs, and routine depression screening to enhance road safety and preserve independence,” Babulal said.
“Encouraging older adults with MDD to self-regulate their driving habits (eg, avoiding night driving or high-traffic situations) and educating them about potential driving challenges related to their condition can enhance safety,” he added.
Commenting on this study, Ipsit Vahia, MD, McLean Hospital, Belmont, Massachusetts, and Harvard Medical School, Boston, Massachusetts, said it “adds nuance to our understanding of how depression can impact driving among older adults.
“While the connection between depression and a higher incident of crashes is known, this study demonstrates an association with riskier driving behaviors such as speeding,” Vahia said. “It highlights the importance of clinicians proactively initiating discussion of driving and safety when working with older adults with depressive symptoms.”
This work was funded by grants from the National Institutes of Health and National Institute on Aging. Babulal had no relevant disclosures. Vahia had served as a consultant for Otsuka.
A version of this article appeared on Medscape.com.
Older adults with major depressive disorder (MDD) exhibit riskier driving behaviors, compared with their nondepressed peers, including hard braking, cornering, and unpredictable driving patterns, new research showed.
Data for the study came from commercial vehicle data trackers installed in participants’ vehicles. After about a year of follow-up, the investigators found that MDD was associated with an increase in the amount and severity of risking driving, even after they controlled for antidepressant use.
Late-life depression often goes undiagnosed, and the new findings highlight the importance of routine depression screening and targeted interventions to ensure driving safety among older adults, the study team said.
“By using longitudinal, real-world driving data rather than controlled settings or self-reports, the study provides robust evidence of how MDD influences driving behaviors in day-to-day contexts,” first author Ganesh M. Babulal, PhD, OTD, with the Department of Neurology, Washington University School of Medicine in St Louis, Missouri, said in an interview.
“By analyzing the influence of antidepressant use and overall medication load, the study disentangles the effects of MDD from those of driver-impairing medications, further clarifying the unique contributions of depression to driving behaviors,” Babulal noted.
The study was published online in JAMA Network Open.
Road Risks
As the number of older adults grows, safe driving practices in this age group become increasingly crucial. By 2050, one quarter of drivers in the United States will be older than 65 years. MDD affects about 8% of US adults and is linked to cognitive impairments that may compromise driving safety.
Prior studies revealed a link between depression and increased car crash risk, regardless of age. And earlier research by Babulal and colleagues showed that older adults with depression were three times more likely to receive a marginal or failing score on a standardized road test.
To further study the issue, Babulal and colleagues examined the impact of MDD on naturalistic driving behaviors among older adults using longitudinal data.
Participants were recruited from the Driving Real-World In-Vehicle Evaluation System Project, where their daily driving behaviors were recorded using commercial vehicle data loggers installed in their personal vehicles.
The cohort included 85 adults with MDD (mean age, 69 years; 71% women) and 310 adults without MDD (mean age, 70 years; 49% women). The majority of participants in both groups were non-Hispanic White individuals.
Based on intercepts, adults with MDD had a propensity toward riskier driving habits with a higher frequency of speeding events and spending more time on the road than those without MDD, they found.
During a mean of 1.1 years of follow-up, compared with older adults without MDD, those with MDD exhibited significantly more hard braking (P < .001) and hard cornering events per trip (P = .04) over time. They also traveled farther from home and visited more unique destinations (P < .001 for both).
Over time, older adults also displayed increased entropy in driving patterns (P < .001), indicated less predictable driving routes.
“Driving unpredictability, as evidenced by increased random entropy, highlights the unique challenges posed by MDD in maintaining safe driving practices,” the researchers wrote.
Adjustment for antidepressant use, which could impair driving, or total medication burden did not change the findings, suggesting MDD independently affects driving.
“Most importantly, our findings demonstrate that MDD — a common and treatable illness in older adults — was associated with an increase in both the amount and magnitude of risky driving behaviors over time,” the researchers wrote.
The researchers noted that the study did not account for changes in depression severity over time and other psychiatric conditions co-occurring with MDD were not adjusted for. Also, situational factors like weather or traffic conditions were not assessed.
Clear Clinical Implications
There is a “pressing need” for targeted interventions to manage and mitigate the driving risks associated with late-life depression, the researchers wrote.
“The study emphasizes the need for interventions tailored to the mental health and driving behaviors of older adults. These could include cognitive retraining, driver rehabilitation programs, and routine depression screening to enhance road safety and preserve independence,” Babulal said.
“Encouraging older adults with MDD to self-regulate their driving habits (eg, avoiding night driving or high-traffic situations) and educating them about potential driving challenges related to their condition can enhance safety,” he added.
Commenting on this study, Ipsit Vahia, MD, McLean Hospital, Belmont, Massachusetts, and Harvard Medical School, Boston, Massachusetts, said it “adds nuance to our understanding of how depression can impact driving among older adults.
“While the connection between depression and a higher incident of crashes is known, this study demonstrates an association with riskier driving behaviors such as speeding,” Vahia said. “It highlights the importance of clinicians proactively initiating discussion of driving and safety when working with older adults with depressive symptoms.”
This work was funded by grants from the National Institutes of Health and National Institute on Aging. Babulal had no relevant disclosures. Vahia had served as a consultant for Otsuka.
A version of this article appeared on Medscape.com.
Older adults with major depressive disorder (MDD) exhibit riskier driving behaviors, compared with their nondepressed peers, including hard braking, cornering, and unpredictable driving patterns, new research showed.
Data for the study came from commercial vehicle data trackers installed in participants’ vehicles. After about a year of follow-up, the investigators found that MDD was associated with an increase in the amount and severity of risking driving, even after they controlled for antidepressant use.
Late-life depression often goes undiagnosed, and the new findings highlight the importance of routine depression screening and targeted interventions to ensure driving safety among older adults, the study team said.
“By using longitudinal, real-world driving data rather than controlled settings or self-reports, the study provides robust evidence of how MDD influences driving behaviors in day-to-day contexts,” first author Ganesh M. Babulal, PhD, OTD, with the Department of Neurology, Washington University School of Medicine in St Louis, Missouri, said in an interview.
“By analyzing the influence of antidepressant use and overall medication load, the study disentangles the effects of MDD from those of driver-impairing medications, further clarifying the unique contributions of depression to driving behaviors,” Babulal noted.
The study was published online in JAMA Network Open.
Road Risks
As the number of older adults grows, safe driving practices in this age group become increasingly crucial. By 2050, one quarter of drivers in the United States will be older than 65 years. MDD affects about 8% of US adults and is linked to cognitive impairments that may compromise driving safety.
Prior studies revealed a link between depression and increased car crash risk, regardless of age. And earlier research by Babulal and colleagues showed that older adults with depression were three times more likely to receive a marginal or failing score on a standardized road test.
To further study the issue, Babulal and colleagues examined the impact of MDD on naturalistic driving behaviors among older adults using longitudinal data.
Participants were recruited from the Driving Real-World In-Vehicle Evaluation System Project, where their daily driving behaviors were recorded using commercial vehicle data loggers installed in their personal vehicles.
The cohort included 85 adults with MDD (mean age, 69 years; 71% women) and 310 adults without MDD (mean age, 70 years; 49% women). The majority of participants in both groups were non-Hispanic White individuals.
Based on intercepts, adults with MDD had a propensity toward riskier driving habits with a higher frequency of speeding events and spending more time on the road than those without MDD, they found.
During a mean of 1.1 years of follow-up, compared with older adults without MDD, those with MDD exhibited significantly more hard braking (P < .001) and hard cornering events per trip (P = .04) over time. They also traveled farther from home and visited more unique destinations (P < .001 for both).
Over time, older adults also displayed increased entropy in driving patterns (P < .001), indicated less predictable driving routes.
“Driving unpredictability, as evidenced by increased random entropy, highlights the unique challenges posed by MDD in maintaining safe driving practices,” the researchers wrote.
Adjustment for antidepressant use, which could impair driving, or total medication burden did not change the findings, suggesting MDD independently affects driving.
“Most importantly, our findings demonstrate that MDD — a common and treatable illness in older adults — was associated with an increase in both the amount and magnitude of risky driving behaviors over time,” the researchers wrote.
The researchers noted that the study did not account for changes in depression severity over time and other psychiatric conditions co-occurring with MDD were not adjusted for. Also, situational factors like weather or traffic conditions were not assessed.
Clear Clinical Implications
There is a “pressing need” for targeted interventions to manage and mitigate the driving risks associated with late-life depression, the researchers wrote.
“The study emphasizes the need for interventions tailored to the mental health and driving behaviors of older adults. These could include cognitive retraining, driver rehabilitation programs, and routine depression screening to enhance road safety and preserve independence,” Babulal said.
“Encouraging older adults with MDD to self-regulate their driving habits (eg, avoiding night driving or high-traffic situations) and educating them about potential driving challenges related to their condition can enhance safety,” he added.
Commenting on this study, Ipsit Vahia, MD, McLean Hospital, Belmont, Massachusetts, and Harvard Medical School, Boston, Massachusetts, said it “adds nuance to our understanding of how depression can impact driving among older adults.
“While the connection between depression and a higher incident of crashes is known, this study demonstrates an association with riskier driving behaviors such as speeding,” Vahia said. “It highlights the importance of clinicians proactively initiating discussion of driving and safety when working with older adults with depressive symptoms.”
This work was funded by grants from the National Institutes of Health and National Institute on Aging. Babulal had no relevant disclosures. Vahia had served as a consultant for Otsuka.
A version of this article appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Americans’ Top Causes of Anxiety Revealed
What current events are keeping Americans up at night? The economy, gun violence, and hate crimes top the list, results from a newly released American Psychiatric Association (APA) survey showed.
Anxiety about international conflicts — namely, the Russia-Ukraine and Israel-Hamas wars — also remains high.
“While we like to stay informed, the news can also impact our mental health, and being mindful of that impact is important. If current events seem overwhelming it may be time to limit your news consumption,” APA CEO and Medical Director Marketa M. Wills, MD, MBD, said in a statement.
Survey results also revealed the election and the holidays were common sources of stress.
“Election stress is common, and it’s important to recognize that, as we’re spending more time with family around the holidays, we might need to have a strategy to manage our own mental health during these times,” Howard Liu, MD, MBA, chair of the Department of Psychiatry, University of Nebraska Medical Center, Omaha, told this news organization.
“As with any difficult topic, we all have different levels of avoidance or desire to engage, and it’s okay to set boundaries based on past conversations with family. I think sometimes we get drawn into arguments that we don’t want to have or may not be productive for either side,” said Liu, who chairs the APA Council on Communications.
In line with trends throughout 2024, adults polled by the APA in November were most anxious about the economy (75%), gun violence (64%), and hate crimes (60%). The survey included 2200 US adults as part of the APA’s Healthy Minds monthly series.
Anxiety about international conflicts remained high in November at 57% — but was down from 65% in August.
Election anxiety remained high in mid-November but not as high as before the election. In August, 72% of Americans said they were anxious about the 2024 election. In November, just after the election, 50% reported anxiety over the election outcome.
“I think the anticipation of change can sometimes be worse than the change itself. So I think a lot of people are now taking the attitude of — let’s wait and see what actually happens,” said Liu.
Half the adults (50%) anticipate the same amount of stress as the 2023 holiday season, while almost one third expect more stress (28%), and one fourth anticipate less stress (23%).
When asked how the holidays generally affect their mental health, 38% said it has positive effects, and 21% said the opposite was true.
Anxiety About the Future
After a divisive election, most Americans were ready to avoid politics at holiday gatherings, results of a separate poll conducted by the American Psychological Association in late November showed.
That poll, which included 2000 US adults, showed that more than 7 in 10 (72%) said they wanted to avoid talking about politics with family and friends over the holidays.
In addition, nearly two in five adults (39%) reported they were stressed by the thought of politics being raised at holiday gatherings and would try to avoid family members they disagree with. Younger adults were significantly more likely than were their older counterparts to report they planned to avoid family over the holidays.
The future of the nation also weighs on the minds of many Americans.
Another poll conducted by the American Psychological Association in August prior to the 2024 US presidential election showed that 77% of respondents said the future of the nation was a significant source of stress for them.
In the postelection poll, more than one third of adults (35%) said they are more stressed about the future of the nation now than they were leading up to the election, and another third reported they are now less stressed (32%). A quarter of adults (24%) said their stress about the future of the nation was unchanged, and 9% said they were not stressed about the future of the nation then or now.
“There’s still clearly a lot of uncertainty, and there’s a lot of activity right now for the president-elect,” which can contribute to anxiety, C. Vaile Wright, PhD, psychologist, researcher and spokesperson for the American Psychological Association, told this news organization.
These data also show that many Americans have little or no trust in the government, with some wanting to leave the United States.
“It’s a reflection of the lack of strong leadership across the board in this country. We have a governmental system in place that does not seem to serve the people, but to serve corporations and maintenance of power. I think people are disillusioned with it and that creates a lack of trust and hopelessness,” Wright noted.
Liu and Wright reported no relevant disclosures.
A version of this article appeared on Medscape.com.
What current events are keeping Americans up at night? The economy, gun violence, and hate crimes top the list, results from a newly released American Psychiatric Association (APA) survey showed.
Anxiety about international conflicts — namely, the Russia-Ukraine and Israel-Hamas wars — also remains high.
“While we like to stay informed, the news can also impact our mental health, and being mindful of that impact is important. If current events seem overwhelming it may be time to limit your news consumption,” APA CEO and Medical Director Marketa M. Wills, MD, MBD, said in a statement.
Survey results also revealed the election and the holidays were common sources of stress.
“Election stress is common, and it’s important to recognize that, as we’re spending more time with family around the holidays, we might need to have a strategy to manage our own mental health during these times,” Howard Liu, MD, MBA, chair of the Department of Psychiatry, University of Nebraska Medical Center, Omaha, told this news organization.
“As with any difficult topic, we all have different levels of avoidance or desire to engage, and it’s okay to set boundaries based on past conversations with family. I think sometimes we get drawn into arguments that we don’t want to have or may not be productive for either side,” said Liu, who chairs the APA Council on Communications.
In line with trends throughout 2024, adults polled by the APA in November were most anxious about the economy (75%), gun violence (64%), and hate crimes (60%). The survey included 2200 US adults as part of the APA’s Healthy Minds monthly series.
Anxiety about international conflicts remained high in November at 57% — but was down from 65% in August.
Election anxiety remained high in mid-November but not as high as before the election. In August, 72% of Americans said they were anxious about the 2024 election. In November, just after the election, 50% reported anxiety over the election outcome.
“I think the anticipation of change can sometimes be worse than the change itself. So I think a lot of people are now taking the attitude of — let’s wait and see what actually happens,” said Liu.
Half the adults (50%) anticipate the same amount of stress as the 2023 holiday season, while almost one third expect more stress (28%), and one fourth anticipate less stress (23%).
When asked how the holidays generally affect their mental health, 38% said it has positive effects, and 21% said the opposite was true.
Anxiety About the Future
After a divisive election, most Americans were ready to avoid politics at holiday gatherings, results of a separate poll conducted by the American Psychological Association in late November showed.
That poll, which included 2000 US adults, showed that more than 7 in 10 (72%) said they wanted to avoid talking about politics with family and friends over the holidays.
In addition, nearly two in five adults (39%) reported they were stressed by the thought of politics being raised at holiday gatherings and would try to avoid family members they disagree with. Younger adults were significantly more likely than were their older counterparts to report they planned to avoid family over the holidays.
The future of the nation also weighs on the minds of many Americans.
Another poll conducted by the American Psychological Association in August prior to the 2024 US presidential election showed that 77% of respondents said the future of the nation was a significant source of stress for them.
In the postelection poll, more than one third of adults (35%) said they are more stressed about the future of the nation now than they were leading up to the election, and another third reported they are now less stressed (32%). A quarter of adults (24%) said their stress about the future of the nation was unchanged, and 9% said they were not stressed about the future of the nation then or now.
“There’s still clearly a lot of uncertainty, and there’s a lot of activity right now for the president-elect,” which can contribute to anxiety, C. Vaile Wright, PhD, psychologist, researcher and spokesperson for the American Psychological Association, told this news organization.
These data also show that many Americans have little or no trust in the government, with some wanting to leave the United States.
“It’s a reflection of the lack of strong leadership across the board in this country. We have a governmental system in place that does not seem to serve the people, but to serve corporations and maintenance of power. I think people are disillusioned with it and that creates a lack of trust and hopelessness,” Wright noted.
Liu and Wright reported no relevant disclosures.
A version of this article appeared on Medscape.com.
What current events are keeping Americans up at night? The economy, gun violence, and hate crimes top the list, results from a newly released American Psychiatric Association (APA) survey showed.
Anxiety about international conflicts — namely, the Russia-Ukraine and Israel-Hamas wars — also remains high.
“While we like to stay informed, the news can also impact our mental health, and being mindful of that impact is important. If current events seem overwhelming it may be time to limit your news consumption,” APA CEO and Medical Director Marketa M. Wills, MD, MBD, said in a statement.
Survey results also revealed the election and the holidays were common sources of stress.
“Election stress is common, and it’s important to recognize that, as we’re spending more time with family around the holidays, we might need to have a strategy to manage our own mental health during these times,” Howard Liu, MD, MBA, chair of the Department of Psychiatry, University of Nebraska Medical Center, Omaha, told this news organization.
“As with any difficult topic, we all have different levels of avoidance or desire to engage, and it’s okay to set boundaries based on past conversations with family. I think sometimes we get drawn into arguments that we don’t want to have or may not be productive for either side,” said Liu, who chairs the APA Council on Communications.
In line with trends throughout 2024, adults polled by the APA in November were most anxious about the economy (75%), gun violence (64%), and hate crimes (60%). The survey included 2200 US adults as part of the APA’s Healthy Minds monthly series.
Anxiety about international conflicts remained high in November at 57% — but was down from 65% in August.
Election anxiety remained high in mid-November but not as high as before the election. In August, 72% of Americans said they were anxious about the 2024 election. In November, just after the election, 50% reported anxiety over the election outcome.
“I think the anticipation of change can sometimes be worse than the change itself. So I think a lot of people are now taking the attitude of — let’s wait and see what actually happens,” said Liu.
Half the adults (50%) anticipate the same amount of stress as the 2023 holiday season, while almost one third expect more stress (28%), and one fourth anticipate less stress (23%).
When asked how the holidays generally affect their mental health, 38% said it has positive effects, and 21% said the opposite was true.
Anxiety About the Future
After a divisive election, most Americans were ready to avoid politics at holiday gatherings, results of a separate poll conducted by the American Psychological Association in late November showed.
That poll, which included 2000 US adults, showed that more than 7 in 10 (72%) said they wanted to avoid talking about politics with family and friends over the holidays.
In addition, nearly two in five adults (39%) reported they were stressed by the thought of politics being raised at holiday gatherings and would try to avoid family members they disagree with. Younger adults were significantly more likely than were their older counterparts to report they planned to avoid family over the holidays.
The future of the nation also weighs on the minds of many Americans.
Another poll conducted by the American Psychological Association in August prior to the 2024 US presidential election showed that 77% of respondents said the future of the nation was a significant source of stress for them.
In the postelection poll, more than one third of adults (35%) said they are more stressed about the future of the nation now than they were leading up to the election, and another third reported they are now less stressed (32%). A quarter of adults (24%) said their stress about the future of the nation was unchanged, and 9% said they were not stressed about the future of the nation then or now.
“There’s still clearly a lot of uncertainty, and there’s a lot of activity right now for the president-elect,” which can contribute to anxiety, C. Vaile Wright, PhD, psychologist, researcher and spokesperson for the American Psychological Association, told this news organization.
These data also show that many Americans have little or no trust in the government, with some wanting to leave the United States.
“It’s a reflection of the lack of strong leadership across the board in this country. We have a governmental system in place that does not seem to serve the people, but to serve corporations and maintenance of power. I think people are disillusioned with it and that creates a lack of trust and hopelessness,” Wright noted.
Liu and Wright reported no relevant disclosures.
A version of this article appeared on Medscape.com.
New Guidance Recommends Metformin to Prevent Antipsychotic Weight Gain
A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.
There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.
“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.”
The guideline was published online on December 9 in Schizophrenia Bulletin.
It offers three key recommendations:
- Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
- Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
- Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.
The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.
The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.
In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.
Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.
While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.
“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.
Experts Weigh In
This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.
Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”
While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.
Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.
“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.
Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.
“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.
“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.
Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.
Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.
This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.
A version of this article appeared on Medscape.com.
A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.
There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.
“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.”
The guideline was published online on December 9 in Schizophrenia Bulletin.
It offers three key recommendations:
- Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
- Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
- Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.
The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.
The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.
In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.
Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.
While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.
“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.
Experts Weigh In
This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.
Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”
While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.
Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.
“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.
Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.
“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.
“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.
Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.
Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.
This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.
A version of this article appeared on Medscape.com.
A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.
There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.
“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.”
The guideline was published online on December 9 in Schizophrenia Bulletin.
It offers three key recommendations:
- Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
- Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
- Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.
The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.
The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.
In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.
Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.
While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.
“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.
Experts Weigh In
This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.
Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”
While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.
Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.
“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.
Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.
“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.
“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.
Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.
Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.
This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.
A version of this article appeared on Medscape.com.
FROM SCHIZOPHRENIA BULLETIN
Most Effective Treatments for Adult ADHD Identified
, results of a large comprehensive meta-analysis showed.
The study of 113 randomized controlled trials with nearly 15,000 adults with a formal diagnosis of ADHD also revealed that atomoxetine is less acceptable to patients and that results of efficacy of nonpharmacological strategies are inconsistent.
Data on long-term efficacy of ADHD therapies are lacking, investigators noted, so these results only apply to short-term efficacy.
“There is a lot of controversy about medication, so these are quite reassuring data and certainly reinforce the role of medication as a treatment for ADHD,” study investigator Samuele Cortese, MD, PhD, with University of Southampton, England, said during a press briefing hosted by the UK Science Media Center where the findings were released.
The results also point to the “possible role of nonpharmacological interventions, which are currently not well established in current guidelines. However, there is a need for better evidence to fully understand the exact effect of these nonpharmacological interventions,” Cortese noted.
The study was published online in The Lancet Psychiatry.
Bridging the Knowledge Gap
Once thought to be a childhood disorder only, ADHD is now well-known to persist into adulthood, affecting roughly 2.5% of the general adult population worldwide. The comparative benefits and harms of available interventions for ADHD in adults remain unclear.
To address this knowledge gap, researchers did a comprehensive systematic review and component network meta-analysis comparing a broad range of drug and nondrug treatments for adults with ADHD across several outcomes.
For reducing core ADHD symptoms at 12 weeks, only stimulants and atomoxetine were better than placebo in self-reported and clinician-reported rating scales, the study team found.
For stimulants, the standardized mean differences (SMDs) on the self-reported and clinician-reported scales were 0.39 and 0.61, respectively. The corresponding SMDs for atomoxetine were 0.38 and 0.51.
There was no evidence that ADHD medications were better than placebo in improving additional relevant outcomes such as quality of life.
In terms of nondrug interventions, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation were better than placebo only on clinician-reported measures, with SMDs of −1.35, −0.79, −0.77, and −0.78, respectively.
However, the evidence for nondrug strategies is less conclusive overall, with “discordant results across types of raters and based on a small body of evidence,” the authors wrote in their article.
And evidence for long-term efficacy (beyond 12 weeks) for ADHD interventions is “limited and under-investigated,” they said.
Regarding acceptability, all strategies were similar to placebo except for atomoxetine and guanfacine which had lower acceptability than placebo.
“It’s very important to emphasize that we focused on the average effect, not at an individual level,” first author Edoardo Ostinelli, MD, with University of Oxford, England, said at the briefing. “Therefore, we cannot make any recommendation at an individual level. We need studies with individual participant data so that we can personalize treatment.”
Cortese said the information from this analysis may be particularly important for “psychoeducation” of the patient before actually starting with a treatment plan. Patients often ask about nonpharmacological interventions and this study provides the “best synthesis of available data to inform these discussions,” he said.
Experts Weigh In
Several experts weighed in on the results in a statement from the UK Science Media Center.
Celso Arango, MD, PhD, psychiatrist with Gregorio Marañón General University Hospital, Madrid, Spain, noted that there is a “clear shortage of research on ADHD in adulthood, particularly regarding medium-term (beyond 12 weeks) and long-term treatment outcomes. Consequently, the findings are applicable only to short-term treatment.”
Another strength of the study is that it was developed with input from people with ADHD, Arango added, making it “highly relevant.”
The majority of studies available for the analysis involved pharmacological treatments, which is important to consider when interpreting the findings, noted Katya Rubia, PhD, professor of cognitive neuroscience, King’s College London, England.
“For example, for neurostimulation, only 10 studies were included and on very heterogeneous stimulation methods,” Rubia said. “The evidence on the efficacy of neurostimulation is therefore hardly conclusive and more studies are needed to establish their efficacy.”
Roi Cohen Kadosh, PhD, professor of cognitive neuroscience, University of Surrey, Guildford, England, agreed. While the study is a “valuable contribution to the literature,” it sheds light on “both the scarcity of neurostimulation research and the limited exploration of combined treatment approaches for ADHD,” he said.
“While novel neurostimulation methods linked to neuroplasticity — such as those we have demonstrated to be superior in children with ADHD — were not covered here, they have shown promising and lasting benefits. In contrast, research in adults remains relatively underdeveloped. Moving forward, greater emphasis on innovative, tolerable, personalized, and sustainable neurostimulation approaches is essential to meet the unmet clinical needs of adults with ADHD,” Kadosh added.
In a commentary in The Lancet Psychiatry, David Coghill, MD, with The University of Melbourne, Australia, cautioned that the findings do not mean that potential benefits of nonpharmacological interventions should be dismissed.
“While some of the nonpharmacological treatments (eg, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation) showed effects on clinician-rated outcomes similar to, and in some cases greater than, the pharmacological treatments, they did not show the same effects on self-reported outcomes. These interventions were therefore considered less robust than the pharmacological treatments that showed changes on both measurement types,” he wrote.
This study had no commercial funding. Ostinelli had received research and consultancy fees from Angelini Pharma. Cortese received reimbursement for travel and accommodation expenses in relation to lectures delivered for the Association for Child and Adolescent Central Health, the Canadian ADHD Alliance Resource, and the British Association of Psychopharmacology; and had received honoraria from MEDICE; and is chair of the European ADHD Guidelines Group. Arango, Rubia, and Kadosh had no relevant disclosures. Coghill had received honoraria from CCM Conecta, Takeda, Novartis, Servier, and MEDICE.
A version of this article first appeared on Medscape.com.
, results of a large comprehensive meta-analysis showed.
The study of 113 randomized controlled trials with nearly 15,000 adults with a formal diagnosis of ADHD also revealed that atomoxetine is less acceptable to patients and that results of efficacy of nonpharmacological strategies are inconsistent.
Data on long-term efficacy of ADHD therapies are lacking, investigators noted, so these results only apply to short-term efficacy.
“There is a lot of controversy about medication, so these are quite reassuring data and certainly reinforce the role of medication as a treatment for ADHD,” study investigator Samuele Cortese, MD, PhD, with University of Southampton, England, said during a press briefing hosted by the UK Science Media Center where the findings were released.
The results also point to the “possible role of nonpharmacological interventions, which are currently not well established in current guidelines. However, there is a need for better evidence to fully understand the exact effect of these nonpharmacological interventions,” Cortese noted.
The study was published online in The Lancet Psychiatry.
Bridging the Knowledge Gap
Once thought to be a childhood disorder only, ADHD is now well-known to persist into adulthood, affecting roughly 2.5% of the general adult population worldwide. The comparative benefits and harms of available interventions for ADHD in adults remain unclear.
To address this knowledge gap, researchers did a comprehensive systematic review and component network meta-analysis comparing a broad range of drug and nondrug treatments for adults with ADHD across several outcomes.
For reducing core ADHD symptoms at 12 weeks, only stimulants and atomoxetine were better than placebo in self-reported and clinician-reported rating scales, the study team found.
For stimulants, the standardized mean differences (SMDs) on the self-reported and clinician-reported scales were 0.39 and 0.61, respectively. The corresponding SMDs for atomoxetine were 0.38 and 0.51.
There was no evidence that ADHD medications were better than placebo in improving additional relevant outcomes such as quality of life.
In terms of nondrug interventions, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation were better than placebo only on clinician-reported measures, with SMDs of −1.35, −0.79, −0.77, and −0.78, respectively.
However, the evidence for nondrug strategies is less conclusive overall, with “discordant results across types of raters and based on a small body of evidence,” the authors wrote in their article.
And evidence for long-term efficacy (beyond 12 weeks) for ADHD interventions is “limited and under-investigated,” they said.
Regarding acceptability, all strategies were similar to placebo except for atomoxetine and guanfacine which had lower acceptability than placebo.
“It’s very important to emphasize that we focused on the average effect, not at an individual level,” first author Edoardo Ostinelli, MD, with University of Oxford, England, said at the briefing. “Therefore, we cannot make any recommendation at an individual level. We need studies with individual participant data so that we can personalize treatment.”
Cortese said the information from this analysis may be particularly important for “psychoeducation” of the patient before actually starting with a treatment plan. Patients often ask about nonpharmacological interventions and this study provides the “best synthesis of available data to inform these discussions,” he said.
Experts Weigh In
Several experts weighed in on the results in a statement from the UK Science Media Center.
Celso Arango, MD, PhD, psychiatrist with Gregorio Marañón General University Hospital, Madrid, Spain, noted that there is a “clear shortage of research on ADHD in adulthood, particularly regarding medium-term (beyond 12 weeks) and long-term treatment outcomes. Consequently, the findings are applicable only to short-term treatment.”
Another strength of the study is that it was developed with input from people with ADHD, Arango added, making it “highly relevant.”
The majority of studies available for the analysis involved pharmacological treatments, which is important to consider when interpreting the findings, noted Katya Rubia, PhD, professor of cognitive neuroscience, King’s College London, England.
“For example, for neurostimulation, only 10 studies were included and on very heterogeneous stimulation methods,” Rubia said. “The evidence on the efficacy of neurostimulation is therefore hardly conclusive and more studies are needed to establish their efficacy.”
Roi Cohen Kadosh, PhD, professor of cognitive neuroscience, University of Surrey, Guildford, England, agreed. While the study is a “valuable contribution to the literature,” it sheds light on “both the scarcity of neurostimulation research and the limited exploration of combined treatment approaches for ADHD,” he said.
“While novel neurostimulation methods linked to neuroplasticity — such as those we have demonstrated to be superior in children with ADHD — were not covered here, they have shown promising and lasting benefits. In contrast, research in adults remains relatively underdeveloped. Moving forward, greater emphasis on innovative, tolerable, personalized, and sustainable neurostimulation approaches is essential to meet the unmet clinical needs of adults with ADHD,” Kadosh added.
In a commentary in The Lancet Psychiatry, David Coghill, MD, with The University of Melbourne, Australia, cautioned that the findings do not mean that potential benefits of nonpharmacological interventions should be dismissed.
“While some of the nonpharmacological treatments (eg, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation) showed effects on clinician-rated outcomes similar to, and in some cases greater than, the pharmacological treatments, they did not show the same effects on self-reported outcomes. These interventions were therefore considered less robust than the pharmacological treatments that showed changes on both measurement types,” he wrote.
This study had no commercial funding. Ostinelli had received research and consultancy fees from Angelini Pharma. Cortese received reimbursement for travel and accommodation expenses in relation to lectures delivered for the Association for Child and Adolescent Central Health, the Canadian ADHD Alliance Resource, and the British Association of Psychopharmacology; and had received honoraria from MEDICE; and is chair of the European ADHD Guidelines Group. Arango, Rubia, and Kadosh had no relevant disclosures. Coghill had received honoraria from CCM Conecta, Takeda, Novartis, Servier, and MEDICE.
A version of this article first appeared on Medscape.com.
, results of a large comprehensive meta-analysis showed.
The study of 113 randomized controlled trials with nearly 15,000 adults with a formal diagnosis of ADHD also revealed that atomoxetine is less acceptable to patients and that results of efficacy of nonpharmacological strategies are inconsistent.
Data on long-term efficacy of ADHD therapies are lacking, investigators noted, so these results only apply to short-term efficacy.
“There is a lot of controversy about medication, so these are quite reassuring data and certainly reinforce the role of medication as a treatment for ADHD,” study investigator Samuele Cortese, MD, PhD, with University of Southampton, England, said during a press briefing hosted by the UK Science Media Center where the findings were released.
The results also point to the “possible role of nonpharmacological interventions, which are currently not well established in current guidelines. However, there is a need for better evidence to fully understand the exact effect of these nonpharmacological interventions,” Cortese noted.
The study was published online in The Lancet Psychiatry.
Bridging the Knowledge Gap
Once thought to be a childhood disorder only, ADHD is now well-known to persist into adulthood, affecting roughly 2.5% of the general adult population worldwide. The comparative benefits and harms of available interventions for ADHD in adults remain unclear.
To address this knowledge gap, researchers did a comprehensive systematic review and component network meta-analysis comparing a broad range of drug and nondrug treatments for adults with ADHD across several outcomes.
For reducing core ADHD symptoms at 12 weeks, only stimulants and atomoxetine were better than placebo in self-reported and clinician-reported rating scales, the study team found.
For stimulants, the standardized mean differences (SMDs) on the self-reported and clinician-reported scales were 0.39 and 0.61, respectively. The corresponding SMDs for atomoxetine were 0.38 and 0.51.
There was no evidence that ADHD medications were better than placebo in improving additional relevant outcomes such as quality of life.
In terms of nondrug interventions, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation were better than placebo only on clinician-reported measures, with SMDs of −1.35, −0.79, −0.77, and −0.78, respectively.
However, the evidence for nondrug strategies is less conclusive overall, with “discordant results across types of raters and based on a small body of evidence,” the authors wrote in their article.
And evidence for long-term efficacy (beyond 12 weeks) for ADHD interventions is “limited and under-investigated,” they said.
Regarding acceptability, all strategies were similar to placebo except for atomoxetine and guanfacine which had lower acceptability than placebo.
“It’s very important to emphasize that we focused on the average effect, not at an individual level,” first author Edoardo Ostinelli, MD, with University of Oxford, England, said at the briefing. “Therefore, we cannot make any recommendation at an individual level. We need studies with individual participant data so that we can personalize treatment.”
Cortese said the information from this analysis may be particularly important for “psychoeducation” of the patient before actually starting with a treatment plan. Patients often ask about nonpharmacological interventions and this study provides the “best synthesis of available data to inform these discussions,” he said.
Experts Weigh In
Several experts weighed in on the results in a statement from the UK Science Media Center.
Celso Arango, MD, PhD, psychiatrist with Gregorio Marañón General University Hospital, Madrid, Spain, noted that there is a “clear shortage of research on ADHD in adulthood, particularly regarding medium-term (beyond 12 weeks) and long-term treatment outcomes. Consequently, the findings are applicable only to short-term treatment.”
Another strength of the study is that it was developed with input from people with ADHD, Arango added, making it “highly relevant.”
The majority of studies available for the analysis involved pharmacological treatments, which is important to consider when interpreting the findings, noted Katya Rubia, PhD, professor of cognitive neuroscience, King’s College London, England.
“For example, for neurostimulation, only 10 studies were included and on very heterogeneous stimulation methods,” Rubia said. “The evidence on the efficacy of neurostimulation is therefore hardly conclusive and more studies are needed to establish their efficacy.”
Roi Cohen Kadosh, PhD, professor of cognitive neuroscience, University of Surrey, Guildford, England, agreed. While the study is a “valuable contribution to the literature,” it sheds light on “both the scarcity of neurostimulation research and the limited exploration of combined treatment approaches for ADHD,” he said.
“While novel neurostimulation methods linked to neuroplasticity — such as those we have demonstrated to be superior in children with ADHD — were not covered here, they have shown promising and lasting benefits. In contrast, research in adults remains relatively underdeveloped. Moving forward, greater emphasis on innovative, tolerable, personalized, and sustainable neurostimulation approaches is essential to meet the unmet clinical needs of adults with ADHD,” Kadosh added.
In a commentary in The Lancet Psychiatry, David Coghill, MD, with The University of Melbourne, Australia, cautioned that the findings do not mean that potential benefits of nonpharmacological interventions should be dismissed.
“While some of the nonpharmacological treatments (eg, cognitive behavioral therapy, cognitive remediation, mindfulness, psychoeducation, and transcranial direct current stimulation) showed effects on clinician-rated outcomes similar to, and in some cases greater than, the pharmacological treatments, they did not show the same effects on self-reported outcomes. These interventions were therefore considered less robust than the pharmacological treatments that showed changes on both measurement types,” he wrote.
This study had no commercial funding. Ostinelli had received research and consultancy fees from Angelini Pharma. Cortese received reimbursement for travel and accommodation expenses in relation to lectures delivered for the Association for Child and Adolescent Central Health, the Canadian ADHD Alliance Resource, and the British Association of Psychopharmacology; and had received honoraria from MEDICE; and is chair of the European ADHD Guidelines Group. Arango, Rubia, and Kadosh had no relevant disclosures. Coghill had received honoraria from CCM Conecta, Takeda, Novartis, Servier, and MEDICE.
A version of this article first appeared on Medscape.com.
FROM THE LANCET PSYCHIATRY
APA Updates Guidance on Borderline Personality Disorder
For the first time since 2001, the American Psychiatric Association (APA) has updated its clinical practice guideline on borderline personality disorder (BPD).
The new guideline is “quite substantial and really serves as a rich textbook of the literature, about borderline personality disorder that any clinician would find very valuable,” John Oldham, MD, MS, member of the guideline writing group, said in an interview.
“The overall goal is to improve the quality of care and treatment outcomes for patients with BPD,” said Oldham, distinguished emeritus professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine in Houston, Texas.
The updated guideline was published online in The American Journal of Psychiatry.
It includes eight evidence-based recommendation statements covering assessment and determination of treatment plan, psychosocial interventions, and pharmacology.
Recommendations denoted by the numeral 1 after the guideline statement indicates confidence that the benefits of the intervention clearly outweigh the harms. A suggestion (denoted by the numeral 2 after the guideline statement) indicates greater uncertainty.
Each guideline statement also has an associated rating for the strength of supporting research evidence — high, moderate, and low, denoted by the letters A, B, and C, respectively.
The APA recommends (1C) that the initial assessment of a patient with possible BPD include the reason the individual is presenting for evaluation; the patient’s goals and preferences for treatment; a review of psychiatric symptoms, including core features of personality disorders and common co-occurring disorders; a psychiatric treatment history; assessment of physical health and psychosocial and cultural factors; a mental status examination; and an assessment of risk of suicide, self-injury, and aggressive behaviors, as outlined in APA Practice Guidelines for the Psychiatric Evaluation of Adults, Third Edition.
The APA suggests (2C) that the initial psychiatric evaluation of a patient with BPD include a quantitative measure to identify and determine the severity of symptoms and impairments of functioning that may be a focus of treatment.
The guideline lists several options, including (but not limited to) the 23-item version of the Borderline Symptom List; the Borderline Evaluation of Severity Over Time; 11-item Borderline Personality Features Scale for Children; and Difficulty in Emotional Regulation Scale.
The APA recommends (1C) that a patient with BPD have a documented, comprehensive, and person-centered treatment plan and be engaged in a collaborative discussion about their diagnosis and treatment, which includes psychoeducation related to the disorder. “This is a new recommendation,” Oldham said.
Another new recommendation (1B) advises a structured approach to psychotherapy that has support in the literature and targets the core features of the disorder. These include dialectical behavior therapy and mentalization-based therapy along with other therapies that have demonstrated efficacy in recent studies.
The APA recommends (1C) that a patient with BPD have a review of co-occurring disorders, prior psychotherapies, other nonpharmacological treatments, past medication trials, and current medications before initiating any new medication.
The APA suggests (2C) that that any psychotropic medication treatment of BPD be “time-limited, aimed at addressing a specific measurable target symptom, and adjunctive to psychotherapy.”
“Medication is not a primary treatment but may help diminish symptoms such as affective instability, impulsivity, or psychotic-like symptoms in individual patients, helping them to remain engaged in treatment or reducing short-term risks of self-harm,” said Oldham.
The APA recommends (1C) a review and reconciliation of medications at least every 6 months to assess the effectiveness of treatment and identify medications that warrant tapering or discontinuation.
An Alternative Model of Care
Oldham said it’s important to note that the Alternative DSM-5 Model for Personality Disorders (AMPD) is increasingly being integrated into clinical practice with adolescents and adults.
Unlike the traditional categorical system, which diagnoses personality disorders as distinct and separate conditions, the AMPD views personality disorders along a continuum of severity and impairment.
The AMPD recognizes the variability and overlap in personality disorder symptoms and provides a nuanced, individualized framework for assessment and treatment planning.
Oldham co-chaired the work group that developed the proposal for the alternative model.
“Despite the growing recognition of the importance of the alternative model, our systematic reviews did not identify treatment studies using the alternative model that met our inclusion criteria. Therefore, it is not included in the new guideline,” he said.
Development of the guideline had no commercial funding. Oldham reported no conflicts of interest with his work on the guideline.
A version of this article first appeared on Medscape.com.
For the first time since 2001, the American Psychiatric Association (APA) has updated its clinical practice guideline on borderline personality disorder (BPD).
The new guideline is “quite substantial and really serves as a rich textbook of the literature, about borderline personality disorder that any clinician would find very valuable,” John Oldham, MD, MS, member of the guideline writing group, said in an interview.
“The overall goal is to improve the quality of care and treatment outcomes for patients with BPD,” said Oldham, distinguished emeritus professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine in Houston, Texas.
The updated guideline was published online in The American Journal of Psychiatry.
It includes eight evidence-based recommendation statements covering assessment and determination of treatment plan, psychosocial interventions, and pharmacology.
Recommendations denoted by the numeral 1 after the guideline statement indicates confidence that the benefits of the intervention clearly outweigh the harms. A suggestion (denoted by the numeral 2 after the guideline statement) indicates greater uncertainty.
Each guideline statement also has an associated rating for the strength of supporting research evidence — high, moderate, and low, denoted by the letters A, B, and C, respectively.
The APA recommends (1C) that the initial assessment of a patient with possible BPD include the reason the individual is presenting for evaluation; the patient’s goals and preferences for treatment; a review of psychiatric symptoms, including core features of personality disorders and common co-occurring disorders; a psychiatric treatment history; assessment of physical health and psychosocial and cultural factors; a mental status examination; and an assessment of risk of suicide, self-injury, and aggressive behaviors, as outlined in APA Practice Guidelines for the Psychiatric Evaluation of Adults, Third Edition.
The APA suggests (2C) that the initial psychiatric evaluation of a patient with BPD include a quantitative measure to identify and determine the severity of symptoms and impairments of functioning that may be a focus of treatment.
The guideline lists several options, including (but not limited to) the 23-item version of the Borderline Symptom List; the Borderline Evaluation of Severity Over Time; 11-item Borderline Personality Features Scale for Children; and Difficulty in Emotional Regulation Scale.
The APA recommends (1C) that a patient with BPD have a documented, comprehensive, and person-centered treatment plan and be engaged in a collaborative discussion about their diagnosis and treatment, which includes psychoeducation related to the disorder. “This is a new recommendation,” Oldham said.
Another new recommendation (1B) advises a structured approach to psychotherapy that has support in the literature and targets the core features of the disorder. These include dialectical behavior therapy and mentalization-based therapy along with other therapies that have demonstrated efficacy in recent studies.
The APA recommends (1C) that a patient with BPD have a review of co-occurring disorders, prior psychotherapies, other nonpharmacological treatments, past medication trials, and current medications before initiating any new medication.
The APA suggests (2C) that that any psychotropic medication treatment of BPD be “time-limited, aimed at addressing a specific measurable target symptom, and adjunctive to psychotherapy.”
“Medication is not a primary treatment but may help diminish symptoms such as affective instability, impulsivity, or psychotic-like symptoms in individual patients, helping them to remain engaged in treatment or reducing short-term risks of self-harm,” said Oldham.
The APA recommends (1C) a review and reconciliation of medications at least every 6 months to assess the effectiveness of treatment and identify medications that warrant tapering or discontinuation.
An Alternative Model of Care
Oldham said it’s important to note that the Alternative DSM-5 Model for Personality Disorders (AMPD) is increasingly being integrated into clinical practice with adolescents and adults.
Unlike the traditional categorical system, which diagnoses personality disorders as distinct and separate conditions, the AMPD views personality disorders along a continuum of severity and impairment.
The AMPD recognizes the variability and overlap in personality disorder symptoms and provides a nuanced, individualized framework for assessment and treatment planning.
Oldham co-chaired the work group that developed the proposal for the alternative model.
“Despite the growing recognition of the importance of the alternative model, our systematic reviews did not identify treatment studies using the alternative model that met our inclusion criteria. Therefore, it is not included in the new guideline,” he said.
Development of the guideline had no commercial funding. Oldham reported no conflicts of interest with his work on the guideline.
A version of this article first appeared on Medscape.com.
For the first time since 2001, the American Psychiatric Association (APA) has updated its clinical practice guideline on borderline personality disorder (BPD).
The new guideline is “quite substantial and really serves as a rich textbook of the literature, about borderline personality disorder that any clinician would find very valuable,” John Oldham, MD, MS, member of the guideline writing group, said in an interview.
“The overall goal is to improve the quality of care and treatment outcomes for patients with BPD,” said Oldham, distinguished emeritus professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine in Houston, Texas.
The updated guideline was published online in The American Journal of Psychiatry.
It includes eight evidence-based recommendation statements covering assessment and determination of treatment plan, psychosocial interventions, and pharmacology.
Recommendations denoted by the numeral 1 after the guideline statement indicates confidence that the benefits of the intervention clearly outweigh the harms. A suggestion (denoted by the numeral 2 after the guideline statement) indicates greater uncertainty.
Each guideline statement also has an associated rating for the strength of supporting research evidence — high, moderate, and low, denoted by the letters A, B, and C, respectively.
The APA recommends (1C) that the initial assessment of a patient with possible BPD include the reason the individual is presenting for evaluation; the patient’s goals and preferences for treatment; a review of psychiatric symptoms, including core features of personality disorders and common co-occurring disorders; a psychiatric treatment history; assessment of physical health and psychosocial and cultural factors; a mental status examination; and an assessment of risk of suicide, self-injury, and aggressive behaviors, as outlined in APA Practice Guidelines for the Psychiatric Evaluation of Adults, Third Edition.
The APA suggests (2C) that the initial psychiatric evaluation of a patient with BPD include a quantitative measure to identify and determine the severity of symptoms and impairments of functioning that may be a focus of treatment.
The guideline lists several options, including (but not limited to) the 23-item version of the Borderline Symptom List; the Borderline Evaluation of Severity Over Time; 11-item Borderline Personality Features Scale for Children; and Difficulty in Emotional Regulation Scale.
The APA recommends (1C) that a patient with BPD have a documented, comprehensive, and person-centered treatment plan and be engaged in a collaborative discussion about their diagnosis and treatment, which includes psychoeducation related to the disorder. “This is a new recommendation,” Oldham said.
Another new recommendation (1B) advises a structured approach to psychotherapy that has support in the literature and targets the core features of the disorder. These include dialectical behavior therapy and mentalization-based therapy along with other therapies that have demonstrated efficacy in recent studies.
The APA recommends (1C) that a patient with BPD have a review of co-occurring disorders, prior psychotherapies, other nonpharmacological treatments, past medication trials, and current medications before initiating any new medication.
The APA suggests (2C) that that any psychotropic medication treatment of BPD be “time-limited, aimed at addressing a specific measurable target symptom, and adjunctive to psychotherapy.”
“Medication is not a primary treatment but may help diminish symptoms such as affective instability, impulsivity, or psychotic-like symptoms in individual patients, helping them to remain engaged in treatment or reducing short-term risks of self-harm,” said Oldham.
The APA recommends (1C) a review and reconciliation of medications at least every 6 months to assess the effectiveness of treatment and identify medications that warrant tapering or discontinuation.
An Alternative Model of Care
Oldham said it’s important to note that the Alternative DSM-5 Model for Personality Disorders (AMPD) is increasingly being integrated into clinical practice with adolescents and adults.
Unlike the traditional categorical system, which diagnoses personality disorders as distinct and separate conditions, the AMPD views personality disorders along a continuum of severity and impairment.
The AMPD recognizes the variability and overlap in personality disorder symptoms and provides a nuanced, individualized framework for assessment and treatment planning.
Oldham co-chaired the work group that developed the proposal for the alternative model.
“Despite the growing recognition of the importance of the alternative model, our systematic reviews did not identify treatment studies using the alternative model that met our inclusion criteria. Therefore, it is not included in the new guideline,” he said.
Development of the guideline had no commercial funding. Oldham reported no conflicts of interest with his work on the guideline.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF PSYCHIATRY
Do Risk-Reducing Surgeries Benefit BRCA Carriers With Early-Onset Breast Cancer History?
according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.
Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.
“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”
“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing.
Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.
The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery.
Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.
During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported.
The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not.
During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).
For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.
“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.
Overall survival results were similar in patients who underwent one or both surgeries.
Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”
In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.
The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.
In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?”
This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said.
“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.
The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.
A version of this article first appeared on Medscape.com.
according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.
Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.
“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”
“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing.
Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.
The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery.
Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.
During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported.
The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not.
During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).
For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.
“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.
Overall survival results were similar in patients who underwent one or both surgeries.
Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”
In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.
The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.
In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?”
This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said.
“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.
The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.
A version of this article first appeared on Medscape.com.
according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.
Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.
“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”
“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing.
Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.
The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery.
Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.
During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported.
The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not.
During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).
For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.
“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.
Overall survival results were similar in patients who underwent one or both surgeries.
Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”
In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.
The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.
In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?”
This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said.
“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.
The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM SABCS 2024
New Cancer Drugs: Do Patients Prefer Faster Access or Clinical Benefit?
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
FROM THE LANCET ONCOLOGY