Clinical Psychiatry News

A strategy developed by Canadian researchers for encouraging older patients with insomnia to wean themselves from sleeping pills and improve their sleep through behavioral techniques is effective, data suggest. If proven helpful for the millions of older Canadians who currently rely on nightly benzodiazepines (BZDs) and non-BZDs (colloquially known as Z drugs) for their sleep, it might yield an additional benefit: Reducing resource utilization.

“We know that cognitive behavioral therapy for insomnia (CBTI) works. It’s recommended as first-line therapy because it works,” study author David Gardner, PharmD, professor of psychiatry at Dalhousie University in Halifax, Nova Scotia, Canada, told this news organization.

“We’re sharing information about sleeping pills, information that has been embedded with behavior-change techniques that lead people to second-guess or rethink their long-term use of sedative hypnotics and then bring that information to their provider or pharmacist to discuss it,” he said.

The results were published in JAMA Psychiatry.
 

Better Sleep, Fewer Pills

Dr. Gardner and his team created a direct-to-patient, patient-directed, multicomponent knowledge mobilization intervention called Sleepwell. It incorporates best practice– and guideline-based evidence and multiple behavioral change techniques with content and graphics. Dr. Gardner emphasized that it represents a directional shift in care that alleviates providers’ burden without removing it entirely.

To test the intervention’s effectiveness, Dr. Gardner and his team chose New Brunswick as a location for a 6-month, three-arm, open-label, randomized controlled trial; the province has one of the highest rates of sedative use and an older adult population that is vulnerable to the serious side effects of these drugs (eg, cognitive impairment, falls, and frailty). The study was called Your Answers When Needing Sleep in New Brunswick (YAWNS NB).

Eligible participants were aged ≥ 65 years, lived in the community, and had taken benzodiazepine receptor agonists (BZRAs) for ≥ 3 nights per week for 3 or more months. Participants were randomly assigned to a control group or one of the two intervention groups. The YAWNS-1 intervention group (n = 195) received a mailed package containing a cover letter, a booklet outlining how to stop sleeping pills, a booklet on how to “get your sleep back,” and a companion website. The YAWNS-2 group (n = 193) received updated versions of the booklets used in a prior trial. The control group (n = 192) was assigned treatment as usual (TAU).

A greater proportion of YAWNS-1 participants discontinued BZRAs at 6 months (26.2%) and had dose reductions (20.4%), compared with YAWNS-2 participants (20.3% and 14.4%, respectively) and TAU participants (7.5% and 12.8%, respectively). The corresponding numbers needed to mail to achieve an additional discontinuation was 5.3 YAWNS-1 packages and 7.8 YAWNS-2 packages.

At 6 months, BZRA cessation was sustained a mean 13.6 weeks for YAWNS-1, 14.3 weeks for YAWNS-2, and 16.9 weeks for TAU.

Sleep measures also improved with YAWNS-1, compared with YAWNs-2 and TAU. Sleep onset latency was reduced by 26.1 minutes among YAWNS-1 participants, compared with YAWNS-2 (P < .001), and by 27.7 minutes, compared with TAU (P < .001). Wake after sleep onset increased by 4.1 minutes in YAWNS-1, 11.1 minutes in YAWNS-2, and 7.5 minutes in TAU.

Although all participants underwent rigorous assessment before inclusion, less than half of participants receiving either intervention (36% in YAWNS-1 and 43% in YAWNS-2) contacted their provider or pharmacist to discuss BZD dose reductions. This finding may have resulted partly from limited access because of the COVID-19 pandemic, according to the authors.
 

A Stepped-Care Model

The intervention is intended to help patients “change their approach from sleeping pills to a short-term CBTI course for long-term sleep benefits, and then speak to their provider,” said Dr. Gardner.

He pointed to a post-study follow-up of the study participants’ health providers, most of whom had moderate to extensive experience deprescribing BZRAs, which showed that 87.5%-100% fully or nearly fully agreed with or supported using the Sleepwell strategy and its content with older patients who rely on sedatives.

“Providers said that deprescribing is difficult, time-consuming, and often not a productive use of their time,” said Dr. Gardner. “I see insomnia as a health issue well set up for a stepped-care model. Self-help approaches are at the very bottom of that model and can help shift the initial burden to patients and out of the healthcare system.”

Poor uptake has prevented CBTI from demonstrating its potential, which is a challenge that Charles M. Morin, PhD, professor of psychology at Laval University in Quebec City, Quebec, Canada, attributes to two factors. “Clearly, there aren’t enough providers with this kind of expertise, and it’s not always covered by public health insurance, so people have to pay out of pocket to treat their insomnia,” he said.

“Overall, I think that this was a very nice study, well conducted, with an impressive sample size,” said Dr. Morin, who was not involved in the study. “The results are quite encouraging, telling us that even when older adults have used sleep medications for an average of 10 years, it’s still possible to reduce the medication. But this doesn’t happen alone. People need to be guided in doing that, not only to decrease medication use, but they also need an alternative,” he said.

Dr. Morin questioned how many patients agree to start with a low intensity. “Ideally, it should be a shared decision paradigm, where the physician or whoever sees the patient first presents the available options and explains the pluses and minuses of each. Some patients might choose medication because it’s a quick fix,” he said. “But some might want to do CBTI, even if it takes more work. The results are sustainable over time,” he added.

The study was jointly funded by the Public Health Agency of Canada and the government of New Brunswick as a Healthy Seniors Pilot Project. Dr. Gardner and Dr. Morin reported no relevant financial relationships.

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

A strategy developed by Canadian researchers for encouraging older patients with insomnia to wean themselves from sleeping pills and improve their sleep through behavioral techniques is effective, data suggest. If proven helpful for the millions of older Canadians who currently rely on nightly benzodiazepines (BZDs) and non-BZDs (colloquially known as Z drugs) for their sleep, it might yield an additional benefit: Reducing resource utilization.

“We know that cognitive behavioral therapy for insomnia (CBTI) works. It’s recommended as first-line therapy because it works,” study author David Gardner, PharmD, professor of psychiatry at Dalhousie University in Halifax, Nova Scotia, Canada, told this news organization.

“We’re sharing information about sleeping pills, information that has been embedded with behavior-change techniques that lead people to second-guess or rethink their long-term use of sedative hypnotics and then bring that information to their provider or pharmacist to discuss it,” he said.

The results were published in JAMA Psychiatry.
 

Better Sleep, Fewer Pills

Dr. Gardner and his team created a direct-to-patient, patient-directed, multicomponent knowledge mobilization intervention called Sleepwell. It incorporates best practice– and guideline-based evidence and multiple behavioral change techniques with content and graphics. Dr. Gardner emphasized that it represents a directional shift in care that alleviates providers’ burden without removing it entirely.

To test the intervention’s effectiveness, Dr. Gardner and his team chose New Brunswick as a location for a 6-month, three-arm, open-label, randomized controlled trial; the province has one of the highest rates of sedative use and an older adult population that is vulnerable to the serious side effects of these drugs (eg, cognitive impairment, falls, and frailty). The study was called Your Answers When Needing Sleep in New Brunswick (YAWNS NB).

Eligible participants were aged ≥ 65 years, lived in the community, and had taken benzodiazepine receptor agonists (BZRAs) for ≥ 3 nights per week for 3 or more months. Participants were randomly assigned to a control group or one of the two intervention groups. The YAWNS-1 intervention group (n = 195) received a mailed package containing a cover letter, a booklet outlining how to stop sleeping pills, a booklet on how to “get your sleep back,” and a companion website. The YAWNS-2 group (n = 193) received updated versions of the booklets used in a prior trial. The control group (n = 192) was assigned treatment as usual (TAU).

A greater proportion of YAWNS-1 participants discontinued BZRAs at 6 months (26.2%) and had dose reductions (20.4%), compared with YAWNS-2 participants (20.3% and 14.4%, respectively) and TAU participants (7.5% and 12.8%, respectively). The corresponding numbers needed to mail to achieve an additional discontinuation was 5.3 YAWNS-1 packages and 7.8 YAWNS-2 packages.

At 6 months, BZRA cessation was sustained a mean 13.6 weeks for YAWNS-1, 14.3 weeks for YAWNS-2, and 16.9 weeks for TAU.

Sleep measures also improved with YAWNS-1, compared with YAWNs-2 and TAU. Sleep onset latency was reduced by 26.1 minutes among YAWNS-1 participants, compared with YAWNS-2 (P < .001), and by 27.7 minutes, compared with TAU (P < .001). Wake after sleep onset increased by 4.1 minutes in YAWNS-1, 11.1 minutes in YAWNS-2, and 7.5 minutes in TAU.

Although all participants underwent rigorous assessment before inclusion, less than half of participants receiving either intervention (36% in YAWNS-1 and 43% in YAWNS-2) contacted their provider or pharmacist to discuss BZD dose reductions. This finding may have resulted partly from limited access because of the COVID-19 pandemic, according to the authors.
 

A Stepped-Care Model

The intervention is intended to help patients “change their approach from sleeping pills to a short-term CBTI course for long-term sleep benefits, and then speak to their provider,” said Dr. Gardner.

He pointed to a post-study follow-up of the study participants’ health providers, most of whom had moderate to extensive experience deprescribing BZRAs, which showed that 87.5%-100% fully or nearly fully agreed with or supported using the Sleepwell strategy and its content with older patients who rely on sedatives.

“Providers said that deprescribing is difficult, time-consuming, and often not a productive use of their time,” said Dr. Gardner. “I see insomnia as a health issue well set up for a stepped-care model. Self-help approaches are at the very bottom of that model and can help shift the initial burden to patients and out of the healthcare system.”

Poor uptake has prevented CBTI from demonstrating its potential, which is a challenge that Charles M. Morin, PhD, professor of psychology at Laval University in Quebec City, Quebec, Canada, attributes to two factors. “Clearly, there aren’t enough providers with this kind of expertise, and it’s not always covered by public health insurance, so people have to pay out of pocket to treat their insomnia,” he said.

“Overall, I think that this was a very nice study, well conducted, with an impressive sample size,” said Dr. Morin, who was not involved in the study. “The results are quite encouraging, telling us that even when older adults have used sleep medications for an average of 10 years, it’s still possible to reduce the medication. But this doesn’t happen alone. People need to be guided in doing that, not only to decrease medication use, but they also need an alternative,” he said.

Dr. Morin questioned how many patients agree to start with a low intensity. “Ideally, it should be a shared decision paradigm, where the physician or whoever sees the patient first presents the available options and explains the pluses and minuses of each. Some patients might choose medication because it’s a quick fix,” he said. “But some might want to do CBTI, even if it takes more work. The results are sustainable over time,” he added.

The study was jointly funded by the Public Health Agency of Canada and the government of New Brunswick as a Healthy Seniors Pilot Project. Dr. Gardner and Dr. Morin reported no relevant financial relationships.

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

A strategy developed by Canadian researchers for encouraging older patients with insomnia to wean themselves from sleeping pills and improve their sleep through behavioral techniques is effective, data suggest. If proven helpful for the millions of older Canadians who currently rely on nightly benzodiazepines (BZDs) and non-BZDs (colloquially known as Z drugs) for their sleep, it might yield an additional benefit: Reducing resource utilization.

“We know that cognitive behavioral therapy for insomnia (CBTI) works. It’s recommended as first-line therapy because it works,” study author David Gardner, PharmD, professor of psychiatry at Dalhousie University in Halifax, Nova Scotia, Canada, told this news organization.

“We’re sharing information about sleeping pills, information that has been embedded with behavior-change techniques that lead people to second-guess or rethink their long-term use of sedative hypnotics and then bring that information to their provider or pharmacist to discuss it,” he said.

The results were published in JAMA Psychiatry.
 

Better Sleep, Fewer Pills

Dr. Gardner and his team created a direct-to-patient, patient-directed, multicomponent knowledge mobilization intervention called Sleepwell. It incorporates best practice– and guideline-based evidence and multiple behavioral change techniques with content and graphics. Dr. Gardner emphasized that it represents a directional shift in care that alleviates providers’ burden without removing it entirely.

To test the intervention’s effectiveness, Dr. Gardner and his team chose New Brunswick as a location for a 6-month, three-arm, open-label, randomized controlled trial; the province has one of the highest rates of sedative use and an older adult population that is vulnerable to the serious side effects of these drugs (eg, cognitive impairment, falls, and frailty). The study was called Your Answers When Needing Sleep in New Brunswick (YAWNS NB).

Eligible participants were aged ≥ 65 years, lived in the community, and had taken benzodiazepine receptor agonists (BZRAs) for ≥ 3 nights per week for 3 or more months. Participants were randomly assigned to a control group or one of the two intervention groups. The YAWNS-1 intervention group (n = 195) received a mailed package containing a cover letter, a booklet outlining how to stop sleeping pills, a booklet on how to “get your sleep back,” and a companion website. The YAWNS-2 group (n = 193) received updated versions of the booklets used in a prior trial. The control group (n = 192) was assigned treatment as usual (TAU).

A greater proportion of YAWNS-1 participants discontinued BZRAs at 6 months (26.2%) and had dose reductions (20.4%), compared with YAWNS-2 participants (20.3% and 14.4%, respectively) and TAU participants (7.5% and 12.8%, respectively). The corresponding numbers needed to mail to achieve an additional discontinuation was 5.3 YAWNS-1 packages and 7.8 YAWNS-2 packages.

At 6 months, BZRA cessation was sustained a mean 13.6 weeks for YAWNS-1, 14.3 weeks for YAWNS-2, and 16.9 weeks for TAU.

Sleep measures also improved with YAWNS-1, compared with YAWNs-2 and TAU. Sleep onset latency was reduced by 26.1 minutes among YAWNS-1 participants, compared with YAWNS-2 (P < .001), and by 27.7 minutes, compared with TAU (P < .001). Wake after sleep onset increased by 4.1 minutes in YAWNS-1, 11.1 minutes in YAWNS-2, and 7.5 minutes in TAU.

Although all participants underwent rigorous assessment before inclusion, less than half of participants receiving either intervention (36% in YAWNS-1 and 43% in YAWNS-2) contacted their provider or pharmacist to discuss BZD dose reductions. This finding may have resulted partly from limited access because of the COVID-19 pandemic, according to the authors.
 

A Stepped-Care Model

The intervention is intended to help patients “change their approach from sleeping pills to a short-term CBTI course for long-term sleep benefits, and then speak to their provider,” said Dr. Gardner.

He pointed to a post-study follow-up of the study participants’ health providers, most of whom had moderate to extensive experience deprescribing BZRAs, which showed that 87.5%-100% fully or nearly fully agreed with or supported using the Sleepwell strategy and its content with older patients who rely on sedatives.

“Providers said that deprescribing is difficult, time-consuming, and often not a productive use of their time,” said Dr. Gardner. “I see insomnia as a health issue well set up for a stepped-care model. Self-help approaches are at the very bottom of that model and can help shift the initial burden to patients and out of the healthcare system.”

Poor uptake has prevented CBTI from demonstrating its potential, which is a challenge that Charles M. Morin, PhD, professor of psychology at Laval University in Quebec City, Quebec, Canada, attributes to two factors. “Clearly, there aren’t enough providers with this kind of expertise, and it’s not always covered by public health insurance, so people have to pay out of pocket to treat their insomnia,” he said.

“Overall, I think that this was a very nice study, well conducted, with an impressive sample size,” said Dr. Morin, who was not involved in the study. “The results are quite encouraging, telling us that even when older adults have used sleep medications for an average of 10 years, it’s still possible to reduce the medication. But this doesn’t happen alone. People need to be guided in doing that, not only to decrease medication use, but they also need an alternative,” he said.

Dr. Morin questioned how many patients agree to start with a low intensity. “Ideally, it should be a shared decision paradigm, where the physician or whoever sees the patient first presents the available options and explains the pluses and minuses of each. Some patients might choose medication because it’s a quick fix,” he said. “But some might want to do CBTI, even if it takes more work. The results are sustainable over time,” he added.

The study was jointly funded by the Public Health Agency of Canada and the government of New Brunswick as a Healthy Seniors Pilot Project. Dr. Gardner and Dr. Morin reported no relevant financial relationships.

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

The peer-review process, which is used by scientific journals to validate legitimate research, is now under legal scrutiny. The US District Court for the Southern District of New York will soon rule on whether scientific publishers have compromised this system for profit. In mid-September, University of California, Los Angeles neuroscientist Lucina Uddin filed a class action lawsuit against six leading academic publishers — Elsevier, Wolters Kluwer, Wiley, Sage Publications, Taylor & Francis, and Springer Nature — accusing them of violating antitrust laws and obstructing academic research.

The lawsuit targets several long-standing practices in scientific publishing, including the lack of compensation for peer reviewers, restrictions that require submitting to only one journal at a time, and bans on sharing manuscripts under review. Uddin’s complaint argues that these practices contribute to inefficiencies in the review process, thus delaying the publication of critical discoveries, which could hinder research, clinical advancements, and the development of new medical treatments.

The suit also noted that these publishers generated $10 billion in revenue in 2023 in peer-reviewed journals. However, the complaint seemingly overlooks the widespread practice of preprint repositories, where many manuscripts are shared while awaiting peer review.
 

Flawed Reviews

A growing number of studies have highlighted subpar or unethical behaviors among reviewers, who are supposed to adhere to the highest standards of methodological rigor, both in conducting research and reviewing work for journals. One recent study published in Scientometrics in August examined 263 reviews from 37 journals across various disciplines and found alarming patterns of duplication. Many of the reviews contained identical or highly similar language. Some reviewers were found to be suggesting that the authors expand their bibliographies to include the reviewers’ own work, thus inflating their citation counts.

As María Ángeles Oviedo-García from the University of Seville in Spain, pointed out: “The analysis of 263 review reports shows a pattern of vague, repetitive statements — often identical or very similar — along with coercive citations, ultimately resulting in misleading reviews.”

Experts in research integrity and ethics argue that while issues persist, the integrity of scientific research is improving. Increasing research and public disclosure reflect a heightened awareness of problems long overlooked.

“There is indeed a problem with research reliability, but it’s not as widespread or severe as some portray,” said Daniele Fanelli, a metascientist at the London School of Economics and Political Science in England. Speaking to this news organization, Fanelli, who has been studying scientific misconduct for about 20 years, noted that while his early work left him disillusioned, further research has replaced his cynicism with what he describes as healthy skepticism and a more optimistic outlook. Fanelli also collaborates with the Luxembourg Agency for Research Integrity and the Advisory Committee on Research Ethics and Bioethics at the Italian National Research Council (CNR), where he helped develop the first research integrity guidelines.
 

Lack of Awareness

A recurring challenge is the difficulty in distinguishing between honest mistakes and intentional misconduct. “This is why greater investment in education is essential,” said Daniel Pizzolato, European Network of Research Ethics Committees, Bonn, Germany, and the Centre for Biomedical Ethics and Law, KU Leuven in Belgium.

While Pizzolato acknowledged that institutions such as the CNR in Italy provide a positive example, awareness of research integrity is generally still lacking across much of Europe, and there are few offices dedicated to promoting research integrity. However, he pointed to promising developments in other countries. “In France and Denmark, researchers are required to be familiar with integrity norms because codes of conduct have legal standing. Some major international funding bodies like the European Molecular Biology Organization are making participation in research integrity courses a condition for receiving grants.”

Pizzolato remains optimistic. “There is a growing willingness to move past this impasse,” he said.

A recent study published in The Journal of Clinical Epidemiology reveals troubling gaps in how retracted biomedical articles are flagged and cited. Led by Caitlin Bakkera, Department of Epidemiology, Maastricht University, Maastricht, the Netherlands, the research sought to determine whether articles retracted because of errors or fraud were properly flagged across various databases.

The results were concerning: Less than 5% of retracted articles had consistent retraction notices across all databases that hosted them, and less than 50% of citations referenced the retraction. None of the 414 retraction notices analyzed met best-practice guidelines for completeness. Bakkera and colleagues warned that these shortcomings threaten the integrity of public health research.
 

Fanelli’s Perspective

Despite the concerns, Fanelli remains calm. “Science is based on debate and a perspective called organized skepticism, which helps reveal the truth,” he explained. “While there is often excessive skepticism today, the overall quality of clinical trials is improving.

“It’s important to remember that reliable results take time and shouldn’t depend on the outcome of a single study. It’s essential to consider the broader context, the history of the research field, and potential conflicts of interest, both financial and otherwise. Biomedical research requires constant updates,” he concluded.

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

The peer-review process, which is used by scientific journals to validate legitimate research, is now under legal scrutiny. The US District Court for the Southern District of New York will soon rule on whether scientific publishers have compromised this system for profit. In mid-September, University of California, Los Angeles neuroscientist Lucina Uddin filed a class action lawsuit against six leading academic publishers — Elsevier, Wolters Kluwer, Wiley, Sage Publications, Taylor & Francis, and Springer Nature — accusing them of violating antitrust laws and obstructing academic research.

The lawsuit targets several long-standing practices in scientific publishing, including the lack of compensation for peer reviewers, restrictions that require submitting to only one journal at a time, and bans on sharing manuscripts under review. Uddin’s complaint argues that these practices contribute to inefficiencies in the review process, thus delaying the publication of critical discoveries, which could hinder research, clinical advancements, and the development of new medical treatments.

The suit also noted that these publishers generated $10 billion in revenue in 2023 in peer-reviewed journals. However, the complaint seemingly overlooks the widespread practice of preprint repositories, where many manuscripts are shared while awaiting peer review.
 

Flawed Reviews

A growing number of studies have highlighted subpar or unethical behaviors among reviewers, who are supposed to adhere to the highest standards of methodological rigor, both in conducting research and reviewing work for journals. One recent study published in Scientometrics in August examined 263 reviews from 37 journals across various disciplines and found alarming patterns of duplication. Many of the reviews contained identical or highly similar language. Some reviewers were found to be suggesting that the authors expand their bibliographies to include the reviewers’ own work, thus inflating their citation counts.

As María Ángeles Oviedo-García from the University of Seville in Spain, pointed out: “The analysis of 263 review reports shows a pattern of vague, repetitive statements — often identical or very similar — along with coercive citations, ultimately resulting in misleading reviews.”

Experts in research integrity and ethics argue that while issues persist, the integrity of scientific research is improving. Increasing research and public disclosure reflect a heightened awareness of problems long overlooked.

“There is indeed a problem with research reliability, but it’s not as widespread or severe as some portray,” said Daniele Fanelli, a metascientist at the London School of Economics and Political Science in England. Speaking to this news organization, Fanelli, who has been studying scientific misconduct for about 20 years, noted that while his early work left him disillusioned, further research has replaced his cynicism with what he describes as healthy skepticism and a more optimistic outlook. Fanelli also collaborates with the Luxembourg Agency for Research Integrity and the Advisory Committee on Research Ethics and Bioethics at the Italian National Research Council (CNR), where he helped develop the first research integrity guidelines.
 

Lack of Awareness

A recurring challenge is the difficulty in distinguishing between honest mistakes and intentional misconduct. “This is why greater investment in education is essential,” said Daniel Pizzolato, European Network of Research Ethics Committees, Bonn, Germany, and the Centre for Biomedical Ethics and Law, KU Leuven in Belgium.

While Pizzolato acknowledged that institutions such as the CNR in Italy provide a positive example, awareness of research integrity is generally still lacking across much of Europe, and there are few offices dedicated to promoting research integrity. However, he pointed to promising developments in other countries. “In France and Denmark, researchers are required to be familiar with integrity norms because codes of conduct have legal standing. Some major international funding bodies like the European Molecular Biology Organization are making participation in research integrity courses a condition for receiving grants.”

Pizzolato remains optimistic. “There is a growing willingness to move past this impasse,” he said.

A recent study published in The Journal of Clinical Epidemiology reveals troubling gaps in how retracted biomedical articles are flagged and cited. Led by Caitlin Bakkera, Department of Epidemiology, Maastricht University, Maastricht, the Netherlands, the research sought to determine whether articles retracted because of errors or fraud were properly flagged across various databases.

The results were concerning: Less than 5% of retracted articles had consistent retraction notices across all databases that hosted them, and less than 50% of citations referenced the retraction. None of the 414 retraction notices analyzed met best-practice guidelines for completeness. Bakkera and colleagues warned that these shortcomings threaten the integrity of public health research.
 

Fanelli’s Perspective

Despite the concerns, Fanelli remains calm. “Science is based on debate and a perspective called organized skepticism, which helps reveal the truth,” he explained. “While there is often excessive skepticism today, the overall quality of clinical trials is improving.

“It’s important to remember that reliable results take time and shouldn’t depend on the outcome of a single study. It’s essential to consider the broader context, the history of the research field, and potential conflicts of interest, both financial and otherwise. Biomedical research requires constant updates,” he concluded.

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

The peer-review process, which is used by scientific journals to validate legitimate research, is now under legal scrutiny. The US District Court for the Southern District of New York will soon rule on whether scientific publishers have compromised this system for profit. In mid-September, University of California, Los Angeles neuroscientist Lucina Uddin filed a class action lawsuit against six leading academic publishers — Elsevier, Wolters Kluwer, Wiley, Sage Publications, Taylor & Francis, and Springer Nature — accusing them of violating antitrust laws and obstructing academic research.

The lawsuit targets several long-standing practices in scientific publishing, including the lack of compensation for peer reviewers, restrictions that require submitting to only one journal at a time, and bans on sharing manuscripts under review. Uddin’s complaint argues that these practices contribute to inefficiencies in the review process, thus delaying the publication of critical discoveries, which could hinder research, clinical advancements, and the development of new medical treatments.

The suit also noted that these publishers generated $10 billion in revenue in 2023 in peer-reviewed journals. However, the complaint seemingly overlooks the widespread practice of preprint repositories, where many manuscripts are shared while awaiting peer review.
 

Flawed Reviews

A growing number of studies have highlighted subpar or unethical behaviors among reviewers, who are supposed to adhere to the highest standards of methodological rigor, both in conducting research and reviewing work for journals. One recent study published in Scientometrics in August examined 263 reviews from 37 journals across various disciplines and found alarming patterns of duplication. Many of the reviews contained identical or highly similar language. Some reviewers were found to be suggesting that the authors expand their bibliographies to include the reviewers’ own work, thus inflating their citation counts.

As María Ángeles Oviedo-García from the University of Seville in Spain, pointed out: “The analysis of 263 review reports shows a pattern of vague, repetitive statements — often identical or very similar — along with coercive citations, ultimately resulting in misleading reviews.”

Experts in research integrity and ethics argue that while issues persist, the integrity of scientific research is improving. Increasing research and public disclosure reflect a heightened awareness of problems long overlooked.

“There is indeed a problem with research reliability, but it’s not as widespread or severe as some portray,” said Daniele Fanelli, a metascientist at the London School of Economics and Political Science in England. Speaking to this news organization, Fanelli, who has been studying scientific misconduct for about 20 years, noted that while his early work left him disillusioned, further research has replaced his cynicism with what he describes as healthy skepticism and a more optimistic outlook. Fanelli also collaborates with the Luxembourg Agency for Research Integrity and the Advisory Committee on Research Ethics and Bioethics at the Italian National Research Council (CNR), where he helped develop the first research integrity guidelines.
 

Lack of Awareness

A recurring challenge is the difficulty in distinguishing between honest mistakes and intentional misconduct. “This is why greater investment in education is essential,” said Daniel Pizzolato, European Network of Research Ethics Committees, Bonn, Germany, and the Centre for Biomedical Ethics and Law, KU Leuven in Belgium.

While Pizzolato acknowledged that institutions such as the CNR in Italy provide a positive example, awareness of research integrity is generally still lacking across much of Europe, and there are few offices dedicated to promoting research integrity. However, he pointed to promising developments in other countries. “In France and Denmark, researchers are required to be familiar with integrity norms because codes of conduct have legal standing. Some major international funding bodies like the European Molecular Biology Organization are making participation in research integrity courses a condition for receiving grants.”

Pizzolato remains optimistic. “There is a growing willingness to move past this impasse,” he said.

A recent study published in The Journal of Clinical Epidemiology reveals troubling gaps in how retracted biomedical articles are flagged and cited. Led by Caitlin Bakkera, Department of Epidemiology, Maastricht University, Maastricht, the Netherlands, the research sought to determine whether articles retracted because of errors or fraud were properly flagged across various databases.

The results were concerning: Less than 5% of retracted articles had consistent retraction notices across all databases that hosted them, and less than 50% of citations referenced the retraction. None of the 414 retraction notices analyzed met best-practice guidelines for completeness. Bakkera and colleagues warned that these shortcomings threaten the integrity of public health research.
 

Fanelli’s Perspective

Despite the concerns, Fanelli remains calm. “Science is based on debate and a perspective called organized skepticism, which helps reveal the truth,” he explained. “While there is often excessive skepticism today, the overall quality of clinical trials is improving.

“It’s important to remember that reliable results take time and shouldn’t depend on the outcome of a single study. It’s essential to consider the broader context, the history of the research field, and potential conflicts of interest, both financial and otherwise. Biomedical research requires constant updates,” he concluded.

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

Black box warnings added to antidepressant medications on increased risk for suicidality were associated with a decline in mental health treatment and an increase in suicide attempts and deaths in young people, a new analysis suggests. 

Investigators said the totality of evidence supports “reevaluation and possible replacement” of the US Food and Drug Administration (FDA) black box warning with routine warnings in product labeling. 

“The sudden, simultaneous, and sweeping effects of these warnings — the reduction in depression treatment and increase in suicide — are documented across 14 years of strong research. The consistency in observed harms and absence of observed benefits after the black box warnings indicate this is not a coincidence,” lead author Stephen Soumerai, ScD, professor of population medicine, Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, said in a news release. 

The study was published online in Health Affairs. 
 

How Did We Get Here?

In October 2003, the FDA warned that antidepressants may be associated with suicidality among people younger than age 18 years soon after starting treatment. In January 2005, the FDA required a permanent black box warning of this risk on product labels and in television and print advertising for all antidepressant drugs. 

In May 2007, the FDA expanded the 2005 black box warning to include young adults through age 24, and this broader warning remains in effect today. 

Dr. Soumerai and colleagues evaluated the intended and unintended outcomes of the youth antidepressant warnings through a systematic review of “the most credible evidence in the field,” Dr. Soumerai said. 

Through an exhaustive literature search, the researchers identified 34 studies of depression and suicide-related outcomes published in peer-reviewed journals after the warnings were issued. 

Eleven of these studies measured abrupt changes in outcome trends following the warnings and were included in their analyses. These outcomes included monitoring for suicidality, physician visits for depression, depression diagnoses, psychotherapy visits, antidepressant treatment and use and psychotropic drug poisonings (a proxy for suicide attempts), and suicide deaths. 
 

More Harms Than Benefits

Four studies, with more than 12 million patients, found “consistent evidence of sudden and substantial” long-term declines in doctor visits for depression and depression diagnoses after the FDA warnings, the study team noted.

These studies showed increases in physician visits for depression and depression diagnoses in the years before the warnings and abrupt, sustained declines, ranging from 20% to 45%, in visits and diagnoses after the warnings. “Some spillover occurred in comparison groups of adults, who were not targeted by the FDA warnings,” the study team said. 

Seven studies revealed evidence that the FDA warnings were followed by abrupt reductions in antidepressant treatment and use, ranging from 20% to 50%. Most of these studies showed increasing use of antidepressants in the years before the FDA warnings, followed by abrupt and sustained reductions in use afterward. 

Three studies found evidence of declining or flat trends in psychotropic drug poisonings and suicide deaths among pediatric patients before the warnings, followed by abrupt increases in these trends after the warnings were issued. 

The intent of the warnings was to increase physician monitoring of suicidality of patients treated with antidepressants, but the data suggest that this did not occur. 

Less than 5% of pediatric patients were monitored in accordance with FDA’s recommended contact schedule recommendations after the warnings were issued. This low rate was unchanged from the rate before the warnings. 

No study documented improvements in mental health care or declines in suicide attempts or suicides after the warnings went into effect. 

“The overwhelming evidence suggests that the ongoing use of these warnings may result in more harms than benefits,” the authors wrote. 
 

Concerning Data 

The results are “very concerning and provide reason to pause, rethink, and possibly recalibrate boxed warning recommendations as it relates to antidepressants in younger populations,” said Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Canada, and head of the Mood Disorders Psychopharmacology Unit.

Dr. McIntyre, who wasn’t involved in the study, said the data “unfortunately” provide evidence suggesting that the boxed warning had the “unintended consequence of increasing the likelihood that persons would not receive adequate healthcare for their mental disorder, consequently resulting in unfavorable outcomes, including suicidality.”

He added, “Two decades have now passed with additional information available, which not only appears to recalibrate the initial risk assessment but provides an opportunity for us to reduce the externality of decreasing access to healthcare for people living with mental illness during their youth years.” 

A spokesperson for the FDA said that “generally, the FDA does not comment on specific studies, but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

The study had no commercial funding. Disclosures for the authors are listed with the original article. Dr. McIntyre has received speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, and Neurocrine.
 

A version of this article appeared on Medscape.com.

Black box warnings added to antidepressant medications on increased risk for suicidality were associated with a decline in mental health treatment and an increase in suicide attempts and deaths in young people, a new analysis suggests. 

Investigators said the totality of evidence supports “reevaluation and possible replacement” of the US Food and Drug Administration (FDA) black box warning with routine warnings in product labeling. 

“The sudden, simultaneous, and sweeping effects of these warnings — the reduction in depression treatment and increase in suicide — are documented across 14 years of strong research. The consistency in observed harms and absence of observed benefits after the black box warnings indicate this is not a coincidence,” lead author Stephen Soumerai, ScD, professor of population medicine, Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, said in a news release. 

The study was published online in Health Affairs. 
 

How Did We Get Here?

In October 2003, the FDA warned that antidepressants may be associated with suicidality among people younger than age 18 years soon after starting treatment. In January 2005, the FDA required a permanent black box warning of this risk on product labels and in television and print advertising for all antidepressant drugs. 

In May 2007, the FDA expanded the 2005 black box warning to include young adults through age 24, and this broader warning remains in effect today. 

Dr. Soumerai and colleagues evaluated the intended and unintended outcomes of the youth antidepressant warnings through a systematic review of “the most credible evidence in the field,” Dr. Soumerai said. 

Through an exhaustive literature search, the researchers identified 34 studies of depression and suicide-related outcomes published in peer-reviewed journals after the warnings were issued. 

Eleven of these studies measured abrupt changes in outcome trends following the warnings and were included in their analyses. These outcomes included monitoring for suicidality, physician visits for depression, depression diagnoses, psychotherapy visits, antidepressant treatment and use and psychotropic drug poisonings (a proxy for suicide attempts), and suicide deaths. 
 

More Harms Than Benefits

Four studies, with more than 12 million patients, found “consistent evidence of sudden and substantial” long-term declines in doctor visits for depression and depression diagnoses after the FDA warnings, the study team noted.

These studies showed increases in physician visits for depression and depression diagnoses in the years before the warnings and abrupt, sustained declines, ranging from 20% to 45%, in visits and diagnoses after the warnings. “Some spillover occurred in comparison groups of adults, who were not targeted by the FDA warnings,” the study team said. 

Seven studies revealed evidence that the FDA warnings were followed by abrupt reductions in antidepressant treatment and use, ranging from 20% to 50%. Most of these studies showed increasing use of antidepressants in the years before the FDA warnings, followed by abrupt and sustained reductions in use afterward. 

Three studies found evidence of declining or flat trends in psychotropic drug poisonings and suicide deaths among pediatric patients before the warnings, followed by abrupt increases in these trends after the warnings were issued. 

The intent of the warnings was to increase physician monitoring of suicidality of patients treated with antidepressants, but the data suggest that this did not occur. 

Less than 5% of pediatric patients were monitored in accordance with FDA’s recommended contact schedule recommendations after the warnings were issued. This low rate was unchanged from the rate before the warnings. 

No study documented improvements in mental health care or declines in suicide attempts or suicides after the warnings went into effect. 

“The overwhelming evidence suggests that the ongoing use of these warnings may result in more harms than benefits,” the authors wrote. 
 

Concerning Data 

The results are “very concerning and provide reason to pause, rethink, and possibly recalibrate boxed warning recommendations as it relates to antidepressants in younger populations,” said Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Canada, and head of the Mood Disorders Psychopharmacology Unit.

Dr. McIntyre, who wasn’t involved in the study, said the data “unfortunately” provide evidence suggesting that the boxed warning had the “unintended consequence of increasing the likelihood that persons would not receive adequate healthcare for their mental disorder, consequently resulting in unfavorable outcomes, including suicidality.”

He added, “Two decades have now passed with additional information available, which not only appears to recalibrate the initial risk assessment but provides an opportunity for us to reduce the externality of decreasing access to healthcare for people living with mental illness during their youth years.” 

A spokesperson for the FDA said that “generally, the FDA does not comment on specific studies, but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

The study had no commercial funding. Disclosures for the authors are listed with the original article. Dr. McIntyre has received speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, and Neurocrine.
 

A version of this article appeared on Medscape.com.

Black box warnings added to antidepressant medications on increased risk for suicidality were associated with a decline in mental health treatment and an increase in suicide attempts and deaths in young people, a new analysis suggests. 

Investigators said the totality of evidence supports “reevaluation and possible replacement” of the US Food and Drug Administration (FDA) black box warning with routine warnings in product labeling. 

“The sudden, simultaneous, and sweeping effects of these warnings — the reduction in depression treatment and increase in suicide — are documented across 14 years of strong research. The consistency in observed harms and absence of observed benefits after the black box warnings indicate this is not a coincidence,” lead author Stephen Soumerai, ScD, professor of population medicine, Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, said in a news release. 

The study was published online in Health Affairs. 
 

How Did We Get Here?

In October 2003, the FDA warned that antidepressants may be associated with suicidality among people younger than age 18 years soon after starting treatment. In January 2005, the FDA required a permanent black box warning of this risk on product labels and in television and print advertising for all antidepressant drugs. 

In May 2007, the FDA expanded the 2005 black box warning to include young adults through age 24, and this broader warning remains in effect today. 

Dr. Soumerai and colleagues evaluated the intended and unintended outcomes of the youth antidepressant warnings through a systematic review of “the most credible evidence in the field,” Dr. Soumerai said. 

Through an exhaustive literature search, the researchers identified 34 studies of depression and suicide-related outcomes published in peer-reviewed journals after the warnings were issued. 

Eleven of these studies measured abrupt changes in outcome trends following the warnings and were included in their analyses. These outcomes included monitoring for suicidality, physician visits for depression, depression diagnoses, psychotherapy visits, antidepressant treatment and use and psychotropic drug poisonings (a proxy for suicide attempts), and suicide deaths. 
 

More Harms Than Benefits

Four studies, with more than 12 million patients, found “consistent evidence of sudden and substantial” long-term declines in doctor visits for depression and depression diagnoses after the FDA warnings, the study team noted.

These studies showed increases in physician visits for depression and depression diagnoses in the years before the warnings and abrupt, sustained declines, ranging from 20% to 45%, in visits and diagnoses after the warnings. “Some spillover occurred in comparison groups of adults, who were not targeted by the FDA warnings,” the study team said. 

Seven studies revealed evidence that the FDA warnings were followed by abrupt reductions in antidepressant treatment and use, ranging from 20% to 50%. Most of these studies showed increasing use of antidepressants in the years before the FDA warnings, followed by abrupt and sustained reductions in use afterward. 

Three studies found evidence of declining or flat trends in psychotropic drug poisonings and suicide deaths among pediatric patients before the warnings, followed by abrupt increases in these trends after the warnings were issued. 

The intent of the warnings was to increase physician monitoring of suicidality of patients treated with antidepressants, but the data suggest that this did not occur. 

Less than 5% of pediatric patients were monitored in accordance with FDA’s recommended contact schedule recommendations after the warnings were issued. This low rate was unchanged from the rate before the warnings. 

No study documented improvements in mental health care or declines in suicide attempts or suicides after the warnings went into effect. 

“The overwhelming evidence suggests that the ongoing use of these warnings may result in more harms than benefits,” the authors wrote. 
 

Concerning Data 

The results are “very concerning and provide reason to pause, rethink, and possibly recalibrate boxed warning recommendations as it relates to antidepressants in younger populations,” said Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Canada, and head of the Mood Disorders Psychopharmacology Unit.

Dr. McIntyre, who wasn’t involved in the study, said the data “unfortunately” provide evidence suggesting that the boxed warning had the “unintended consequence of increasing the likelihood that persons would not receive adequate healthcare for their mental disorder, consequently resulting in unfavorable outcomes, including suicidality.”

He added, “Two decades have now passed with additional information available, which not only appears to recalibrate the initial risk assessment but provides an opportunity for us to reduce the externality of decreasing access to healthcare for people living with mental illness during their youth years.” 

A spokesperson for the FDA said that “generally, the FDA does not comment on specific studies, but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

The study had no commercial funding. Disclosures for the authors are listed with the original article. Dr. McIntyre has received speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, and Neurocrine.
 

A version of this article appeared on Medscape.com.

Many people who lose weight, whether through diet and lifestyle changes, medication, or bariatric surgery, recognize their body has changed. While they also experience improvements in quality of life and psychosocial areas, that’s not true for everyone. Some patients don’t “see” they’ve lost weight — a phenomenon referred to as “phantom fat,” “ghost fat,” or “vestigial body image.”

“Most people are happy with their appearance, or at least their body shape, after weight loss — although some are unhappy with the loose, sagging skin that can follow weight loss and seek plastic surgery to remedy that,” David B. Sarwer, PhD, director of the Center for Obesity Research and Education and professor of social and behavioral sciences, Temple University College of Public Health, Philadelphia, told this news organization. “There’s a subset of people who remain dissatisfied with their body image, including their shape.”

This body dissatisfaction of people who lose weight may be long-standing, predating the weight loss, or may be new because weight loss has catalyzed a host of previously unaddressed psychosocial issues. Some may show up at assessments on treatment onset, while others may be detected by monitoring changes during or after weight loss. “Mental health counseling after bariatric surgery is greatly underutilized,” Dr. Sarwer observed.
 

Ghost Fat

Research has corroborated the lingering self-perception of being “obese” vs “ex-obese.” In one study, patients who had undergone bariatric surgery reported being unable to see the difference in their size and shape 18-30 months following their procedure, despite substantial weight loss.

Some research suggests that rapid weight loss (eg, through bariatric surgery) is more likely to generate the perception of “phantom fat,” but additional research is needed to investigate whether the mode and speed of weight loss affect subsequent body image.

Being habituated to one’s former appearance may play a role, Dr. Sarwer suggested. “We see this not only with weight loss but with other body-altering procedures. It takes the brain time to catch up to the new appearance. In rhinoplasty, for example, it may take patients a while before they become accustomed to looking at their new face in the mirror after decades of looking at a more prominent nose.”
 

Years of Social Stigma

It may also take time for people to overcome years of enduring the stigma of obesity.

There are “pervasive” negative attitudes implying that individuals who are overweight and/or obese are “lazy, weak-willed, lacking in self-discipline and willpower” — a problem compounded by social media and media in general, which present unrealistic, glorified body images and disparaging messages about those with weight problems.

“Body image is a construct, rather than what you see in the mirror,” Sheethal Reddy, PhD, a psychologist at the Emory Bariatric Center, Emory University Hospital Midtown, Atlanta, told this news organization. “It’s the mental construct of our physical selves.”

According to Dr. Reddy, body image develops “within a broader societal context and is influenced by the person’s ethnic, racial, and cultural heritage.”

Adolescents are particularly vulnerable to body dissatisfaction. This is compounded in those with obesity, who often experience weight-based victimization and internalized weight-based stigma, compared with adolescents with lower weights. Weight stigma often takes the form of teasing and bullying.

“Appearance-related bullying and teasing during childhood and adolescence can reverberate into adulthood and persist throughout the lifespan,” Dr. Sarwer said. “When we see these patients and ask if they’ve ever been teased or bullied, not only do many say yes but it takes them back to those moments, to that origin story, and they remember someone saying something mean, cruel, and hurtful.”

Stigmatizing experiences can affect subjective body image, even after the weight has been lost and the person’s body is objectively thinner. Research comparing individuals who were overweight and lost weight to individuals who are currently overweight and haven’t lost weight and individuals who were never overweight suggests that “vestigial” body disparagement may persist following weight loss — especially in those with early-onset obesity.
 

The Role of Genetics

Genetics may contribute to people’s self-perception and body dissatisfaction, both before and after weight loss. A study of 827 community-based adolescents examined the association between polygenic risk scores (PRS) for body mass index (BMI) and type 2 diabetes and symptoms of body dissatisfaction and depression.

“Given the significant genetic role in BMI, we wanted to explore whether genetic risk for BMI might also predict body dissatisfaction,” lead author Krista Ekberg, MS, a doctoral candidate in clinical psychology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, told this news organization.

Genetic influences on BMI, as measured by PRS, were significantly associated with both phenotypic BMI and body dissatisfaction. “The association between PRS and body dissatisfaction was largely explained by BMI, suggesting that BMI itself accounts for much of the link between genetic risk and body dissatisfaction.”
 

Psychiatric History and Trauma

Adverse experiences, particularly sexual or physical abuse, may also account for body dissatisfaction after weight loss. “When some people with a history of this type of abuse lose a large amount of weight — typically after bariatric surgery — they often go through a period of emotional turbulence,” Dr. Sarwer said.

Childhood maltreatment can also be associated with body image disturbances in adulthood, according to a meta-analysis of 12 studies, encompassing 15,481 participants. Sexual abuse is “surprisingly common” among patients with obesity, according to Dr. Sarwer. A chart review of 131 patients revealed that 60% of those who reported a history of rape or sexual molestation were ≥ 50 pounds overweight vs only 28% of age- and sex-matched controls without a history of abuse. Other studies have corroborated these findings.

Excess weight can serve an “adaptive function,” Dr. Sarwer noted. It can be a self-protective mechanism that “insulates” them from sexual advances by potential romantic partners or abusers. Some may find that, after weight loss, repressed memories of a sexual assault surface as a result of the newer, more “attractive” appearance. Feeling vulnerable in their thinner bodies, they may need to regard themselves as overweight to maintain that feeling of “protection.” Weight loss may also trigger memories, flashbacks, or nightmares, as people return to a weight at which they were abused.

Dissociation is another mechanism linking trauma with post–weight loss body dysmorphia, Supatra Tovar, PsyD, RD, a clinical psychologist and registered dietitian with a practice in California, told this news organization. Dissociation from the body is often a coping mechanism for dealing with an overwhelming traumatic experience.

Individuals with a history of depression, anxiety, or posttraumatic stress disorder have higher levels of body dysmorphia, both before and after weight loss. One study found that patients undergoing bariatric surgery who had some type of psychopathology and other psychological risk factors were significantly more likely to report body image concerns 3 months after the surgery. Body image concerns were also more common in patients with preoperative depression, current psychotropic medication use, and a history of outpatient therapy or psychotropic medication use.

“Depression, anxiety, and trauma play a role in how you see yourself and how you carry yourself,” Dr. Reddy said. “This is wrapped up in any type of psychopathology. Being depressed is like looking at yourself through a cloud. It’s the opposite of ‘rose-colored glasses’ and instead, looking at yourself through a negative lens.”
 

Diagnosis and Interventions

Some helpful tools to assess the presence and extent of weight dissatisfaction and body dysmorphia include the Eating Disorder Inventory — Body Dissatisfaction Subscale and the Body Shape Questionnaire. It’s also important to take into account “the extent to which people are invested in their appearance psychologically,” Dr. Sarwer advised. The AO subscale of the Multidimensional Body-Self Relations Questionnaire generally assesses this. The Body Image Quality of Life Inventory assesses how and to what extent the perceived body image affects the person’s quality of life.

Experts recommend cognitive behavioral therapy (CBT) as an evidence-based intervention for body image issues, including those following weight loss.

“There’s an extensive CBT body image therapy program specifically tailored to the needs of overweight and obese individuals,” Dr. Sarwer said. “We don’t ignore historical variables that may have contributed to the problem, like early bullying, but we encourage people to think about what’s going on in their day-to-day life today. We drill down not only into the maladaptive behaviors but also the cognition and beliefs that may be erroneous but underlie these behaviors.”

The aim of CBT is to “modify irrational and dysfunctional thoughts, emotions, and behaviors through techniques such as self-monitoring, cognitive structuring, psychoeducation, desensitization, and exposure and response prevention.” The program laid out in Cash’s body image workbook includes eight steps. (Figure).

Weight Loss Doesn’t Automatically Equate With Happiness

Another realistic expectation runs counter to a common misperception that becoming thin will automatically translate into becoming happier. That’s not always the case, according to Dr. Tovar.

“If you haven’t worked deeply on addressing self-compassion and understanding that who you are at the core has nothing to do with your physical appearance, you can have an empty feeling once you’ve reached this point,” she said. “You still don’t know who you are and what you’re contributing to the world [because] you’ve been so focused on losing weight.”

Weight loss can also “unmask” questions about self-worth, even when receiving compliments about one’s “improved” appearance. “Praise and compliments after weight loss can be a double-edged sword,” Dr. Tovar observed. “You might think, ‘I wasn’t accepted or praised when I was overweight. The only way to be acceptable or validated is by losing weight, so I have to continue losing weight.’ ” This fuels fear of regaining the weight and can lead to continuing to see oneself as overweight, perhaps as a way to stay motivated to continue with weight loss. “Feeling that one’s value depends on remaining thin hampers body satisfaction,” she said.

Dr. Tovar, author of the book Deprogram Diet Culture: Rethink Your Relationship with Food, Heal Your Mind, and Live a Diet-Free Life, encourages people to shift the emphasis from weight loss to a holistic focus on self-worth and to explore obstacles to those feelings both before and after weight loss.

Endocrinologists and other medical professionals can help by not engaging in “weight and body shaming,” Dr. Tovar said.

She recommends physicians “encourage patients to tune in to their own bodies, helping them become more aware of how different foods affect their physical and emotional well-being.”

Set realistic expectations through “open, nonjudgmental conversations about the complexities of metabolism, weight, and health.”

Dr. Tovar advises rather than focusing on weight loss as the primary goal, physicians should focus on health markers such as blood glucose, energy levels, mental well-being, and physical fitness.

Prioritize “listening over lecturing.” Begin with empathy, asking questions such as “How do you feel about your health right now? What changes have you noticed in your body lately?” Doing this “creates space for the patient to express their concerns without feeling judged or shamed.”

Refer patients to a mental health professional when a patient exhibits signs of disordered eating or poor body image or when emotional factors are playing a significant role in the relationship with food and weight. “If a patient is caught in a cycle of dieting and weight gain, struggles with binge eating, or displays symptoms of depression or anxiety related to body, then psychological help is crucial.”

Ultimately, the goal of treatment “should be to provide a safe, supportive environment where patients can heal — not just physically but also emotionally and mentally,” Dr. Tovar added.

Dr. Tovar, Ms. Ekberg, and Dr. Reddy reported no relevant financial relationships. Dr. Sarwer received grant funding from the National Institute of Dental and Craniofacial Research and National Institute of Diabetes and Digestive and Kidney Diseases. He has consulting relationships with Novo Nordisk and Twenty30 Health. He is an associate editor for Obesity Surgery and editor in chief of Obesity Science & Practice.
 

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

Many people who lose weight, whether through diet and lifestyle changes, medication, or bariatric surgery, recognize their body has changed. While they also experience improvements in quality of life and psychosocial areas, that’s not true for everyone. Some patients don’t “see” they’ve lost weight — a phenomenon referred to as “phantom fat,” “ghost fat,” or “vestigial body image.”

“Most people are happy with their appearance, or at least their body shape, after weight loss — although some are unhappy with the loose, sagging skin that can follow weight loss and seek plastic surgery to remedy that,” David B. Sarwer, PhD, director of the Center for Obesity Research and Education and professor of social and behavioral sciences, Temple University College of Public Health, Philadelphia, told this news organization. “There’s a subset of people who remain dissatisfied with their body image, including their shape.”

This body dissatisfaction of people who lose weight may be long-standing, predating the weight loss, or may be new because weight loss has catalyzed a host of previously unaddressed psychosocial issues. Some may show up at assessments on treatment onset, while others may be detected by monitoring changes during or after weight loss. “Mental health counseling after bariatric surgery is greatly underutilized,” Dr. Sarwer observed.
 

Ghost Fat

Research has corroborated the lingering self-perception of being “obese” vs “ex-obese.” In one study, patients who had undergone bariatric surgery reported being unable to see the difference in their size and shape 18-30 months following their procedure, despite substantial weight loss.

Some research suggests that rapid weight loss (eg, through bariatric surgery) is more likely to generate the perception of “phantom fat,” but additional research is needed to investigate whether the mode and speed of weight loss affect subsequent body image.

Being habituated to one’s former appearance may play a role, Dr. Sarwer suggested. “We see this not only with weight loss but with other body-altering procedures. It takes the brain time to catch up to the new appearance. In rhinoplasty, for example, it may take patients a while before they become accustomed to looking at their new face in the mirror after decades of looking at a more prominent nose.”
 

Years of Social Stigma

It may also take time for people to overcome years of enduring the stigma of obesity.

There are “pervasive” negative attitudes implying that individuals who are overweight and/or obese are “lazy, weak-willed, lacking in self-discipline and willpower” — a problem compounded by social media and media in general, which present unrealistic, glorified body images and disparaging messages about those with weight problems.

“Body image is a construct, rather than what you see in the mirror,” Sheethal Reddy, PhD, a psychologist at the Emory Bariatric Center, Emory University Hospital Midtown, Atlanta, told this news organization. “It’s the mental construct of our physical selves.”

According to Dr. Reddy, body image develops “within a broader societal context and is influenced by the person’s ethnic, racial, and cultural heritage.”

Adolescents are particularly vulnerable to body dissatisfaction. This is compounded in those with obesity, who often experience weight-based victimization and internalized weight-based stigma, compared with adolescents with lower weights. Weight stigma often takes the form of teasing and bullying.

“Appearance-related bullying and teasing during childhood and adolescence can reverberate into adulthood and persist throughout the lifespan,” Dr. Sarwer said. “When we see these patients and ask if they’ve ever been teased or bullied, not only do many say yes but it takes them back to those moments, to that origin story, and they remember someone saying something mean, cruel, and hurtful.”

Stigmatizing experiences can affect subjective body image, even after the weight has been lost and the person’s body is objectively thinner. Research comparing individuals who were overweight and lost weight to individuals who are currently overweight and haven’t lost weight and individuals who were never overweight suggests that “vestigial” body disparagement may persist following weight loss — especially in those with early-onset obesity.
 

The Role of Genetics

Genetics may contribute to people’s self-perception and body dissatisfaction, both before and after weight loss. A study of 827 community-based adolescents examined the association between polygenic risk scores (PRS) for body mass index (BMI) and type 2 diabetes and symptoms of body dissatisfaction and depression.

“Given the significant genetic role in BMI, we wanted to explore whether genetic risk for BMI might also predict body dissatisfaction,” lead author Krista Ekberg, MS, a doctoral candidate in clinical psychology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, told this news organization.

Genetic influences on BMI, as measured by PRS, were significantly associated with both phenotypic BMI and body dissatisfaction. “The association between PRS and body dissatisfaction was largely explained by BMI, suggesting that BMI itself accounts for much of the link between genetic risk and body dissatisfaction.”
 

Psychiatric History and Trauma

Adverse experiences, particularly sexual or physical abuse, may also account for body dissatisfaction after weight loss. “When some people with a history of this type of abuse lose a large amount of weight — typically after bariatric surgery — they often go through a period of emotional turbulence,” Dr. Sarwer said.

Childhood maltreatment can also be associated with body image disturbances in adulthood, according to a meta-analysis of 12 studies, encompassing 15,481 participants. Sexual abuse is “surprisingly common” among patients with obesity, according to Dr. Sarwer. A chart review of 131 patients revealed that 60% of those who reported a history of rape or sexual molestation were ≥ 50 pounds overweight vs only 28% of age- and sex-matched controls without a history of abuse. Other studies have corroborated these findings.

Excess weight can serve an “adaptive function,” Dr. Sarwer noted. It can be a self-protective mechanism that “insulates” them from sexual advances by potential romantic partners or abusers. Some may find that, after weight loss, repressed memories of a sexual assault surface as a result of the newer, more “attractive” appearance. Feeling vulnerable in their thinner bodies, they may need to regard themselves as overweight to maintain that feeling of “protection.” Weight loss may also trigger memories, flashbacks, or nightmares, as people return to a weight at which they were abused.

Dissociation is another mechanism linking trauma with post–weight loss body dysmorphia, Supatra Tovar, PsyD, RD, a clinical psychologist and registered dietitian with a practice in California, told this news organization. Dissociation from the body is often a coping mechanism for dealing with an overwhelming traumatic experience.

Individuals with a history of depression, anxiety, or posttraumatic stress disorder have higher levels of body dysmorphia, both before and after weight loss. One study found that patients undergoing bariatric surgery who had some type of psychopathology and other psychological risk factors were significantly more likely to report body image concerns 3 months after the surgery. Body image concerns were also more common in patients with preoperative depression, current psychotropic medication use, and a history of outpatient therapy or psychotropic medication use.

“Depression, anxiety, and trauma play a role in how you see yourself and how you carry yourself,” Dr. Reddy said. “This is wrapped up in any type of psychopathology. Being depressed is like looking at yourself through a cloud. It’s the opposite of ‘rose-colored glasses’ and instead, looking at yourself through a negative lens.”
 

Diagnosis and Interventions

Some helpful tools to assess the presence and extent of weight dissatisfaction and body dysmorphia include the Eating Disorder Inventory — Body Dissatisfaction Subscale and the Body Shape Questionnaire. It’s also important to take into account “the extent to which people are invested in their appearance psychologically,” Dr. Sarwer advised. The AO subscale of the Multidimensional Body-Self Relations Questionnaire generally assesses this. The Body Image Quality of Life Inventory assesses how and to what extent the perceived body image affects the person’s quality of life.

Experts recommend cognitive behavioral therapy (CBT) as an evidence-based intervention for body image issues, including those following weight loss.

“There’s an extensive CBT body image therapy program specifically tailored to the needs of overweight and obese individuals,” Dr. Sarwer said. “We don’t ignore historical variables that may have contributed to the problem, like early bullying, but we encourage people to think about what’s going on in their day-to-day life today. We drill down not only into the maladaptive behaviors but also the cognition and beliefs that may be erroneous but underlie these behaviors.”

The aim of CBT is to “modify irrational and dysfunctional thoughts, emotions, and behaviors through techniques such as self-monitoring, cognitive structuring, psychoeducation, desensitization, and exposure and response prevention.” The program laid out in Cash’s body image workbook includes eight steps. (Figure).

Weight Loss Doesn’t Automatically Equate With Happiness

Another realistic expectation runs counter to a common misperception that becoming thin will automatically translate into becoming happier. That’s not always the case, according to Dr. Tovar.

“If you haven’t worked deeply on addressing self-compassion and understanding that who you are at the core has nothing to do with your physical appearance, you can have an empty feeling once you’ve reached this point,” she said. “You still don’t know who you are and what you’re contributing to the world [because] you’ve been so focused on losing weight.”

Weight loss can also “unmask” questions about self-worth, even when receiving compliments about one’s “improved” appearance. “Praise and compliments after weight loss can be a double-edged sword,” Dr. Tovar observed. “You might think, ‘I wasn’t accepted or praised when I was overweight. The only way to be acceptable or validated is by losing weight, so I have to continue losing weight.’ ” This fuels fear of regaining the weight and can lead to continuing to see oneself as overweight, perhaps as a way to stay motivated to continue with weight loss. “Feeling that one’s value depends on remaining thin hampers body satisfaction,” she said.

Dr. Tovar, author of the book Deprogram Diet Culture: Rethink Your Relationship with Food, Heal Your Mind, and Live a Diet-Free Life, encourages people to shift the emphasis from weight loss to a holistic focus on self-worth and to explore obstacles to those feelings both before and after weight loss.

Endocrinologists and other medical professionals can help by not engaging in “weight and body shaming,” Dr. Tovar said.

She recommends physicians “encourage patients to tune in to their own bodies, helping them become more aware of how different foods affect their physical and emotional well-being.”

Set realistic expectations through “open, nonjudgmental conversations about the complexities of metabolism, weight, and health.”

Dr. Tovar advises rather than focusing on weight loss as the primary goal, physicians should focus on health markers such as blood glucose, energy levels, mental well-being, and physical fitness.

Prioritize “listening over lecturing.” Begin with empathy, asking questions such as “How do you feel about your health right now? What changes have you noticed in your body lately?” Doing this “creates space for the patient to express their concerns without feeling judged or shamed.”

Refer patients to a mental health professional when a patient exhibits signs of disordered eating or poor body image or when emotional factors are playing a significant role in the relationship with food and weight. “If a patient is caught in a cycle of dieting and weight gain, struggles with binge eating, or displays symptoms of depression or anxiety related to body, then psychological help is crucial.”

Ultimately, the goal of treatment “should be to provide a safe, supportive environment where patients can heal — not just physically but also emotionally and mentally,” Dr. Tovar added.

Dr. Tovar, Ms. Ekberg, and Dr. Reddy reported no relevant financial relationships. Dr. Sarwer received grant funding from the National Institute of Dental and Craniofacial Research and National Institute of Diabetes and Digestive and Kidney Diseases. He has consulting relationships with Novo Nordisk and Twenty30 Health. He is an associate editor for Obesity Surgery and editor in chief of Obesity Science & Practice.
 

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

Many people who lose weight, whether through diet and lifestyle changes, medication, or bariatric surgery, recognize their body has changed. While they also experience improvements in quality of life and psychosocial areas, that’s not true for everyone. Some patients don’t “see” they’ve lost weight — a phenomenon referred to as “phantom fat,” “ghost fat,” or “vestigial body image.”

“Most people are happy with their appearance, or at least their body shape, after weight loss — although some are unhappy with the loose, sagging skin that can follow weight loss and seek plastic surgery to remedy that,” David B. Sarwer, PhD, director of the Center for Obesity Research and Education and professor of social and behavioral sciences, Temple University College of Public Health, Philadelphia, told this news organization. “There’s a subset of people who remain dissatisfied with their body image, including their shape.”

This body dissatisfaction of people who lose weight may be long-standing, predating the weight loss, or may be new because weight loss has catalyzed a host of previously unaddressed psychosocial issues. Some may show up at assessments on treatment onset, while others may be detected by monitoring changes during or after weight loss. “Mental health counseling after bariatric surgery is greatly underutilized,” Dr. Sarwer observed.
 

Ghost Fat

Research has corroborated the lingering self-perception of being “obese” vs “ex-obese.” In one study, patients who had undergone bariatric surgery reported being unable to see the difference in their size and shape 18-30 months following their procedure, despite substantial weight loss.

Some research suggests that rapid weight loss (eg, through bariatric surgery) is more likely to generate the perception of “phantom fat,” but additional research is needed to investigate whether the mode and speed of weight loss affect subsequent body image.

Being habituated to one’s former appearance may play a role, Dr. Sarwer suggested. “We see this not only with weight loss but with other body-altering procedures. It takes the brain time to catch up to the new appearance. In rhinoplasty, for example, it may take patients a while before they become accustomed to looking at their new face in the mirror after decades of looking at a more prominent nose.”
 

Years of Social Stigma

It may also take time for people to overcome years of enduring the stigma of obesity.

There are “pervasive” negative attitudes implying that individuals who are overweight and/or obese are “lazy, weak-willed, lacking in self-discipline and willpower” — a problem compounded by social media and media in general, which present unrealistic, glorified body images and disparaging messages about those with weight problems.

“Body image is a construct, rather than what you see in the mirror,” Sheethal Reddy, PhD, a psychologist at the Emory Bariatric Center, Emory University Hospital Midtown, Atlanta, told this news organization. “It’s the mental construct of our physical selves.”

According to Dr. Reddy, body image develops “within a broader societal context and is influenced by the person’s ethnic, racial, and cultural heritage.”

Adolescents are particularly vulnerable to body dissatisfaction. This is compounded in those with obesity, who often experience weight-based victimization and internalized weight-based stigma, compared with adolescents with lower weights. Weight stigma often takes the form of teasing and bullying.

“Appearance-related bullying and teasing during childhood and adolescence can reverberate into adulthood and persist throughout the lifespan,” Dr. Sarwer said. “When we see these patients and ask if they’ve ever been teased or bullied, not only do many say yes but it takes them back to those moments, to that origin story, and they remember someone saying something mean, cruel, and hurtful.”

Stigmatizing experiences can affect subjective body image, even after the weight has been lost and the person’s body is objectively thinner. Research comparing individuals who were overweight and lost weight to individuals who are currently overweight and haven’t lost weight and individuals who were never overweight suggests that “vestigial” body disparagement may persist following weight loss — especially in those with early-onset obesity.
 

The Role of Genetics

Genetics may contribute to people’s self-perception and body dissatisfaction, both before and after weight loss. A study of 827 community-based adolescents examined the association between polygenic risk scores (PRS) for body mass index (BMI) and type 2 diabetes and symptoms of body dissatisfaction and depression.

“Given the significant genetic role in BMI, we wanted to explore whether genetic risk for BMI might also predict body dissatisfaction,” lead author Krista Ekberg, MS, a doctoral candidate in clinical psychology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, told this news organization.

Genetic influences on BMI, as measured by PRS, were significantly associated with both phenotypic BMI and body dissatisfaction. “The association between PRS and body dissatisfaction was largely explained by BMI, suggesting that BMI itself accounts for much of the link between genetic risk and body dissatisfaction.”
 

Psychiatric History and Trauma

Adverse experiences, particularly sexual or physical abuse, may also account for body dissatisfaction after weight loss. “When some people with a history of this type of abuse lose a large amount of weight — typically after bariatric surgery — they often go through a period of emotional turbulence,” Dr. Sarwer said.

Childhood maltreatment can also be associated with body image disturbances in adulthood, according to a meta-analysis of 12 studies, encompassing 15,481 participants. Sexual abuse is “surprisingly common” among patients with obesity, according to Dr. Sarwer. A chart review of 131 patients revealed that 60% of those who reported a history of rape or sexual molestation were ≥ 50 pounds overweight vs only 28% of age- and sex-matched controls without a history of abuse. Other studies have corroborated these findings.

Excess weight can serve an “adaptive function,” Dr. Sarwer noted. It can be a self-protective mechanism that “insulates” them from sexual advances by potential romantic partners or abusers. Some may find that, after weight loss, repressed memories of a sexual assault surface as a result of the newer, more “attractive” appearance. Feeling vulnerable in their thinner bodies, they may need to regard themselves as overweight to maintain that feeling of “protection.” Weight loss may also trigger memories, flashbacks, or nightmares, as people return to a weight at which they were abused.

Dissociation is another mechanism linking trauma with post–weight loss body dysmorphia, Supatra Tovar, PsyD, RD, a clinical psychologist and registered dietitian with a practice in California, told this news organization. Dissociation from the body is often a coping mechanism for dealing with an overwhelming traumatic experience.

Individuals with a history of depression, anxiety, or posttraumatic stress disorder have higher levels of body dysmorphia, both before and after weight loss. One study found that patients undergoing bariatric surgery who had some type of psychopathology and other psychological risk factors were significantly more likely to report body image concerns 3 months after the surgery. Body image concerns were also more common in patients with preoperative depression, current psychotropic medication use, and a history of outpatient therapy or psychotropic medication use.

“Depression, anxiety, and trauma play a role in how you see yourself and how you carry yourself,” Dr. Reddy said. “This is wrapped up in any type of psychopathology. Being depressed is like looking at yourself through a cloud. It’s the opposite of ‘rose-colored glasses’ and instead, looking at yourself through a negative lens.”
 

Diagnosis and Interventions

Some helpful tools to assess the presence and extent of weight dissatisfaction and body dysmorphia include the Eating Disorder Inventory — Body Dissatisfaction Subscale and the Body Shape Questionnaire. It’s also important to take into account “the extent to which people are invested in their appearance psychologically,” Dr. Sarwer advised. The AO subscale of the Multidimensional Body-Self Relations Questionnaire generally assesses this. The Body Image Quality of Life Inventory assesses how and to what extent the perceived body image affects the person’s quality of life.

Experts recommend cognitive behavioral therapy (CBT) as an evidence-based intervention for body image issues, including those following weight loss.

“There’s an extensive CBT body image therapy program specifically tailored to the needs of overweight and obese individuals,” Dr. Sarwer said. “We don’t ignore historical variables that may have contributed to the problem, like early bullying, but we encourage people to think about what’s going on in their day-to-day life today. We drill down not only into the maladaptive behaviors but also the cognition and beliefs that may be erroneous but underlie these behaviors.”

The aim of CBT is to “modify irrational and dysfunctional thoughts, emotions, and behaviors through techniques such as self-monitoring, cognitive structuring, psychoeducation, desensitization, and exposure and response prevention.” The program laid out in Cash’s body image workbook includes eight steps. (Figure).

Weight Loss Doesn’t Automatically Equate With Happiness

Another realistic expectation runs counter to a common misperception that becoming thin will automatically translate into becoming happier. That’s not always the case, according to Dr. Tovar.

“If you haven’t worked deeply on addressing self-compassion and understanding that who you are at the core has nothing to do with your physical appearance, you can have an empty feeling once you’ve reached this point,” she said. “You still don’t know who you are and what you’re contributing to the world [because] you’ve been so focused on losing weight.”

Weight loss can also “unmask” questions about self-worth, even when receiving compliments about one’s “improved” appearance. “Praise and compliments after weight loss can be a double-edged sword,” Dr. Tovar observed. “You might think, ‘I wasn’t accepted or praised when I was overweight. The only way to be acceptable or validated is by losing weight, so I have to continue losing weight.’ ” This fuels fear of regaining the weight and can lead to continuing to see oneself as overweight, perhaps as a way to stay motivated to continue with weight loss. “Feeling that one’s value depends on remaining thin hampers body satisfaction,” she said.

Dr. Tovar, author of the book Deprogram Diet Culture: Rethink Your Relationship with Food, Heal Your Mind, and Live a Diet-Free Life, encourages people to shift the emphasis from weight loss to a holistic focus on self-worth and to explore obstacles to those feelings both before and after weight loss.

Endocrinologists and other medical professionals can help by not engaging in “weight and body shaming,” Dr. Tovar said.

She recommends physicians “encourage patients to tune in to their own bodies, helping them become more aware of how different foods affect their physical and emotional well-being.”

Set realistic expectations through “open, nonjudgmental conversations about the complexities of metabolism, weight, and health.”

Dr. Tovar advises rather than focusing on weight loss as the primary goal, physicians should focus on health markers such as blood glucose, energy levels, mental well-being, and physical fitness.

Prioritize “listening over lecturing.” Begin with empathy, asking questions such as “How do you feel about your health right now? What changes have you noticed in your body lately?” Doing this “creates space for the patient to express their concerns without feeling judged or shamed.”

Refer patients to a mental health professional when a patient exhibits signs of disordered eating or poor body image or when emotional factors are playing a significant role in the relationship with food and weight. “If a patient is caught in a cycle of dieting and weight gain, struggles with binge eating, or displays symptoms of depression or anxiety related to body, then psychological help is crucial.”

Ultimately, the goal of treatment “should be to provide a safe, supportive environment where patients can heal — not just physically but also emotionally and mentally,” Dr. Tovar added.

Dr. Tovar, Ms. Ekberg, and Dr. Reddy reported no relevant financial relationships. Dr. Sarwer received grant funding from the National Institute of Dental and Craniofacial Research and National Institute of Diabetes and Digestive and Kidney Diseases. He has consulting relationships with Novo Nordisk and Twenty30 Health. He is an associate editor for Obesity Surgery and editor in chief of Obesity Science & Practice.
 

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

Before the 350 residents finalized their union contract at the University of Vermont (UVM) Medical Center, Burlington, in 2022, Jesse Mostoller, DO, now a third-year pathology resident, recalls hearing about another resident at the hospital who resorted to moonlighting as an Uber driver to make ends meet.

“In Vermont, rent and childcare are expensive,” said Dr. Mostoller, adding that, thanks to union bargaining, first-year residents at UVM are now paid $71,000 per year instead of $61,000. In addition, residents now receive $1800 per year for food (up from $200-$300 annually) and a $1800 annual fund to help pay for board exams that can be carried over for 2 years. “When we were negotiating, the biggest item on our list of demands was to help alleviate the financial pressure residents have been facing for years.”

The UVM residents’ collective bargaining also includes a cap on working hours so that residents don’t work 80 hours a week, paid parental leave, affordable housing, and funds for education and wellness.

These are some of the most common challenges that are faced by residents all over the country, said A. Taylor Walker, MD, MPH, family medicine chief physician at Tufts University School of Medicine/Cambridge Health Alliance in Boston, Massachusetts, and national president of the Committee of Interns and Residents (CIR), which is part of the Service Employees International Union.

For these reasons, residents at Montefiore Medical Center, Stanford Health Care, George Washington University, and the University of Pennsylvania have recently voted to unionize, according to Dr. Walker.

And while there are several small local unions that have picked up residents at local hospitals, CIR is the largest union of physicians in the United States, with a total of 33,000 residents and fellows across the country (15% of the staff at more than 60 hospitals nationwide).

“We’ve doubled in size in the last 4 years,” said Dr. Walker. “The reason is that we’re in a national reckoning on the corporatization of American medicine and the way in which graduate medical education is rooted in a cycle of exploitation that doesn’t center on the health, well-being, or safety of our doctors and ultimately negatively affects our patients.”

Here’s what residents are fighting for — right now.
 

Adequate Parental Leave

Christopher Domanski, MD, a first-year resident in psychiatry at California Pacific Medical Center (CPMC) in San Francisco, is also a new dad to a 5-month-old son and is currently in the sixth week of parental leave. One goal of CPMC’s union, started a year and a half ago, is to expand parental leave to 8 weeks.

“I started as a resident here in mid-June, but the fight with CPMC leaders has been going on for a year and a half,” Dr. Domanski said. “It can feel very frustrating because many times there’s no budge in the conversations we want to have.”

Contract negotiations here continue to be slow — and arduous.

“It goes back and forth,” said Dr. Domanski, who makes about $75,000 a year. “Sometimes they listen to our proposals, but they deny the vast majority or make a paltry increase in salary or time off. It goes like this: We’ll have a negotiation; we’ll talk about it, and then they say, ‘we’re not comfortable doing this’ and it stalls again.”

If a resident hasn’t started a family yet, access to fertility benefits and reproductive healthcare is paramount because most residents are in their 20s and 30s, Dr. Walker said.

“Our reproductive futures are really hindered by what care we have access to and what care is covered,” she added. “We don’t make enough money to pay for reproductive care out of pocket.”
 

Fair Pay

In Boston, the residents at Mass General Brigham certified their union in June 2023, but they still don’t have a contract.

“When I applied for a residency in September 2023, I spoke to the folks here, and I was basically under the impression that we would have a contract by the time I matched,” said Madison Masters, MD, a resident in internal medicine. “We are not there.”

This timeline isn’t unusual — the 1400 Penn Medicine residents who unionized in 2023 only recently secured a tentative union contract at the end of September, and at Stanford, the process to ratify their first contract took 13 months.

Still, the salary issue remains frustrating as resident compensation doesn’t line up with the cost of living or the amount of work residents do, said Dr. Masters, who says starting salaries at Mass General Brigham are $78,500 plus a $10,000 stipend for housing.

“There’s been a long tradition of underpaying residents — we’re treated like trainees, but we’re also a primary labor force,” Dr. Masters said, adding that nurse practitioners and physician assistants are paid almost twice as much as residents — some make $120,000 per year or more, while the salary range for residents nationwide is $49,000-$65,000 per year.

“Every time we discuss the contract and talk about a financial package, they offer a 1.5% raise for the next 3 years while we had asked for closer to 8%,” Dr. Masters said. “Then, when they come back for the next bargaining session, they go up a quarter of a percent each time. Recently, they said we will need to go to a mediator to try and resolve this.”
 

Adequate Healthcare

The biggest — and perhaps the most shocking — ask is for robust health insurance coverage.

“At my hospital, they’re telling us to get Amazon One Medical for health insurance,” Dr. Masters said. “They’re saying it’s hard for anyone to get primary care coverage here.”

Inadequate health insurance is a big issue, as burnout among residents and fellows remains a problem. At UVM, a $10,000 annual wellness stipend has helped address some of these issues. Even so, union members at UVM are planning to return to the table within 18 months to continue their collective bargaining.

The ability to access mental health services anywhere you want is also critical for residents, Dr. Walker said.

“If you can only go to a therapist at your own institution, there is a hesitation to utilize that specialist if that’s even offered,” Dr. Walker said. “Do you want to go to therapy with a colleague? Probably not.”

Ultimately, the residents we spoke to are committed to fighting for their workplace rights — no matter how time-consuming or difficult this has been.

“No administration wants us to have to have a union, but it’s necessary,” Dr. Mostoller said. “As an individual, you don’t have leverage to get a seat at the table, but now we have a seat at the table. We have a wonderful contract, but we’re going to keep fighting to make it even better.”

Paving the way for future residents is a key motivator, too.

“There’s this idea of leaving the campsite cleaner than you found it,” Dr. Mostoller told this news organization. “It’s the same thing here — we’re trying to fix this so that the next generation of residents won’t have to.”

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

Before the 350 residents finalized their union contract at the University of Vermont (UVM) Medical Center, Burlington, in 2022, Jesse Mostoller, DO, now a third-year pathology resident, recalls hearing about another resident at the hospital who resorted to moonlighting as an Uber driver to make ends meet.

“In Vermont, rent and childcare are expensive,” said Dr. Mostoller, adding that, thanks to union bargaining, first-year residents at UVM are now paid $71,000 per year instead of $61,000. In addition, residents now receive $1800 per year for food (up from $200-$300 annually) and a $1800 annual fund to help pay for board exams that can be carried over for 2 years. “When we were negotiating, the biggest item on our list of demands was to help alleviate the financial pressure residents have been facing for years.”

The UVM residents’ collective bargaining also includes a cap on working hours so that residents don’t work 80 hours a week, paid parental leave, affordable housing, and funds for education and wellness.

These are some of the most common challenges that are faced by residents all over the country, said A. Taylor Walker, MD, MPH, family medicine chief physician at Tufts University School of Medicine/Cambridge Health Alliance in Boston, Massachusetts, and national president of the Committee of Interns and Residents (CIR), which is part of the Service Employees International Union.

For these reasons, residents at Montefiore Medical Center, Stanford Health Care, George Washington University, and the University of Pennsylvania have recently voted to unionize, according to Dr. Walker.

And while there are several small local unions that have picked up residents at local hospitals, CIR is the largest union of physicians in the United States, with a total of 33,000 residents and fellows across the country (15% of the staff at more than 60 hospitals nationwide).

“We’ve doubled in size in the last 4 years,” said Dr. Walker. “The reason is that we’re in a national reckoning on the corporatization of American medicine and the way in which graduate medical education is rooted in a cycle of exploitation that doesn’t center on the health, well-being, or safety of our doctors and ultimately negatively affects our patients.”

Here’s what residents are fighting for — right now.
 

Adequate Parental Leave

Christopher Domanski, MD, a first-year resident in psychiatry at California Pacific Medical Center (CPMC) in San Francisco, is also a new dad to a 5-month-old son and is currently in the sixth week of parental leave. One goal of CPMC’s union, started a year and a half ago, is to expand parental leave to 8 weeks.

“I started as a resident here in mid-June, but the fight with CPMC leaders has been going on for a year and a half,” Dr. Domanski said. “It can feel very frustrating because many times there’s no budge in the conversations we want to have.”

Contract negotiations here continue to be slow — and arduous.

“It goes back and forth,” said Dr. Domanski, who makes about $75,000 a year. “Sometimes they listen to our proposals, but they deny the vast majority or make a paltry increase in salary or time off. It goes like this: We’ll have a negotiation; we’ll talk about it, and then they say, ‘we’re not comfortable doing this’ and it stalls again.”

If a resident hasn’t started a family yet, access to fertility benefits and reproductive healthcare is paramount because most residents are in their 20s and 30s, Dr. Walker said.

“Our reproductive futures are really hindered by what care we have access to and what care is covered,” she added. “We don’t make enough money to pay for reproductive care out of pocket.”
 

Fair Pay

In Boston, the residents at Mass General Brigham certified their union in June 2023, but they still don’t have a contract.

“When I applied for a residency in September 2023, I spoke to the folks here, and I was basically under the impression that we would have a contract by the time I matched,” said Madison Masters, MD, a resident in internal medicine. “We are not there.”

This timeline isn’t unusual — the 1400 Penn Medicine residents who unionized in 2023 only recently secured a tentative union contract at the end of September, and at Stanford, the process to ratify their first contract took 13 months.

Still, the salary issue remains frustrating as resident compensation doesn’t line up with the cost of living or the amount of work residents do, said Dr. Masters, who says starting salaries at Mass General Brigham are $78,500 plus a $10,000 stipend for housing.

“There’s been a long tradition of underpaying residents — we’re treated like trainees, but we’re also a primary labor force,” Dr. Masters said, adding that nurse practitioners and physician assistants are paid almost twice as much as residents — some make $120,000 per year or more, while the salary range for residents nationwide is $49,000-$65,000 per year.

“Every time we discuss the contract and talk about a financial package, they offer a 1.5% raise for the next 3 years while we had asked for closer to 8%,” Dr. Masters said. “Then, when they come back for the next bargaining session, they go up a quarter of a percent each time. Recently, they said we will need to go to a mediator to try and resolve this.”
 

Adequate Healthcare

The biggest — and perhaps the most shocking — ask is for robust health insurance coverage.

“At my hospital, they’re telling us to get Amazon One Medical for health insurance,” Dr. Masters said. “They’re saying it’s hard for anyone to get primary care coverage here.”

Inadequate health insurance is a big issue, as burnout among residents and fellows remains a problem. At UVM, a $10,000 annual wellness stipend has helped address some of these issues. Even so, union members at UVM are planning to return to the table within 18 months to continue their collective bargaining.

The ability to access mental health services anywhere you want is also critical for residents, Dr. Walker said.

“If you can only go to a therapist at your own institution, there is a hesitation to utilize that specialist if that’s even offered,” Dr. Walker said. “Do you want to go to therapy with a colleague? Probably not.”

Ultimately, the residents we spoke to are committed to fighting for their workplace rights — no matter how time-consuming or difficult this has been.

“No administration wants us to have to have a union, but it’s necessary,” Dr. Mostoller said. “As an individual, you don’t have leverage to get a seat at the table, but now we have a seat at the table. We have a wonderful contract, but we’re going to keep fighting to make it even better.”

Paving the way for future residents is a key motivator, too.

“There’s this idea of leaving the campsite cleaner than you found it,” Dr. Mostoller told this news organization. “It’s the same thing here — we’re trying to fix this so that the next generation of residents won’t have to.”

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

Before the 350 residents finalized their union contract at the University of Vermont (UVM) Medical Center, Burlington, in 2022, Jesse Mostoller, DO, now a third-year pathology resident, recalls hearing about another resident at the hospital who resorted to moonlighting as an Uber driver to make ends meet.

“In Vermont, rent and childcare are expensive,” said Dr. Mostoller, adding that, thanks to union bargaining, first-year residents at UVM are now paid $71,000 per year instead of $61,000. In addition, residents now receive $1800 per year for food (up from $200-$300 annually) and a $1800 annual fund to help pay for board exams that can be carried over for 2 years. “When we were negotiating, the biggest item on our list of demands was to help alleviate the financial pressure residents have been facing for years.”

The UVM residents’ collective bargaining also includes a cap on working hours so that residents don’t work 80 hours a week, paid parental leave, affordable housing, and funds for education and wellness.

These are some of the most common challenges that are faced by residents all over the country, said A. Taylor Walker, MD, MPH, family medicine chief physician at Tufts University School of Medicine/Cambridge Health Alliance in Boston, Massachusetts, and national president of the Committee of Interns and Residents (CIR), which is part of the Service Employees International Union.

For these reasons, residents at Montefiore Medical Center, Stanford Health Care, George Washington University, and the University of Pennsylvania have recently voted to unionize, according to Dr. Walker.

And while there are several small local unions that have picked up residents at local hospitals, CIR is the largest union of physicians in the United States, with a total of 33,000 residents and fellows across the country (15% of the staff at more than 60 hospitals nationwide).

“We’ve doubled in size in the last 4 years,” said Dr. Walker. “The reason is that we’re in a national reckoning on the corporatization of American medicine and the way in which graduate medical education is rooted in a cycle of exploitation that doesn’t center on the health, well-being, or safety of our doctors and ultimately negatively affects our patients.”

Here’s what residents are fighting for — right now.
 

Adequate Parental Leave

Christopher Domanski, MD, a first-year resident in psychiatry at California Pacific Medical Center (CPMC) in San Francisco, is also a new dad to a 5-month-old son and is currently in the sixth week of parental leave. One goal of CPMC’s union, started a year and a half ago, is to expand parental leave to 8 weeks.

“I started as a resident here in mid-June, but the fight with CPMC leaders has been going on for a year and a half,” Dr. Domanski said. “It can feel very frustrating because many times there’s no budge in the conversations we want to have.”

Contract negotiations here continue to be slow — and arduous.

“It goes back and forth,” said Dr. Domanski, who makes about $75,000 a year. “Sometimes they listen to our proposals, but they deny the vast majority or make a paltry increase in salary or time off. It goes like this: We’ll have a negotiation; we’ll talk about it, and then they say, ‘we’re not comfortable doing this’ and it stalls again.”

If a resident hasn’t started a family yet, access to fertility benefits and reproductive healthcare is paramount because most residents are in their 20s and 30s, Dr. Walker said.

“Our reproductive futures are really hindered by what care we have access to and what care is covered,” she added. “We don’t make enough money to pay for reproductive care out of pocket.”
 

Fair Pay

In Boston, the residents at Mass General Brigham certified their union in June 2023, but they still don’t have a contract.

“When I applied for a residency in September 2023, I spoke to the folks here, and I was basically under the impression that we would have a contract by the time I matched,” said Madison Masters, MD, a resident in internal medicine. “We are not there.”

This timeline isn’t unusual — the 1400 Penn Medicine residents who unionized in 2023 only recently secured a tentative union contract at the end of September, and at Stanford, the process to ratify their first contract took 13 months.

Still, the salary issue remains frustrating as resident compensation doesn’t line up with the cost of living or the amount of work residents do, said Dr. Masters, who says starting salaries at Mass General Brigham are $78,500 plus a $10,000 stipend for housing.

“There’s been a long tradition of underpaying residents — we’re treated like trainees, but we’re also a primary labor force,” Dr. Masters said, adding that nurse practitioners and physician assistants are paid almost twice as much as residents — some make $120,000 per year or more, while the salary range for residents nationwide is $49,000-$65,000 per year.

“Every time we discuss the contract and talk about a financial package, they offer a 1.5% raise for the next 3 years while we had asked for closer to 8%,” Dr. Masters said. “Then, when they come back for the next bargaining session, they go up a quarter of a percent each time. Recently, they said we will need to go to a mediator to try and resolve this.”
 

Adequate Healthcare

The biggest — and perhaps the most shocking — ask is for robust health insurance coverage.

“At my hospital, they’re telling us to get Amazon One Medical for health insurance,” Dr. Masters said. “They’re saying it’s hard for anyone to get primary care coverage here.”

Inadequate health insurance is a big issue, as burnout among residents and fellows remains a problem. At UVM, a $10,000 annual wellness stipend has helped address some of these issues. Even so, union members at UVM are planning to return to the table within 18 months to continue their collective bargaining.

The ability to access mental health services anywhere you want is also critical for residents, Dr. Walker said.

“If you can only go to a therapist at your own institution, there is a hesitation to utilize that specialist if that’s even offered,” Dr. Walker said. “Do you want to go to therapy with a colleague? Probably not.”

Ultimately, the residents we spoke to are committed to fighting for their workplace rights — no matter how time-consuming or difficult this has been.

“No administration wants us to have to have a union, but it’s necessary,” Dr. Mostoller said. “As an individual, you don’t have leverage to get a seat at the table, but now we have a seat at the table. We have a wonderful contract, but we’re going to keep fighting to make it even better.”

Paving the way for future residents is a key motivator, too.

“There’s this idea of leaving the campsite cleaner than you found it,” Dr. Mostoller told this news organization. “It’s the same thing here — we’re trying to fix this so that the next generation of residents won’t have to.”

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

Clozapine is considered the drug of choice for treatment-resistant schizophrenia in guidelines globally, but it remains significantly underutilized. This is largely due to its range of side effects, particularly its increased infection risk which prompted the US Food and Drug Administration (FDA) to mandate regular blood testing to monitor neutrophil counts.

The COVID-19 pandemic raised new concerns about the care of clozapine-treated patients, leading clinicians and patients to urge the FDA to relax prescription requirements for the drug under the Risk Evaluation and Mitigation Strategy (REMS) program.

As the FDA prepares for a public hearing in November on proposed adjustments to the drug’s REMS criteria, a growing body of research is challenging the previous understanding of clozapine and infection risk.
 

Clarifying the Risk

Research on the link between clozapine and respiratory infections has produced conflicting results. Some studies indicate little to no increased risk for mild COVID-19 and other respiratory illnesses, while others have shown a higher likelihood of severe infection.

A recent nationwide Danish registry study of respiratory infections in people with a schizophrenia spectrum disorder could bring some clarity, Maxime Taquet, MD, a clinical lecturer at the University of Oxford, Warneford Hospital, Oxford, England, told this news organization.

By tracking periods when patients were on and off clozapine and other antipsychotics, the study offers more precise risk estimates, distinguishing the risks associated with the antipsychotic from those related to underlying schizophrenia, said Dr. Taquet, who authored an accompanying editorial on the study.

“It’s very important to try to disentangle the effects of schizophrenia, its severity, from the medication,” Dr. Taquet said. “I think that the Danish study is the first to try and really do that with as much precision as possible.”

After adjusting for key confounders including economic status and COVID-19 vaccination status, the researchers found that individuals taking antipsychotics had lower odds of testing positive for SARS-CoV-2 and similar rates of filled anti-infective prescriptions as those not taking the drugs.

Although antipsychotic use was not linked to higher rates of mild infection, it was linked to an increased risk for COVID-19 hospitalization in individuals older than 70 years, as well as hospitalization and death from other respiratory infections, mainly pneumonia, in those older than 40 years.

Notably, there was no excess risk for any outcome with clozapine vs other antipsychotics.
 

Strong Link to Pneumonia Risk

Results from a longitudinal Finnish study, just published in The American Journal of Psychiatry, also show an increased risk for severe outcomes from ileus and pneumonia among more than 2600 patients with schizophrenia taking clozapine.

Twenty years after initiating clozapine, the cumulative incidence estimate for ileus was 5.3% — more than sixfold higher than previously reported. The incidence of pneumonia was also high, at 29.5%.

Both illnesses were significantly associated with mortality, with odds ratios of 4.5 and 2.8, respectively.

These findings align with previous pharmacovigilance studies, with reported mortality rates for gastrointestinal hypomotility and pneumonia that were 4-10 times higher than those for agranulocytosis, the researchers said.

The study “really adds to a growing body of research suggesting a connection between clozapine use and a higher risk of developing pneumonia,” Robert O. Cotes, MD, a professor of psychiatry and behavioral sciences at Emory University, Atlanta, who specializes in the use of clozapine, told this news organization.

“Additionally, when people on clozapine do contract pneumonia, there’s concern the condition may be more dangerous,” he added.
 

A Closer Look at Neutropenia Risk

Neutropenia receives the lion’s share of attention among clozapine’s potential side effects, but this focus may need to be re-evaluated, Dr. Cotes said.

He pointed out that recent data suggest the risk for severe neutropenia, 2-3 years after initiating clozapine, is comparable to that of other antipsychotics.

A study of 26,630 clozapine users in Australia and New Zealand showed that most cases of severe neutropenia leading to clozapine cessation peaked within 18 weeks and was negligible after 2 years. This suggests weekly hematologic monitoring could potentially be discontinued after the 2-year mark.

Another study reported earlier this year by this news organization showed a low risk for mild or moderate neutropenia and no severe cases in nearly 1000 people taking clozapine.

“I worry that we may be missing the forest for the trees by hyperfocusing on neutropenia and not considering clozapine’s other potential serious side effects like pneumonia, myocarditis, and gastrointestinal hypermotility,” Dr. Cotes said.
 

Importance of Vaccines

The findings of these studies highlight the importance of vaccines in this at-risk group, said Dr. Taquet, a point emphasized by investigators of the Danish study he reviewed.

“Inspired by the experience of COVID-19 vaccine prioritization in severe mental illness and based on our findings, there is momentum for preventive action,” the authors wrote. “Our findings do not suggest the avoidance of specific antipsychotics but rather a call for increased vigilance regarding this at-risk group.”

This includes recommending pneumococcal, influenza, COVID-19, and other anti-infective vaccines in those older than 40 years treated with, or due to start, an antipsychotic.

“It’s not mandatory, but we do recommend that patients on clozapine get the regular vaccines,” Dr. Taquet said.

Pointing to the recent study on pneumonia risk, Dr. Cotes said addressing underlying risk factors, such as smoking, obesity, and possibly sedation and excessive salivation caused by clozapine, is key.

“And to make sure that vaccinations are up to date, particularly heading into this fall,” he added.
 

Rethinking Clozapine REMS

One of the most challenging issues facing clinicians and researchers is how to help people understand the safety profile of clozapine and to use it with more confidence, Dr. Cotes said.

“A lot of people hear about clozapine and they think about neutropenia, they think about side effects, the REMS system, and all of these factors really drive down clozapine utilization,” he said.

Treatment-resistant schizophrenia affects about a quarter of those with schizophrenia, yet only 4% of these patients receive clozapine in the United States, Dr. Cotes said. That number may be even lower for its other indication of reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder.

The clozapine REMS is viewed as a major barrier to utilization and requires certification of pharmacists and physicians and use of a central system to monitor absolute neutrophil counts for neutropenia in patients.

As previously reported by this news organization in November 2022, the FDA opted to temporarily exercise enforcement discretion for certain aspects of the drug safety program to ensure continuity of care for patients after concerns were raised by the American Psychiatric Association (APA) along with other professional organizations.

Even with that temporary enforcement discretion, “reports have shown that over half of those prescribed clozapine have trouble accessing the medication because of the REMS program,” a spokesperson for the APA told this news organization.

“Not only are patients having trouble accessing the medication, many have trouble finding a prescriber in their geographic locations and others because of the monitoring requirements have their treatment discontinued leading to negative outcomes,” the spokesperson said.

The FDA is currently reviewing the clozapine REMS and is holding a joint advisory committee meeting on November 19 to discuss the review and “possible changes to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of clozapine.”

The APA plans to submit written and oral comments to the advisory committees.

“We are hopeful that the re-evaluation meeting in November will remove barriers and increase access to clozapine, which is currently highly underutilized, especially in marginalized communities,” the spokesperson said.

Dr. Cotes reported serving as a speaker and consultant for Saladax Biomedical and as a consultant for Syneos Health. Dr. Taquet reported having no competing interests.
 

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

Clozapine is considered the drug of choice for treatment-resistant schizophrenia in guidelines globally, but it remains significantly underutilized. This is largely due to its range of side effects, particularly its increased infection risk which prompted the US Food and Drug Administration (FDA) to mandate regular blood testing to monitor neutrophil counts.

The COVID-19 pandemic raised new concerns about the care of clozapine-treated patients, leading clinicians and patients to urge the FDA to relax prescription requirements for the drug under the Risk Evaluation and Mitigation Strategy (REMS) program.

As the FDA prepares for a public hearing in November on proposed adjustments to the drug’s REMS criteria, a growing body of research is challenging the previous understanding of clozapine and infection risk.
 

Clarifying the Risk

Research on the link between clozapine and respiratory infections has produced conflicting results. Some studies indicate little to no increased risk for mild COVID-19 and other respiratory illnesses, while others have shown a higher likelihood of severe infection.

A recent nationwide Danish registry study of respiratory infections in people with a schizophrenia spectrum disorder could bring some clarity, Maxime Taquet, MD, a clinical lecturer at the University of Oxford, Warneford Hospital, Oxford, England, told this news organization.

By tracking periods when patients were on and off clozapine and other antipsychotics, the study offers more precise risk estimates, distinguishing the risks associated with the antipsychotic from those related to underlying schizophrenia, said Dr. Taquet, who authored an accompanying editorial on the study.

“It’s very important to try to disentangle the effects of schizophrenia, its severity, from the medication,” Dr. Taquet said. “I think that the Danish study is the first to try and really do that with as much precision as possible.”

After adjusting for key confounders including economic status and COVID-19 vaccination status, the researchers found that individuals taking antipsychotics had lower odds of testing positive for SARS-CoV-2 and similar rates of filled anti-infective prescriptions as those not taking the drugs.

Although antipsychotic use was not linked to higher rates of mild infection, it was linked to an increased risk for COVID-19 hospitalization in individuals older than 70 years, as well as hospitalization and death from other respiratory infections, mainly pneumonia, in those older than 40 years.

Notably, there was no excess risk for any outcome with clozapine vs other antipsychotics.
 

Strong Link to Pneumonia Risk

Results from a longitudinal Finnish study, just published in The American Journal of Psychiatry, also show an increased risk for severe outcomes from ileus and pneumonia among more than 2600 patients with schizophrenia taking clozapine.

Twenty years after initiating clozapine, the cumulative incidence estimate for ileus was 5.3% — more than sixfold higher than previously reported. The incidence of pneumonia was also high, at 29.5%.

Both illnesses were significantly associated with mortality, with odds ratios of 4.5 and 2.8, respectively.

These findings align with previous pharmacovigilance studies, with reported mortality rates for gastrointestinal hypomotility and pneumonia that were 4-10 times higher than those for agranulocytosis, the researchers said.

The study “really adds to a growing body of research suggesting a connection between clozapine use and a higher risk of developing pneumonia,” Robert O. Cotes, MD, a professor of psychiatry and behavioral sciences at Emory University, Atlanta, who specializes in the use of clozapine, told this news organization.

“Additionally, when people on clozapine do contract pneumonia, there’s concern the condition may be more dangerous,” he added.
 

A Closer Look at Neutropenia Risk

Neutropenia receives the lion’s share of attention among clozapine’s potential side effects, but this focus may need to be re-evaluated, Dr. Cotes said.

He pointed out that recent data suggest the risk for severe neutropenia, 2-3 years after initiating clozapine, is comparable to that of other antipsychotics.

A study of 26,630 clozapine users in Australia and New Zealand showed that most cases of severe neutropenia leading to clozapine cessation peaked within 18 weeks and was negligible after 2 years. This suggests weekly hematologic monitoring could potentially be discontinued after the 2-year mark.

Another study reported earlier this year by this news organization showed a low risk for mild or moderate neutropenia and no severe cases in nearly 1000 people taking clozapine.

“I worry that we may be missing the forest for the trees by hyperfocusing on neutropenia and not considering clozapine’s other potential serious side effects like pneumonia, myocarditis, and gastrointestinal hypermotility,” Dr. Cotes said.
 

Importance of Vaccines

The findings of these studies highlight the importance of vaccines in this at-risk group, said Dr. Taquet, a point emphasized by investigators of the Danish study he reviewed.

“Inspired by the experience of COVID-19 vaccine prioritization in severe mental illness and based on our findings, there is momentum for preventive action,” the authors wrote. “Our findings do not suggest the avoidance of specific antipsychotics but rather a call for increased vigilance regarding this at-risk group.”

This includes recommending pneumococcal, influenza, COVID-19, and other anti-infective vaccines in those older than 40 years treated with, or due to start, an antipsychotic.

“It’s not mandatory, but we do recommend that patients on clozapine get the regular vaccines,” Dr. Taquet said.

Pointing to the recent study on pneumonia risk, Dr. Cotes said addressing underlying risk factors, such as smoking, obesity, and possibly sedation and excessive salivation caused by clozapine, is key.

“And to make sure that vaccinations are up to date, particularly heading into this fall,” he added.
 

Rethinking Clozapine REMS

One of the most challenging issues facing clinicians and researchers is how to help people understand the safety profile of clozapine and to use it with more confidence, Dr. Cotes said.

“A lot of people hear about clozapine and they think about neutropenia, they think about side effects, the REMS system, and all of these factors really drive down clozapine utilization,” he said.

Treatment-resistant schizophrenia affects about a quarter of those with schizophrenia, yet only 4% of these patients receive clozapine in the United States, Dr. Cotes said. That number may be even lower for its other indication of reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder.

The clozapine REMS is viewed as a major barrier to utilization and requires certification of pharmacists and physicians and use of a central system to monitor absolute neutrophil counts for neutropenia in patients.

As previously reported by this news organization in November 2022, the FDA opted to temporarily exercise enforcement discretion for certain aspects of the drug safety program to ensure continuity of care for patients after concerns were raised by the American Psychiatric Association (APA) along with other professional organizations.

Even with that temporary enforcement discretion, “reports have shown that over half of those prescribed clozapine have trouble accessing the medication because of the REMS program,” a spokesperson for the APA told this news organization.

“Not only are patients having trouble accessing the medication, many have trouble finding a prescriber in their geographic locations and others because of the monitoring requirements have their treatment discontinued leading to negative outcomes,” the spokesperson said.

The FDA is currently reviewing the clozapine REMS and is holding a joint advisory committee meeting on November 19 to discuss the review and “possible changes to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of clozapine.”

The APA plans to submit written and oral comments to the advisory committees.

“We are hopeful that the re-evaluation meeting in November will remove barriers and increase access to clozapine, which is currently highly underutilized, especially in marginalized communities,” the spokesperson said.

Dr. Cotes reported serving as a speaker and consultant for Saladax Biomedical and as a consultant for Syneos Health. Dr. Taquet reported having no competing interests.
 

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

Clozapine is considered the drug of choice for treatment-resistant schizophrenia in guidelines globally, but it remains significantly underutilized. This is largely due to its range of side effects, particularly its increased infection risk which prompted the US Food and Drug Administration (FDA) to mandate regular blood testing to monitor neutrophil counts.

The COVID-19 pandemic raised new concerns about the care of clozapine-treated patients, leading clinicians and patients to urge the FDA to relax prescription requirements for the drug under the Risk Evaluation and Mitigation Strategy (REMS) program.

As the FDA prepares for a public hearing in November on proposed adjustments to the drug’s REMS criteria, a growing body of research is challenging the previous understanding of clozapine and infection risk.
 

Clarifying the Risk

Research on the link between clozapine and respiratory infections has produced conflicting results. Some studies indicate little to no increased risk for mild COVID-19 and other respiratory illnesses, while others have shown a higher likelihood of severe infection.

A recent nationwide Danish registry study of respiratory infections in people with a schizophrenia spectrum disorder could bring some clarity, Maxime Taquet, MD, a clinical lecturer at the University of Oxford, Warneford Hospital, Oxford, England, told this news organization.

By tracking periods when patients were on and off clozapine and other antipsychotics, the study offers more precise risk estimates, distinguishing the risks associated with the antipsychotic from those related to underlying schizophrenia, said Dr. Taquet, who authored an accompanying editorial on the study.

“It’s very important to try to disentangle the effects of schizophrenia, its severity, from the medication,” Dr. Taquet said. “I think that the Danish study is the first to try and really do that with as much precision as possible.”

After adjusting for key confounders including economic status and COVID-19 vaccination status, the researchers found that individuals taking antipsychotics had lower odds of testing positive for SARS-CoV-2 and similar rates of filled anti-infective prescriptions as those not taking the drugs.

Although antipsychotic use was not linked to higher rates of mild infection, it was linked to an increased risk for COVID-19 hospitalization in individuals older than 70 years, as well as hospitalization and death from other respiratory infections, mainly pneumonia, in those older than 40 years.

Notably, there was no excess risk for any outcome with clozapine vs other antipsychotics.
 

Strong Link to Pneumonia Risk

Results from a longitudinal Finnish study, just published in The American Journal of Psychiatry, also show an increased risk for severe outcomes from ileus and pneumonia among more than 2600 patients with schizophrenia taking clozapine.

Twenty years after initiating clozapine, the cumulative incidence estimate for ileus was 5.3% — more than sixfold higher than previously reported. The incidence of pneumonia was also high, at 29.5%.

Both illnesses were significantly associated with mortality, with odds ratios of 4.5 and 2.8, respectively.

These findings align with previous pharmacovigilance studies, with reported mortality rates for gastrointestinal hypomotility and pneumonia that were 4-10 times higher than those for agranulocytosis, the researchers said.

The study “really adds to a growing body of research suggesting a connection between clozapine use and a higher risk of developing pneumonia,” Robert O. Cotes, MD, a professor of psychiatry and behavioral sciences at Emory University, Atlanta, who specializes in the use of clozapine, told this news organization.

“Additionally, when people on clozapine do contract pneumonia, there’s concern the condition may be more dangerous,” he added.
 

A Closer Look at Neutropenia Risk

Neutropenia receives the lion’s share of attention among clozapine’s potential side effects, but this focus may need to be re-evaluated, Dr. Cotes said.

He pointed out that recent data suggest the risk for severe neutropenia, 2-3 years after initiating clozapine, is comparable to that of other antipsychotics.

A study of 26,630 clozapine users in Australia and New Zealand showed that most cases of severe neutropenia leading to clozapine cessation peaked within 18 weeks and was negligible after 2 years. This suggests weekly hematologic monitoring could potentially be discontinued after the 2-year mark.

Another study reported earlier this year by this news organization showed a low risk for mild or moderate neutropenia and no severe cases in nearly 1000 people taking clozapine.

“I worry that we may be missing the forest for the trees by hyperfocusing on neutropenia and not considering clozapine’s other potential serious side effects like pneumonia, myocarditis, and gastrointestinal hypermotility,” Dr. Cotes said.
 

Importance of Vaccines

The findings of these studies highlight the importance of vaccines in this at-risk group, said Dr. Taquet, a point emphasized by investigators of the Danish study he reviewed.

“Inspired by the experience of COVID-19 vaccine prioritization in severe mental illness and based on our findings, there is momentum for preventive action,” the authors wrote. “Our findings do not suggest the avoidance of specific antipsychotics but rather a call for increased vigilance regarding this at-risk group.”

This includes recommending pneumococcal, influenza, COVID-19, and other anti-infective vaccines in those older than 40 years treated with, or due to start, an antipsychotic.

“It’s not mandatory, but we do recommend that patients on clozapine get the regular vaccines,” Dr. Taquet said.

Pointing to the recent study on pneumonia risk, Dr. Cotes said addressing underlying risk factors, such as smoking, obesity, and possibly sedation and excessive salivation caused by clozapine, is key.

“And to make sure that vaccinations are up to date, particularly heading into this fall,” he added.
 

Rethinking Clozapine REMS

One of the most challenging issues facing clinicians and researchers is how to help people understand the safety profile of clozapine and to use it with more confidence, Dr. Cotes said.

“A lot of people hear about clozapine and they think about neutropenia, they think about side effects, the REMS system, and all of these factors really drive down clozapine utilization,” he said.

Treatment-resistant schizophrenia affects about a quarter of those with schizophrenia, yet only 4% of these patients receive clozapine in the United States, Dr. Cotes said. That number may be even lower for its other indication of reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder.

The clozapine REMS is viewed as a major barrier to utilization and requires certification of pharmacists and physicians and use of a central system to monitor absolute neutrophil counts for neutropenia in patients.

As previously reported by this news organization in November 2022, the FDA opted to temporarily exercise enforcement discretion for certain aspects of the drug safety program to ensure continuity of care for patients after concerns were raised by the American Psychiatric Association (APA) along with other professional organizations.

Even with that temporary enforcement discretion, “reports have shown that over half of those prescribed clozapine have trouble accessing the medication because of the REMS program,” a spokesperson for the APA told this news organization.

“Not only are patients having trouble accessing the medication, many have trouble finding a prescriber in their geographic locations and others because of the monitoring requirements have their treatment discontinued leading to negative outcomes,” the spokesperson said.

The FDA is currently reviewing the clozapine REMS and is holding a joint advisory committee meeting on November 19 to discuss the review and “possible changes to minimize burden on patients, pharmacies, and prescribers while maintaining safe use of clozapine.”

The APA plans to submit written and oral comments to the advisory committees.

“We are hopeful that the re-evaluation meeting in November will remove barriers and increase access to clozapine, which is currently highly underutilized, especially in marginalized communities,” the spokesperson said.

Dr. Cotes reported serving as a speaker and consultant for Saladax Biomedical and as a consultant for Syneos Health. Dr. Taquet reported having no competing interests.
 

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

Palliative care has proven to be one of the most promising fields for research on interventions with psychedelic substances. One of the most prominent researchers in this area was the American psychopharmacologist Roland Griffiths, PhD.

In 2016, Dr. Griffiths and his team at Johns Hopkins University in Baltimore, Maryland, published one of the most relevant contributions to the field by demonstrating in a placebo-controlled study that psilocybin can reduce depressive and anxiety symptoms in patients with cancer. The study, conducted with 51 patients diagnosed with advanced-stage cancer, compared the effects of a low dose and a high dose of psilocybin, showing that the high dose resulted in improvements in mood, quality of life, and sense of life, reducing death-related anxiety.

In 2021, after a routine examination, Dr. Griffiths himself was diagnosed with advanced colon cancer. Unexpectedly, the researcher found himself in the position of his research subjects. In an interview with The New York Times in April 2023, he stated that, after some resistance, he agreed to undergo an LSD session.

In the conversation, he revealed that he had a 50% chance of being alive by Halloween. Despite the diagnosis, he showed no discouragement. “As a scientist, I feel like a kid in a candy store, considering all the research and questions that need to be answered about psychedelics and the theme of human flourishing,” he said.

In his last months of life, in the various appearances and interviews he gave, Dr. Griffiths demonstrated a perception of life uncommon in people facing death. “I’m excited to communicate, to shake off the dust and tell people: ‘Come on, wake up!’ ”

He passed away on October 16, 2023, at age 77 years, opening new horizons for clinical research with psychedelics and becoming an example of the therapeutic potential of these substances.
 

Innovative Treatments

“I believe this will be one of the next conditions, if not the next condition, to be considered for the designation of innovative treatment in future psilocybin regulation in the United States, where the field is more advanced,” said Lucas Maia, PhD, a psychopharmacologist and researcher affiliated with the Advanced Center for Psychedelic Medicine (CAMP) at the Federal University of Rio Grande do Norte (UFRN) and the Interdisciplinary Cooperation for Ayahuasca Research and Outreach (ICARO) at the State University of Campinas in São Paulo, Brazil.

Currently, MDMA (for the treatment of posttraumatic stress disorder), psilocybin (for depressive disorder), and MM120 (an LSD analogue used to treat generalized anxiety disorder) are the only psychedelic substances that have received the designation of innovative treatment by the Food and Drug Administration (FDA).

In 2022, Dr. Maia and a colleague from ICARO, Ana Cláudia Mesquita Garcia, PhD, a professor at the School of Nursing at the Federal University of Alfenas in Brazil and leader of the Interdisciplinary Center for Studies in Palliative Care, published a systematic review in the Journal of Pain and Symptom Management that evaluated the use of psychedelic-assisted treatments for symptom control in patients with serious or terminal illnesses.

Of the 20 articles reviewed, 9 (45%) used LSD, 5 (25%) psilocybin, 2 (10%) dipropyltryptamine (DPT), 1 (5%) used ketamine, and 1 (5%) used MDMA. In 10% of the studies, LSD and DPT were combined. Altogether, 347 participants (54%) received LSD, 116 (18%) psilocybin, 81 (13%) LSD and DPT, 64 (10%) DPT, 18 (3%) MDMA, and 14 (2%) ketamine.

The conclusion of the study is that psychedelics provide therapeutic effects on physical, psychological, social, and existential outcomes. They are associated with a reduction in pain and improvement in sleep. A decrease in depressive and anxiety symptoms is also observed; such symptoms are common in patients with serious diseases. In addition, interpersonal relationships become closer and more empathetic. Finally, there is a reduction in the fear of death and suffering, an increase in acceptance, and a redefinition of the disease.

In 55% of the studies, the adverse effects were mild to moderate and transient. They included nausea, vomiting, dry mouth, and fatigue, as well as anxiety, panic, and hallucinations. The researchers concluded that the scarcity and difficulty of access to professional training in psychedelic-assisted treatments represent a significant challenge for the advancement of these interventions, especially in countries in the Global South.

Another systematic review and meta-analysis published in July by researchers at the University of Michigan in Ann Arbor, Michigan, included seven studies with 132 participants and showed significant improvements in quality of life, pain control, and anxiety relief after psychedelic-assisted psychotherapy with psilocybin. The combined effects indicated statistically significant reductions in anxiety symptoms after 4.0-4.5 months and after 6.0-6.5 months post administration, compared with the initial evaluations.

One of the most advanced research studies currently being conducted is led by Stephen Ross, MD, a psychiatrist affiliated with New York University’s Langone Medical Center, New York City. The phase 2b clinical study is randomized, double blind, and placebo controlled, and involves 300 participants. The study aims to evaluate the effects of psilocybin-assisted psychotherapy on psychiatric and existential distress in patients with advanced cancer. Its expected completion date is in 2027.

“We still lack effective interventions in minimizing psychological, spiritual, and existential suffering,” said Dr. Garcia. “In this sense, respecting the contraindications of a physical nature (including pre-existing illnesses at study initiation, disease staging, patient functionality level, comorbidities, concurrent pharmacological treatments, etc) and of a psychiatric nature for the use of psychedelics, depending on the clinical picture, end-of-life patients facing existential crises and psychological suffering will likely benefit more from psychedelic-assisted psychotherapy, which highlights the need for more research and the integration of this treatment into clinical practice.”
 

Changing Perceptions

Since 2021, the Cancer Institute of the State of São Paulo (Icesp) has been providing palliative treatment with ketamine — an atypical psychedelic — following a rigorous and carefully monitored clinical protocol. The substance is already used off label to treat refractory depressive disorder. In addition, in 2020, Brazil’s National Health Surveillance Agency approved the use of Spravato, an intranasal antidepressant based on the ketamine derivative esketamine.

Icesp has hospice beds for clinical oncology patients, and a pain management team evaluates which patients meet the inclusion criteria for ketamine use. In addition to difficult-to-control pain, it is important that the patient present emotional, existential, or spiritual symptoms that amplify that pain.

After this evaluation, a psychoeducation process takes place, in which the patient receives clear information about the treatment, its potential benefits and risks, and understands how ketamine can be a viable option for managing their symptoms. Finally, it is essential that the patient accept the referral and demonstrate a willingness to participate in the treatment, agreeing to the proposed terms.

The treatment takes place in a hospital environment, with an ambiance that aims to provide comfort and safety. Clinicians consider not only the substance dose (such as 0.5 mg/kg) but also the emotional state (“set”) and the treatment environment (“setting”). The experience is facilitated through psychological support for the patient during and after treatment.

According to Alessandro Campolina, MD, PhD, a researcher at the Center for Translational Oncology Research at Icesp, it is important to highlight that quality of life is intrinsically linked to the patient’s self-perception, including how they see themselves in terms of health and in the context in which they live.

The doctor explains that psychedelic interventions can provide a “window of opportunity,” allowing a qualified clinician to help the patient explore new perspectives based on their experiences.

“Often, although the intensity of pain remains the same, the way the patient perceives it can change significantly. For example, a patient may report that, despite the pain, they now feel less concerned about it because they were able to contemplate more significant aspects of their life,” said Dr. Campolina.

“This observation shows that treatment is not limited to addressing the pain or primary symptoms, but also addresses the associated suffering. While some patients have profound insights, many others experience more subtle changes that, under the guidance of a competent therapist, can turn into valuable clinical insights, thus improving quality of life and how they deal with their pathologies.”

Dr. Griffiths exemplified this in the interview with the Times when he reflected on his own cancer. He came to believe, as if guided an external observer, that “there is a meaning and a purpose in this [disease] that go beyond your understanding, and the way you are dealing with it is exactly how you should.”

Toshio Chiba, MD, chief physician of the Palliative Care Service at Icesp, emphasized that ketamine is already in use. “It is not feasible to wait years for the approval of psilocybin or for the FDA’s decision on MDMA, especially if the patient needs immediate care,” he said.

Furthermore, recreational and therapeutic uses are distinct. “It is essential to note that responsibilities are shared between the professional and the patient,” said Dr. Chiba. “In the therapeutic setting, there is an ethical and civil responsibility of the medical professional, as well as the patient actively engaging in treatment.”

Early palliative care can also facilitate the establishment of care goals. “I prefer to avoid terms like ‘coping’ or ‘fighting the disease,’” said Dr. Chiba. “Nowadays, dealing with cancer is more about coexisting with the disease properly, as treatments can last for years. 

“Of course, there are still highly lethal tumors. However, for neoplasms like breast, colorectal, and prostate cancers, we often talk about 5, 10, or even 15 years of coexistence [with the condition]. The lack of this information [about the disease, treatments, and existential issues] can generate distress in some patients, who end up excessively worrying about the future,” he added.

But palliative treatment with psychedelics as a panacea, he said.

In addition, Marcelo Falchi, MD, medical director of CAMP at UFRN, also emphasized that psychedelics are not a risk-free intervention. Substances like LSD and psilocybin, for example, can cause increases in blood pressure and tachycardia, which, may limit their use for patients at high cardiovascular risk. Crises of anxiety or dissociative symptoms also may occur, and they require mitigation strategies such as psychological support and attention to set and setting.

“But research seems to agree that the risks can be managed effectively through a diligent process, allowing for the responsible exploration of the therapeutic potential of psychedelics,” said Dr. Falchi, who is responsible for CAMP’s postgraduate course in psychedelic therapies. The program provides training in substances used in Brazil, such as ketamine and ibogaine.

The use of psychedelics in palliative care requires a significant shift in how professionals relate to patients.

Unlike in traditional practice, where the prescription is followed by quick consultations, palliative care with psychedelics requires deep and continuous involvement, as Dr. Campolina pointed out. “We joke that it’s not a high-tech specialty, but ‘high touch,’ because it demands the constant presence of the doctor or therapist with the patient. This can involve sessions of several hours, with frequent monitoring and regular contact after sessions. This dynamic emphasizes the importance of human touch and connection during the process, reflecting a new way of practicing medicine.”

In his last months of life, Dr. Griffiths sought to emphasize this point, suggesting that, from a broader perspective, doctors and patients face the same fundamental questions. “We all know we are terminal,” he said. “Essentially, we shouldn’t need a stage 4 cancer diagnosis to awaken to this reality.”

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

Palliative care has proven to be one of the most promising fields for research on interventions with psychedelic substances. One of the most prominent researchers in this area was the American psychopharmacologist Roland Griffiths, PhD.

In 2016, Dr. Griffiths and his team at Johns Hopkins University in Baltimore, Maryland, published one of the most relevant contributions to the field by demonstrating in a placebo-controlled study that psilocybin can reduce depressive and anxiety symptoms in patients with cancer. The study, conducted with 51 patients diagnosed with advanced-stage cancer, compared the effects of a low dose and a high dose of psilocybin, showing that the high dose resulted in improvements in mood, quality of life, and sense of life, reducing death-related anxiety.

In 2021, after a routine examination, Dr. Griffiths himself was diagnosed with advanced colon cancer. Unexpectedly, the researcher found himself in the position of his research subjects. In an interview with The New York Times in April 2023, he stated that, after some resistance, he agreed to undergo an LSD session.

In the conversation, he revealed that he had a 50% chance of being alive by Halloween. Despite the diagnosis, he showed no discouragement. “As a scientist, I feel like a kid in a candy store, considering all the research and questions that need to be answered about psychedelics and the theme of human flourishing,” he said.

In his last months of life, in the various appearances and interviews he gave, Dr. Griffiths demonstrated a perception of life uncommon in people facing death. “I’m excited to communicate, to shake off the dust and tell people: ‘Come on, wake up!’ ”

He passed away on October 16, 2023, at age 77 years, opening new horizons for clinical research with psychedelics and becoming an example of the therapeutic potential of these substances.
 

Innovative Treatments

“I believe this will be one of the next conditions, if not the next condition, to be considered for the designation of innovative treatment in future psilocybin regulation in the United States, where the field is more advanced,” said Lucas Maia, PhD, a psychopharmacologist and researcher affiliated with the Advanced Center for Psychedelic Medicine (CAMP) at the Federal University of Rio Grande do Norte (UFRN) and the Interdisciplinary Cooperation for Ayahuasca Research and Outreach (ICARO) at the State University of Campinas in São Paulo, Brazil.

Currently, MDMA (for the treatment of posttraumatic stress disorder), psilocybin (for depressive disorder), and MM120 (an LSD analogue used to treat generalized anxiety disorder) are the only psychedelic substances that have received the designation of innovative treatment by the Food and Drug Administration (FDA).

In 2022, Dr. Maia and a colleague from ICARO, Ana Cláudia Mesquita Garcia, PhD, a professor at the School of Nursing at the Federal University of Alfenas in Brazil and leader of the Interdisciplinary Center for Studies in Palliative Care, published a systematic review in the Journal of Pain and Symptom Management that evaluated the use of psychedelic-assisted treatments for symptom control in patients with serious or terminal illnesses.

Of the 20 articles reviewed, 9 (45%) used LSD, 5 (25%) psilocybin, 2 (10%) dipropyltryptamine (DPT), 1 (5%) used ketamine, and 1 (5%) used MDMA. In 10% of the studies, LSD and DPT were combined. Altogether, 347 participants (54%) received LSD, 116 (18%) psilocybin, 81 (13%) LSD and DPT, 64 (10%) DPT, 18 (3%) MDMA, and 14 (2%) ketamine.

The conclusion of the study is that psychedelics provide therapeutic effects on physical, psychological, social, and existential outcomes. They are associated with a reduction in pain and improvement in sleep. A decrease in depressive and anxiety symptoms is also observed; such symptoms are common in patients with serious diseases. In addition, interpersonal relationships become closer and more empathetic. Finally, there is a reduction in the fear of death and suffering, an increase in acceptance, and a redefinition of the disease.

In 55% of the studies, the adverse effects were mild to moderate and transient. They included nausea, vomiting, dry mouth, and fatigue, as well as anxiety, panic, and hallucinations. The researchers concluded that the scarcity and difficulty of access to professional training in psychedelic-assisted treatments represent a significant challenge for the advancement of these interventions, especially in countries in the Global South.

Another systematic review and meta-analysis published in July by researchers at the University of Michigan in Ann Arbor, Michigan, included seven studies with 132 participants and showed significant improvements in quality of life, pain control, and anxiety relief after psychedelic-assisted psychotherapy with psilocybin. The combined effects indicated statistically significant reductions in anxiety symptoms after 4.0-4.5 months and after 6.0-6.5 months post administration, compared with the initial evaluations.

One of the most advanced research studies currently being conducted is led by Stephen Ross, MD, a psychiatrist affiliated with New York University’s Langone Medical Center, New York City. The phase 2b clinical study is randomized, double blind, and placebo controlled, and involves 300 participants. The study aims to evaluate the effects of psilocybin-assisted psychotherapy on psychiatric and existential distress in patients with advanced cancer. Its expected completion date is in 2027.

“We still lack effective interventions in minimizing psychological, spiritual, and existential suffering,” said Dr. Garcia. “In this sense, respecting the contraindications of a physical nature (including pre-existing illnesses at study initiation, disease staging, patient functionality level, comorbidities, concurrent pharmacological treatments, etc) and of a psychiatric nature for the use of psychedelics, depending on the clinical picture, end-of-life patients facing existential crises and psychological suffering will likely benefit more from psychedelic-assisted psychotherapy, which highlights the need for more research and the integration of this treatment into clinical practice.”
 

Changing Perceptions

Since 2021, the Cancer Institute of the State of São Paulo (Icesp) has been providing palliative treatment with ketamine — an atypical psychedelic — following a rigorous and carefully monitored clinical protocol. The substance is already used off label to treat refractory depressive disorder. In addition, in 2020, Brazil’s National Health Surveillance Agency approved the use of Spravato, an intranasal antidepressant based on the ketamine derivative esketamine.

Icesp has hospice beds for clinical oncology patients, and a pain management team evaluates which patients meet the inclusion criteria for ketamine use. In addition to difficult-to-control pain, it is important that the patient present emotional, existential, or spiritual symptoms that amplify that pain.

After this evaluation, a psychoeducation process takes place, in which the patient receives clear information about the treatment, its potential benefits and risks, and understands how ketamine can be a viable option for managing their symptoms. Finally, it is essential that the patient accept the referral and demonstrate a willingness to participate in the treatment, agreeing to the proposed terms.

The treatment takes place in a hospital environment, with an ambiance that aims to provide comfort and safety. Clinicians consider not only the substance dose (such as 0.5 mg/kg) but also the emotional state (“set”) and the treatment environment (“setting”). The experience is facilitated through psychological support for the patient during and after treatment.

According to Alessandro Campolina, MD, PhD, a researcher at the Center for Translational Oncology Research at Icesp, it is important to highlight that quality of life is intrinsically linked to the patient’s self-perception, including how they see themselves in terms of health and in the context in which they live.

The doctor explains that psychedelic interventions can provide a “window of opportunity,” allowing a qualified clinician to help the patient explore new perspectives based on their experiences.

“Often, although the intensity of pain remains the same, the way the patient perceives it can change significantly. For example, a patient may report that, despite the pain, they now feel less concerned about it because they were able to contemplate more significant aspects of their life,” said Dr. Campolina.

“This observation shows that treatment is not limited to addressing the pain or primary symptoms, but also addresses the associated suffering. While some patients have profound insights, many others experience more subtle changes that, under the guidance of a competent therapist, can turn into valuable clinical insights, thus improving quality of life and how they deal with their pathologies.”

Dr. Griffiths exemplified this in the interview with the Times when he reflected on his own cancer. He came to believe, as if guided an external observer, that “there is a meaning and a purpose in this [disease] that go beyond your understanding, and the way you are dealing with it is exactly how you should.”

Toshio Chiba, MD, chief physician of the Palliative Care Service at Icesp, emphasized that ketamine is already in use. “It is not feasible to wait years for the approval of psilocybin or for the FDA’s decision on MDMA, especially if the patient needs immediate care,” he said.

Furthermore, recreational and therapeutic uses are distinct. “It is essential to note that responsibilities are shared between the professional and the patient,” said Dr. Chiba. “In the therapeutic setting, there is an ethical and civil responsibility of the medical professional, as well as the patient actively engaging in treatment.”

Early palliative care can also facilitate the establishment of care goals. “I prefer to avoid terms like ‘coping’ or ‘fighting the disease,’” said Dr. Chiba. “Nowadays, dealing with cancer is more about coexisting with the disease properly, as treatments can last for years. 

“Of course, there are still highly lethal tumors. However, for neoplasms like breast, colorectal, and prostate cancers, we often talk about 5, 10, or even 15 years of coexistence [with the condition]. The lack of this information [about the disease, treatments, and existential issues] can generate distress in some patients, who end up excessively worrying about the future,” he added.

But palliative treatment with psychedelics as a panacea, he said.

In addition, Marcelo Falchi, MD, medical director of CAMP at UFRN, also emphasized that psychedelics are not a risk-free intervention. Substances like LSD and psilocybin, for example, can cause increases in blood pressure and tachycardia, which, may limit their use for patients at high cardiovascular risk. Crises of anxiety or dissociative symptoms also may occur, and they require mitigation strategies such as psychological support and attention to set and setting.

“But research seems to agree that the risks can be managed effectively through a diligent process, allowing for the responsible exploration of the therapeutic potential of psychedelics,” said Dr. Falchi, who is responsible for CAMP’s postgraduate course in psychedelic therapies. The program provides training in substances used in Brazil, such as ketamine and ibogaine.

The use of psychedelics in palliative care requires a significant shift in how professionals relate to patients.

Unlike in traditional practice, where the prescription is followed by quick consultations, palliative care with psychedelics requires deep and continuous involvement, as Dr. Campolina pointed out. “We joke that it’s not a high-tech specialty, but ‘high touch,’ because it demands the constant presence of the doctor or therapist with the patient. This can involve sessions of several hours, with frequent monitoring and regular contact after sessions. This dynamic emphasizes the importance of human touch and connection during the process, reflecting a new way of practicing medicine.”

In his last months of life, Dr. Griffiths sought to emphasize this point, suggesting that, from a broader perspective, doctors and patients face the same fundamental questions. “We all know we are terminal,” he said. “Essentially, we shouldn’t need a stage 4 cancer diagnosis to awaken to this reality.”

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

Palliative care has proven to be one of the most promising fields for research on interventions with psychedelic substances. One of the most prominent researchers in this area was the American psychopharmacologist Roland Griffiths, PhD.

In 2016, Dr. Griffiths and his team at Johns Hopkins University in Baltimore, Maryland, published one of the most relevant contributions to the field by demonstrating in a placebo-controlled study that psilocybin can reduce depressive and anxiety symptoms in patients with cancer. The study, conducted with 51 patients diagnosed with advanced-stage cancer, compared the effects of a low dose and a high dose of psilocybin, showing that the high dose resulted in improvements in mood, quality of life, and sense of life, reducing death-related anxiety.

In 2021, after a routine examination, Dr. Griffiths himself was diagnosed with advanced colon cancer. Unexpectedly, the researcher found himself in the position of his research subjects. In an interview with The New York Times in April 2023, he stated that, after some resistance, he agreed to undergo an LSD session.

In the conversation, he revealed that he had a 50% chance of being alive by Halloween. Despite the diagnosis, he showed no discouragement. “As a scientist, I feel like a kid in a candy store, considering all the research and questions that need to be answered about psychedelics and the theme of human flourishing,” he said.

In his last months of life, in the various appearances and interviews he gave, Dr. Griffiths demonstrated a perception of life uncommon in people facing death. “I’m excited to communicate, to shake off the dust and tell people: ‘Come on, wake up!’ ”

He passed away on October 16, 2023, at age 77 years, opening new horizons for clinical research with psychedelics and becoming an example of the therapeutic potential of these substances.
 

Innovative Treatments

“I believe this will be one of the next conditions, if not the next condition, to be considered for the designation of innovative treatment in future psilocybin regulation in the United States, where the field is more advanced,” said Lucas Maia, PhD, a psychopharmacologist and researcher affiliated with the Advanced Center for Psychedelic Medicine (CAMP) at the Federal University of Rio Grande do Norte (UFRN) and the Interdisciplinary Cooperation for Ayahuasca Research and Outreach (ICARO) at the State University of Campinas in São Paulo, Brazil.

Currently, MDMA (for the treatment of posttraumatic stress disorder), psilocybin (for depressive disorder), and MM120 (an LSD analogue used to treat generalized anxiety disorder) are the only psychedelic substances that have received the designation of innovative treatment by the Food and Drug Administration (FDA).

In 2022, Dr. Maia and a colleague from ICARO, Ana Cláudia Mesquita Garcia, PhD, a professor at the School of Nursing at the Federal University of Alfenas in Brazil and leader of the Interdisciplinary Center for Studies in Palliative Care, published a systematic review in the Journal of Pain and Symptom Management that evaluated the use of psychedelic-assisted treatments for symptom control in patients with serious or terminal illnesses.

Of the 20 articles reviewed, 9 (45%) used LSD, 5 (25%) psilocybin, 2 (10%) dipropyltryptamine (DPT), 1 (5%) used ketamine, and 1 (5%) used MDMA. In 10% of the studies, LSD and DPT were combined. Altogether, 347 participants (54%) received LSD, 116 (18%) psilocybin, 81 (13%) LSD and DPT, 64 (10%) DPT, 18 (3%) MDMA, and 14 (2%) ketamine.

The conclusion of the study is that psychedelics provide therapeutic effects on physical, psychological, social, and existential outcomes. They are associated with a reduction in pain and improvement in sleep. A decrease in depressive and anxiety symptoms is also observed; such symptoms are common in patients with serious diseases. In addition, interpersonal relationships become closer and more empathetic. Finally, there is a reduction in the fear of death and suffering, an increase in acceptance, and a redefinition of the disease.

In 55% of the studies, the adverse effects were mild to moderate and transient. They included nausea, vomiting, dry mouth, and fatigue, as well as anxiety, panic, and hallucinations. The researchers concluded that the scarcity and difficulty of access to professional training in psychedelic-assisted treatments represent a significant challenge for the advancement of these interventions, especially in countries in the Global South.

Another systematic review and meta-analysis published in July by researchers at the University of Michigan in Ann Arbor, Michigan, included seven studies with 132 participants and showed significant improvements in quality of life, pain control, and anxiety relief after psychedelic-assisted psychotherapy with psilocybin. The combined effects indicated statistically significant reductions in anxiety symptoms after 4.0-4.5 months and after 6.0-6.5 months post administration, compared with the initial evaluations.

One of the most advanced research studies currently being conducted is led by Stephen Ross, MD, a psychiatrist affiliated with New York University’s Langone Medical Center, New York City. The phase 2b clinical study is randomized, double blind, and placebo controlled, and involves 300 participants. The study aims to evaluate the effects of psilocybin-assisted psychotherapy on psychiatric and existential distress in patients with advanced cancer. Its expected completion date is in 2027.

“We still lack effective interventions in minimizing psychological, spiritual, and existential suffering,” said Dr. Garcia. “In this sense, respecting the contraindications of a physical nature (including pre-existing illnesses at study initiation, disease staging, patient functionality level, comorbidities, concurrent pharmacological treatments, etc) and of a psychiatric nature for the use of psychedelics, depending on the clinical picture, end-of-life patients facing existential crises and psychological suffering will likely benefit more from psychedelic-assisted psychotherapy, which highlights the need for more research and the integration of this treatment into clinical practice.”
 

Changing Perceptions

Since 2021, the Cancer Institute of the State of São Paulo (Icesp) has been providing palliative treatment with ketamine — an atypical psychedelic — following a rigorous and carefully monitored clinical protocol. The substance is already used off label to treat refractory depressive disorder. In addition, in 2020, Brazil’s National Health Surveillance Agency approved the use of Spravato, an intranasal antidepressant based on the ketamine derivative esketamine.

Icesp has hospice beds for clinical oncology patients, and a pain management team evaluates which patients meet the inclusion criteria for ketamine use. In addition to difficult-to-control pain, it is important that the patient present emotional, existential, or spiritual symptoms that amplify that pain.

After this evaluation, a psychoeducation process takes place, in which the patient receives clear information about the treatment, its potential benefits and risks, and understands how ketamine can be a viable option for managing their symptoms. Finally, it is essential that the patient accept the referral and demonstrate a willingness to participate in the treatment, agreeing to the proposed terms.

The treatment takes place in a hospital environment, with an ambiance that aims to provide comfort and safety. Clinicians consider not only the substance dose (such as 0.5 mg/kg) but also the emotional state (“set”) and the treatment environment (“setting”). The experience is facilitated through psychological support for the patient during and after treatment.

According to Alessandro Campolina, MD, PhD, a researcher at the Center for Translational Oncology Research at Icesp, it is important to highlight that quality of life is intrinsically linked to the patient’s self-perception, including how they see themselves in terms of health and in the context in which they live.

The doctor explains that psychedelic interventions can provide a “window of opportunity,” allowing a qualified clinician to help the patient explore new perspectives based on their experiences.

“Often, although the intensity of pain remains the same, the way the patient perceives it can change significantly. For example, a patient may report that, despite the pain, they now feel less concerned about it because they were able to contemplate more significant aspects of their life,” said Dr. Campolina.

“This observation shows that treatment is not limited to addressing the pain or primary symptoms, but also addresses the associated suffering. While some patients have profound insights, many others experience more subtle changes that, under the guidance of a competent therapist, can turn into valuable clinical insights, thus improving quality of life and how they deal with their pathologies.”

Dr. Griffiths exemplified this in the interview with the Times when he reflected on his own cancer. He came to believe, as if guided an external observer, that “there is a meaning and a purpose in this [disease] that go beyond your understanding, and the way you are dealing with it is exactly how you should.”

Toshio Chiba, MD, chief physician of the Palliative Care Service at Icesp, emphasized that ketamine is already in use. “It is not feasible to wait years for the approval of psilocybin or for the FDA’s decision on MDMA, especially if the patient needs immediate care,” he said.

Furthermore, recreational and therapeutic uses are distinct. “It is essential to note that responsibilities are shared between the professional and the patient,” said Dr. Chiba. “In the therapeutic setting, there is an ethical and civil responsibility of the medical professional, as well as the patient actively engaging in treatment.”

Early palliative care can also facilitate the establishment of care goals. “I prefer to avoid terms like ‘coping’ or ‘fighting the disease,’” said Dr. Chiba. “Nowadays, dealing with cancer is more about coexisting with the disease properly, as treatments can last for years. 

“Of course, there are still highly lethal tumors. However, for neoplasms like breast, colorectal, and prostate cancers, we often talk about 5, 10, or even 15 years of coexistence [with the condition]. The lack of this information [about the disease, treatments, and existential issues] can generate distress in some patients, who end up excessively worrying about the future,” he added.

But palliative treatment with psychedelics as a panacea, he said.

In addition, Marcelo Falchi, MD, medical director of CAMP at UFRN, also emphasized that psychedelics are not a risk-free intervention. Substances like LSD and psilocybin, for example, can cause increases in blood pressure and tachycardia, which, may limit their use for patients at high cardiovascular risk. Crises of anxiety or dissociative symptoms also may occur, and they require mitigation strategies such as psychological support and attention to set and setting.

“But research seems to agree that the risks can be managed effectively through a diligent process, allowing for the responsible exploration of the therapeutic potential of psychedelics,” said Dr. Falchi, who is responsible for CAMP’s postgraduate course in psychedelic therapies. The program provides training in substances used in Brazil, such as ketamine and ibogaine.

The use of psychedelics in palliative care requires a significant shift in how professionals relate to patients.

Unlike in traditional practice, where the prescription is followed by quick consultations, palliative care with psychedelics requires deep and continuous involvement, as Dr. Campolina pointed out. “We joke that it’s not a high-tech specialty, but ‘high touch,’ because it demands the constant presence of the doctor or therapist with the patient. This can involve sessions of several hours, with frequent monitoring and regular contact after sessions. This dynamic emphasizes the importance of human touch and connection during the process, reflecting a new way of practicing medicine.”

In his last months of life, Dr. Griffiths sought to emphasize this point, suggesting that, from a broader perspective, doctors and patients face the same fundamental questions. “We all know we are terminal,” he said. “Essentially, we shouldn’t need a stage 4 cancer diagnosis to awaken to this reality.”

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

TOPLINE:

High levels of urinary cadmium are associated with double the risk for global cognitive impairment in White adults, a new study shows. There was no such association between the heavy metal and cognitive function in Black adults.

METHODOLOGY:

• Investigators reviewed data on 2172 adults (mean age, 64 years; 61% White; 39% Black; 55% women) from the ongoing REGARDS population-based prospective cohort study in the United States who were free of cognitive impairment or stroke at baseline.
• Global cognitive impairment was assessed annually using the Six-Item Screener, and domain-based cognitive impairment was assessed every 2 years using the Enhanced Cognitive Battery.
• Blood and urine samples were collected from the participants at baseline, and levels of urinary cadmium were assessed using a urinary creatinine-correction method.
• Covariates included participants’ age, sex, smoking pack-years, alcohol consumption, and education level.
• Mean follow-up was 10 years.

TAKEAWAY:

• Global cognitive impairment was observed in 195 cases and domain-based cognitive impairment in 53 cases.
• High levels of urinary cadmium were associated with double the risk of developing global cognitive impairment in White adults (odds ratio [OR], 2.07; 95% CI, 1.18-3.64).
• No association was observed between urinary cadmium and global cognitive impairment in the overall cohort or in Black adults.
• Median smoking pack-years — a significant source of cadmium exposure for the US population — was significantly higher in White participants than Black participants (P = .001 for the highest tertile of urinary cadmium concentration).

IN PRACTICE:

“These results need to be confirmed with studies that measure cadmium levels over time, include more people and follow people over a longer time, but there are many reasons to reduce exposure to cadmium, whether it’s through implementing policies and regulations for air pollution and drinking water or people changing their behaviors by stopping smoking or being around cigarette smoke,” lead author Liping Lu, MD, PhD, MS, Columbia University, New York City, said in a press release.

SOURCE:

The study was published online in Neurology.

LIMITATIONS:

Urinary cadmium levels were tested only at baseline, which may not have captured changes in exposure over time. A limited number of patients with cognitive impairment used the Enhanced Cognitive Battery. The study did not include occupational information, and the potential for residual confounding from smoking could not be completely excluded. The follow-up time may have been insufficient for observing a significant effect on cognition, and competing risks for mortality associated with cadmium exposure could also have affected the findings.

DISCLOSURES:

The study was co-funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health (NIH). Several authors were partially supported by the NIH. Detailed disclosures are provided in the original article.

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

TOPLINE:

High levels of urinary cadmium are associated with double the risk for global cognitive impairment in White adults, a new study shows. There was no such association between the heavy metal and cognitive function in Black adults.

METHODOLOGY:

• Investigators reviewed data on 2172 adults (mean age, 64 years; 61% White; 39% Black; 55% women) from the ongoing REGARDS population-based prospective cohort study in the United States who were free of cognitive impairment or stroke at baseline.
• Global cognitive impairment was assessed annually using the Six-Item Screener, and domain-based cognitive impairment was assessed every 2 years using the Enhanced Cognitive Battery.
• Blood and urine samples were collected from the participants at baseline, and levels of urinary cadmium were assessed using a urinary creatinine-correction method.
• Covariates included participants’ age, sex, smoking pack-years, alcohol consumption, and education level.
• Mean follow-up was 10 years.

TAKEAWAY:

• Global cognitive impairment was observed in 195 cases and domain-based cognitive impairment in 53 cases.
• High levels of urinary cadmium were associated with double the risk of developing global cognitive impairment in White adults (odds ratio [OR], 2.07; 95% CI, 1.18-3.64).
• No association was observed between urinary cadmium and global cognitive impairment in the overall cohort or in Black adults.
• Median smoking pack-years — a significant source of cadmium exposure for the US population — was significantly higher in White participants than Black participants (P = .001 for the highest tertile of urinary cadmium concentration).

IN PRACTICE:

“These results need to be confirmed with studies that measure cadmium levels over time, include more people and follow people over a longer time, but there are many reasons to reduce exposure to cadmium, whether it’s through implementing policies and regulations for air pollution and drinking water or people changing their behaviors by stopping smoking or being around cigarette smoke,” lead author Liping Lu, MD, PhD, MS, Columbia University, New York City, said in a press release.

SOURCE:

The study was published online in Neurology.

LIMITATIONS:

Urinary cadmium levels were tested only at baseline, which may not have captured changes in exposure over time. A limited number of patients with cognitive impairment used the Enhanced Cognitive Battery. The study did not include occupational information, and the potential for residual confounding from smoking could not be completely excluded. The follow-up time may have been insufficient for observing a significant effect on cognition, and competing risks for mortality associated with cadmium exposure could also have affected the findings.

DISCLOSURES:

The study was co-funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health (NIH). Several authors were partially supported by the NIH. Detailed disclosures are provided in the original article.

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

TOPLINE:

High levels of urinary cadmium are associated with double the risk for global cognitive impairment in White adults, a new study shows. There was no such association between the heavy metal and cognitive function in Black adults.

METHODOLOGY:

• Investigators reviewed data on 2172 adults (mean age, 64 years; 61% White; 39% Black; 55% women) from the ongoing REGARDS population-based prospective cohort study in the United States who were free of cognitive impairment or stroke at baseline.
• Global cognitive impairment was assessed annually using the Six-Item Screener, and domain-based cognitive impairment was assessed every 2 years using the Enhanced Cognitive Battery.
• Blood and urine samples were collected from the participants at baseline, and levels of urinary cadmium were assessed using a urinary creatinine-correction method.
• Covariates included participants’ age, sex, smoking pack-years, alcohol consumption, and education level.
• Mean follow-up was 10 years.

TAKEAWAY:

• Global cognitive impairment was observed in 195 cases and domain-based cognitive impairment in 53 cases.
• High levels of urinary cadmium were associated with double the risk of developing global cognitive impairment in White adults (odds ratio [OR], 2.07; 95% CI, 1.18-3.64).
• No association was observed between urinary cadmium and global cognitive impairment in the overall cohort or in Black adults.
• Median smoking pack-years — a significant source of cadmium exposure for the US population — was significantly higher in White participants than Black participants (P = .001 for the highest tertile of urinary cadmium concentration).

IN PRACTICE:

“These results need to be confirmed with studies that measure cadmium levels over time, include more people and follow people over a longer time, but there are many reasons to reduce exposure to cadmium, whether it’s through implementing policies and regulations for air pollution and drinking water or people changing their behaviors by stopping smoking or being around cigarette smoke,” lead author Liping Lu, MD, PhD, MS, Columbia University, New York City, said in a press release.

SOURCE:

The study was published online in Neurology.

LIMITATIONS:

Urinary cadmium levels were tested only at baseline, which may not have captured changes in exposure over time. A limited number of patients with cognitive impairment used the Enhanced Cognitive Battery. The study did not include occupational information, and the potential for residual confounding from smoking could not be completely excluded. The follow-up time may have been insufficient for observing a significant effect on cognition, and competing risks for mortality associated with cadmium exposure could also have affected the findings.

DISCLOSURES:

The study was co-funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health (NIH). Several authors were partially supported by the NIH. Detailed disclosures are provided in the original article.

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

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

Alzheimer’s disease (AD), the most common cause of dementia, is the fifth leading cause of death in the United States. An estimated 6.9 million Americans aged 65 years or older have AD. Comorbid conditions in AD may exacerbate the progression of dementia and negatively affect overall health.

Although the exact mechanisms remain unclear, systemic inflammation is thought to play a significant role in the development of many common comorbidities associated with AD. Among the most frequently observed comorbid conditions are hypertension, diabetes, and depression. The presence of these comorbidities affects the treatment and management of AD, underscoring the need to understand the mechanisms of their interrelationship and develop effective management strategies. 
 

Hypertension 

Hypertension is a well-established risk factor for numerous health conditions, including AD. A comprehensive review of five meta-analyses and 52 primary studies revealed that elevated systolic blood pressure (SBP) correlates with an 11 % increased risk of developing AD, raising the question of whether early intervention and control of blood pressure would mitigate the risk for AD later in life. 

Findings from the Northern Manhattan Study suggest that although elevated SBP contributes to cognitive decline in older patients, the use of antihypertensive medications can neutralize the effects of high SBP on certain cognitive functions. Furthermore, a systematic review and meta-analysis comprising 12 trials (92,135 participants) demonstrated a significant reduction in the risk for dementia and cognitive impairment with antihypertensive treatment.

Notably, a retrospective cohort study involving 69,081 participants treated with beta-blockers for hypertension found that beta-blockers with high blood-brain barrier permeability were associated with a reduced risk for AD compared with those with low blood-brain barrier permeability. Additionally, a secondary analysis of the SPRINT trial found antihypertensive medications that stimulate vs inhibit type 2 and 4 angiotensin II receptors were associated with a lower incidence of cognitive impairment. Although further clinical trials are necessary to directly assess specific medications, these findings emphasize the potential of antihypertensive treatment as a strategic approach to reduce the risk for AD.
 

Type 2 Diabetes 

The connection between AD and type 2 diabetes is such that AD is sometimes referred to as “type 3 diabetes.” Both diseases share some of the same underlying pathophysiologic mechanisms, particularly the development of insulin resistance and oxidative stress. A prospective cohort study of 10,095 participants showed that diabetes was significantly associated with a higher risk of developing dementia; this risk is even greater in patients who develop diabetes at an earlier age.

In an interview with this news organization, Alvaro Pascual-Leone, MD, PhD, a professor of neurology at Harvard Medical School, Boston, said, “In addition to being a comorbidity factor, diabetes appears to be a predisposing risk factor for AD.” This is supported by a comprehensive literature review showing an increased progression from mild cognitive impairment (MCI) to dementia in patients with diabetes, prediabetes, or metabolic syndrome, with a pooled odds ratio for dementia progression in individuals with diabetes of 1.53.

Owing to the overlapping pathophysiologic mechanisms in AD and diabetes, treating one condition may have beneficial effects on the other. A systematic umbrella review and meta-analysis that included 10 meta-analyses across nine classes of diabetes drugs found a protective effect against dementia with the use of metformin, thiazolidinediones (including pioglitazone), glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors. Moreover, a cohort study of 12,220 patients who discontinued metformin early (ie, stopped using metformin without a prior history of abnormal kidney function) and 29,126 patients considered routine users found an increased risk for dementia in the early terminator group. Although further research is warranted, the concurrent treatment of AD and diabetes with antidiabetic agents holds considerable promise.
 

Depression and Anxiety

Anxiety and depression are significant risk factors for AD, and conversely, AD increases the likelihood of developing these psychiatric conditions. A systematic review of 14,760 studies showed dysthymia often emerges during the early stages of AD as an emotional response to cognitive decline. 

Data from the Australian Imaging Biomarkers and Lifestyle study showed a markedly elevated risk for AD and MCI among individuals with preexisting anxiety or depression. This study also found that age, sex, and marital status are important determinants, with men and single individuals with depression being particularly susceptible to developing AD. Conversely, a cohort study of 129,410 AD patients with AD, 390,088 patients with all-cause dementia, and 3,900,880 age-matched controls without a history of depression showed a cumulative incidence of depression of 13% in the AD group vs 3% in the control group, suggesting a heightened risk for depression following an AD diagnosis. 

These findings underscore the importance of targeted screening and assessment for patients with anxiety and depression who may be at risk for AD or those diagnosed with AD who are at risk for subsequent depression and anxiety. Although antidepressants are effective in treating depression in general, their efficacy in AD-related depression is of variable quality, probably owing to differing pathophysiologic mechanisms of the disease. Further research is necessary to explore both pharmacologic and nonpharmacologic interventions for treating depression in AD patients. Some studies have found that cognitive behavioral-therapy can be effective in improving depression in patients with AD.
 

Sleep Disorders

Research has shown a strong correlation between AD and sleep disorders, particularly obstructive sleep apnea, insomnia, and circadian rhythm disruptions. Additionally, studies suggest that insomnia and sleep deprivation contribute to increased amyloid beta production and tau pathology, hallmark features of AD. A scoping review of 70 studies proposed that this relationship is mediated by the glymphatic system (glial-dependent waste clearance pathway in the central nervous system), and that sleep deprivation disrupts its function, leading to protein accumulation and subsequent neurologic symptoms of AD. Another study showed that sleep deprivation triggers glial cell activation, initiating an inflammatory cascade that accelerates AD progression.

Given that the gold standard treatment for obstructive sleep apnea is continuous positive airway pressure (CPAP), it has been hypothesized that CPAP could also alleviate AD symptoms owing to shared pathophysiologic mechanisms of these conditions. A large systemic review found that CPAP use improved AD symptoms in patients with mild AD or MCI, though other sleep interventions, such as cognitive-behavioral therapy and melatonin supplementation, have yielded mixed outcomes. However, most studies in this area are small in scale, and there remains a paucity of research on treating sleep disorders in AD patients, indicating a need for further investigation.
 

Musculoskeletal Disorders

Although no direct causative link has been established, research indicates an association between osteoarthritis (OA) and dementia, likely because of similar pathophysiologic mechanisms, including systemic inflammation. Longitudinal analyses of data from the Alzheimer’s Disease Neuroimaging Initiative study found cognitively normal older individuals with OA experience more rapid declines in hippocampal volumes compared to those without OA, suggesting that OA may elevate the risk of cognitive impairment. Current treatments for OA, such as nonsteroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying OA drugs, might also help alleviate AD symptoms related to inflammation, though the research in this area is limited.

AD has also been linked to osteoporosis. In a longitudinal follow-up study involving 78,994 patients with osteoporosis and 78,994 controls, AD developed in 5856 patients with osteoporosis compared with 3761 patients in the control group. These findings represent a 1.27-fold higher incidence of AD in patients with osteoporosis than in the control group, suggesting that osteoporosis might be a risk factor for AD.

Additionally, research has identified a relationship between AD and increased fracture risk and decreased bone mineral density, with AD patients exhibiting a significantly higher likelihood of bone fractures compared with those without AD. “Falls and fractures, aside from the risk they pose in all geriatric patients, in individuals with cognitive impairment — whether due to AD or another cause — have higher risk to cause delirium and that can result in greater morbidity and mortality and a lasting increase in cognitive disability,” stated Dr. Pascual-Leone. Current recommendations emphasize exercise and fall prevention strategies to reduce fracture risk in patients with AD, but there is a lack of comprehensive research on the safety and efficacy of osteoporosis medications in this population.
 

Implications for Clinical Practice

The intricate interplay between AD and its comorbidities highlights the need for a comprehensive and integrated approach to patient care. The overlapping pathophysiologic mechanisms suggest that these comorbidities can contribute to the evolution and progression of AD. Likewise, AD can exacerbate comorbid conditions. As such, a holistic assessment strategy that prioritizes early detection and management of comorbid conditions to mitigate their impact on AD progression would be beneficial. Dr. Pascual-Leone added, “The presence of any of these comorbidities suggests a need to screen for MCI earlier than might otherwise be indicated or as part of the treatment for the comorbid condition. In many cases, patients can make lifestyle modifications that improve not only the comorbid condition but also reduce its effect on dementia.” In doing so, healthcare providers can help improve patient outcomes and enhance the overall quality of life for individuals living with AD.

Alissa Hershberger, Professor of Nursing, University of Central Missouri, Lee’s Summit, Missouri, has disclosed no relevant financial relationships.

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

Alzheimer’s disease (AD), the most common cause of dementia, is the fifth leading cause of death in the United States. An estimated 6.9 million Americans aged 65 years or older have AD. Comorbid conditions in AD may exacerbate the progression of dementia and negatively affect overall health.

Although the exact mechanisms remain unclear, systemic inflammation is thought to play a significant role in the development of many common comorbidities associated with AD. Among the most frequently observed comorbid conditions are hypertension, diabetes, and depression. The presence of these comorbidities affects the treatment and management of AD, underscoring the need to understand the mechanisms of their interrelationship and develop effective management strategies. 
 

Hypertension 

Hypertension is a well-established risk factor for numerous health conditions, including AD. A comprehensive review of five meta-analyses and 52 primary studies revealed that elevated systolic blood pressure (SBP) correlates with an 11 % increased risk of developing AD, raising the question of whether early intervention and control of blood pressure would mitigate the risk for AD later in life. 

Findings from the Northern Manhattan Study suggest that although elevated SBP contributes to cognitive decline in older patients, the use of antihypertensive medications can neutralize the effects of high SBP on certain cognitive functions. Furthermore, a systematic review and meta-analysis comprising 12 trials (92,135 participants) demonstrated a significant reduction in the risk for dementia and cognitive impairment with antihypertensive treatment.

Notably, a retrospective cohort study involving 69,081 participants treated with beta-blockers for hypertension found that beta-blockers with high blood-brain barrier permeability were associated with a reduced risk for AD compared with those with low blood-brain barrier permeability. Additionally, a secondary analysis of the SPRINT trial found antihypertensive medications that stimulate vs inhibit type 2 and 4 angiotensin II receptors were associated with a lower incidence of cognitive impairment. Although further clinical trials are necessary to directly assess specific medications, these findings emphasize the potential of antihypertensive treatment as a strategic approach to reduce the risk for AD.
 

Type 2 Diabetes 

The connection between AD and type 2 diabetes is such that AD is sometimes referred to as “type 3 diabetes.” Both diseases share some of the same underlying pathophysiologic mechanisms, particularly the development of insulin resistance and oxidative stress. A prospective cohort study of 10,095 participants showed that diabetes was significantly associated with a higher risk of developing dementia; this risk is even greater in patients who develop diabetes at an earlier age.

In an interview with this news organization, Alvaro Pascual-Leone, MD, PhD, a professor of neurology at Harvard Medical School, Boston, said, “In addition to being a comorbidity factor, diabetes appears to be a predisposing risk factor for AD.” This is supported by a comprehensive literature review showing an increased progression from mild cognitive impairment (MCI) to dementia in patients with diabetes, prediabetes, or metabolic syndrome, with a pooled odds ratio for dementia progression in individuals with diabetes of 1.53.

Owing to the overlapping pathophysiologic mechanisms in AD and diabetes, treating one condition may have beneficial effects on the other. A systematic umbrella review and meta-analysis that included 10 meta-analyses across nine classes of diabetes drugs found a protective effect against dementia with the use of metformin, thiazolidinediones (including pioglitazone), glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors. Moreover, a cohort study of 12,220 patients who discontinued metformin early (ie, stopped using metformin without a prior history of abnormal kidney function) and 29,126 patients considered routine users found an increased risk for dementia in the early terminator group. Although further research is warranted, the concurrent treatment of AD and diabetes with antidiabetic agents holds considerable promise.
 

Depression and Anxiety

Anxiety and depression are significant risk factors for AD, and conversely, AD increases the likelihood of developing these psychiatric conditions. A systematic review of 14,760 studies showed dysthymia often emerges during the early stages of AD as an emotional response to cognitive decline. 

Data from the Australian Imaging Biomarkers and Lifestyle study showed a markedly elevated risk for AD and MCI among individuals with preexisting anxiety or depression. This study also found that age, sex, and marital status are important determinants, with men and single individuals with depression being particularly susceptible to developing AD. Conversely, a cohort study of 129,410 AD patients with AD, 390,088 patients with all-cause dementia, and 3,900,880 age-matched controls without a history of depression showed a cumulative incidence of depression of 13% in the AD group vs 3% in the control group, suggesting a heightened risk for depression following an AD diagnosis. 

These findings underscore the importance of targeted screening and assessment for patients with anxiety and depression who may be at risk for AD or those diagnosed with AD who are at risk for subsequent depression and anxiety. Although antidepressants are effective in treating depression in general, their efficacy in AD-related depression is of variable quality, probably owing to differing pathophysiologic mechanisms of the disease. Further research is necessary to explore both pharmacologic and nonpharmacologic interventions for treating depression in AD patients. Some studies have found that cognitive behavioral-therapy can be effective in improving depression in patients with AD.
 

Sleep Disorders

Research has shown a strong correlation between AD and sleep disorders, particularly obstructive sleep apnea, insomnia, and circadian rhythm disruptions. Additionally, studies suggest that insomnia and sleep deprivation contribute to increased amyloid beta production and tau pathology, hallmark features of AD. A scoping review of 70 studies proposed that this relationship is mediated by the glymphatic system (glial-dependent waste clearance pathway in the central nervous system), and that sleep deprivation disrupts its function, leading to protein accumulation and subsequent neurologic symptoms of AD. Another study showed that sleep deprivation triggers glial cell activation, initiating an inflammatory cascade that accelerates AD progression.

Given that the gold standard treatment for obstructive sleep apnea is continuous positive airway pressure (CPAP), it has been hypothesized that CPAP could also alleviate AD symptoms owing to shared pathophysiologic mechanisms of these conditions. A large systemic review found that CPAP use improved AD symptoms in patients with mild AD or MCI, though other sleep interventions, such as cognitive-behavioral therapy and melatonin supplementation, have yielded mixed outcomes. However, most studies in this area are small in scale, and there remains a paucity of research on treating sleep disorders in AD patients, indicating a need for further investigation.
 

Musculoskeletal Disorders

Although no direct causative link has been established, research indicates an association between osteoarthritis (OA) and dementia, likely because of similar pathophysiologic mechanisms, including systemic inflammation. Longitudinal analyses of data from the Alzheimer’s Disease Neuroimaging Initiative study found cognitively normal older individuals with OA experience more rapid declines in hippocampal volumes compared to those without OA, suggesting that OA may elevate the risk of cognitive impairment. Current treatments for OA, such as nonsteroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying OA drugs, might also help alleviate AD symptoms related to inflammation, though the research in this area is limited.

AD has also been linked to osteoporosis. In a longitudinal follow-up study involving 78,994 patients with osteoporosis and 78,994 controls, AD developed in 5856 patients with osteoporosis compared with 3761 patients in the control group. These findings represent a 1.27-fold higher incidence of AD in patients with osteoporosis than in the control group, suggesting that osteoporosis might be a risk factor for AD.

Additionally, research has identified a relationship between AD and increased fracture risk and decreased bone mineral density, with AD patients exhibiting a significantly higher likelihood of bone fractures compared with those without AD. “Falls and fractures, aside from the risk they pose in all geriatric patients, in individuals with cognitive impairment — whether due to AD or another cause — have higher risk to cause delirium and that can result in greater morbidity and mortality and a lasting increase in cognitive disability,” stated Dr. Pascual-Leone. Current recommendations emphasize exercise and fall prevention strategies to reduce fracture risk in patients with AD, but there is a lack of comprehensive research on the safety and efficacy of osteoporosis medications in this population.
 

Implications for Clinical Practice

The intricate interplay between AD and its comorbidities highlights the need for a comprehensive and integrated approach to patient care. The overlapping pathophysiologic mechanisms suggest that these comorbidities can contribute to the evolution and progression of AD. Likewise, AD can exacerbate comorbid conditions. As such, a holistic assessment strategy that prioritizes early detection and management of comorbid conditions to mitigate their impact on AD progression would be beneficial. Dr. Pascual-Leone added, “The presence of any of these comorbidities suggests a need to screen for MCI earlier than might otherwise be indicated or as part of the treatment for the comorbid condition. In many cases, patients can make lifestyle modifications that improve not only the comorbid condition but also reduce its effect on dementia.” In doing so, healthcare providers can help improve patient outcomes and enhance the overall quality of life for individuals living with AD.

Alissa Hershberger, Professor of Nursing, University of Central Missouri, Lee’s Summit, Missouri, has disclosed no relevant financial relationships.

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

Alzheimer’s disease (AD), the most common cause of dementia, is the fifth leading cause of death in the United States. An estimated 6.9 million Americans aged 65 years or older have AD. Comorbid conditions in AD may exacerbate the progression of dementia and negatively affect overall health.

Although the exact mechanisms remain unclear, systemic inflammation is thought to play a significant role in the development of many common comorbidities associated with AD. Among the most frequently observed comorbid conditions are hypertension, diabetes, and depression. The presence of these comorbidities affects the treatment and management of AD, underscoring the need to understand the mechanisms of their interrelationship and develop effective management strategies. 
 

Hypertension 

Hypertension is a well-established risk factor for numerous health conditions, including AD. A comprehensive review of five meta-analyses and 52 primary studies revealed that elevated systolic blood pressure (SBP) correlates with an 11 % increased risk of developing AD, raising the question of whether early intervention and control of blood pressure would mitigate the risk for AD later in life. 

Findings from the Northern Manhattan Study suggest that although elevated SBP contributes to cognitive decline in older patients, the use of antihypertensive medications can neutralize the effects of high SBP on certain cognitive functions. Furthermore, a systematic review and meta-analysis comprising 12 trials (92,135 participants) demonstrated a significant reduction in the risk for dementia and cognitive impairment with antihypertensive treatment.

Notably, a retrospective cohort study involving 69,081 participants treated with beta-blockers for hypertension found that beta-blockers with high blood-brain barrier permeability were associated with a reduced risk for AD compared with those with low blood-brain barrier permeability. Additionally, a secondary analysis of the SPRINT trial found antihypertensive medications that stimulate vs inhibit type 2 and 4 angiotensin II receptors were associated with a lower incidence of cognitive impairment. Although further clinical trials are necessary to directly assess specific medications, these findings emphasize the potential of antihypertensive treatment as a strategic approach to reduce the risk for AD.
 

Type 2 Diabetes 

The connection between AD and type 2 diabetes is such that AD is sometimes referred to as “type 3 diabetes.” Both diseases share some of the same underlying pathophysiologic mechanisms, particularly the development of insulin resistance and oxidative stress. A prospective cohort study of 10,095 participants showed that diabetes was significantly associated with a higher risk of developing dementia; this risk is even greater in patients who develop diabetes at an earlier age.

In an interview with this news organization, Alvaro Pascual-Leone, MD, PhD, a professor of neurology at Harvard Medical School, Boston, said, “In addition to being a comorbidity factor, diabetes appears to be a predisposing risk factor for AD.” This is supported by a comprehensive literature review showing an increased progression from mild cognitive impairment (MCI) to dementia in patients with diabetes, prediabetes, or metabolic syndrome, with a pooled odds ratio for dementia progression in individuals with diabetes of 1.53.

Owing to the overlapping pathophysiologic mechanisms in AD and diabetes, treating one condition may have beneficial effects on the other. A systematic umbrella review and meta-analysis that included 10 meta-analyses across nine classes of diabetes drugs found a protective effect against dementia with the use of metformin, thiazolidinediones (including pioglitazone), glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors. Moreover, a cohort study of 12,220 patients who discontinued metformin early (ie, stopped using metformin without a prior history of abnormal kidney function) and 29,126 patients considered routine users found an increased risk for dementia in the early terminator group. Although further research is warranted, the concurrent treatment of AD and diabetes with antidiabetic agents holds considerable promise.
 

Depression and Anxiety

Anxiety and depression are significant risk factors for AD, and conversely, AD increases the likelihood of developing these psychiatric conditions. A systematic review of 14,760 studies showed dysthymia often emerges during the early stages of AD as an emotional response to cognitive decline. 

Data from the Australian Imaging Biomarkers and Lifestyle study showed a markedly elevated risk for AD and MCI among individuals with preexisting anxiety or depression. This study also found that age, sex, and marital status are important determinants, with men and single individuals with depression being particularly susceptible to developing AD. Conversely, a cohort study of 129,410 AD patients with AD, 390,088 patients with all-cause dementia, and 3,900,880 age-matched controls without a history of depression showed a cumulative incidence of depression of 13% in the AD group vs 3% in the control group, suggesting a heightened risk for depression following an AD diagnosis. 

These findings underscore the importance of targeted screening and assessment for patients with anxiety and depression who may be at risk for AD or those diagnosed with AD who are at risk for subsequent depression and anxiety. Although antidepressants are effective in treating depression in general, their efficacy in AD-related depression is of variable quality, probably owing to differing pathophysiologic mechanisms of the disease. Further research is necessary to explore both pharmacologic and nonpharmacologic interventions for treating depression in AD patients. Some studies have found that cognitive behavioral-therapy can be effective in improving depression in patients with AD.
 

Sleep Disorders

Research has shown a strong correlation between AD and sleep disorders, particularly obstructive sleep apnea, insomnia, and circadian rhythm disruptions. Additionally, studies suggest that insomnia and sleep deprivation contribute to increased amyloid beta production and tau pathology, hallmark features of AD. A scoping review of 70 studies proposed that this relationship is mediated by the glymphatic system (glial-dependent waste clearance pathway in the central nervous system), and that sleep deprivation disrupts its function, leading to protein accumulation and subsequent neurologic symptoms of AD. Another study showed that sleep deprivation triggers glial cell activation, initiating an inflammatory cascade that accelerates AD progression.

Given that the gold standard treatment for obstructive sleep apnea is continuous positive airway pressure (CPAP), it has been hypothesized that CPAP could also alleviate AD symptoms owing to shared pathophysiologic mechanisms of these conditions. A large systemic review found that CPAP use improved AD symptoms in patients with mild AD or MCI, though other sleep interventions, such as cognitive-behavioral therapy and melatonin supplementation, have yielded mixed outcomes. However, most studies in this area are small in scale, and there remains a paucity of research on treating sleep disorders in AD patients, indicating a need for further investigation.
 

Musculoskeletal Disorders

Although no direct causative link has been established, research indicates an association between osteoarthritis (OA) and dementia, likely because of similar pathophysiologic mechanisms, including systemic inflammation. Longitudinal analyses of data from the Alzheimer’s Disease Neuroimaging Initiative study found cognitively normal older individuals with OA experience more rapid declines in hippocampal volumes compared to those without OA, suggesting that OA may elevate the risk of cognitive impairment. Current treatments for OA, such as nonsteroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying OA drugs, might also help alleviate AD symptoms related to inflammation, though the research in this area is limited.

AD has also been linked to osteoporosis. In a longitudinal follow-up study involving 78,994 patients with osteoporosis and 78,994 controls, AD developed in 5856 patients with osteoporosis compared with 3761 patients in the control group. These findings represent a 1.27-fold higher incidence of AD in patients with osteoporosis than in the control group, suggesting that osteoporosis might be a risk factor for AD.

Additionally, research has identified a relationship between AD and increased fracture risk and decreased bone mineral density, with AD patients exhibiting a significantly higher likelihood of bone fractures compared with those without AD. “Falls and fractures, aside from the risk they pose in all geriatric patients, in individuals with cognitive impairment — whether due to AD or another cause — have higher risk to cause delirium and that can result in greater morbidity and mortality and a lasting increase in cognitive disability,” stated Dr. Pascual-Leone. Current recommendations emphasize exercise and fall prevention strategies to reduce fracture risk in patients with AD, but there is a lack of comprehensive research on the safety and efficacy of osteoporosis medications in this population.
 

Implications for Clinical Practice

The intricate interplay between AD and its comorbidities highlights the need for a comprehensive and integrated approach to patient care. The overlapping pathophysiologic mechanisms suggest that these comorbidities can contribute to the evolution and progression of AD. Likewise, AD can exacerbate comorbid conditions. As such, a holistic assessment strategy that prioritizes early detection and management of comorbid conditions to mitigate their impact on AD progression would be beneficial. Dr. Pascual-Leone added, “The presence of any of these comorbidities suggests a need to screen for MCI earlier than might otherwise be indicated or as part of the treatment for the comorbid condition. In many cases, patients can make lifestyle modifications that improve not only the comorbid condition but also reduce its effect on dementia.” In doing so, healthcare providers can help improve patient outcomes and enhance the overall quality of life for individuals living with AD.

Alissa Hershberger, Professor of Nursing, University of Central Missouri, Lee’s Summit, Missouri, has disclosed no relevant financial relationships.

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