GLP-1 receptor agonist use and risk of suicide death

JAMA Internal Medicine

About The Study: 

This cohort study, including mostly patients with type 2 diabetes, does not show an association between use of glucagon-like peptide-1 (GLP-1) receptor agonists and an increased risk of suicide death, self-harm, or incident depression and anxiety-related disorders.

Corresponding Author: To contact the corresponding author, Peter Ueda, MD, PhD, email peter.ueda@ki.se.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2024.4369)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2024.4369?guestAccessKey=2dc15077-db5b-45cf-b2f1-f1fcf6020c5c&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=090324

 

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Journal

JAMA Internal Medicine

No link found between popular diabetes medication and suicide

Karolinska Institutet

 

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Peter Ueda

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Credit: Stefan Zimmerman

There has been concern that common diabetes drugs could increase the risk of suicide and self-harm. In a new study, led by researchers at Karolinska Institutet and published in Jama Internal Medicine, no such risk increase was observed.

Drugs of the type GLP-1 analogues lower blood sugar levels and are used by millions of people worldwide. They are mainly used to treat diabetes, but drugs such as Ozempic have also been shown to be effective against obesity, which has increased their popularity.

At the same time, both American and European drug authorities have warned that there may be risks associated with the drugs.

Last year, the European Medicines Agency (EMA) launched an investigation following around 150 reported possible cases of suicidal thoughts and self-injury with use of GLP-1 analogues.

The investigation was completed in the spring and based on the limited data available at the time, it concluded that there were no obvious connections. Researchers at Karolinska Institutet can now further support this conclusion. They have analyzed large amounts of data from people treated with GLP-1 analogues in Sweden and Denmark .

"We found no clear link between the use of the drugs and an increased risk of suicide death, self-harm or depression and anxiety-related disorders. This is reassuring." says Björn Pasternak, principal researcher at the Department of Medicine, Solna, Karolinska Institutet, and one of the study's lead authors.

The data includes approximately 300,000 adults aged 18–84 who started treatment with either GLP-1 analogues or SGLT2 inhibitors, another type of diabetes medication, during the years 2013–2021.

After a mean follow-up period of just over two years, there was no apparent increase in the proportion of people who committed suicide, engaged in self-harm, or suffered from depression or anxiety-related disorders among users of GLP-1 receptor agonists.

Peter Ueda, assistant professor at the same department and one of the study's main authors, nevertheless emphasizes the importance of larger studies as more data is collected.

"It is important to specifically examine people with previous self-harm or suicidal thoughts as they are at increased risk and it is possible that the drug’s safety profile differs in this group," he says. 

The study was conducted in collaboration with researchers in Denmark and mainly funded by Karolinska Institutet. Some of the researchers report conflicts of interest, see the study for more information.

Publication: "GLP-1 receptor agonists and risk of suicide death: nationwide cohort study in Sweden and Denmark", Peter Ueda, Jonas Söderling, Viktor Wintzell, Henrik Svanström, Laura Pazzagli, Björn Eliasson, Mads Melbye, Anders Hviid, Björn Pasternak. JAMA Internal Medicine, online September 3, 2024. 

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Journal

JAMA Internal Medicine

Method of Research

Observational study

Subject of Research

People

Article Title

GLP-1 receptor agonists and risk of suicide death: nationwide cohort study in Sweden and Denmark

Article Publication Date

3-Sep-2024

Penn study finds taking semaglutide for weight management does not increase risk of depression or suicidal behavior in people without known major psychopathology

Analysis of over 3,500 participants in clinical trials finds no increased risk of mental health issues among those using the weight loss medication

University of Pennsylvania School of Medicine

PHILADELPHIA— Taking the weight loss medication semaglutide did not increase the risk of depressive symptoms, suicidal thoughts, or suicidal behavior in persons without known major mental health disorders, according to a new study led by researchers from the Perelman School of Medicine at the University of Pennsylvania published this week in JAMA Internal Medicine. Both the Food and Drug Administration (FDA) and the European Medicines Agency are actively monitoring the psychiatric safety of semaglutide and similar medications after post marketing surveillance reports of depression, suicidal thoughts (ideation), and suicidal behavior in patients taking the drugs for the management of type 2 diabetes or obesity.

Semaglutide has emerged as a significant advancement in the field of weight management. Initially developed as a treatment for type 2 diabetes, the drug gained widespread attention after clinical trials showed it reduced baseline body weight by approximately 10%-15%. Weekly injectable medications like semaglutide have become a popular option for healthcare providers to prescribe for patients. As many as 5 million Americans were prescribed semaglutide in 2023, with nearly four in ten taking it for weight management.

The new study, led by Thomas Wadden, PhD, a professor of Psychology in Psychiatry and the former director of Penn’s Center for Weight and Eating Disorders, analyzed data from over 3,500 participants across four major clinical trials. Researchers examined data from the Semaglutide Treatment Effect in People with obesity (STEP) trials – STEP 1, 2, 3, and 5. These studies were crucial in gaining approval from the FDA to use semaglutide 2.4 mg for obesity.

"The STEP trials provide strong evidence that semaglutide 2.4 mg reduces body weight and improves numerous health complications associated with obesity. Our new analyses provide assurance that the medication, when taken by individuals who are free of significant mental health concerns, does not increase the risk of depression, suicidal thoughts, or suicidal behavior,” Wadden said. He noted, however, that further study is needed of the psychiatric safety of semaglutide 2.4 mg when used by persons with current major depressive disorder, other serious mental illness (such as schizophrenia), or a history of suicide attempt. Individuals with such conditions were not included in the STEP trials.

The study examined changes in depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9) and assessed suicidal ideation and behavior using the Columbia Suicide Severity Rating Scale. Across the 68-week STEP 1-3 trials, semaglutide-treated participants, as compared to those who received placebo, did not show an increased risk of developing moderately severe symptoms of depression or of suicidal thoughts or behavior. Similar findings were observed in the 104-week STEP 5 study.

Examining all four STEP trials, researchers found that 1% or fewer of participants reported suicidal ideation or behavior during treatment, with no differences between semaglutide 2.4 mg and placebo. Moreover, only 2.8% of the semaglutide-treated participants, versus 4.1% of those who received placebo, reported levels of depression at some point during treatment that required evaluation by a mental health professional. These rates are consistent with the risk of significant depression in the general population. “It is certainly possible that individuals with overweight or obesity who take semaglutide may experience depressive symptoms or suicidal ideation or behavior, but the data suggest that persons not taking semaglutide – in the placebo group in this study - are equally likely to experience these conditions,” said Gregory Brown, PhD, a study co-author and Director of the Penn Center for the Prevention of Suicide at the Perelman School of Medicine. Wadden and Brown noted that their study’s findings for semaglutide are consistent with results of the FDA’s most recent analysis of post-marketing surveillance data for this class of medications which did not find “evidence that use of these medicines causes suicidal thoughts or actions." 

If you or a loved one are experiencing a suicidal crisis or emotional distress call the Suicide and Crisis Lifeline at 988.

The study was funded by Novo Nordisk.

Editor’s Note: Wadden has received grants from Novo Nordisk, as well as consulting fees from Novo Nordisk, advisory board service fees from Weight Watchers, and grant support from Eli Lilly.

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Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.

The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.

The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.

 

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Journal

JAMA Internal Medicine

 SYSTEMIC RACIST MEDICINE

Study: racial and ethnic designation inaccuracies in children’s medical records may impede equity efforts

Michigan hospital collaborative uncovers substantial errors in data critical to identifying and addressing inequities and disparities in children’s health

Michigan Medicine - University of Michigan

ANN ARBOR, Mich. – Leaders at three Michigan hospitals aiming to address equity issues for pediatric patients wanted to start with inspecting data key to identifying potential inequities.

What they learned: much of those data are inaccurate.

A study from the Michigan Child Health Equity Collaborative, or Mi-CHEC, found substantial errors across the three health systems in racial and ethnic designations in their electronic medical records. Accuracy of these designations are important to clinical care improvement efforts yet error rates of race in electronic medical records ranged from 22% to 59% while errors in ethnicity ranged from 5% to 35%, according to the findings in JAMA Network Open.

“The goal of MI-CHEC is to identify inequities affecting children’s health and implement improvement strategies to address them. But if the data regarding race and ethnicity are wrong, there’s a real risk of missing some inequities and even trying to correct inequities that may not exist,” said lead author and Mi-CHEC founder Gary L. Freed, M.D., M.P.H., professor in the department of pediatrics at the U-M Medical School.

“This is the first step to better understanding the misattribution in racial and ethnic designations in medical records. There are no perfect data; however, if we don’t know the degree of accuracy in the race and ethnicity of our patient populations, we are truly flying blind when we and others are assessing equity and disparity.”   

The study reflects the first published data from Mi-CHEC, which comprises the state’s three largest pediatric hospitals, including U-M Health C.S. Mott Children’s Hospital, Children’s Hospital of Michigan and Corewell Health Helen DeVos Children’s Hospital.

Expanded designation choices associated with greater errors

Researchers compared the specific racial and designations made by more than 3,400 parents to what was listed in their children’s medical records in outpatient clinics, emergency departments and hospital units across health systems between 2023 and 2024.

Reasons for the discrepancies are still being assessed, but authors point out associations between errors in designations and the evolving range and number of potential categories used by health systems for racial and ethnic attribution.

Options for race designation across hospitals ranged from six at one system to 49 in another while options for ethnicity ranged from two to 10. 

Some health systems have chosen consistency with the U.S. Census Bureau designations, Freed notes, while others have expanded the choices available for patients as part of inclusivity programs. 

Additionally, hospitals rarely verify the accuracy of racial and ethnic attribution in secondary data or health records, especially for children.

“There have been significant, well-intentioned efforts over the last several years at many institutions to expand the choices for patients to designate their own race or ethnicity to promote inclusion among our patient populations,” Freed said. “However, we found that a greater number of choices may lead to greater error in the electronic medical record.”

It’s important to understand how these errors may affect quality improvement efforts when working to identify health inequities or disparities for children with such conditions as asthma, obesity, diabetes and other health issues, Freed notes.

“Error rates of this magnitude influence the reliability of studies focused on inequities and disparities,” he said. “If we don’t know which children are which race or ethnicity we won’t know if there’s a problem and if efforts to fix the problem are successful or not.”

“This may undermine strategies to improve care.”

Freed adds that similar errors may be prevalent at other hospitals across the country, and collaborative members hope to encourage other systems to assess their own data accuracy as well.

Mi-CHEC will also be working on quality improvement efforts to both correct current error rates within the collaborative’s health systems and prevent future errors from occurring, he says. In the interim period, teams have developed statistical correction factors to improve accuracy in the collaborative’s assessments of inequities.

“These findings help us understand the limitations of our data and how we can account for those limitations as we continue our work to address inequities and disparities affecting pediatric patients and their families,” Freed said.

Additional authors include Brittany Bogan, MHSA, and Susan Woolford, M.D., of U-M; Adam Nicholson, M.D., of Corewell Health Helen DeVos Children’s Hospital; and Deborah Niedbala, M.S.N., of the Children's Hospital of Michigan.

About Mi-CHEC: Mi-CHEC, funded in partnership with the Michigan Department of Health and Human Services, is designed to engage hospitals in identifying and measuring pediatric healthcare inequities within their organizations. Mi-CHEC facilitates the sharing of topics for investigation, research methods, data, and quality improvement strategies across member hospitals. Learn more.

 

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Journal

JAMA Network Open

Article Title

Error Rates in Race and Ethnicity Designation Across Large Pediatric Health Systems

Article Publication Date

3-Sep-2024

Research Brief: 50-year generation gap in Minnesota’s longest-lived fish

Three-year study identifies conservation concern for native Minnesota fish

University of Minnesota

 

image: 

Bigmouth buffalo migration in an around Rice Lake National Wildlife Refuge

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Credit: Credit: Alec Lackmann

Duluth, MN – A recent study in one of the most pristine spawning grounds for a Minnesota fish found a half-century gap between successful broods. And that number's climbing.

That’s according to new research on the bigmouth buffalo (Ictiobus cyprinellus) from the University of Minnesota Duluth (UMD), recently published in Scientific Reports. The study was led by Alec Lackmann, PhD, an ichthyologist and assistant professor of Mathematics and Statistics, and Mark Clark, PhD, a professor of Biology, both from the Swenson College of Science and Engineering at UMD. 

The bigmouth buffalo is a fish that’s native to Minnesota and known for its longevity. Researchers wanted to find out more about the species, especially how they migrate, spawn, and how often their offspring live into adulthood. For three years, from 2021 through 2023, Lackmann and his team studied the recreational exploitation (bowfishing, spearfishing, hook-and-line angling) of the species, and analyzed the bigmouth buffalo migration in and around Rice Lake National Wildlife Refuge, near McGregor, Minnesota. 

Results of the study include:

• Discovery of one of the oldest known populations of vertebrate (median age of 79 years as of 2024)
• A more than 60-year generation gap since the last major recruitment event occurred in this population, again exposing the stark vulnerability of bigmouth buffalo in Minnesota.
• Confirmation that fish are successfully migrating and breeding, but the young are not surviving, likely due to the predator gauntlet they face on their way to adulthood.
• Highlights the unique management challenges of bigmouth buffalo, including highly variable spawning durations year to year, and the need to protect adults as they grow and invest disproportionately more into reproduction.

Lackmann and Clark have studied buffalofishes before, and their research from 2019 went so far as to extend the previously thought maximum age of bigmouth buffalo from around 25 years of age, to more than 100 years of age through improved aging techniques. Lackmann et al.’s subsequent bigmouth buffalo studies in North Dakota (2021) and Canada (2023) documented environmental conditions related to their sporadic recruitment success, and his team’s 2023 study published in Scientific Reports found the second genus of animal ever for which three or more species (buffalofishes) have known lifespans greater than 100 years.

“No one's really looked at the spawning phenology of bigmouth buffalo before,” said Lackmann.

Over the course of the Rice Lake study, he and his team examined nearly 400 adult fish, taking measurements of each fish’s length and weight, whether it had spawned, its physical features, and age. Researchers were able to conclude that water control measures established in 1953 were correlated with a reduced likelihood of later generations, and of the 390 fish studied, only one was from a hatch-year after 1971. The study also revealed bigmouth buffalo were successfully reproducing, but by mid‐to‐late summer, the young were conspicuously absent, having likely succumbed to predation by northern pike and other predators. 

“We have found that more than 95 percent of the current population hatched prior to the 1960s,” said Lackmann. With that much of a gap, it's surprising that the buffalofish have survived for generations. But, according to Lackmann, it speaks to the amazing attributes of these fish. “This species evolved to have a long lifespan for an adaptive reason: to bridge these long gaps that can naturally occur.”

During the 1970s, the bigmouth buffalo was recorded as declining in Canada, Minnesota, and North Dakota and became a protected species in Canada. In the USA, population declines are exacerbated by wasteful recreational bowfishing, lack of fisheries management, and overall lack of knowledge. 

For Lackmann, this study further underscores the importance of implementing basic principles of fisheries management to protect bigmouth buffalo and other native species. Lackmann acknowledges that steps are currently underway to protect native fishes in the state of Minnesota, such as the “No Junk Fish Bill” that became law this spring, but he says there remains much work to be done in practice. For example, unlimited exploitation across the entire year remains open on bigmouth buffalo throughout Minnesota as of September 2024.

“There is 50-year recruitment failure for bigmouth buffalo in this system, even though we know that they're migrating and spawning annually. This is something that's completely unparalleled in the animal kingdom as far as we know, for a species to be going so long without successfully having another generation,” said Lackmann. “When you couple that with the current, unlimited and unregulated nature of their exploitation that's been increasing, especially in the past 10 years with the rise of bowfishing, there is extreme concern for the long-term sustainability of this species.”

Multiple lines of evidence indicate that the long‐lived bigmouth buffalo is vulnerable, that a precautionary approach is immediately needed, and that the unlimited and unregulated kill‐fishery be closed. Lackmann et. al.

In addition to Lackmann and Clark from the University of Minnesota Duluth, the study was in collaboration with the Aitkin County Soil and Water Conservation District, the United States Fish and Wildlife Service, and North Dakota State University.

 

 

 

 

 

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Journal

Scientific Reports

DOI

10.1038/s41598-024-70237-5 

Method of Research

Observational study

Subject of Research

Animals

Article Title

Analysis of bigmouth buffalo Ictiobus cyprinellus spawning phenology in Minnesota reveals 50‑year recruitment failure and conservation concern

Article Publication Date

3-Sep-2024

Think simpler, flow faster

 LAO TZU 

Researchers use deep learning to accelerate solution of Navier-Stokes equations for fluid dynamics problems

Peer-Reviewed Publication

Intelligent Computing

 

image: 

Contour plots (A, C, E, G) compare the input conditions, traditional finite difference method solutions, and the solutions generated by model B3, the most advanced model in the study. Velocity profiles (B, D, F, H) display detailed velocity information at specific cross-sections of the simulation domain.

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Credit: SHEN WANG ET AL.

Analyzing and simulating fluid flow is a challenging mathematical problem that impacts various scenarios, including video game engines, ocean current modeling and hurricane forecasting. The core of this challenge lies in solving the Navier–Stokes equations, a set of classical equations that describe fluid dynamics. Recently, deep learning has emerged as a powerful tool to accelerate equation solving. Using this technique, a team designed a novel approach that can provide accurate solutions 1,000 times faster than traditional equation solvers. The team’s study was published June 26 in Intelligent Computing, a Science Partner Journal.

The team tested their approach on a three-variable lid-driven cavity flow problem in a large 512 × 512 computational domain. In the experiment, conducted on a consumer desktop system with an Intel Core i5 8400 processor, their method achieved inference latencies of just 7 milliseconds per input, a great improvement compared to the 10 seconds required by traditional finite difference methods.

Apart from being swift, the new deep learning approach is also low-cost and highly adaptable, thus could be used to make real-time predictions on everyday digital devices. It integrates the efficiency of supervised learning techniques with the necessary physics of traditional methods.

Although other supervised learning models can rapidly simulate and predict the closest numerical solutions to the Navier–Stokes equations, their performance is constrained by the labeled training data, which could lack the size, diversity and fundamental physical information needed to solve the equations.

To work around data-driven limitations and reduce computation load, the team trained a series of models stage by stage in a weakly supervised way. Initially, only a minimal amount of pre-computed “warm-up” data was used to facilitate model initialization. This allowed the base models to quickly adapt to the fundamental dynamics of fluid flow before progressing to more complex scenarios and eliminated the need for extensive labeled datasets.

All models are based on a convolutional U-Net architecture, which the team customized for complex fluid dynamics problems. As a modified autoencoder, the U-Net consists of an encoder that compresses the input data into compact representations, and a decoder that reconstructs this data back into high-resolution outputs. The encoder and decoder are connected through skip connections, which help preserve important features and improve the quality of the outputs.

To ensure the outputs adhere to the necessary constraints, the team also developed a custom loss function that incorporates both data-driven and physics-informed components.

Like traditional methods, the team's approach uses a 2D matrix to represent the computational domain, which sets the determining constraints of the fluid dynamics problems. The constraints include geometric constraints such as the size and shape of the domain, physical constraints such as the physical features of the flow and applicable physical laws, and boundary conditions that define the problems mathematically. This format allows unknown variables to be directly integrated into the constraints as part of the input data so that the trained models can handle various boundary conditions and geometries, including unseen complicated cases.

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Journal

Intelligent Computing

DOI

10.34133/icomputing.0093 

Article Title

Stacked Deep Learning Models for Fast Approximations of Steady-State Navier–Stokes Equations for Low Re Flow

 

Ketamine clinics vary widely in pregnancy-related safeguards, study finds

With use growing for treatment-resistant depression and other mental health conditions, more use of tests and contraception by patients who could become pregnant is needed, authors say

Michigan Medicine - University of Michigan

 

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A patient receives a ketamine infusion for depression at the University of Michigan Health clinic, which requires pregnancy testing before treatment begins and weekly testing during treatment, as well as specifically recommending the use of highly reliable forms of contraception during the course of ketamine therapy, for all patients who could become pregnant.

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Credit: University of Michigan/Leisa Thompson

More hospitals and clinics now offer patients ketamine therapy for severe depression, post-traumatic stress disorder and other mental health conditions that haven’t responded to other treatments.

While ketamine is a safe medication when used with medical supervision, it does have a little-known complication: it may be very harmful to a developing fetus. It should not be used during pregnancy. 

But a new study suggests that ketamine prescribers aren’t paying enough attention to this risk and should do more to make sure that patients receiving ketamine aren’t pregnant and are aware of the need to use contraception while undergoing a course of treatment over multiple months.

The new article in the Journal of Clinical Psychiatry was written by researchers from the University of Michigan’s academic medical center, Michigan Medicine. It reports the results of a survey and document review conducted of ketamine clinics nationwide, and a review of records from the ketamine clinic for depression at U-M Health. 

In all, they found a wide variation in policies, practices and warnings about ketamine use related to pregnancy and reproduction. This is despite the fact that the 119 clinics that answered the survey report treating a total of more than 7,000 patients with ketamine per month, and estimate that a third of patients they serve are female and pre-menopausal. 

Key findings

More than 75% of responding clinics said they have a formal pregnancy screening process, but only 20% actually require a pregnancy test at least once prior to or during treatment.

More than 90% of clinics said they note that pregnancy is a contraindication to ketamine treatment in their informed consent documents and/or conversations. But less than half of clinics reported discussing specific potential risks with patients.

The researchers also looked at informed consent documents on the websites of 70 other ketamine clinics. In all, 39% did not include language about pregnancy in their documents, and those that did were generally vague.

When it came to contraception counseling, only 26% of the clinics that answered the survey said they discuss the potential need for contraception with ketamine patients. Less than 15% of the clinics specifically recommend or require contraception use during treatment.

This is especially striking, the authors say, because more than 80% of clinics reported prescribing long-term maintenance ketamine, with nearly 70% of these saying their patients receive care for more than six months and many saying patients receive ketamine for a year or more.

The review of records from 24 patients treated with ketamine at U-M’s clinic in the past showed all had taken a pregnancy test before beginning treatment and weekly during treatment, and but only half had documentation in their records that they were using contraception.

Inspiration for the study

Lead author Rachel Pacilio, M.D., a psychiatrist who recently joined Michigan Medicine as a clinical assistant professor after completing her residency at U-M Health, said the idea for the study came to her during a rotation in the perinatal psychiatry clinic.

Patients who were pregnant or had recently given birth asked her about ketamine as an option for their treatment-resistant depression. They had heard of the potential positive impact of the drug when given intravenously as an off-label use of a common anesthetic, or as an intranasal spray of esketamine that’s marketed as Spravato and approved by the U.S. Food and Drug Administration.

“There was little guidance available to prescribers other than the general recommendation to avoid ketamine in patients who are pregnant, because of the unknown potential impact on a fetus or a breastfeeding newborn,” says Pacilio. “That sparked our interest in surveying clinics to see how they were handling this during their intake processes, initial treatment courses, and during the maintenance therapy phase. As far as we know, this is the first time this has been looked into.”

Variation in oversight

Clinics offering intravenous ketamine require specialized staff and post-administration monitoring for each session. And the FDA specifically requires least two hours of in-person observation after dosing of intranasal Spravato to ensure safety and monitor for complications.

By contrast, other formulations of ketamine can be administered outside the clinical setting with minimal oversight. Some clinics surveyed reported prescribing sublingual ketamine for at-home use.

The new study did not include online, direct-to-consumer ketamine providers that offer treatment exclusively via telehealth consultations. It is unknown how these companies address reproductive and other safety concerns despite their growing popularity among patients.

“These data suggest that a large population of patients could be pregnant, or could become pregnant, while receiving ketamine treatment via multiple routes of administration. This risk increases with the duration of therapy which can last weeks for the initial course and a year or more for maintenance,” said Pacilio. “Many patients do not know that they’re pregnant in the first weeks, and animal studies of ketamine are very concerning for potential harm to the fetus during this time.”

She noted that while many psychotropic medications have been studied extensively and found to be safe for use in pregnancy, including a variety of antidepressants, antipsychotics and other psychiatric drugs, there is no data to support the use of ketamine for psychiatric illness in pregnancy.

Pacilio pointed out that the FDA’s risk mitigation program for Spravato, the nasal form of ketamine, does not include any provisions about pregnancy. A warning issued by the FDA last fall about the risks of compounded forms of ketamine available online also does not mention precautions about pregnancy.

“The variability in practice that we see among clinics in the community in this study is stark,” said Pacilio. “The field is really in need of standardization around reproductive counseling, pregnancy testing and the recommendation for contraception during ketamine treatment.”

If someone becomes pregnant while undergoing ketamine treatment, and has to stop receiving the drug for the remainder of the pregnancy, they are at risk for a depression relapse that could continue after the baby is born. Perinatal and postpartum depression are major risk factors for a range of issues in both the birthing parent and the infant.

Need for standard guidance

After sharing their findings about U-M patients in the new study with leaders of the U-M Health ketamine clinic, Pacilio said that the clinic began recommending the use of highly-reliable forms of contraception to patients who could become pregnant while receiving ketamine treatment.

Small standalone community clinics offering ketamine therapy may not have the same resources that a large clinic like U-M’s does, so standard guidance could especially benefit them.

Interventions including improved patient education with an emphasis on the requirement for pregnancy prevention for the duration ketamine treatment during the informed consent process, routine pregnancy testing before and during treatment for appropriate patients, and effective contraceptive counseling are needed. Many of these could be easily implemented and have the potential to positively impact public health.

“Ketamine is a really effective, potentially lifesaving, treatment for the right patients, but not everyone is a good candidate for it,” she said. “As psychiatrists, we need to ensure this treatment is being delivered in a way that benefits patients while preventing harm.”

In a commentary in the journal about the U-M team’s findings, psychiatrist and journal editor Marlene Freeman, M.D., wrote that based on the new findings, “It is imperative that best practices for women of reproductive age for the use of ketamine and esketamine are determined and utilized.” She added that this is especially important in light of the changing landscape of abortion-related laws.

Freeman also noted that those who have used ketamine in any form during pregnancy, as well as other psychotropic medications, can join the National Pregnancy Registry for Psychiatric Medications during pregnancy and help provide much-needed information on the impacts of these medications.

In addition to Pacilio, the study’s authors include Jamarie Geller, M.D., M.A., a psychiatry fellow at U-M, and faculty members Juan F. Lopez, M.D.; Sagar V. Parikh, M.D. and Paresh D. Patel, M.D., Ph.D.

The study was funded by U-M Department of Psychiatry.

Safe ketamine use and pregnancy: a nationwide survey and retrospective review of informed consent, counseling, and testing practices. J Clin Psychiatry, DOI:10.4088/JCP.24m15293.

Journal

Journal of Clinical Psychiatry

DOI

10.4088/JCP.24m15293 

Method of Research

Survey

Subject of Research

People

Article Title

Safe ketamine use and pregnancy: a nationwide survey and retrospective review of informed consent, counseling, and testing practices

 

Pregnancy-related heart failure is under-detected; AI-enabled stethoscope helped doctors diagnose twice as many cases

Mayo Clinic

ROCHESTER, Minn. — Heart failure during pregnancy is a dangerous and often under-detected condition because common symptoms – shortness of breath, extreme fatigue and trouble breathing while lying down – are easily mistaken for typical pregnancy discomforts. Late-breaking research presented at the European Society of Cardiology Congress on a Mayo Clinic study showed an artificial intelligence (AI)-enabled digital stethoscope helped doctors identify twice as many cases of heart failure compared to a control group that received usual obstetric care and screening. Full study findings are published in Nature Medicine.

The trial was conducted in Nigeria, where more women experience pregnancy-related heart failure than anywhere in the world. The results also indicate that screening including the AI-enabled digital stethoscope were 12-times more likely than traditional screening to flag heart pump weakness when evaluated at a ejection fraction threshold lower than 45%, which is the cutoff indicating a specific type of heart failure called peripartum cardiomyopathy.

"Recognizing this type of heart failure early is important to the mother's health and well-being," says Demilade Adedinsewo, M.D., a cardiologist at Mayo Clinic and lead investigator of the study. "The symptoms of peripartum cardiomyopathy can get progressively worse as pregnancy advances, or more commonly following childbirth, and can endanger the mother's life if her heart becomes too weak. Medicines can help when the condition is identified but severe cases may require intensive care, a mechanical heart pump, or sometimes a heart transplant, if not controlled with medical therapy."

The randomized, controlled, open-label clinical trial included nearly 1,200 participants who were screened for heart conditions through typical obstetric care or AI-enhanced solutions. Mayo Clinic researchers previously developed a foundational 12-lead AI-electrocardiogram (ECG) algorithm to predict a weak heart pump, clinically known as low ejection fraction. A version of this algorithm was further enhanced by Eko Health for its point-of-care digital stethoscope which is U.S. Food and Drug Administration (FDA)-cleared to detect heart failure with low ejection fraction.

The researchers found that doctors using AI-based screening with the digital stethoscope and 12-lead ECG detected weak heart function with high accuracy. Within the study cohort, the digital stethoscope helped flag twice as many cases of low ejection fraction <50% and doctors using it were 12-times more likely to identify an ejection fraction <45% as compared to usual care.

The AI-supported tools were evaluated at three different levels of ejection fraction used in clinical diagnosis. Less than 45% is the cut point for diagnosing peripartum cardiomyopathy. Less than 40% indicates heart failure with reduced ejection fraction and has strong evidence in favor of specific medications to reduce symptoms and the risk of death. An ejection fraction of less than 35% signals severely low heart pump function that often requires more intense management, including advanced heart failure therapies and an implantable defibrillator if pump function does not recover. Patients in the intervention group each had an echocardiogram at study entry to provide confirmation of the AI-predictions.

"This study provides evidence that we can better detect peripartum cardiomyopathy among women in Nigeria. However, there are more questions to be answered," says Dr. Adedinsewo. "Our next steps would be to evaluate usability and adoption of this tool by Nigerian healthcare providers (including doctors and nurses) and importantly, its impact on patient care. Peripartum cardiomyopathy affects approximately 1 in 2,000 women within the U.S. and as many as 1 in 700 African American women. Evaluating this AI tool in the U.S. will further test its abilities in varied populations and healthcare settings."

Funding for this clinical trial includes Mayo Clinic (Centers for Digital Health and Community Health and Engagement Research), the Mayo Clinic Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Program funded by the National Institutes of Health (NIH), and Mayo Clinic’s Center for Clinical and Translational Sciences (CCATS) funded by the NIH.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

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Journal

Nature Medicine

DOI

10.1038/s41591-024-03243-9 

Article Title

Artificial intelligence guided screening for cardiomyopathies in an obstetric population: a pragmatic randomized clinical trial

Article Publication Date

3-Sep-2024

Eating fish but not omega-3 supplements during pregnancy associated with lower likelihood of autism diagnosis, NIH-funded study finds

Environmental influences on Child Health Outcomes

 

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 For more information, visit echochildren.org.

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Credit: NIH Environmental influences on Child Health Outcomes (ECHO) Program

Eating any amount of fish during pregnancy was associated with about a 20% lower likelihood of autism spectrum disorder (ASD) diagnosis, particularly in females, and a slight reduction in autism-related traits in offspring, according to a new study funded by the Environmental influences on Child Health Outcomes (ECHO) Program at the National Institutes of Health.

However, researchers did not find the same association with supplements containing omega-3 fatty acids.

Fish is an important source of omega-3 fatty acids, an essential nutrient during pregnancy for supporting maternal health and child neurodevelopment. A recent analysis of ECHO Cohort data revealed that about 25% of the pregnant participants reported never eating fish or consuming it less than once a month during their pregnancy. Even fewer participants reported taking omega-3 fish oil supplements.

ECHO Cohort researchers wanted to see whether low fish consumption and omega-3 supplement use during pregnancy might be associated with the occurrence of an autism diagnosis or parent-reported autism-related traits.

“Our study contributes to a growing body of evidence that demonstrates the role that prenatal diet can play in autism-related outcomes in offspring,” said ECHO Cohort researcher Emily Oken, MD, MPH, of Harvard Medical School.

Dr. Oken said the findings underscored the need for better public health messaging about guidelines for fish consumption for pregnant people, considering the low fish intake in the U.S. and the rising diagnoses of autism.

What happened during the study?

Researchers analyzed data from about 4,000 participants, examining the relationships among fish intake, supplement use, and neurodevelopmental outcomes related to autism.

Fish consumption and omega-3 supplement use were measured with dietary information reported by participants. Participants’ fish consumption was categorized as less than once a month, more than once a month but less than weekly, weekly, and two or more servings per week. About 20% of adult participants reported no fish intake, and most reported not using omega-3 or fish oil supplements.

The researchers then looked at the relationship between maternal fish intake and omega-3 fish oil supplement use during pregnancy and the occurrence of clinician-diagnosed autism and parent-reported autism-related traits. These traits were measured using the Social Responsiveness Scale (SRS), a widely used survey completed by parents or caregivers. Higher scores on the SRS indicate the presence of more autism-related behaviors. 

Consuming fish during pregnancy was associated with a lower likelihood of offspring being diagnosed with autism and a slight decrease in total SRS scores compared to not eating fish. These results were consistent across all levels of fish consumption, from "any" amount or "less than once per week" to "more than twice per week." No significant associations were found between omega-3 fish oil supplements and autism diagnosis compared to no use.

Experts recommend that people consume additional omega-3 fatty acids during pregnancy. Prenatal fish intake is a key source of omega-3 fatty acids that are critical for fetal brain development. However, fish and omega-3 fatty acid supplementation in the U.S. is low.

“This study provides yet more evidence for the safety and benefit of regular fish consumption during pregnancy,” said Dr. Oken. “Other proven benefits include lower risk for preterm birth and improved cognitive development.”

Dr. Oken led this collaborative research published in the American Journal of Clinical Nutrition.

Oken, E. & Lyall, K. (2024) Association of maternal fish consumption and ω-3 supplement use during pregnancy with child autism-related outcomes: results from a cohort consortium analysis. American Journal of Clinical Nutrition. 10.1016/j.ajcnut.2024.06.013

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About ECHO: Launched in 2016, the Environmental influences on Child Health Outcomes (ECHO) Program is a research program in the Office of the Director at the NIH with the mission to enhance the health of children for generations to come. ECHO investigators study the effects of a broad range of early environmental influences on child health and development. For more information, visit echochildren.org.

About the NIH: NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information, visit www.nih.gov.

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Journal

American Journal of Clinical Nutrition

DOI

10.1016/j.ajcnut.2024.06.013 

Method of Research

Observational study

Subject of Research

People

Article Title

Association of maternal fish consumption and ω-3 supplement use during pregnancy with child autism-related outcomes: results from a cohort consortium analysis