Mental Health

With tens of millions of Euros in the offing, researchers across the European Union have eagerly taken up the gauntlet to find novel interventions for difficult-to-treat mental health and pain conditions. Their target is psychedelics, including classic compounds like psilocybin and atypical ones like ketamine and MDMA. Some of these still carry a stigma as party drugs and spiritual gateways to holotropic experiences.

Twelve groups make up the European College of Neuropsychopharmacology’s psychedelic research network. Along with several affiliates, the groups span nine countries (Denmark, Sweden, Finland, Switzerland, Germany, the Netherlands, the Czech Republic, Greece, and the United Kingdom) and are focused on the use of psychedelic compounds as potential treatments for psychiatric conditions like treatment-resistant depression, addiction, attention-deficit/hyperactivity disorder, anorexia, and obsessive-compulsive disorder.

One of the largest endeavors is PsyPal, a 4-year, randomized controlled trial investigating the potential of psilocybin for treating psychological distress in palliative care patients with life-limiting conditions. PsyPal is the first multisite clinical trial funded by the European Union to explore psychedelic-assisted therapy.

At PsyPal’s helm is Robert Schoevers, MD, PhD, professor of psychiatry and Department Head at University Medical Center Groningen (UMCG), Groningen, the Netherlands, a major hub for psychedelic research.

Schoevers is a bit of a pioneer who said he entered psychedelic research somewhat reluctantly. A decade ago, a colleague showed him a few papers on ketamine and depression. Because UMCG has a large population of patients with treatment-resistant depression, he agreed to do a pilot study. Since then, he has put together an interdisciplinary team of 25 researchers, published numerous papers, and currently has seven studies, including PsyPal, in various stages of progress.

Schoevers is also building a large national consortium that aims to investigate and, if shown effective, implement novel psychiatry treatments much more rapidly and efficiently than current drug development and approval processes, which can take 12 years or longer. He has just secured millions in government funding to start this process.

Next year, Schoevers and his team will decide to test either MDMA for posttraumatic stress disorder (PTSD) or psilocybin for depression in a large clinical trial, with the aim of getting a treatment as near to formal registration as possible. This will involve working with the European Medicines Agency and its Dutch counterpart, talking to experts who are familiar with the US Food and Drug Administration’s rejection of Lykos Therapeutics’ MDMA treatment for PTSD, and working directly with patients through the National Patient Alliance. The team is also talking to insurers and pharma companies.

The ultimate goal is to “see if we can build a platform in the Netherlands that would have a European perspective, serve as a point of entry for researchers with good ideas, and [attract] public funding as well as companies who have interesting compounds we think would be worthwhile to study,” Schoevers said.

His multiple endeavors emphasize a transdisciplinary and transdiagnostic approach he has been honing for decades. He and his colleagues are investigating the clinical, psychological, and neurobiological parallels between different treatment- resistant conditions and seeking to understand how contextual factors might influence patients, experiences, and outcomes.
 

Connecting the Dots

Jens H. van Dalfsen, PhD, a postdoctoral researcher in biological psychiatry, is the principal investigator of another UMCG group looking into the neurobiological mechanisms of major depressive disorder and treatment-resistant depression. His team’s strategy entails an elaborate coordination between the preclinical and clinical research settings.

For example, Sarah Massetti, a PhD candidate in biological psychiatry, is using blood samples collected in clinical trials to investigate the molecular mechanisms underpinning the neuroplasticity and immune-modulating effects produced by psychedelic compounds.

Another line of research spearheaded by Rutger Boesjes, a PhD candidate in biological psychiatry, is exploring the interactions between drugs like ketamine and the circadian system and how they might relate to antidepressant responses in animal models. It could be that the timing of administration of these drugs is relevant, he explained.
 

The Patient Factor

How psychedelics work and in whom is a big question for the UMCG team and across the research landscape.

“When researchers and the general public talk about psychedelics, they frequently refer to how they promote synaptic plasticity and new connections in the brain,” said van Dalfsen. “But traditional compounds also do that. So the ultimate question that we’ve been exploring is whether findings reflect an actual pharmacological effect or if expectancy also plays a role. In other words: How can we explain why psychedelics might or might not be effective in treatment-resistant patients?” he explained.

This is where the connection to the clinical experience becomes paramount and Joost Breeksema, PhD, comes in.

Breeksema divides his time between UMCG research and his role as executive director and co-founder of the Open Foundation, a nonprofit dedicated to advancing scientific psychedelic research. The work he’s doing outside the university is helping to frame the investigations of the wider group.

So far he has conducted two qualitative studies.

One was an off-label study in which patients with treatment-resistant depression were administered esketamine.

The other was a randomized clinical trial in which participants were blinded to a single 10- or 25-mg dose of psilocybin versus a 1-mg psilocybin microdose placebo that is too small to invoke any effects.

A key insight was the degree to which participants were unprepared for the intensity of their experiences, especially with regards to ketamine. Breeksema said the sessions might not have been so intense or negative for some participants had they been informed beforehand to expect the drugs could provoke “quite overwhelming experiences” and had they been accompanied by an experienced guide providing reassurance and support.

The format for the psilocybin trial met part of this criteria. Participants received a micro (placebo), medium, or high dose in a single session accompanied by two trained therapists. They then engaged in two sessions afterward to process their experiences. A single psilocybin experience appeared to be not enough or too much depending on the dose they were assigned and if they had prior experience with the compound.

Trial participants also felt they needed more help making sense of the experience. “This is a common and important theme,” said Breeksema. “Think about it. If you’ve been depressed for 10, 15 years and … you uncover something and break through something that’s been stuck, you need to process it.”

Jeanine Kamphuis, PhD, a psychiatrist and senior researcher at UMCG and one of the trial study co-authors, explained that they want to find a way to identify who will be too overwhelmed by these experiences if the dose should be adjusted or if some time needs to pass between dosing sessions. They also want to spend more time preparing patients for these sessions.

She emphasized that the studies have provided a reality check. “These are not wonder pills or wonder experiences. And in these types of patients, they’re not intended for a personal growth experience,” she said. “You have a patient who is sitting in front of you who seeks therapy and relief from very severe mood complaints, and the suffering is high,” she said, adding that expectancy bias further complicates patient participation and, likely, outcomes.
 

The Challenges

For all the potential and opportunity that psychedelics may hold for treatment, UMCG’s work has underscored some challenges.

The field of psychedelic research is characterized by methodological issues, explained van Dalfsen, such as blinding, expectancy, and overestimation of treatment effects. When looking at efficacy, “Is it the compound or the expectancy and promise? This is why it’s important to study how the drugs differ from each other in their biological effects and why they are or are not effective,” he said.

The team has also experienced issues with trial recruitment.

Martijn Godschalk, MD, a PhD candidate in psychiatry, has been addressing this problem while working on RESET-TRD, a phase 3, randomized controlled trial comparing an oral esketamine drink with electroconvulsive therapy in patients with treatment-resistant depression.

He’s been coordinating with local university hospitals, general hospitals, and municipal healthcare clinics to meet inclusion criteria and ensure the trial has enough power to demonstrate effectiveness. In turn, these sites are able to participate in a trial they wouldn’t normally be involved in due to lack of resources.

But Godschalk said he was concerned that many patients have gotten wind of the hype surrounding psychedelic treatments within psychiatry — a factor that has contributed to recruitment challenges. “There are a lot of patients who are interested in the non-registered drug and don’t necessarily have an interest in the other [control] arm,” he said.

Despite the challenges, the classic psychedelics such as MDMA and psilocybin “seem to catalyze a psychological process that may be harder to get with regular psychotherapies,” said Schoevers.

He remains cautious, noting there are still unanswered questions, such as who are the best candidates for these drugs and whether they might cause harm in certain patients while benefiting others. “I do think that this is the first time in 20 or 30 years that there is a group of potential treatments that would really make a difference.”

Schoevers received grants and other funding from The Netherlands Organisation for Health Research & Development, Horizon 2020, Horizon 2023, the National Institute of Mental Health (USA), UMCG, Stichting tot Steun VCVGZ, Nationaal programma Groningen, Healthcare Innovation Funds, Janssen Pharmaceuticals, Novartis, Compass Pathways, Clexio Biosciences, and GH research.
 

A version of this article appeared on Medscape.com.

With tens of millions of Euros in the offing, researchers across the European Union have eagerly taken up the gauntlet to find novel interventions for difficult-to-treat mental health and pain conditions. Their target is psychedelics, including classic compounds like psilocybin and atypical ones like ketamine and MDMA. Some of these still carry a stigma as party drugs and spiritual gateways to holotropic experiences.

Twelve groups make up the European College of Neuropsychopharmacology’s psychedelic research network. Along with several affiliates, the groups span nine countries (Denmark, Sweden, Finland, Switzerland, Germany, the Netherlands, the Czech Republic, Greece, and the United Kingdom) and are focused on the use of psychedelic compounds as potential treatments for psychiatric conditions like treatment-resistant depression, addiction, attention-deficit/hyperactivity disorder, anorexia, and obsessive-compulsive disorder.

One of the largest endeavors is PsyPal, a 4-year, randomized controlled trial investigating the potential of psilocybin for treating psychological distress in palliative care patients with life-limiting conditions. PsyPal is the first multisite clinical trial funded by the European Union to explore psychedelic-assisted therapy.

At PsyPal’s helm is Robert Schoevers, MD, PhD, professor of psychiatry and Department Head at University Medical Center Groningen (UMCG), Groningen, the Netherlands, a major hub for psychedelic research.

Schoevers is a bit of a pioneer who said he entered psychedelic research somewhat reluctantly. A decade ago, a colleague showed him a few papers on ketamine and depression. Because UMCG has a large population of patients with treatment-resistant depression, he agreed to do a pilot study. Since then, he has put together an interdisciplinary team of 25 researchers, published numerous papers, and currently has seven studies, including PsyPal, in various stages of progress.

Schoevers is also building a large national consortium that aims to investigate and, if shown effective, implement novel psychiatry treatments much more rapidly and efficiently than current drug development and approval processes, which can take 12 years or longer. He has just secured millions in government funding to start this process.

Next year, Schoevers and his team will decide to test either MDMA for posttraumatic stress disorder (PTSD) or psilocybin for depression in a large clinical trial, with the aim of getting a treatment as near to formal registration as possible. This will involve working with the European Medicines Agency and its Dutch counterpart, talking to experts who are familiar with the US Food and Drug Administration’s rejection of Lykos Therapeutics’ MDMA treatment for PTSD, and working directly with patients through the National Patient Alliance. The team is also talking to insurers and pharma companies.

The ultimate goal is to “see if we can build a platform in the Netherlands that would have a European perspective, serve as a point of entry for researchers with good ideas, and [attract] public funding as well as companies who have interesting compounds we think would be worthwhile to study,” Schoevers said.

His multiple endeavors emphasize a transdisciplinary and transdiagnostic approach he has been honing for decades. He and his colleagues are investigating the clinical, psychological, and neurobiological parallels between different treatment- resistant conditions and seeking to understand how contextual factors might influence patients, experiences, and outcomes.
 

Connecting the Dots

Jens H. van Dalfsen, PhD, a postdoctoral researcher in biological psychiatry, is the principal investigator of another UMCG group looking into the neurobiological mechanisms of major depressive disorder and treatment-resistant depression. His team’s strategy entails an elaborate coordination between the preclinical and clinical research settings.

For example, Sarah Massetti, a PhD candidate in biological psychiatry, is using blood samples collected in clinical trials to investigate the molecular mechanisms underpinning the neuroplasticity and immune-modulating effects produced by psychedelic compounds.

Another line of research spearheaded by Rutger Boesjes, a PhD candidate in biological psychiatry, is exploring the interactions between drugs like ketamine and the circadian system and how they might relate to antidepressant responses in animal models. It could be that the timing of administration of these drugs is relevant, he explained.
 

The Patient Factor

How psychedelics work and in whom is a big question for the UMCG team and across the research landscape.

“When researchers and the general public talk about psychedelics, they frequently refer to how they promote synaptic plasticity and new connections in the brain,” said van Dalfsen. “But traditional compounds also do that. So the ultimate question that we’ve been exploring is whether findings reflect an actual pharmacological effect or if expectancy also plays a role. In other words: How can we explain why psychedelics might or might not be effective in treatment-resistant patients?” he explained.

This is where the connection to the clinical experience becomes paramount and Joost Breeksema, PhD, comes in.

Breeksema divides his time between UMCG research and his role as executive director and co-founder of the Open Foundation, a nonprofit dedicated to advancing scientific psychedelic research. The work he’s doing outside the university is helping to frame the investigations of the wider group.

So far he has conducted two qualitative studies.

One was an off-label study in which patients with treatment-resistant depression were administered esketamine.

The other was a randomized clinical trial in which participants were blinded to a single 10- or 25-mg dose of psilocybin versus a 1-mg psilocybin microdose placebo that is too small to invoke any effects.

A key insight was the degree to which participants were unprepared for the intensity of their experiences, especially with regards to ketamine. Breeksema said the sessions might not have been so intense or negative for some participants had they been informed beforehand to expect the drugs could provoke “quite overwhelming experiences” and had they been accompanied by an experienced guide providing reassurance and support.

The format for the psilocybin trial met part of this criteria. Participants received a micro (placebo), medium, or high dose in a single session accompanied by two trained therapists. They then engaged in two sessions afterward to process their experiences. A single psilocybin experience appeared to be not enough or too much depending on the dose they were assigned and if they had prior experience with the compound.

Trial participants also felt they needed more help making sense of the experience. “This is a common and important theme,” said Breeksema. “Think about it. If you’ve been depressed for 10, 15 years and … you uncover something and break through something that’s been stuck, you need to process it.”

Jeanine Kamphuis, PhD, a psychiatrist and senior researcher at UMCG and one of the trial study co-authors, explained that they want to find a way to identify who will be too overwhelmed by these experiences if the dose should be adjusted or if some time needs to pass between dosing sessions. They also want to spend more time preparing patients for these sessions.

She emphasized that the studies have provided a reality check. “These are not wonder pills or wonder experiences. And in these types of patients, they’re not intended for a personal growth experience,” she said. “You have a patient who is sitting in front of you who seeks therapy and relief from very severe mood complaints, and the suffering is high,” she said, adding that expectancy bias further complicates patient participation and, likely, outcomes.
 

The Challenges

For all the potential and opportunity that psychedelics may hold for treatment, UMCG’s work has underscored some challenges.

The field of psychedelic research is characterized by methodological issues, explained van Dalfsen, such as blinding, expectancy, and overestimation of treatment effects. When looking at efficacy, “Is it the compound or the expectancy and promise? This is why it’s important to study how the drugs differ from each other in their biological effects and why they are or are not effective,” he said.

The team has also experienced issues with trial recruitment.

Martijn Godschalk, MD, a PhD candidate in psychiatry, has been addressing this problem while working on RESET-TRD, a phase 3, randomized controlled trial comparing an oral esketamine drink with electroconvulsive therapy in patients with treatment-resistant depression.

He’s been coordinating with local university hospitals, general hospitals, and municipal healthcare clinics to meet inclusion criteria and ensure the trial has enough power to demonstrate effectiveness. In turn, these sites are able to participate in a trial they wouldn’t normally be involved in due to lack of resources.

But Godschalk said he was concerned that many patients have gotten wind of the hype surrounding psychedelic treatments within psychiatry — a factor that has contributed to recruitment challenges. “There are a lot of patients who are interested in the non-registered drug and don’t necessarily have an interest in the other [control] arm,” he said.

Despite the challenges, the classic psychedelics such as MDMA and psilocybin “seem to catalyze a psychological process that may be harder to get with regular psychotherapies,” said Schoevers.

He remains cautious, noting there are still unanswered questions, such as who are the best candidates for these drugs and whether they might cause harm in certain patients while benefiting others. “I do think that this is the first time in 20 or 30 years that there is a group of potential treatments that would really make a difference.”

Schoevers received grants and other funding from The Netherlands Organisation for Health Research & Development, Horizon 2020, Horizon 2023, the National Institute of Mental Health (USA), UMCG, Stichting tot Steun VCVGZ, Nationaal programma Groningen, Healthcare Innovation Funds, Janssen Pharmaceuticals, Novartis, Compass Pathways, Clexio Biosciences, and GH research.
 

A version of this article appeared on Medscape.com.

With tens of millions of Euros in the offing, researchers across the European Union have eagerly taken up the gauntlet to find novel interventions for difficult-to-treat mental health and pain conditions. Their target is psychedelics, including classic compounds like psilocybin and atypical ones like ketamine and MDMA. Some of these still carry a stigma as party drugs and spiritual gateways to holotropic experiences.

Twelve groups make up the European College of Neuropsychopharmacology’s psychedelic research network. Along with several affiliates, the groups span nine countries (Denmark, Sweden, Finland, Switzerland, Germany, the Netherlands, the Czech Republic, Greece, and the United Kingdom) and are focused on the use of psychedelic compounds as potential treatments for psychiatric conditions like treatment-resistant depression, addiction, attention-deficit/hyperactivity disorder, anorexia, and obsessive-compulsive disorder.

One of the largest endeavors is PsyPal, a 4-year, randomized controlled trial investigating the potential of psilocybin for treating psychological distress in palliative care patients with life-limiting conditions. PsyPal is the first multisite clinical trial funded by the European Union to explore psychedelic-assisted therapy.

At PsyPal’s helm is Robert Schoevers, MD, PhD, professor of psychiatry and Department Head at University Medical Center Groningen (UMCG), Groningen, the Netherlands, a major hub for psychedelic research.

Schoevers is a bit of a pioneer who said he entered psychedelic research somewhat reluctantly. A decade ago, a colleague showed him a few papers on ketamine and depression. Because UMCG has a large population of patients with treatment-resistant depression, he agreed to do a pilot study. Since then, he has put together an interdisciplinary team of 25 researchers, published numerous papers, and currently has seven studies, including PsyPal, in various stages of progress.

Schoevers is also building a large national consortium that aims to investigate and, if shown effective, implement novel psychiatry treatments much more rapidly and efficiently than current drug development and approval processes, which can take 12 years or longer. He has just secured millions in government funding to start this process.

Next year, Schoevers and his team will decide to test either MDMA for posttraumatic stress disorder (PTSD) or psilocybin for depression in a large clinical trial, with the aim of getting a treatment as near to formal registration as possible. This will involve working with the European Medicines Agency and its Dutch counterpart, talking to experts who are familiar with the US Food and Drug Administration’s rejection of Lykos Therapeutics’ MDMA treatment for PTSD, and working directly with patients through the National Patient Alliance. The team is also talking to insurers and pharma companies.

The ultimate goal is to “see if we can build a platform in the Netherlands that would have a European perspective, serve as a point of entry for researchers with good ideas, and [attract] public funding as well as companies who have interesting compounds we think would be worthwhile to study,” Schoevers said.

His multiple endeavors emphasize a transdisciplinary and transdiagnostic approach he has been honing for decades. He and his colleagues are investigating the clinical, psychological, and neurobiological parallels between different treatment- resistant conditions and seeking to understand how contextual factors might influence patients, experiences, and outcomes.
 

Connecting the Dots

Jens H. van Dalfsen, PhD, a postdoctoral researcher in biological psychiatry, is the principal investigator of another UMCG group looking into the neurobiological mechanisms of major depressive disorder and treatment-resistant depression. His team’s strategy entails an elaborate coordination between the preclinical and clinical research settings.

For example, Sarah Massetti, a PhD candidate in biological psychiatry, is using blood samples collected in clinical trials to investigate the molecular mechanisms underpinning the neuroplasticity and immune-modulating effects produced by psychedelic compounds.

Another line of research spearheaded by Rutger Boesjes, a PhD candidate in biological psychiatry, is exploring the interactions between drugs like ketamine and the circadian system and how they might relate to antidepressant responses in animal models. It could be that the timing of administration of these drugs is relevant, he explained.
 

The Patient Factor

How psychedelics work and in whom is a big question for the UMCG team and across the research landscape.

“When researchers and the general public talk about psychedelics, they frequently refer to how they promote synaptic plasticity and new connections in the brain,” said van Dalfsen. “But traditional compounds also do that. So the ultimate question that we’ve been exploring is whether findings reflect an actual pharmacological effect or if expectancy also plays a role. In other words: How can we explain why psychedelics might or might not be effective in treatment-resistant patients?” he explained.

This is where the connection to the clinical experience becomes paramount and Joost Breeksema, PhD, comes in.

Breeksema divides his time between UMCG research and his role as executive director and co-founder of the Open Foundation, a nonprofit dedicated to advancing scientific psychedelic research. The work he’s doing outside the university is helping to frame the investigations of the wider group.

So far he has conducted two qualitative studies.

One was an off-label study in which patients with treatment-resistant depression were administered esketamine.

The other was a randomized clinical trial in which participants were blinded to a single 10- or 25-mg dose of psilocybin versus a 1-mg psilocybin microdose placebo that is too small to invoke any effects.

A key insight was the degree to which participants were unprepared for the intensity of their experiences, especially with regards to ketamine. Breeksema said the sessions might not have been so intense or negative for some participants had they been informed beforehand to expect the drugs could provoke “quite overwhelming experiences” and had they been accompanied by an experienced guide providing reassurance and support.

The format for the psilocybin trial met part of this criteria. Participants received a micro (placebo), medium, or high dose in a single session accompanied by two trained therapists. They then engaged in two sessions afterward to process their experiences. A single psilocybin experience appeared to be not enough or too much depending on the dose they were assigned and if they had prior experience with the compound.

Trial participants also felt they needed more help making sense of the experience. “This is a common and important theme,” said Breeksema. “Think about it. If you’ve been depressed for 10, 15 years and … you uncover something and break through something that’s been stuck, you need to process it.”

Jeanine Kamphuis, PhD, a psychiatrist and senior researcher at UMCG and one of the trial study co-authors, explained that they want to find a way to identify who will be too overwhelmed by these experiences if the dose should be adjusted or if some time needs to pass between dosing sessions. They also want to spend more time preparing patients for these sessions.

She emphasized that the studies have provided a reality check. “These are not wonder pills or wonder experiences. And in these types of patients, they’re not intended for a personal growth experience,” she said. “You have a patient who is sitting in front of you who seeks therapy and relief from very severe mood complaints, and the suffering is high,” she said, adding that expectancy bias further complicates patient participation and, likely, outcomes.
 

The Challenges

For all the potential and opportunity that psychedelics may hold for treatment, UMCG’s work has underscored some challenges.

The field of psychedelic research is characterized by methodological issues, explained van Dalfsen, such as blinding, expectancy, and overestimation of treatment effects. When looking at efficacy, “Is it the compound or the expectancy and promise? This is why it’s important to study how the drugs differ from each other in their biological effects and why they are or are not effective,” he said.

The team has also experienced issues with trial recruitment.

Martijn Godschalk, MD, a PhD candidate in psychiatry, has been addressing this problem while working on RESET-TRD, a phase 3, randomized controlled trial comparing an oral esketamine drink with electroconvulsive therapy in patients with treatment-resistant depression.

He’s been coordinating with local university hospitals, general hospitals, and municipal healthcare clinics to meet inclusion criteria and ensure the trial has enough power to demonstrate effectiveness. In turn, these sites are able to participate in a trial they wouldn’t normally be involved in due to lack of resources.

But Godschalk said he was concerned that many patients have gotten wind of the hype surrounding psychedelic treatments within psychiatry — a factor that has contributed to recruitment challenges. “There are a lot of patients who are interested in the non-registered drug and don’t necessarily have an interest in the other [control] arm,” he said.

Despite the challenges, the classic psychedelics such as MDMA and psilocybin “seem to catalyze a psychological process that may be harder to get with regular psychotherapies,” said Schoevers.

He remains cautious, noting there are still unanswered questions, such as who are the best candidates for these drugs and whether they might cause harm in certain patients while benefiting others. “I do think that this is the first time in 20 or 30 years that there is a group of potential treatments that would really make a difference.”

Schoevers received grants and other funding from The Netherlands Organisation for Health Research & Development, Horizon 2020, Horizon 2023, the National Institute of Mental Health (USA), UMCG, Stichting tot Steun VCVGZ, Nationaal programma Groningen, Healthcare Innovation Funds, Janssen Pharmaceuticals, Novartis, Compass Pathways, Clexio Biosciences, and GH research.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has announced a voluntary manufacturer-initiated recall of more than 7000 bottles of duloxetine delayed-release capsules due to unacceptable levels of a potential carcinogen.

Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, chronic musculoskeletal pain, and neuropathic pain associated with diabetic peripheral neuropathy.

The recall is due to the detection of the nitrosamine impurity, N-nitroso duloxetine, above the proposed interim limit.

Nitrosamines are common in water and foods, and exposure to some levels of the chemical is common. Exposure to nitrosamine impurities above acceptable levels and over long periods may increase cancer risk, the FDA reported.

“If drugs contain levels of nitrosamines above the acceptable daily intake limits, FDA recommends these drugs be recalled by the manufacturer as appropriate,” the agency noted on its website.

The recall was initiated by Breckenridge Pharmaceutical and covers 7107 bottles of 500-count, 20 mg duloxetine delayed-release capsules. The drug is manufactured by Towa Pharmaceutical Europe and distributed nationwide by BPI.

The affected bottles are from lot number 220128 with an expiration date of 12/2024 and NDC of 51991-746-05.

The recall was initiated on October 10 and is ongoing.

“Healthcare professionals can educate patients about alternative treatment options to medications with potential nitrosamine impurities if available and clinically appropriate,” the FDA advises. “If a medication has been recalled, pharmacists may be able to dispense the same medication from a manufacturing lot that has not been recalled. Prescribers may also determine whether there is an alternative treatment option for patients.”

The FDA has labeled this a “class II” recall, which the agency defines as “a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.”

Nitrosamine impurities have prompted a number of drug recalls in recent years, including oral anticoagulants, metformin, and skeletal muscle relaxants.

The impurities may be found in drugs for a number of reasons, the agency reported. The source may be from a drug’s manufacturing process, chemical structure, or the conditions under which it is stored or packaged.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has announced a voluntary manufacturer-initiated recall of more than 7000 bottles of duloxetine delayed-release capsules due to unacceptable levels of a potential carcinogen.

Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, chronic musculoskeletal pain, and neuropathic pain associated with diabetic peripheral neuropathy.

The recall is due to the detection of the nitrosamine impurity, N-nitroso duloxetine, above the proposed interim limit.

Nitrosamines are common in water and foods, and exposure to some levels of the chemical is common. Exposure to nitrosamine impurities above acceptable levels and over long periods may increase cancer risk, the FDA reported.

“If drugs contain levels of nitrosamines above the acceptable daily intake limits, FDA recommends these drugs be recalled by the manufacturer as appropriate,” the agency noted on its website.

The recall was initiated by Breckenridge Pharmaceutical and covers 7107 bottles of 500-count, 20 mg duloxetine delayed-release capsules. The drug is manufactured by Towa Pharmaceutical Europe and distributed nationwide by BPI.

The affected bottles are from lot number 220128 with an expiration date of 12/2024 and NDC of 51991-746-05.

The recall was initiated on October 10 and is ongoing.

“Healthcare professionals can educate patients about alternative treatment options to medications with potential nitrosamine impurities if available and clinically appropriate,” the FDA advises. “If a medication has been recalled, pharmacists may be able to dispense the same medication from a manufacturing lot that has not been recalled. Prescribers may also determine whether there is an alternative treatment option for patients.”

The FDA has labeled this a “class II” recall, which the agency defines as “a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.”

Nitrosamine impurities have prompted a number of drug recalls in recent years, including oral anticoagulants, metformin, and skeletal muscle relaxants.

The impurities may be found in drugs for a number of reasons, the agency reported. The source may be from a drug’s manufacturing process, chemical structure, or the conditions under which it is stored or packaged.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has announced a voluntary manufacturer-initiated recall of more than 7000 bottles of duloxetine delayed-release capsules due to unacceptable levels of a potential carcinogen.

Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, chronic musculoskeletal pain, and neuropathic pain associated with diabetic peripheral neuropathy.

The recall is due to the detection of the nitrosamine impurity, N-nitroso duloxetine, above the proposed interim limit.

Nitrosamines are common in water and foods, and exposure to some levels of the chemical is common. Exposure to nitrosamine impurities above acceptable levels and over long periods may increase cancer risk, the FDA reported.

“If drugs contain levels of nitrosamines above the acceptable daily intake limits, FDA recommends these drugs be recalled by the manufacturer as appropriate,” the agency noted on its website.

The recall was initiated by Breckenridge Pharmaceutical and covers 7107 bottles of 500-count, 20 mg duloxetine delayed-release capsules. The drug is manufactured by Towa Pharmaceutical Europe and distributed nationwide by BPI.

The affected bottles are from lot number 220128 with an expiration date of 12/2024 and NDC of 51991-746-05.

The recall was initiated on October 10 and is ongoing.

“Healthcare professionals can educate patients about alternative treatment options to medications with potential nitrosamine impurities if available and clinically appropriate,” the FDA advises. “If a medication has been recalled, pharmacists may be able to dispense the same medication from a manufacturing lot that has not been recalled. Prescribers may also determine whether there is an alternative treatment option for patients.”

The FDA has labeled this a “class II” recall, which the agency defines as “a situation in which use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.”

Nitrosamine impurities have prompted a number of drug recalls in recent years, including oral anticoagulants, metformin, and skeletal muscle relaxants.

The impurities may be found in drugs for a number of reasons, the agency reported. The source may be from a drug’s manufacturing process, chemical structure, or the conditions under which it is stored or packaged.
 

A version of this article appeared on Medscape.com.

About 7 of every 10 veterans who die by suicide involve the use of a firearm. A reason for this high rate is access, as half of veterans report owning ≥ 1 personal firearms. Of those individuals, more than half report storing firearms loaded and/or unsecured and one-third of veterans who store their firearms loaded and unlocked do not own a lockbox or safe. 

Suicide death prevention has improved as firearms have become more difficult to obtain. That’s why Navy veteran Rep. Chris Deluzio (D-PA), former FBI Special Agent and federal prosecutor Rep. Brian Fitzpatrick (R-PA), and Rep. Greg Landsman (D-OH) have teamed up to introduce the Saving Our Veterans Lives Act of 2024. Under the proposed act, any veteran would be able to get a free lockbox from the US Department of Veterans Affairs (VA).

Suicidal crises can be brief. According to the VA, if a person experiencing a suicidal crisis can’t access the method they planned to use, they generally do not seek out other lethal means. Lockboxes are a way of “putting space between thought and trigger,” the VA said.

The VA Suicide Prevention Program distributes free firearm cable locks to any veteran who requests one. However, many veterans favor lockboxes and safes to secure their guns. A VA pilot program offers free lockboxes to veterans enrolled in the Veterans Health Administration who are at an elevated risk for suicide. The program is set to launch in late 2024 and is a collaboration between the Rocky Mountain Mental Illness Research, Education, and Clinical Center for Suicide Prevention, VA National Prosthetics Service, and VA Office of Suicide Prevention.

The proposed bill would make the lockboxes (which typically cost between $25 and $350) free to any veteran, regardless of VA enrollment status or diagnosis. It ensures “sufficient funding for many tens of thousands of lockboxes to be distributed.” The bill would also direct the VA to create a public education campaign on the availability of lockboxes and the importance of secure firearm storage in suicide prevention.

“The alarming and tragic reality is that our veterans face a suicide rate 57% higher than that of civilians,” Rep. Fitzpatrick said. “This commonsense, bipartisan initiative is more than a solution—it's a lifeline.”

The representatives report that the bill has been endorsed by an “unprecedented” number of organizations, including the National Shooting Sports Foundation, Disabled American Veterans, The American Legion, GIFFORDS, Everytown for Gun Safety, Brady, American Psychological Association, American Foundation for Suicide Prevention, and Association of VA Psychologist Leaders.

“Did you know that in some cases only 10 minutes elapse between an individual having suicidal ideation and acting?” American Legion National Commander James LaCoursiere said in the representatives’ press release. “The Saving Our Veterans Lives Act is an important part of preventing suicide as it will provide veterans with the information and means to securely store their firearms to prevent suicide, while still protecting their Second Amendment rights. The Legion commends Rep. Deluzio and his team for bringing this bill forward and for their continued dedication to the welfare of our nation’s veterans.” 

"I hear colleagues all the time talk about veteran suicide," Rep. Deluzio said in an interview with Military.com. "It is a problem in my community. It's a problem across the country. Let's take action. This is a chance where we can do it that I think can cut through the politics that normally divide us on these [gun] issues. And I think the coalition supporting the bill tells you, we've got a path to pass it."

About 7 of every 10 veterans who die by suicide involve the use of a firearm. A reason for this high rate is access, as half of veterans report owning ≥ 1 personal firearms. Of those individuals, more than half report storing firearms loaded and/or unsecured and one-third of veterans who store their firearms loaded and unlocked do not own a lockbox or safe. 

Suicide death prevention has improved as firearms have become more difficult to obtain. That’s why Navy veteran Rep. Chris Deluzio (D-PA), former FBI Special Agent and federal prosecutor Rep. Brian Fitzpatrick (R-PA), and Rep. Greg Landsman (D-OH) have teamed up to introduce the Saving Our Veterans Lives Act of 2024. Under the proposed act, any veteran would be able to get a free lockbox from the US Department of Veterans Affairs (VA).

Suicidal crises can be brief. According to the VA, if a person experiencing a suicidal crisis can’t access the method they planned to use, they generally do not seek out other lethal means. Lockboxes are a way of “putting space between thought and trigger,” the VA said.

The VA Suicide Prevention Program distributes free firearm cable locks to any veteran who requests one. However, many veterans favor lockboxes and safes to secure their guns. A VA pilot program offers free lockboxes to veterans enrolled in the Veterans Health Administration who are at an elevated risk for suicide. The program is set to launch in late 2024 and is a collaboration between the Rocky Mountain Mental Illness Research, Education, and Clinical Center for Suicide Prevention, VA National Prosthetics Service, and VA Office of Suicide Prevention.

The proposed bill would make the lockboxes (which typically cost between $25 and $350) free to any veteran, regardless of VA enrollment status or diagnosis. It ensures “sufficient funding for many tens of thousands of lockboxes to be distributed.” The bill would also direct the VA to create a public education campaign on the availability of lockboxes and the importance of secure firearm storage in suicide prevention.

“The alarming and tragic reality is that our veterans face a suicide rate 57% higher than that of civilians,” Rep. Fitzpatrick said. “This commonsense, bipartisan initiative is more than a solution—it's a lifeline.”

The representatives report that the bill has been endorsed by an “unprecedented” number of organizations, including the National Shooting Sports Foundation, Disabled American Veterans, The American Legion, GIFFORDS, Everytown for Gun Safety, Brady, American Psychological Association, American Foundation for Suicide Prevention, and Association of VA Psychologist Leaders.

“Did you know that in some cases only 10 minutes elapse between an individual having suicidal ideation and acting?” American Legion National Commander James LaCoursiere said in the representatives’ press release. “The Saving Our Veterans Lives Act is an important part of preventing suicide as it will provide veterans with the information and means to securely store their firearms to prevent suicide, while still protecting their Second Amendment rights. The Legion commends Rep. Deluzio and his team for bringing this bill forward and for their continued dedication to the welfare of our nation’s veterans.” 

"I hear colleagues all the time talk about veteran suicide," Rep. Deluzio said in an interview with Military.com. "It is a problem in my community. It's a problem across the country. Let's take action. This is a chance where we can do it that I think can cut through the politics that normally divide us on these [gun] issues. And I think the coalition supporting the bill tells you, we've got a path to pass it."

About 7 of every 10 veterans who die by suicide involve the use of a firearm. A reason for this high rate is access, as half of veterans report owning ≥ 1 personal firearms. Of those individuals, more than half report storing firearms loaded and/or unsecured and one-third of veterans who store their firearms loaded and unlocked do not own a lockbox or safe. 

Suicide death prevention has improved as firearms have become more difficult to obtain. That’s why Navy veteran Rep. Chris Deluzio (D-PA), former FBI Special Agent and federal prosecutor Rep. Brian Fitzpatrick (R-PA), and Rep. Greg Landsman (D-OH) have teamed up to introduce the Saving Our Veterans Lives Act of 2024. Under the proposed act, any veteran would be able to get a free lockbox from the US Department of Veterans Affairs (VA).

Suicidal crises can be brief. According to the VA, if a person experiencing a suicidal crisis can’t access the method they planned to use, they generally do not seek out other lethal means. Lockboxes are a way of “putting space between thought and trigger,” the VA said.

The VA Suicide Prevention Program distributes free firearm cable locks to any veteran who requests one. However, many veterans favor lockboxes and safes to secure their guns. A VA pilot program offers free lockboxes to veterans enrolled in the Veterans Health Administration who are at an elevated risk for suicide. The program is set to launch in late 2024 and is a collaboration between the Rocky Mountain Mental Illness Research, Education, and Clinical Center for Suicide Prevention, VA National Prosthetics Service, and VA Office of Suicide Prevention.

The proposed bill would make the lockboxes (which typically cost between $25 and $350) free to any veteran, regardless of VA enrollment status or diagnosis. It ensures “sufficient funding for many tens of thousands of lockboxes to be distributed.” The bill would also direct the VA to create a public education campaign on the availability of lockboxes and the importance of secure firearm storage in suicide prevention.

“The alarming and tragic reality is that our veterans face a suicide rate 57% higher than that of civilians,” Rep. Fitzpatrick said. “This commonsense, bipartisan initiative is more than a solution—it's a lifeline.”

The representatives report that the bill has been endorsed by an “unprecedented” number of organizations, including the National Shooting Sports Foundation, Disabled American Veterans, The American Legion, GIFFORDS, Everytown for Gun Safety, Brady, American Psychological Association, American Foundation for Suicide Prevention, and Association of VA Psychologist Leaders.

“Did you know that in some cases only 10 minutes elapse between an individual having suicidal ideation and acting?” American Legion National Commander James LaCoursiere said in the representatives’ press release. “The Saving Our Veterans Lives Act is an important part of preventing suicide as it will provide veterans with the information and means to securely store their firearms to prevent suicide, while still protecting their Second Amendment rights. The Legion commends Rep. Deluzio and his team for bringing this bill forward and for their continued dedication to the welfare of our nation’s veterans.” 

"I hear colleagues all the time talk about veteran suicide," Rep. Deluzio said in an interview with Military.com. "It is a problem in my community. It's a problem across the country. Let's take action. This is a chance where we can do it that I think can cut through the politics that normally divide us on these [gun] issues. And I think the coalition supporting the bill tells you, we've got a path to pass it."

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

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

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

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

TOPLINE:

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

METHODOLOGY:

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

TAKEAWAY:

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

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

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

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

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

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

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

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

Etiology

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

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

Risk Factors

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

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

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

Diagnosis

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

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

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

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

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

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

Treatments

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Etiology

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

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

Risk Factors

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

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

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

Diagnosis

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

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

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

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

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

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

Treatments

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Etiology

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

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

Risk Factors

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

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

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

Diagnosis

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

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

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

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

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

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

Treatments

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TOPLINE:

Fetuses exposed in utero to SARS-CoV-2 are not at an increased risk for neurodevelopmental problems in early childhood.

METHODOLOGY:

• This prospective study aimed to assess whether in utero exposure to SARS-CoV-2, which causes COVID-19, is associated with abnormal neurodevelopment among children at ages 12, 18, and 24 months.
• It included 2003 pregnant individuals (mean age, 33.3 years) from the ASPIRE cohort who were enrolled before 10 weeks’ gestation and followed through 24 months post partum; 10.8% of them were exposed to SARS-CoV-2 during pregnancy, as determined via self-reported data or dried blood spot cards.
• The birth mothers were required to complete the Ages & Stages Questionnaires, Third Edition (ASQ-3), a validated screening tool for neurodevelopmental delays, at 12, 18, and 24 months postpartum.
• Neurodevelopmental outcomes were available for 1757, 1522, and 1523 children at ages 12, 18, and 24 months, respectively.
• The primary outcome was a score below the cutoff on the ASQ-3 across any of the following developmental domains: Communication, gross motor, fine motor, problem-solving, and social skills.

TAKEAWAY:

• The prevalence of abnormal ASQ-3 scores did not differ between children who were exposed to SARS-CoV-2 in utero and those who were not, at ages 12 (P = .39), 18 (P = .58), and 24 (P = .45) months.
• No association was observed between in utero exposure to SARS-CoV-2 and abnormal ASQ-3 scores among children in any of the age groups.
• The lack of an association between exposure to SARS-CoV-2 during pregnancy and abnormal neurodevelopment remained unchanged even when factors such as preterm delivery and the sex of the infant were considered.
• Supplemental analyses found no difference in risk based on the trimester of infection, presence of fever, or incidence of breakthrough infection following vaccination.

IN PRACTICE:

“In this prospective cohort study of pregnant individuals and offspring, in utero exposure to maternal SARS-CoV-2 infection was not associated with abnormal neurodevelopmental screening scores of children through age 24 months. These findings are critical considering the novelty of the SARS-CoV-2 virus to the human species, the global scale of the initial COVID-19 outbreak, the now-endemic nature of the virus indicating ongoing relevance for pregnant individuals,” the authors of the study wrote. 

“While the scientific consensus resists a link between in utero COVID-19 exposure and impaired offspring neurodevelopment, the question remains whether societal responses to the pandemic impacted developmental trajectories,” the researchers added. “Certain studies comparing infants from a pandemic cohort with historic controls have raised concerns about lower ASQ-3 scores among children living during the pandemic. Critically, socioeconomic factors influence vulnerability, not only to infection itself but also regarding the ability to deploy resources in times of stress (eg, school closures) to mitigate sources of developmental harm. Our data support this theory, with the observed independent protective association of increasing household income with childhood ASQ-3 scores. Additional research is warranted to clarify the potential impact of societal measures on early development and the differential impact of these measures on different communities.”
 

SOURCE:

The study was led by Eleni G. Jaswa, MD, MSc, of the Department of Obstetrics, Gynecology & Reproductive Sciences at the University of California, San Francisco. It was published online in JAMA Network Open.

LIMITATIONS: 

Limitations of the research included the use of self-reported data and dried blood spot cards for determining exposure to SARS-CoV-2, which may have led to misclassification. The ASQ-3 is a modestly sensitive tool for detecting developmental delays that may have affected the study’s power to detect associations. The sample size of this study, while larger than many, may still have been underpowered to detect small differences in neurodevelopmental outcomes.

DISCLOSURES:

The ASPIRE cohort was supported by research grants provided to the University of California, San Francisco, and by the Start Small Foundation, the California Breast Cancer Research Program, the COVID Catalyst Award, and other sources. Some authors reported receiving grants, royalties, and personal fees, serving on medical advisory boards, and having other ties with several institutions.

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

TOPLINE:

Fetuses exposed in utero to SARS-CoV-2 are not at an increased risk for neurodevelopmental problems in early childhood.

METHODOLOGY:

• This prospective study aimed to assess whether in utero exposure to SARS-CoV-2, which causes COVID-19, is associated with abnormal neurodevelopment among children at ages 12, 18, and 24 months.
• It included 2003 pregnant individuals (mean age, 33.3 years) from the ASPIRE cohort who were enrolled before 10 weeks’ gestation and followed through 24 months post partum; 10.8% of them were exposed to SARS-CoV-2 during pregnancy, as determined via self-reported data or dried blood spot cards.
• The birth mothers were required to complete the Ages & Stages Questionnaires, Third Edition (ASQ-3), a validated screening tool for neurodevelopmental delays, at 12, 18, and 24 months postpartum.
• Neurodevelopmental outcomes were available for 1757, 1522, and 1523 children at ages 12, 18, and 24 months, respectively.
• The primary outcome was a score below the cutoff on the ASQ-3 across any of the following developmental domains: Communication, gross motor, fine motor, problem-solving, and social skills.

TAKEAWAY:

• The prevalence of abnormal ASQ-3 scores did not differ between children who were exposed to SARS-CoV-2 in utero and those who were not, at ages 12 (P = .39), 18 (P = .58), and 24 (P = .45) months.
• No association was observed between in utero exposure to SARS-CoV-2 and abnormal ASQ-3 scores among children in any of the age groups.
• The lack of an association between exposure to SARS-CoV-2 during pregnancy and abnormal neurodevelopment remained unchanged even when factors such as preterm delivery and the sex of the infant were considered.
• Supplemental analyses found no difference in risk based on the trimester of infection, presence of fever, or incidence of breakthrough infection following vaccination.

IN PRACTICE:

“In this prospective cohort study of pregnant individuals and offspring, in utero exposure to maternal SARS-CoV-2 infection was not associated with abnormal neurodevelopmental screening scores of children through age 24 months. These findings are critical considering the novelty of the SARS-CoV-2 virus to the human species, the global scale of the initial COVID-19 outbreak, the now-endemic nature of the virus indicating ongoing relevance for pregnant individuals,” the authors of the study wrote. 

“While the scientific consensus resists a link between in utero COVID-19 exposure and impaired offspring neurodevelopment, the question remains whether societal responses to the pandemic impacted developmental trajectories,” the researchers added. “Certain studies comparing infants from a pandemic cohort with historic controls have raised concerns about lower ASQ-3 scores among children living during the pandemic. Critically, socioeconomic factors influence vulnerability, not only to infection itself but also regarding the ability to deploy resources in times of stress (eg, school closures) to mitigate sources of developmental harm. Our data support this theory, with the observed independent protective association of increasing household income with childhood ASQ-3 scores. Additional research is warranted to clarify the potential impact of societal measures on early development and the differential impact of these measures on different communities.”
 

SOURCE:

The study was led by Eleni G. Jaswa, MD, MSc, of the Department of Obstetrics, Gynecology & Reproductive Sciences at the University of California, San Francisco. It was published online in JAMA Network Open.

LIMITATIONS: 

Limitations of the research included the use of self-reported data and dried blood spot cards for determining exposure to SARS-CoV-2, which may have led to misclassification. The ASQ-3 is a modestly sensitive tool for detecting developmental delays that may have affected the study’s power to detect associations. The sample size of this study, while larger than many, may still have been underpowered to detect small differences in neurodevelopmental outcomes.

DISCLOSURES:

The ASPIRE cohort was supported by research grants provided to the University of California, San Francisco, and by the Start Small Foundation, the California Breast Cancer Research Program, the COVID Catalyst Award, and other sources. Some authors reported receiving grants, royalties, and personal fees, serving on medical advisory boards, and having other ties with several institutions.

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

TOPLINE:

Fetuses exposed in utero to SARS-CoV-2 are not at an increased risk for neurodevelopmental problems in early childhood.

METHODOLOGY:

• This prospective study aimed to assess whether in utero exposure to SARS-CoV-2, which causes COVID-19, is associated with abnormal neurodevelopment among children at ages 12, 18, and 24 months.
• It included 2003 pregnant individuals (mean age, 33.3 years) from the ASPIRE cohort who were enrolled before 10 weeks’ gestation and followed through 24 months post partum; 10.8% of them were exposed to SARS-CoV-2 during pregnancy, as determined via self-reported data or dried blood spot cards.
• The birth mothers were required to complete the Ages & Stages Questionnaires, Third Edition (ASQ-3), a validated screening tool for neurodevelopmental delays, at 12, 18, and 24 months postpartum.
• Neurodevelopmental outcomes were available for 1757, 1522, and 1523 children at ages 12, 18, and 24 months, respectively.
• The primary outcome was a score below the cutoff on the ASQ-3 across any of the following developmental domains: Communication, gross motor, fine motor, problem-solving, and social skills.

TAKEAWAY:

• The prevalence of abnormal ASQ-3 scores did not differ between children who were exposed to SARS-CoV-2 in utero and those who were not, at ages 12 (P = .39), 18 (P = .58), and 24 (P = .45) months.
• No association was observed between in utero exposure to SARS-CoV-2 and abnormal ASQ-3 scores among children in any of the age groups.
• The lack of an association between exposure to SARS-CoV-2 during pregnancy and abnormal neurodevelopment remained unchanged even when factors such as preterm delivery and the sex of the infant were considered.
• Supplemental analyses found no difference in risk based on the trimester of infection, presence of fever, or incidence of breakthrough infection following vaccination.

IN PRACTICE:

“In this prospective cohort study of pregnant individuals and offspring, in utero exposure to maternal SARS-CoV-2 infection was not associated with abnormal neurodevelopmental screening scores of children through age 24 months. These findings are critical considering the novelty of the SARS-CoV-2 virus to the human species, the global scale of the initial COVID-19 outbreak, the now-endemic nature of the virus indicating ongoing relevance for pregnant individuals,” the authors of the study wrote. 

“While the scientific consensus resists a link between in utero COVID-19 exposure and impaired offspring neurodevelopment, the question remains whether societal responses to the pandemic impacted developmental trajectories,” the researchers added. “Certain studies comparing infants from a pandemic cohort with historic controls have raised concerns about lower ASQ-3 scores among children living during the pandemic. Critically, socioeconomic factors influence vulnerability, not only to infection itself but also regarding the ability to deploy resources in times of stress (eg, school closures) to mitigate sources of developmental harm. Our data support this theory, with the observed independent protective association of increasing household income with childhood ASQ-3 scores. Additional research is warranted to clarify the potential impact of societal measures on early development and the differential impact of these measures on different communities.”
 

SOURCE:

The study was led by Eleni G. Jaswa, MD, MSc, of the Department of Obstetrics, Gynecology & Reproductive Sciences at the University of California, San Francisco. It was published online in JAMA Network Open.

LIMITATIONS: 

Limitations of the research included the use of self-reported data and dried blood spot cards for determining exposure to SARS-CoV-2, which may have led to misclassification. The ASQ-3 is a modestly sensitive tool for detecting developmental delays that may have affected the study’s power to detect associations. The sample size of this study, while larger than many, may still have been underpowered to detect small differences in neurodevelopmental outcomes.

DISCLOSURES:

The ASPIRE cohort was supported by research grants provided to the University of California, San Francisco, and by the Start Small Foundation, the California Breast Cancer Research Program, the COVID Catalyst Award, and other sources. Some authors reported receiving grants, royalties, and personal fees, serving on medical advisory boards, and having other ties with several institutions.

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

TOPLINE:

Bright light therapy (BLT) is associated with a 41% remission rate in patients with nonseasonal depressive disorders, significantly higher than the remission rates reported with other treatments, a new meta-analysis shows.
 

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of 11 randomized clinical trials with 858 patients with nonseasonal depressive disorders.
• Included studies compared BLT alone or BLT plus antidepressant with placebo, antidepressant monotherapy, or dim red light.
• BLT was administered using a fluorescent light box producing white light at 10,000 lux for at least 30 minutes daily.
• The primary outcomes were the remission of symptoms and response to treatment, assessed using scales such as the Hamilton Rating Scale for Depression (HAM-D).

TAKEAWAY:

• The estimated remission rate was significantly higher for patients with nonseasonal depressive disorders in the BLT group than for those in the control group (41% vs 23.5%; P < .001).
• The response rate was also higher for patients in the BLT group than for those in the control group (60% vs 39%; P < .001).
• In the subgroup analysis on the basis of the duration of follow-up periods, the BLT group had better remission and response rates than the control group for both short-term (< 4 weeks; P < .001) and long-term (> 4 weeks; P = .04) follow-up periods, which suggests that patients achieved remission and responded to treatment more quickly with BLT than with antidepressants alone.
• The BLT group had a significantly greater reduction in HAM-D scores than the control group (mean difference, −1.44; P = .003).

IN PRACTICE:

“These findings suggest that BLT was an effective adjunctive treatment for nonseasonal depressive disorders, and the response time to the initial treatment may be improved with the addition of BLT,” the study authors wrote.
 

SOURCE:

The study was led by Artur Menegaz de Almeida, MS, Federal University of Mato Grosso, Sinop, Brazil. It was published online on October 2, 2024, in JAMA Psychiatry.
 

LIMITATIONS:

Slight differences were observed in the mean follow-up time between the included trials. The definitions for remission rates and response to treatment varied among the included studies, and they also involved different levels of disorder severity. Additionally, the study did not enable the separate analysis of each included depressive disorder, nor bipolar or unipolar subtypes of major depressive disorder. The moderate number of studies included may have affected the generalizability of the findings.
 

DISCLOSURES:

Study funding was not disclosed. No relevant conflicts of interest were disclosed.

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

TOPLINE:

Bright light therapy (BLT) is associated with a 41% remission rate in patients with nonseasonal depressive disorders, significantly higher than the remission rates reported with other treatments, a new meta-analysis shows.
 

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of 11 randomized clinical trials with 858 patients with nonseasonal depressive disorders.
• Included studies compared BLT alone or BLT plus antidepressant with placebo, antidepressant monotherapy, or dim red light.
• BLT was administered using a fluorescent light box producing white light at 10,000 lux for at least 30 minutes daily.
• The primary outcomes were the remission of symptoms and response to treatment, assessed using scales such as the Hamilton Rating Scale for Depression (HAM-D).

TAKEAWAY:

• The estimated remission rate was significantly higher for patients with nonseasonal depressive disorders in the BLT group than for those in the control group (41% vs 23.5%; P < .001).
• The response rate was also higher for patients in the BLT group than for those in the control group (60% vs 39%; P < .001).
• In the subgroup analysis on the basis of the duration of follow-up periods, the BLT group had better remission and response rates than the control group for both short-term (< 4 weeks; P < .001) and long-term (> 4 weeks; P = .04) follow-up periods, which suggests that patients achieved remission and responded to treatment more quickly with BLT than with antidepressants alone.
• The BLT group had a significantly greater reduction in HAM-D scores than the control group (mean difference, −1.44; P = .003).

IN PRACTICE:

“These findings suggest that BLT was an effective adjunctive treatment for nonseasonal depressive disorders, and the response time to the initial treatment may be improved with the addition of BLT,” the study authors wrote.
 

SOURCE:

The study was led by Artur Menegaz de Almeida, MS, Federal University of Mato Grosso, Sinop, Brazil. It was published online on October 2, 2024, in JAMA Psychiatry.
 

LIMITATIONS:

Slight differences were observed in the mean follow-up time between the included trials. The definitions for remission rates and response to treatment varied among the included studies, and they also involved different levels of disorder severity. Additionally, the study did not enable the separate analysis of each included depressive disorder, nor bipolar or unipolar subtypes of major depressive disorder. The moderate number of studies included may have affected the generalizability of the findings.
 

DISCLOSURES:

Study funding was not disclosed. No relevant conflicts of interest were disclosed.

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

TOPLINE:

Bright light therapy (BLT) is associated with a 41% remission rate in patients with nonseasonal depressive disorders, significantly higher than the remission rates reported with other treatments, a new meta-analysis shows.
 

METHODOLOGY:

• Researchers conducted a systematic review and meta-analysis of 11 randomized clinical trials with 858 patients with nonseasonal depressive disorders.
• Included studies compared BLT alone or BLT plus antidepressant with placebo, antidepressant monotherapy, or dim red light.
• BLT was administered using a fluorescent light box producing white light at 10,000 lux for at least 30 minutes daily.
• The primary outcomes were the remission of symptoms and response to treatment, assessed using scales such as the Hamilton Rating Scale for Depression (HAM-D).

TAKEAWAY:

• The estimated remission rate was significantly higher for patients with nonseasonal depressive disorders in the BLT group than for those in the control group (41% vs 23.5%; P < .001).
• The response rate was also higher for patients in the BLT group than for those in the control group (60% vs 39%; P < .001).
• In the subgroup analysis on the basis of the duration of follow-up periods, the BLT group had better remission and response rates than the control group for both short-term (< 4 weeks; P < .001) and long-term (> 4 weeks; P = .04) follow-up periods, which suggests that patients achieved remission and responded to treatment more quickly with BLT than with antidepressants alone.
• The BLT group had a significantly greater reduction in HAM-D scores than the control group (mean difference, −1.44; P = .003).

IN PRACTICE:

“These findings suggest that BLT was an effective adjunctive treatment for nonseasonal depressive disorders, and the response time to the initial treatment may be improved with the addition of BLT,” the study authors wrote.
 

SOURCE:

The study was led by Artur Menegaz de Almeida, MS, Federal University of Mato Grosso, Sinop, Brazil. It was published online on October 2, 2024, in JAMA Psychiatry.
 

LIMITATIONS:

Slight differences were observed in the mean follow-up time between the included trials. The definitions for remission rates and response to treatment varied among the included studies, and they also involved different levels of disorder severity. Additionally, the study did not enable the separate analysis of each included depressive disorder, nor bipolar or unipolar subtypes of major depressive disorder. The moderate number of studies included may have affected the generalizability of the findings.
 

DISCLOSURES:

Study funding was not disclosed. No relevant conflicts of interest were disclosed.

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

A 3-year-old presents to my clinic for evaluation of a possible autism spectrum disorder/difference. He has a history of severe emotional dysregulation, as well as reduced social skills and multiple sensory sensitivities. When I enter the exam room he is watching videos on his mom’s phone, and has some difficulty transitioning to play with toys when I encourage him to do so. He is eventually able to cooperate with my testing, though a bit reluctantly, and scores within the low average range for both language and pre-academic skills. His neurologic exam is within normal limits. He utilizes reasonably well-modulated eye contact paired with some typical use of gestures, and his affect is moderately directed and reactive. He displays typical intonation and prosody of speech, though engages in less spontaneous, imaginative, and reciprocal play than would be expected for his age. His mother reports decreased pretend play at home, minimal interest in toys, and difficulty playing cooperatively with other children.

Upon further history, it becomes apparent that the child spends a majority of his time on electronic devices, and has done so since early toddlerhood. Further dialogue suggests that the family became isolated during the COVID-19 pandemic, and has not yet re-engaged with the community in a meaningful way. The child has had rare opportunity for social interactions with other children, and minimal access to outdoor play. His most severe meltdowns generally involve transitions away from screens, and his overwhelmed parents often resort to use of additional screens to calm him once he is dysregulated.

Oregon Health &amp; Science University (OHSU)

At the end of the visit, through shared decision making, we agree that enrolling the child in a high-quality public preschool will help parents make a concerted effort towards a significant reduction in the hours per day in which the child utilizes electronic devices, while also providing him more exposure to peers. We plan for the child to return in 6 months for a re-evaluation around social-emotional skills, given his current limited exposure to peers and limited “unplugged” play-time.
 

Overutilization of Electronic Devices

As clinicians, we can all see how pervasive the use of electronic devices has become in the lives of the families we care for, as well as in our own lives, and how challenging some aspects of modern parenting have become. The developmental impact of early and excessive use of screens in young children is well documented,¹ but as clinicians it can be tricky to help empower parents to find ways to limit screen time. When parents use screens to comfort and amuse their children during a clinic visit, this situation may serve as an excellent opportunity for a meaningful and respectful conversation around skill deficits which can result from overutilization of electronic devices in young children.

One scenario I often encounter during my patient evaluations as a developmental and behavioral pediatrician is children begging their parents for use of their phone throughout their visits with me. Not infrequently, a child is already on a screen when I enter the exam room, even when there has been a minimal wait time, which often leads to some resistance on behalf of the child as I explain to the family that a significant portion of the visit involves my interactions with the child, testing the child, and observing their child at play. I always provide ample amounts of age-appropriate art supplies, puzzles, fidgets, building toys, and imaginative play items to children during their 30 to 90 minute evaluations, but these are often not appealing to children when they have been very recently engaged with an electronic device. At times I also need to ask caretakers themselves to please disengage from their own electronic devices during the visit so that I can involve them in a detailed discussion about their child.

One challenge with the practice of allowing children access to entertainment on their parent’s smartphones in particular, lies in the fact that these devices are almost always present, meaning there is no natural boundary to inhibit access, in contrast to a television set or stationary computer parked in the family living room. Not dissimilar to candy visible in a parent’s purse, a cell phone becomes a constant temptation for children accustomed to utilizing them at home and public venues, and the incessant begging can wear down already stressed parents.

Children can become conditioned to utilize the distraction of screens to avoid feelings of discomfort or stress, and so can be very persistent and emotional when asking for the use of screens in public settings. Out in the community, I very frequently see young children and toddlers quietly staring at their phones and tablets while at restaurants and stores. While I have empathy for exhausted parents desperate for a moment of quiet, if this type of screen use is the rule rather than the exception for a child, there is risk for missed opportunities for the development of self-regulation skills.

Additionally, I have seen very young children present to my clinic with poor posture and neck pain secondary to chronic smartphone use, and young children who are getting minimal exercise or outdoor time due to excessive screen use, leading to concerns around fine and gross motor skills as well.

While allowing a child to stay occupied with or be soothed by a highly interesting digital experience can create a more calm environment for all, if habitual, this use can come at a cost regarding opportunities for the growth of executive functioning skills, general coping skills, general situational awareness, and experiential learning. Reliance on screens to decrease uncomfortable experiences decreases the opportunity for building distress tolerance, patience, and coping skills.

Of course there are times of extreme distress where a lollipop or bit of screen time might be reasonable to help keep a child safe or further avoid emotional trauma, but in general, other methods of soothing can very often be utilized, and in the long run would serve to increase the child’s general adaptive functioning.
 

A Teachable Moment

When clinicians encounter screens being used by parents to entertain their kids in clinic, it provides a valuable teaching moment around the risks of using screens to keep kids regulated and occupied during life’s less interesting or more anxiety provoking experiences. Having a meaningful conversation about the use of electronic devices with caregivers by clinicians in the exam room can be a delicate dance between providing supportive education while avoiding judgmental tones or verbiage. Normalizing and sympathizing with the difficulty of managing challenging behaviors from children in public spaces can help parents feel less desperate to keep their child quiet at all costs, and thus allow for greater development of coping skills.

Some parents may benefit from learning simple ideas for keeping a child regulated and occupied during times of waiting such as silly songs and dances, verbal games like “I spy,” and clapping routines. For a child with additional sensory or developmental needs, a referral to an occupational therapist to work on emotional regulation by way of specific sensory tools can be helpful. Parent-Child Interaction Therapy for kids ages 2 to 7 can also help build some relational activities and skills that can be utilized during trying situations to help keep a child settled and occupied.

If a child has qualified for Developmental Disability Services (DDS), medical providers can also write “prescriptions’ for sensory calming items which are often covered financially by DDS, such as chewies, weighted vests, stuffed animals, and fidgets. While vilification of all screen time for children is not necessary or helpful, supporting parents as they navigate and implement appropriate boundaries is important for optimizing child development. Encouraging parents to schedule allowed screen time at home in a very predictable and controlled manner is one method to help limit excessive use, as well as it’s utilization as an emotional regulation tool.

For public outings with children with special needs, and in particular in situations where meltdowns are likely to occur, some families find it helpful to dress their children in clothing or accessories that increase community awareness about their child’s condition (such as an autism awareness t-shirt). This effort can also help deflect unhelpful attention or advice from the public. Some parents choose to carry small cards explaining the child’s developmental differences, which can then be easily handed to unsupportive strangers in community settings during trying moments.

Clinicians can work to utilize even quick visits with families as an opportunity to review the American Academy of Pediatrics screen time recommendations with families, and also direct them to the Family Media Plan creation resources. Parenting in the modern era presents many challenges regarding choices around the use of electronic devices with children, and using the exam room experience as a teaching opportunity may be a helpful way to decrease utilization of screens as emotional regulation tools for children, while also providing general education around healthy use of screens.
 

Dr. Roth is a developmental and behavioral pediatrician in Eugene, Oregon.

Reference

1. Takahashi I et al. Screen Time at Age 1 Year and Communication and Problem-Solving Developmental Delays at 2 and 4 years. JAMA Pediatr. 2023 Oct 1;177(10):1039-1046. doi: 10.1001/jamapediatrics.2023.3057.

A 3-year-old presents to my clinic for evaluation of a possible autism spectrum disorder/difference. He has a history of severe emotional dysregulation, as well as reduced social skills and multiple sensory sensitivities. When I enter the exam room he is watching videos on his mom’s phone, and has some difficulty transitioning to play with toys when I encourage him to do so. He is eventually able to cooperate with my testing, though a bit reluctantly, and scores within the low average range for both language and pre-academic skills. His neurologic exam is within normal limits. He utilizes reasonably well-modulated eye contact paired with some typical use of gestures, and his affect is moderately directed and reactive. He displays typical intonation and prosody of speech, though engages in less spontaneous, imaginative, and reciprocal play than would be expected for his age. His mother reports decreased pretend play at home, minimal interest in toys, and difficulty playing cooperatively with other children.

Upon further history, it becomes apparent that the child spends a majority of his time on electronic devices, and has done so since early toddlerhood. Further dialogue suggests that the family became isolated during the COVID-19 pandemic, and has not yet re-engaged with the community in a meaningful way. The child has had rare opportunity for social interactions with other children, and minimal access to outdoor play. His most severe meltdowns generally involve transitions away from screens, and his overwhelmed parents often resort to use of additional screens to calm him once he is dysregulated.

Oregon Health &amp; Science University (OHSU)

At the end of the visit, through shared decision making, we agree that enrolling the child in a high-quality public preschool will help parents make a concerted effort towards a significant reduction in the hours per day in which the child utilizes electronic devices, while also providing him more exposure to peers. We plan for the child to return in 6 months for a re-evaluation around social-emotional skills, given his current limited exposure to peers and limited “unplugged” play-time.
 

Overutilization of Electronic Devices

As clinicians, we can all see how pervasive the use of electronic devices has become in the lives of the families we care for, as well as in our own lives, and how challenging some aspects of modern parenting have become. The developmental impact of early and excessive use of screens in young children is well documented,¹ but as clinicians it can be tricky to help empower parents to find ways to limit screen time. When parents use screens to comfort and amuse their children during a clinic visit, this situation may serve as an excellent opportunity for a meaningful and respectful conversation around skill deficits which can result from overutilization of electronic devices in young children.

One scenario I often encounter during my patient evaluations as a developmental and behavioral pediatrician is children begging their parents for use of their phone throughout their visits with me. Not infrequently, a child is already on a screen when I enter the exam room, even when there has been a minimal wait time, which often leads to some resistance on behalf of the child as I explain to the family that a significant portion of the visit involves my interactions with the child, testing the child, and observing their child at play. I always provide ample amounts of age-appropriate art supplies, puzzles, fidgets, building toys, and imaginative play items to children during their 30 to 90 minute evaluations, but these are often not appealing to children when they have been very recently engaged with an electronic device. At times I also need to ask caretakers themselves to please disengage from their own electronic devices during the visit so that I can involve them in a detailed discussion about their child.

One challenge with the practice of allowing children access to entertainment on their parent’s smartphones in particular, lies in the fact that these devices are almost always present, meaning there is no natural boundary to inhibit access, in contrast to a television set or stationary computer parked in the family living room. Not dissimilar to candy visible in a parent’s purse, a cell phone becomes a constant temptation for children accustomed to utilizing them at home and public venues, and the incessant begging can wear down already stressed parents.

Children can become conditioned to utilize the distraction of screens to avoid feelings of discomfort or stress, and so can be very persistent and emotional when asking for the use of screens in public settings. Out in the community, I very frequently see young children and toddlers quietly staring at their phones and tablets while at restaurants and stores. While I have empathy for exhausted parents desperate for a moment of quiet, if this type of screen use is the rule rather than the exception for a child, there is risk for missed opportunities for the development of self-regulation skills.

Additionally, I have seen very young children present to my clinic with poor posture and neck pain secondary to chronic smartphone use, and young children who are getting minimal exercise or outdoor time due to excessive screen use, leading to concerns around fine and gross motor skills as well.

While allowing a child to stay occupied with or be soothed by a highly interesting digital experience can create a more calm environment for all, if habitual, this use can come at a cost regarding opportunities for the growth of executive functioning skills, general coping skills, general situational awareness, and experiential learning. Reliance on screens to decrease uncomfortable experiences decreases the opportunity for building distress tolerance, patience, and coping skills.

Of course there are times of extreme distress where a lollipop or bit of screen time might be reasonable to help keep a child safe or further avoid emotional trauma, but in general, other methods of soothing can very often be utilized, and in the long run would serve to increase the child’s general adaptive functioning.
 

A Teachable Moment

When clinicians encounter screens being used by parents to entertain their kids in clinic, it provides a valuable teaching moment around the risks of using screens to keep kids regulated and occupied during life’s less interesting or more anxiety provoking experiences. Having a meaningful conversation about the use of electronic devices with caregivers by clinicians in the exam room can be a delicate dance between providing supportive education while avoiding judgmental tones or verbiage. Normalizing and sympathizing with the difficulty of managing challenging behaviors from children in public spaces can help parents feel less desperate to keep their child quiet at all costs, and thus allow for greater development of coping skills.

Some parents may benefit from learning simple ideas for keeping a child regulated and occupied during times of waiting such as silly songs and dances, verbal games like “I spy,” and clapping routines. For a child with additional sensory or developmental needs, a referral to an occupational therapist to work on emotional regulation by way of specific sensory tools can be helpful. Parent-Child Interaction Therapy for kids ages 2 to 7 can also help build some relational activities and skills that can be utilized during trying situations to help keep a child settled and occupied.

If a child has qualified for Developmental Disability Services (DDS), medical providers can also write “prescriptions’ for sensory calming items which are often covered financially by DDS, such as chewies, weighted vests, stuffed animals, and fidgets. While vilification of all screen time for children is not necessary or helpful, supporting parents as they navigate and implement appropriate boundaries is important for optimizing child development. Encouraging parents to schedule allowed screen time at home in a very predictable and controlled manner is one method to help limit excessive use, as well as it’s utilization as an emotional regulation tool.

For public outings with children with special needs, and in particular in situations where meltdowns are likely to occur, some families find it helpful to dress their children in clothing or accessories that increase community awareness about their child’s condition (such as an autism awareness t-shirt). This effort can also help deflect unhelpful attention or advice from the public. Some parents choose to carry small cards explaining the child’s developmental differences, which can then be easily handed to unsupportive strangers in community settings during trying moments.

Clinicians can work to utilize even quick visits with families as an opportunity to review the American Academy of Pediatrics screen time recommendations with families, and also direct them to the Family Media Plan creation resources. Parenting in the modern era presents many challenges regarding choices around the use of electronic devices with children, and using the exam room experience as a teaching opportunity may be a helpful way to decrease utilization of screens as emotional regulation tools for children, while also providing general education around healthy use of screens.
 

Dr. Roth is a developmental and behavioral pediatrician in Eugene, Oregon.

Reference

1. Takahashi I et al. Screen Time at Age 1 Year and Communication and Problem-Solving Developmental Delays at 2 and 4 years. JAMA Pediatr. 2023 Oct 1;177(10):1039-1046. doi: 10.1001/jamapediatrics.2023.3057.

A 3-year-old presents to my clinic for evaluation of a possible autism spectrum disorder/difference. He has a history of severe emotional dysregulation, as well as reduced social skills and multiple sensory sensitivities. When I enter the exam room he is watching videos on his mom’s phone, and has some difficulty transitioning to play with toys when I encourage him to do so. He is eventually able to cooperate with my testing, though a bit reluctantly, and scores within the low average range for both language and pre-academic skills. His neurologic exam is within normal limits. He utilizes reasonably well-modulated eye contact paired with some typical use of gestures, and his affect is moderately directed and reactive. He displays typical intonation and prosody of speech, though engages in less spontaneous, imaginative, and reciprocal play than would be expected for his age. His mother reports decreased pretend play at home, minimal interest in toys, and difficulty playing cooperatively with other children.

Upon further history, it becomes apparent that the child spends a majority of his time on electronic devices, and has done so since early toddlerhood. Further dialogue suggests that the family became isolated during the COVID-19 pandemic, and has not yet re-engaged with the community in a meaningful way. The child has had rare opportunity for social interactions with other children, and minimal access to outdoor play. His most severe meltdowns generally involve transitions away from screens, and his overwhelmed parents often resort to use of additional screens to calm him once he is dysregulated.

Oregon Health &amp; Science University (OHSU)

At the end of the visit, through shared decision making, we agree that enrolling the child in a high-quality public preschool will help parents make a concerted effort towards a significant reduction in the hours per day in which the child utilizes electronic devices, while also providing him more exposure to peers. We plan for the child to return in 6 months for a re-evaluation around social-emotional skills, given his current limited exposure to peers and limited “unplugged” play-time.
 

Overutilization of Electronic Devices

As clinicians, we can all see how pervasive the use of electronic devices has become in the lives of the families we care for, as well as in our own lives, and how challenging some aspects of modern parenting have become. The developmental impact of early and excessive use of screens in young children is well documented,¹ but as clinicians it can be tricky to help empower parents to find ways to limit screen time. When parents use screens to comfort and amuse their children during a clinic visit, this situation may serve as an excellent opportunity for a meaningful and respectful conversation around skill deficits which can result from overutilization of electronic devices in young children.

One scenario I often encounter during my patient evaluations as a developmental and behavioral pediatrician is children begging their parents for use of their phone throughout their visits with me. Not infrequently, a child is already on a screen when I enter the exam room, even when there has been a minimal wait time, which often leads to some resistance on behalf of the child as I explain to the family that a significant portion of the visit involves my interactions with the child, testing the child, and observing their child at play. I always provide ample amounts of age-appropriate art supplies, puzzles, fidgets, building toys, and imaginative play items to children during their 30 to 90 minute evaluations, but these are often not appealing to children when they have been very recently engaged with an electronic device. At times I also need to ask caretakers themselves to please disengage from their own electronic devices during the visit so that I can involve them in a detailed discussion about their child.

One challenge with the practice of allowing children access to entertainment on their parent’s smartphones in particular, lies in the fact that these devices are almost always present, meaning there is no natural boundary to inhibit access, in contrast to a television set or stationary computer parked in the family living room. Not dissimilar to candy visible in a parent’s purse, a cell phone becomes a constant temptation for children accustomed to utilizing them at home and public venues, and the incessant begging can wear down already stressed parents.

Children can become conditioned to utilize the distraction of screens to avoid feelings of discomfort or stress, and so can be very persistent and emotional when asking for the use of screens in public settings. Out in the community, I very frequently see young children and toddlers quietly staring at their phones and tablets while at restaurants and stores. While I have empathy for exhausted parents desperate for a moment of quiet, if this type of screen use is the rule rather than the exception for a child, there is risk for missed opportunities for the development of self-regulation skills.

Additionally, I have seen very young children present to my clinic with poor posture and neck pain secondary to chronic smartphone use, and young children who are getting minimal exercise or outdoor time due to excessive screen use, leading to concerns around fine and gross motor skills as well.

While allowing a child to stay occupied with or be soothed by a highly interesting digital experience can create a more calm environment for all, if habitual, this use can come at a cost regarding opportunities for the growth of executive functioning skills, general coping skills, general situational awareness, and experiential learning. Reliance on screens to decrease uncomfortable experiences decreases the opportunity for building distress tolerance, patience, and coping skills.

Of course there are times of extreme distress where a lollipop or bit of screen time might be reasonable to help keep a child safe or further avoid emotional trauma, but in general, other methods of soothing can very often be utilized, and in the long run would serve to increase the child’s general adaptive functioning.
 

A Teachable Moment

When clinicians encounter screens being used by parents to entertain their kids in clinic, it provides a valuable teaching moment around the risks of using screens to keep kids regulated and occupied during life’s less interesting or more anxiety provoking experiences. Having a meaningful conversation about the use of electronic devices with caregivers by clinicians in the exam room can be a delicate dance between providing supportive education while avoiding judgmental tones or verbiage. Normalizing and sympathizing with the difficulty of managing challenging behaviors from children in public spaces can help parents feel less desperate to keep their child quiet at all costs, and thus allow for greater development of coping skills.

Some parents may benefit from learning simple ideas for keeping a child regulated and occupied during times of waiting such as silly songs and dances, verbal games like “I spy,” and clapping routines. For a child with additional sensory or developmental needs, a referral to an occupational therapist to work on emotional regulation by way of specific sensory tools can be helpful. Parent-Child Interaction Therapy for kids ages 2 to 7 can also help build some relational activities and skills that can be utilized during trying situations to help keep a child settled and occupied.

If a child has qualified for Developmental Disability Services (DDS), medical providers can also write “prescriptions’ for sensory calming items which are often covered financially by DDS, such as chewies, weighted vests, stuffed animals, and fidgets. While vilification of all screen time for children is not necessary or helpful, supporting parents as they navigate and implement appropriate boundaries is important for optimizing child development. Encouraging parents to schedule allowed screen time at home in a very predictable and controlled manner is one method to help limit excessive use, as well as it’s utilization as an emotional regulation tool.

For public outings with children with special needs, and in particular in situations where meltdowns are likely to occur, some families find it helpful to dress their children in clothing or accessories that increase community awareness about their child’s condition (such as an autism awareness t-shirt). This effort can also help deflect unhelpful attention or advice from the public. Some parents choose to carry small cards explaining the child’s developmental differences, which can then be easily handed to unsupportive strangers in community settings during trying moments.

Clinicians can work to utilize even quick visits with families as an opportunity to review the American Academy of Pediatrics screen time recommendations with families, and also direct them to the Family Media Plan creation resources. Parenting in the modern era presents many challenges regarding choices around the use of electronic devices with children, and using the exam room experience as a teaching opportunity may be a helpful way to decrease utilization of screens as emotional regulation tools for children, while also providing general education around healthy use of screens.
 

Dr. Roth is a developmental and behavioral pediatrician in Eugene, Oregon.

Reference

1. Takahashi I et al. Screen Time at Age 1 Year and Communication and Problem-Solving Developmental Delays at 2 and 4 years. JAMA Pediatr. 2023 Oct 1;177(10):1039-1046. doi: 10.1001/jamapediatrics.2023.3057.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) given to adolescents with obesity was associated with a one-third decreased risk for suicidal ideation and suicide attempts compared with lifestyle intervention alone, a large international retrospective study found.

A study published in JAMA Pediatrics suggested that GLP-1 RAs such as semaglutide, liraglutide, and tirzepatide, which are widely used to treat type 2 diabetes (T2D), have a favorable psychiatric safety profile and open up potential avenues for prospective studies of psychiatric outcomes in adolescents with obesity.

Investigators Liya Kerem, MD, MSc, and Joshua Stokar, MD, of Hadassah University Medical Center in Jerusalem, Israel, reported that the reduced risk in GLP-1 RA recipients was maintained up to 3 years follow-up compared with propensity score–matched controls treated with behavioral interventions alone.

“These findings support the notion that childhood obesity does not result from lack of willpower and shed light on underlying mechanisms that can be targeted by pharmacotherapy.” Kerem and Stokar wrote.

Other research has suggested these agents have neurobiologic effects unrelated to weight loss that positively affect mood and mental health.
 

Study Details

The analysis included data from December 2019 to June 2024, drawn from 120 international healthcare organizations, mainly in the United States. A total of 4052 racially and ethnically diverse adolescents with obesity (aged 12-18 years [mean age, about 15.5 years]) being treated with an anti-obesity intervention were identified for the GLP-1 RA cohort and 50,112 for the control cohort. The arms were balanced for baseline demographic characteristics, psychiatric medications and comorbidities, and diagnoses associated with socioeconomic status and healthcare access.

Propensity score matching (PSM) resulted in 3456 participants in each of two balanced cohorts.

Before PSM, intervention patients were older (mean age, 15.5 vs 14.7 years), were more likely to be female (59% vs 49%), and had a higher body mass index (41.9 vs 33.8). They also had a higher prevalence of diabetes (40% vs 4%) and treatment with antidiabetic medications.

GLP-1 RA recipients also had a history of psychiatric diagnoses (17% vs 9% for mood disorders) and psychiatric medications (18% vs 7% for antidepressants). Previous use of non–GLP-1 RA anti-obesity medications was uncommon in the cohort overall, although more common in the GLP-1 RA cohort (2.5% vs 0.2% for phentermine).

Prescription of GLP-1 RA was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up: 1.45% vs 2.26% (hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02). It was also associated with a higher rate of gastrointestinal symptoms: 6.9% vs 5.4% (HR, 1.41; 95% CI, 1.12-1.78; P = .003). There was no difference in rates of upper respiratory tract infections (URTIs), although some research suggests these agents reduce URTIs.
 

Mechanisms

The etiology of childhood obesity is complex and multifactorial, the authors wrote, and genetic predisposition to adiposity, an obesogenic environment, and a sedentary lifestyle synergistically contribute to its development. Variants in genes active in the hypothalamic appetite-regulation neurocircuitry appear to be associated with the development of childhood and adolescent obesity.

The authors noted that adolescence carries an increased risk for psychiatric disorders and suicidal ideation. “The amelioration of obesity could indirectly improve these psychiatric comorbidities,” they wrote. In addition, preclinical studies suggested that GLP-1 RA may improve depression-related neuropathology, including neuroinflammation and neurotransmitter imbalance, and may promote neurogenesis.

A recent meta-analysis found that adults with T2D treated with GLP-1 RA showed significant reduction in depression scale scores compared with those treated with non-GLP-1 RA antidiabetic medications.

Commenting on the study but not involved in it, psychiatrist Robert H. Dicker, MD, associate director of child and adolescent psychiatry at Northwell Zucker Hillside Hospital in Glen Oaks, New York, cautioned that these are preliminary data limited by a retrospective review, not a prospective double-blind, placebo-controlled study.

“The mechanism is unknown — is it a direct effect on weight loss with an improvement of quality of life, more positive feedback by the community, enhanced ability to exercise, and a decrease in depressive symptoms?” he asked.

Dicker suggested an alternative hypothesis: Does the GLP-1 RA have a direct effect on neurotransmitters and inflammation and, thus, an impact on mood, emotional regulation, impulse control, and suicide?

“To further answer these questions, prospective studies must be conducted. It is far too early to conclude that these medications are effective in treating mood disorders in our youth,” Dicker said. “But it is promising that these treatments do not appear to increase suicidal ideas and behavior.”

Adding another outsider’s perspective on the study, Suzanne E. Cuda, MD, FOMA, FAAP, a pediatrician who treats childhood obesity in San Antonio, said that while there was no risk for increased psychiatric disease and a suggestion that GLP-1 RAs may reduce suicidal ideation or attempts, “I don’t think this translates to a treatment for depression in adolescents. Nor does this study indicate there could be a decrease in depression due specifically to the use of GLP1Rs. If the results in this study are replicated, however, it would be reassuring to know that adolescents would not be at risk for an increase in suicidal ideation or attempts.”

This study had no external funding. Kerem reported receiving personal fees from Novo Nordisk for lectures on childhood obesity outside of the submitted work. No other disclosures were reported. Dicker and Cuda had no competing interests relevant to their comments.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) given to adolescents with obesity was associated with a one-third decreased risk for suicidal ideation and suicide attempts compared with lifestyle intervention alone, a large international retrospective study found.

A study published in JAMA Pediatrics suggested that GLP-1 RAs such as semaglutide, liraglutide, and tirzepatide, which are widely used to treat type 2 diabetes (T2D), have a favorable psychiatric safety profile and open up potential avenues for prospective studies of psychiatric outcomes in adolescents with obesity.

Investigators Liya Kerem, MD, MSc, and Joshua Stokar, MD, of Hadassah University Medical Center in Jerusalem, Israel, reported that the reduced risk in GLP-1 RA recipients was maintained up to 3 years follow-up compared with propensity score–matched controls treated with behavioral interventions alone.

“These findings support the notion that childhood obesity does not result from lack of willpower and shed light on underlying mechanisms that can be targeted by pharmacotherapy.” Kerem and Stokar wrote.

Other research has suggested these agents have neurobiologic effects unrelated to weight loss that positively affect mood and mental health.
 

Study Details

The analysis included data from December 2019 to June 2024, drawn from 120 international healthcare organizations, mainly in the United States. A total of 4052 racially and ethnically diverse adolescents with obesity (aged 12-18 years [mean age, about 15.5 years]) being treated with an anti-obesity intervention were identified for the GLP-1 RA cohort and 50,112 for the control cohort. The arms were balanced for baseline demographic characteristics, psychiatric medications and comorbidities, and diagnoses associated with socioeconomic status and healthcare access.

Propensity score matching (PSM) resulted in 3456 participants in each of two balanced cohorts.

Before PSM, intervention patients were older (mean age, 15.5 vs 14.7 years), were more likely to be female (59% vs 49%), and had a higher body mass index (41.9 vs 33.8). They also had a higher prevalence of diabetes (40% vs 4%) and treatment with antidiabetic medications.

GLP-1 RA recipients also had a history of psychiatric diagnoses (17% vs 9% for mood disorders) and psychiatric medications (18% vs 7% for antidepressants). Previous use of non–GLP-1 RA anti-obesity medications was uncommon in the cohort overall, although more common in the GLP-1 RA cohort (2.5% vs 0.2% for phentermine).

Prescription of GLP-1 RA was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up: 1.45% vs 2.26% (hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02). It was also associated with a higher rate of gastrointestinal symptoms: 6.9% vs 5.4% (HR, 1.41; 95% CI, 1.12-1.78; P = .003). There was no difference in rates of upper respiratory tract infections (URTIs), although some research suggests these agents reduce URTIs.
 

Mechanisms

The etiology of childhood obesity is complex and multifactorial, the authors wrote, and genetic predisposition to adiposity, an obesogenic environment, and a sedentary lifestyle synergistically contribute to its development. Variants in genes active in the hypothalamic appetite-regulation neurocircuitry appear to be associated with the development of childhood and adolescent obesity.

The authors noted that adolescence carries an increased risk for psychiatric disorders and suicidal ideation. “The amelioration of obesity could indirectly improve these psychiatric comorbidities,” they wrote. In addition, preclinical studies suggested that GLP-1 RA may improve depression-related neuropathology, including neuroinflammation and neurotransmitter imbalance, and may promote neurogenesis.

A recent meta-analysis found that adults with T2D treated with GLP-1 RA showed significant reduction in depression scale scores compared with those treated with non-GLP-1 RA antidiabetic medications.

Commenting on the study but not involved in it, psychiatrist Robert H. Dicker, MD, associate director of child and adolescent psychiatry at Northwell Zucker Hillside Hospital in Glen Oaks, New York, cautioned that these are preliminary data limited by a retrospective review, not a prospective double-blind, placebo-controlled study.

“The mechanism is unknown — is it a direct effect on weight loss with an improvement of quality of life, more positive feedback by the community, enhanced ability to exercise, and a decrease in depressive symptoms?” he asked.

Dicker suggested an alternative hypothesis: Does the GLP-1 RA have a direct effect on neurotransmitters and inflammation and, thus, an impact on mood, emotional regulation, impulse control, and suicide?

“To further answer these questions, prospective studies must be conducted. It is far too early to conclude that these medications are effective in treating mood disorders in our youth,” Dicker said. “But it is promising that these treatments do not appear to increase suicidal ideas and behavior.”

Adding another outsider’s perspective on the study, Suzanne E. Cuda, MD, FOMA, FAAP, a pediatrician who treats childhood obesity in San Antonio, said that while there was no risk for increased psychiatric disease and a suggestion that GLP-1 RAs may reduce suicidal ideation or attempts, “I don’t think this translates to a treatment for depression in adolescents. Nor does this study indicate there could be a decrease in depression due specifically to the use of GLP1Rs. If the results in this study are replicated, however, it would be reassuring to know that adolescents would not be at risk for an increase in suicidal ideation or attempts.”

This study had no external funding. Kerem reported receiving personal fees from Novo Nordisk for lectures on childhood obesity outside of the submitted work. No other disclosures were reported. Dicker and Cuda had no competing interests relevant to their comments.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) given to adolescents with obesity was associated with a one-third decreased risk for suicidal ideation and suicide attempts compared with lifestyle intervention alone, a large international retrospective study found.

A study published in JAMA Pediatrics suggested that GLP-1 RAs such as semaglutide, liraglutide, and tirzepatide, which are widely used to treat type 2 diabetes (T2D), have a favorable psychiatric safety profile and open up potential avenues for prospective studies of psychiatric outcomes in adolescents with obesity.

Investigators Liya Kerem, MD, MSc, and Joshua Stokar, MD, of Hadassah University Medical Center in Jerusalem, Israel, reported that the reduced risk in GLP-1 RA recipients was maintained up to 3 years follow-up compared with propensity score–matched controls treated with behavioral interventions alone.

“These findings support the notion that childhood obesity does not result from lack of willpower and shed light on underlying mechanisms that can be targeted by pharmacotherapy.” Kerem and Stokar wrote.

Other research has suggested these agents have neurobiologic effects unrelated to weight loss that positively affect mood and mental health.
 

Study Details

The analysis included data from December 2019 to June 2024, drawn from 120 international healthcare organizations, mainly in the United States. A total of 4052 racially and ethnically diverse adolescents with obesity (aged 12-18 years [mean age, about 15.5 years]) being treated with an anti-obesity intervention were identified for the GLP-1 RA cohort and 50,112 for the control cohort. The arms were balanced for baseline demographic characteristics, psychiatric medications and comorbidities, and diagnoses associated with socioeconomic status and healthcare access.

Propensity score matching (PSM) resulted in 3456 participants in each of two balanced cohorts.

Before PSM, intervention patients were older (mean age, 15.5 vs 14.7 years), were more likely to be female (59% vs 49%), and had a higher body mass index (41.9 vs 33.8). They also had a higher prevalence of diabetes (40% vs 4%) and treatment with antidiabetic medications.

GLP-1 RA recipients also had a history of psychiatric diagnoses (17% vs 9% for mood disorders) and psychiatric medications (18% vs 7% for antidepressants). Previous use of non–GLP-1 RA anti-obesity medications was uncommon in the cohort overall, although more common in the GLP-1 RA cohort (2.5% vs 0.2% for phentermine).

Prescription of GLP-1 RA was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up: 1.45% vs 2.26% (hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02). It was also associated with a higher rate of gastrointestinal symptoms: 6.9% vs 5.4% (HR, 1.41; 95% CI, 1.12-1.78; P = .003). There was no difference in rates of upper respiratory tract infections (URTIs), although some research suggests these agents reduce URTIs.
 

Mechanisms

The etiology of childhood obesity is complex and multifactorial, the authors wrote, and genetic predisposition to adiposity, an obesogenic environment, and a sedentary lifestyle synergistically contribute to its development. Variants in genes active in the hypothalamic appetite-regulation neurocircuitry appear to be associated with the development of childhood and adolescent obesity.

The authors noted that adolescence carries an increased risk for psychiatric disorders and suicidal ideation. “The amelioration of obesity could indirectly improve these psychiatric comorbidities,” they wrote. In addition, preclinical studies suggested that GLP-1 RA may improve depression-related neuropathology, including neuroinflammation and neurotransmitter imbalance, and may promote neurogenesis.

A recent meta-analysis found that adults with T2D treated with GLP-1 RA showed significant reduction in depression scale scores compared with those treated with non-GLP-1 RA antidiabetic medications.

Commenting on the study but not involved in it, psychiatrist Robert H. Dicker, MD, associate director of child and adolescent psychiatry at Northwell Zucker Hillside Hospital in Glen Oaks, New York, cautioned that these are preliminary data limited by a retrospective review, not a prospective double-blind, placebo-controlled study.

“The mechanism is unknown — is it a direct effect on weight loss with an improvement of quality of life, more positive feedback by the community, enhanced ability to exercise, and a decrease in depressive symptoms?” he asked.

Dicker suggested an alternative hypothesis: Does the GLP-1 RA have a direct effect on neurotransmitters and inflammation and, thus, an impact on mood, emotional regulation, impulse control, and suicide?

“To further answer these questions, prospective studies must be conducted. It is far too early to conclude that these medications are effective in treating mood disorders in our youth,” Dicker said. “But it is promising that these treatments do not appear to increase suicidal ideas and behavior.”

Adding another outsider’s perspective on the study, Suzanne E. Cuda, MD, FOMA, FAAP, a pediatrician who treats childhood obesity in San Antonio, said that while there was no risk for increased psychiatric disease and a suggestion that GLP-1 RAs may reduce suicidal ideation or attempts, “I don’t think this translates to a treatment for depression in adolescents. Nor does this study indicate there could be a decrease in depression due specifically to the use of GLP1Rs. If the results in this study are replicated, however, it would be reassuring to know that adolescents would not be at risk for an increase in suicidal ideation or attempts.”

This study had no external funding. Kerem reported receiving personal fees from Novo Nordisk for lectures on childhood obesity outside of the submitted work. No other disclosures were reported. Dicker and Cuda had no competing interests relevant to their comments.

A version of this article appeared on Medscape.com.

TOPLINE:

About one third of adult survivors of childhood cancer experience a clinically significant or high fear that their primary cancer may recur or that they will develop a subsequent malignancy, according to a recent analysis. The study finds that several factors are associated with a higher risk of experiencing a clinically significant fear of recurrence, including being unemployed or having elevated anxiety or depression.

METHODOLOGY:

• Adult survivors of childhood cancer face a high risk of developing subsequent malignant neoplasms — about a sixfold greater risk than in the general population — and studies indicate that these cancer survivors also fear their cancer will recur. However, data on the prevalence of and risk factors associated with clinically significant fear of recurrence in this population remain limited.
• This cross-sectional study included 229 adult survivors of childhood cancer (mean age at study completion, 39.6 years), recruited from the Childhood Cancer Survivor Study, who completed online surveys between October 2018 and April 2019.
• Fear of cancer recurrence was assessed using the 9-item Fear of Cancer Recurrence Inventory–Short Form, which defines recurrence as the possibility that cancer might return to the same or a different part of the body.
• Chronic pain, symptoms of depression and anxiety, self-perceived health, and intolerance of uncertainty were also evaluated.
• Among the participants, 21 experienced a recurrence of their primary cancer and 17 were diagnosed with a subsequent malignant neoplasm.
•  

TAKEAWAY:

• Overall, 38 (16.6%) adult survivors of childhood cancer reported clinically significant fear that their cancer would recur, and an additional 36 (15.7%) survivors experienced high levels of fear; the remaining 67.7% of participants reported minimal levels of fear.
• Survivors who were unemployed (prevalence ratio [PR], 2.5) were more likely to experience a clinically significant fear of recurrence, as were survivors who had undergone pelvic radiation (PR, 2.9) or limb-sparing or amputation surgery (PR, 2.4).
• Survivors who had elevated anxiety or depression (PR, 2.6) or both (PR, 3.2) were more likely to experience a clinically significant fear of recurrence, as were survivors who had a chronic neurologic health condition (PR, 3.3) or who perceived their health status to be poor or fair vs good to excellent (PR, 3.0).
• Among 94 participants with chronic pain, 25.5% reported clinically significant fear and 13.8% reported high levels of fear. But chronic pain (PR, 1.2; 95% CI, 0.6-2.4) was not significantly associated with a clinically significant fear of recurrence in a multivariable model.
•  

IN PRACTICE:

“These findings underscore the substantial psychological and functional burden of FCR [fear of cancer recurrence] and suggest healthcare professionals should routinely assess FCR as a part of providing comprehensive care to long-term survivors,” the authors wrote.

SOURCE:

The study, led by Alex Pizzo, MSc, Concordia University, Montréal, Québec, Canada, was published online in JAMA Network Open.

LIMITATIONS:

The cross-sectional design limited causal inference. Self-perceived health was assessed with a single item, limiting its measurement. Internet and smartphone access eligibility could have introduced bias. The study also lacked racial and ethnic diversity.

DISCLOSURES:

The study was supported by the Childhood Cancer Survivor Study Career Development Award and a grant from the National Cancer Institute. Additional funding was provided by the Canada Research Chairs Program. Three authors reported receiving grants from various sources.

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:

About one third of adult survivors of childhood cancer experience a clinically significant or high fear that their primary cancer may recur or that they will develop a subsequent malignancy, according to a recent analysis. The study finds that several factors are associated with a higher risk of experiencing a clinically significant fear of recurrence, including being unemployed or having elevated anxiety or depression.

METHODOLOGY:

• Adult survivors of childhood cancer face a high risk of developing subsequent malignant neoplasms — about a sixfold greater risk than in the general population — and studies indicate that these cancer survivors also fear their cancer will recur. However, data on the prevalence of and risk factors associated with clinically significant fear of recurrence in this population remain limited.
• This cross-sectional study included 229 adult survivors of childhood cancer (mean age at study completion, 39.6 years), recruited from the Childhood Cancer Survivor Study, who completed online surveys between October 2018 and April 2019.
• Fear of cancer recurrence was assessed using the 9-item Fear of Cancer Recurrence Inventory–Short Form, which defines recurrence as the possibility that cancer might return to the same or a different part of the body.
• Chronic pain, symptoms of depression and anxiety, self-perceived health, and intolerance of uncertainty were also evaluated.
• Among the participants, 21 experienced a recurrence of their primary cancer and 17 were diagnosed with a subsequent malignant neoplasm.
•  

TAKEAWAY:

• Overall, 38 (16.6%) adult survivors of childhood cancer reported clinically significant fear that their cancer would recur, and an additional 36 (15.7%) survivors experienced high levels of fear; the remaining 67.7% of participants reported minimal levels of fear.
• Survivors who were unemployed (prevalence ratio [PR], 2.5) were more likely to experience a clinically significant fear of recurrence, as were survivors who had undergone pelvic radiation (PR, 2.9) or limb-sparing or amputation surgery (PR, 2.4).
• Survivors who had elevated anxiety or depression (PR, 2.6) or both (PR, 3.2) were more likely to experience a clinically significant fear of recurrence, as were survivors who had a chronic neurologic health condition (PR, 3.3) or who perceived their health status to be poor or fair vs good to excellent (PR, 3.0).
• Among 94 participants with chronic pain, 25.5% reported clinically significant fear and 13.8% reported high levels of fear. But chronic pain (PR, 1.2; 95% CI, 0.6-2.4) was not significantly associated with a clinically significant fear of recurrence in a multivariable model.
•  

IN PRACTICE:

“These findings underscore the substantial psychological and functional burden of FCR [fear of cancer recurrence] and suggest healthcare professionals should routinely assess FCR as a part of providing comprehensive care to long-term survivors,” the authors wrote.

SOURCE:

The study, led by Alex Pizzo, MSc, Concordia University, Montréal, Québec, Canada, was published online in JAMA Network Open.

LIMITATIONS:

The cross-sectional design limited causal inference. Self-perceived health was assessed with a single item, limiting its measurement. Internet and smartphone access eligibility could have introduced bias. The study also lacked racial and ethnic diversity.

DISCLOSURES:

The study was supported by the Childhood Cancer Survivor Study Career Development Award and a grant from the National Cancer Institute. Additional funding was provided by the Canada Research Chairs Program. Three authors reported receiving grants from various sources.

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:

About one third of adult survivors of childhood cancer experience a clinically significant or high fear that their primary cancer may recur or that they will develop a subsequent malignancy, according to a recent analysis. The study finds that several factors are associated with a higher risk of experiencing a clinically significant fear of recurrence, including being unemployed or having elevated anxiety or depression.

METHODOLOGY:

• Adult survivors of childhood cancer face a high risk of developing subsequent malignant neoplasms — about a sixfold greater risk than in the general population — and studies indicate that these cancer survivors also fear their cancer will recur. However, data on the prevalence of and risk factors associated with clinically significant fear of recurrence in this population remain limited.
• This cross-sectional study included 229 adult survivors of childhood cancer (mean age at study completion, 39.6 years), recruited from the Childhood Cancer Survivor Study, who completed online surveys between October 2018 and April 2019.
• Fear of cancer recurrence was assessed using the 9-item Fear of Cancer Recurrence Inventory–Short Form, which defines recurrence as the possibility that cancer might return to the same or a different part of the body.
• Chronic pain, symptoms of depression and anxiety, self-perceived health, and intolerance of uncertainty were also evaluated.
• Among the participants, 21 experienced a recurrence of their primary cancer and 17 were diagnosed with a subsequent malignant neoplasm.
•  

TAKEAWAY:

• Overall, 38 (16.6%) adult survivors of childhood cancer reported clinically significant fear that their cancer would recur, and an additional 36 (15.7%) survivors experienced high levels of fear; the remaining 67.7% of participants reported minimal levels of fear.
• Survivors who were unemployed (prevalence ratio [PR], 2.5) were more likely to experience a clinically significant fear of recurrence, as were survivors who had undergone pelvic radiation (PR, 2.9) or limb-sparing or amputation surgery (PR, 2.4).
• Survivors who had elevated anxiety or depression (PR, 2.6) or both (PR, 3.2) were more likely to experience a clinically significant fear of recurrence, as were survivors who had a chronic neurologic health condition (PR, 3.3) or who perceived their health status to be poor or fair vs good to excellent (PR, 3.0).
• Among 94 participants with chronic pain, 25.5% reported clinically significant fear and 13.8% reported high levels of fear. But chronic pain (PR, 1.2; 95% CI, 0.6-2.4) was not significantly associated with a clinically significant fear of recurrence in a multivariable model.
•  

IN PRACTICE:

“These findings underscore the substantial psychological and functional burden of FCR [fear of cancer recurrence] and suggest healthcare professionals should routinely assess FCR as a part of providing comprehensive care to long-term survivors,” the authors wrote.

SOURCE:

The study, led by Alex Pizzo, MSc, Concordia University, Montréal, Québec, Canada, was published online in JAMA Network Open.

LIMITATIONS:

The cross-sectional design limited causal inference. Self-perceived health was assessed with a single item, limiting its measurement. Internet and smartphone access eligibility could have introduced bias. The study also lacked racial and ethnic diversity.

DISCLOSURES:

The study was supported by the Childhood Cancer Survivor Study Career Development Award and a grant from the National Cancer Institute. Additional funding was provided by the Canada Research Chairs Program. Three authors reported receiving grants from various sources.

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.