Major Depressive Disorder

What if a walk in a green environment could reshape brains, recalibrate sense of time, and stave off mental health conditions? If the research trends are true, you might soon find yourself writing prescriptions of 20 minutes of nature per day.

Evidence for the health benefits of exposure to green spaces, like parks, open spaces, gardens, outdoor gyms, and woodland trails, has been mostly interventional and observational, but that has not stopped global recognition that these exposures are important. 

In the wake of the pandemic, the British government allocated more than £5 million to pandemic recovery efforts that specifically involved green spaces. Since then, it has committed even more funding toward an expansive social prescribing program that connects patients to “link workers” who determine personal care needs and facilitate community and volunteer-based interventions. These can include group walking and volunteering to help out in community gardens or conservation efforts. Similar green programs can be found in Japan, where shinrin-yoku (forest bathing) was recently adopted as a national health strategy, and in the United States and Canada.

“Disconnection from nature is a major part of the health problems that we have on this planet,” said William Bird, a UK-based general practitioner, green prescriber, and CEO of Intelligent Health, which is geared toward building healthy, active, and connected communities. Dr. Bird received the prestigious Member of the Order of the British Empire (MBE) in 2010 for services related to physical activity and health. 

“Our brains are designed to connect to nature ... and we haven’t lost that instinct,” he explained. “Once we are with birdsong and water flowing and greenery, cortisol levels drop, our central vagus nerve improves, our fight and flight [response] disappears, and we start to be more receptive to other people.” 
 

Shifting Time Perception and Health

Ricardo A. Correia, PhD, a biologist and researcher at the University of Helsinki in Finland, said he believed that the mechanism for at least some of these outcomes might be differences in how time is perceived. In a perspective that appeared in March in People and Nature, Dr. Correia explored how the “services” that nature provides shift time perceptions and, in turn, regulate overall well-being. 

“I reached the realization that there was some evidence for the shift in some of the dimensions that we use to make sense of time in urban vs natural environments,” he told this news organization. 

Dr. Correia explained that human time perception facilitates understanding cause and effect, so we can act in a way that allows us to survive. 

“Time perception in humans is really complex and multifaceted,” he said. “The way that we make sense of time is not directly attached to any sensory organ, but rather goes through a range of cognitive, emotional, and bodily processes, all of which vary from person to person.” 

Dr. Correia pointed to evidence showing that time perception is shorter in urban environments and longer in natural ones. This, in turn, influences attention and attention restoration. “When we live in cities, we are exposed to similar sorts of demanding environments, increased time pressures, less time for oneself and for recreational purposes,” he said. “Ever-mounting pressure on daily demands plus processes we use to make sense of time, especially attention, means that we pay a cognitive toll.”

Dr. Correia posits that it might be possible to recalibrate time perception, but only by breaking the cycle of exposure. 

“If we are always exposed to fast-paced lifestyles, we become attuned to them and get caught up in an endless loop.” This cycle can be broken, Dr. Correia explained, by increasing exposure to natural environments. This leads to positive emotions, a sense of being in the present, and a heightened sense of mindfulness, all of which help mitigate the physical and mental health outcomes commonly associated with time scarcity. 
 

Brain-Mental Health Benefits

To date, there is quite a bit of research exploring the impacts of exposure to nature on the brain. For example, data have shown that adolescents raised exclusively in rural environments have a larger hippocampus and better spatial processing than children exclusively raised in cities. Other research demonstrated that spending just an hour in the forest led to a decline in amygdala activity in adults, whereas it remained stable after walking in an urban setting, underscoring the salutogenic effects on brain regions related to stress. There is also evidence from a 10-year longitudinal study of more than 2 million Welsh adults that highlights the value of proximity to green or blue (eg, lakes and rivers) spaces and common mental health conditions, with every additional 360 meters to the nearest green or blue space associated with 10% greater odds of anxiety and depression.

Dr. Bird said there has been a massive sea change in attitudes among general practitioners, who have come around to embracing the concept of nature as medicine. This shift among peers, who teased him in the 1990s about his green walking and conservation prescriptions, portends a bandwagon of epic proportions that could benefit patients. He said that he was especially hopeful that green prescriptions will become mainstream in certain conditions, especially those like depression and anxiety that are resistant to medication.

But Dr. Bird cautions that primary care professionals need to be mindful. “Patients need to know that it’s real science, otherwise they’ll think that they’re being pawned off or dismissed,” he said. “I try to put real evidence behind it and explain that there’s no contraindication. The main thing is to start where patients are, what they’re feeling, and what they need. Some people just don’t like nature,” he said.
 

A version of this article appeared on Medscape.com.

What if a walk in a green environment could reshape brains, recalibrate sense of time, and stave off mental health conditions? If the research trends are true, you might soon find yourself writing prescriptions of 20 minutes of nature per day.

Evidence for the health benefits of exposure to green spaces, like parks, open spaces, gardens, outdoor gyms, and woodland trails, has been mostly interventional and observational, but that has not stopped global recognition that these exposures are important. 

In the wake of the pandemic, the British government allocated more than £5 million to pandemic recovery efforts that specifically involved green spaces. Since then, it has committed even more funding toward an expansive social prescribing program that connects patients to “link workers” who determine personal care needs and facilitate community and volunteer-based interventions. These can include group walking and volunteering to help out in community gardens or conservation efforts. Similar green programs can be found in Japan, where shinrin-yoku (forest bathing) was recently adopted as a national health strategy, and in the United States and Canada.

“Disconnection from nature is a major part of the health problems that we have on this planet,” said William Bird, a UK-based general practitioner, green prescriber, and CEO of Intelligent Health, which is geared toward building healthy, active, and connected communities. Dr. Bird received the prestigious Member of the Order of the British Empire (MBE) in 2010 for services related to physical activity and health. 

“Our brains are designed to connect to nature ... and we haven’t lost that instinct,” he explained. “Once we are with birdsong and water flowing and greenery, cortisol levels drop, our central vagus nerve improves, our fight and flight [response] disappears, and we start to be more receptive to other people.” 
 

Shifting Time Perception and Health

Ricardo A. Correia, PhD, a biologist and researcher at the University of Helsinki in Finland, said he believed that the mechanism for at least some of these outcomes might be differences in how time is perceived. In a perspective that appeared in March in People and Nature, Dr. Correia explored how the “services” that nature provides shift time perceptions and, in turn, regulate overall well-being. 

“I reached the realization that there was some evidence for the shift in some of the dimensions that we use to make sense of time in urban vs natural environments,” he told this news organization. 

Dr. Correia explained that human time perception facilitates understanding cause and effect, so we can act in a way that allows us to survive. 

“Time perception in humans is really complex and multifaceted,” he said. “The way that we make sense of time is not directly attached to any sensory organ, but rather goes through a range of cognitive, emotional, and bodily processes, all of which vary from person to person.” 

Dr. Correia pointed to evidence showing that time perception is shorter in urban environments and longer in natural ones. This, in turn, influences attention and attention restoration. “When we live in cities, we are exposed to similar sorts of demanding environments, increased time pressures, less time for oneself and for recreational purposes,” he said. “Ever-mounting pressure on daily demands plus processes we use to make sense of time, especially attention, means that we pay a cognitive toll.”

Dr. Correia posits that it might be possible to recalibrate time perception, but only by breaking the cycle of exposure. 

“If we are always exposed to fast-paced lifestyles, we become attuned to them and get caught up in an endless loop.” This cycle can be broken, Dr. Correia explained, by increasing exposure to natural environments. This leads to positive emotions, a sense of being in the present, and a heightened sense of mindfulness, all of which help mitigate the physical and mental health outcomes commonly associated with time scarcity. 
 

Brain-Mental Health Benefits

To date, there is quite a bit of research exploring the impacts of exposure to nature on the brain. For example, data have shown that adolescents raised exclusively in rural environments have a larger hippocampus and better spatial processing than children exclusively raised in cities. Other research demonstrated that spending just an hour in the forest led to a decline in amygdala activity in adults, whereas it remained stable after walking in an urban setting, underscoring the salutogenic effects on brain regions related to stress. There is also evidence from a 10-year longitudinal study of more than 2 million Welsh adults that highlights the value of proximity to green or blue (eg, lakes and rivers) spaces and common mental health conditions, with every additional 360 meters to the nearest green or blue space associated with 10% greater odds of anxiety and depression.

Dr. Bird said there has been a massive sea change in attitudes among general practitioners, who have come around to embracing the concept of nature as medicine. This shift among peers, who teased him in the 1990s about his green walking and conservation prescriptions, portends a bandwagon of epic proportions that could benefit patients. He said that he was especially hopeful that green prescriptions will become mainstream in certain conditions, especially those like depression and anxiety that are resistant to medication.

But Dr. Bird cautions that primary care professionals need to be mindful. “Patients need to know that it’s real science, otherwise they’ll think that they’re being pawned off or dismissed,” he said. “I try to put real evidence behind it and explain that there’s no contraindication. The main thing is to start where patients are, what they’re feeling, and what they need. Some people just don’t like nature,” he said.
 

A version of this article appeared on Medscape.com.

What if a walk in a green environment could reshape brains, recalibrate sense of time, and stave off mental health conditions? If the research trends are true, you might soon find yourself writing prescriptions of 20 minutes of nature per day.

Evidence for the health benefits of exposure to green spaces, like parks, open spaces, gardens, outdoor gyms, and woodland trails, has been mostly interventional and observational, but that has not stopped global recognition that these exposures are important. 

In the wake of the pandemic, the British government allocated more than £5 million to pandemic recovery efforts that specifically involved green spaces. Since then, it has committed even more funding toward an expansive social prescribing program that connects patients to “link workers” who determine personal care needs and facilitate community and volunteer-based interventions. These can include group walking and volunteering to help out in community gardens or conservation efforts. Similar green programs can be found in Japan, where shinrin-yoku (forest bathing) was recently adopted as a national health strategy, and in the United States and Canada.

“Disconnection from nature is a major part of the health problems that we have on this planet,” said William Bird, a UK-based general practitioner, green prescriber, and CEO of Intelligent Health, which is geared toward building healthy, active, and connected communities. Dr. Bird received the prestigious Member of the Order of the British Empire (MBE) in 2010 for services related to physical activity and health. 

“Our brains are designed to connect to nature ... and we haven’t lost that instinct,” he explained. “Once we are with birdsong and water flowing and greenery, cortisol levels drop, our central vagus nerve improves, our fight and flight [response] disappears, and we start to be more receptive to other people.” 
 

Shifting Time Perception and Health

Ricardo A. Correia, PhD, a biologist and researcher at the University of Helsinki in Finland, said he believed that the mechanism for at least some of these outcomes might be differences in how time is perceived. In a perspective that appeared in March in People and Nature, Dr. Correia explored how the “services” that nature provides shift time perceptions and, in turn, regulate overall well-being. 

“I reached the realization that there was some evidence for the shift in some of the dimensions that we use to make sense of time in urban vs natural environments,” he told this news organization. 

Dr. Correia explained that human time perception facilitates understanding cause and effect, so we can act in a way that allows us to survive. 

“Time perception in humans is really complex and multifaceted,” he said. “The way that we make sense of time is not directly attached to any sensory organ, but rather goes through a range of cognitive, emotional, and bodily processes, all of which vary from person to person.” 

Dr. Correia pointed to evidence showing that time perception is shorter in urban environments and longer in natural ones. This, in turn, influences attention and attention restoration. “When we live in cities, we are exposed to similar sorts of demanding environments, increased time pressures, less time for oneself and for recreational purposes,” he said. “Ever-mounting pressure on daily demands plus processes we use to make sense of time, especially attention, means that we pay a cognitive toll.”

Dr. Correia posits that it might be possible to recalibrate time perception, but only by breaking the cycle of exposure. 

“If we are always exposed to fast-paced lifestyles, we become attuned to them and get caught up in an endless loop.” This cycle can be broken, Dr. Correia explained, by increasing exposure to natural environments. This leads to positive emotions, a sense of being in the present, and a heightened sense of mindfulness, all of which help mitigate the physical and mental health outcomes commonly associated with time scarcity. 
 

Brain-Mental Health Benefits

To date, there is quite a bit of research exploring the impacts of exposure to nature on the brain. For example, data have shown that adolescents raised exclusively in rural environments have a larger hippocampus and better spatial processing than children exclusively raised in cities. Other research demonstrated that spending just an hour in the forest led to a decline in amygdala activity in adults, whereas it remained stable after walking in an urban setting, underscoring the salutogenic effects on brain regions related to stress. There is also evidence from a 10-year longitudinal study of more than 2 million Welsh adults that highlights the value of proximity to green or blue (eg, lakes and rivers) spaces and common mental health conditions, with every additional 360 meters to the nearest green or blue space associated with 10% greater odds of anxiety and depression.

Dr. Bird said there has been a massive sea change in attitudes among general practitioners, who have come around to embracing the concept of nature as medicine. This shift among peers, who teased him in the 1990s about his green walking and conservation prescriptions, portends a bandwagon of epic proportions that could benefit patients. He said that he was especially hopeful that green prescriptions will become mainstream in certain conditions, especially those like depression and anxiety that are resistant to medication.

But Dr. Bird cautions that primary care professionals need to be mindful. “Patients need to know that it’s real science, otherwise they’ll think that they’re being pawned off or dismissed,” he said. “I try to put real evidence behind it and explain that there’s no contraindication. The main thing is to start where patients are, what they’re feeling, and what they need. Some people just don’t like nature,” he said.
 

A version of this article appeared on Medscape.com.

Primary care physicians play a critical role in identifying patients at risk for serious mental health issues, including suicidality. But the ever-increasing demands on their clinical time can hinder the ability to identify emotional distress in time to intervene. Can artificial intelligence (AI) help?

This news organization spoke with Tom Zaubler, MD, a psychiatrist and chief medical officer of NeuroFlow, about how AI can improve the ability of primary care physicians and other clinicians to screen their patients for suicidal ideation and boost rates of treatment for mental health issues in their patients. This interview has been edited for clarity and length.

Question: How can AI help in suicide prevention and mental health screening in primary care?

Answer: Recent studies have demonstrated the potential of AI in mental health screening and suicide prevention. One method is natural language processing (NLP), which can analyze patients› journal entries for signs of suicidal thoughts or behaviors. This technology has shown promise in detecting suicidal ideation in patients who may not report such thoughts on traditional screening tools like the Patient Health Questionnaire-9 (PHQ-9). AI can be part of an integrated approach to identify and provide support to individuals at risk for suicide or those without a psychiatric history but who may still be at risk.

Q: A recent study by [Maria] Oquendo and colleagues found that one fifth of patients who attempt suicide do not meet the criteria for a mental health disorder.

Improved screening is obviously important, but in some ways it’s not the most important part of the problem. The lack of accessibility to specialized mental health care is a critical obstacle to treating patients with acute psychiatric needs.

How can primary care doctors effectively connect patients with mental health support, given the scarcity of mental health professionals?

A: Primary care doctors can leverage technology to extend mental health support. This includes using platforms for safety screening and providing patients with immediate access to local and national resources and digital interventions. Alerts can be sent to professionals within the practice or employed by technology companies to offer immediate support, including suicide safety planning and counseling. Users can hit a button to “Find a Therapist.” Also, if they acknowledge feelings of self-harm, these keywords are detected within the app by NLP. “Urgent alerts” are then sent to clinicians who are overseeing patient care. If someone is flagged, a social worker or member of a response services team intervenes and calls the person at risk to tailor care. These interventions do not always require a psychiatrist or masters-prepared clinician but can be effectively managed by trained paraprofessionals. These staff members can provide suicide safety planning and lethal-means-restriction counseling, and can assess the need for escalation of care.

Q: How is technology likely to manifest in physician practices in the near future to support mental health care?

A: Automated screening platforms for depression and anxiety, alerts for physicians when patients screen positively, and integration with collaborative care models are a few of the ways technology will become part of clinical practice. Additionally, advanced data analytics and predictive modeling using electronic health records and claims data will help identify high-risk patients. Technologies like voice recognition and machine learning can analyze patient journals and possibly, in the future, social media feeds to detect mental health issues. These technologies aim to extend and augment the capabilities of healthcare practices, improving the identification and management of patients at risk for mental health issues.

Q: Are these technologies as effective in pediatric populations, and are there any specific challenges?

A: Technologies for mental health screening and support are effective in pediatric populations, with certain age-specific considerations and legal restrictions on technology use. For adolescents and older children comfortable with technology, digital tools can significantly impact mental health care. For younger children, technology must facilitate information-gathering from various sources, including parents and teachers. Despite challenges, technology is crucial for early identification and intervention in pediatric mental health, potentially shortening the time to diagnosis and improving outcomes.

The statistics are horrifying. One third of adolescent girls have seriously thought about suicide over the past year; 13% attempt suicide. So there’s a need in the adolescent population and in the preadolescent population, too, because there’s an 8- to 10-year lag between onset of symptoms and diagnosis of mental illness. If we can shorten that lag, you see improved performance in schools; you see decreased truancy; you see greater economic achievement and so on. It makes such a profound difference. Not to mention it saves lives. So, yes, technology is critical in a pediatric population. It exists and it’s happening right now. There are challenges, but the goal can be met.

Q: A 2014 study found that 45% of people who completed suicide visited a primary care physician in the preceding month. And only 23% of people who attempt suicide have not seen a primary care physician within the past year. What does that say about the importance of screening at the primary care level?

A: The fact that a significant percentage of individuals who die by suicide have visited a primary care physician within a month or year prior to their death underscores the critical role of primary care in suicide prevention. This highlights the potential for primary care settings to identify and intervene with individuals at risk for suicide, making the case for the importance of integrating effective mental health screenings and support technologies in primary care practices.

Q: In other words, we’re not talking about a marginal benefit.

A: No, the potential benefit is huge. The United States Preventive Services Task Force did not endorse universal screening for suicide in its 2023 recommendations; they felt — and I accept that conclusion — there wasn›t enough evidence [at the time] to really support that recommendation. I think when you talk to a lot of suicide researchers, what you will hear is that providing suicide assessments as far upstream as possible is critical, especially when you start seeing more and more research showing that 20% of the population who die by suicide are not likely to have any psychiatric pathology at all. I believe the evidence base will soon support a recommendation for universal screening for adults. I believe it is especially important to screen for suicidal ideation in kids, given the high rates of suicide in this population.

Dr. Zaubler has disclosed the following relevant financial relationships: chief medical officer, NeuroFlow.

A version of this article appeared on Medscape.com.

Primary care physicians play a critical role in identifying patients at risk for serious mental health issues, including suicidality. But the ever-increasing demands on their clinical time can hinder the ability to identify emotional distress in time to intervene. Can artificial intelligence (AI) help?

This news organization spoke with Tom Zaubler, MD, a psychiatrist and chief medical officer of NeuroFlow, about how AI can improve the ability of primary care physicians and other clinicians to screen their patients for suicidal ideation and boost rates of treatment for mental health issues in their patients. This interview has been edited for clarity and length.

Question: How can AI help in suicide prevention and mental health screening in primary care?

Answer: Recent studies have demonstrated the potential of AI in mental health screening and suicide prevention. One method is natural language processing (NLP), which can analyze patients› journal entries for signs of suicidal thoughts or behaviors. This technology has shown promise in detecting suicidal ideation in patients who may not report such thoughts on traditional screening tools like the Patient Health Questionnaire-9 (PHQ-9). AI can be part of an integrated approach to identify and provide support to individuals at risk for suicide or those without a psychiatric history but who may still be at risk.

Q: A recent study by [Maria] Oquendo and colleagues found that one fifth of patients who attempt suicide do not meet the criteria for a mental health disorder.

Improved screening is obviously important, but in some ways it’s not the most important part of the problem. The lack of accessibility to specialized mental health care is a critical obstacle to treating patients with acute psychiatric needs.

How can primary care doctors effectively connect patients with mental health support, given the scarcity of mental health professionals?

A: Primary care doctors can leverage technology to extend mental health support. This includes using platforms for safety screening and providing patients with immediate access to local and national resources and digital interventions. Alerts can be sent to professionals within the practice or employed by technology companies to offer immediate support, including suicide safety planning and counseling. Users can hit a button to “Find a Therapist.” Also, if they acknowledge feelings of self-harm, these keywords are detected within the app by NLP. “Urgent alerts” are then sent to clinicians who are overseeing patient care. If someone is flagged, a social worker or member of a response services team intervenes and calls the person at risk to tailor care. These interventions do not always require a psychiatrist or masters-prepared clinician but can be effectively managed by trained paraprofessionals. These staff members can provide suicide safety planning and lethal-means-restriction counseling, and can assess the need for escalation of care.

Q: How is technology likely to manifest in physician practices in the near future to support mental health care?

A: Automated screening platforms for depression and anxiety, alerts for physicians when patients screen positively, and integration with collaborative care models are a few of the ways technology will become part of clinical practice. Additionally, advanced data analytics and predictive modeling using electronic health records and claims data will help identify high-risk patients. Technologies like voice recognition and machine learning can analyze patient journals and possibly, in the future, social media feeds to detect mental health issues. These technologies aim to extend and augment the capabilities of healthcare practices, improving the identification and management of patients at risk for mental health issues.

Q: Are these technologies as effective in pediatric populations, and are there any specific challenges?

A: Technologies for mental health screening and support are effective in pediatric populations, with certain age-specific considerations and legal restrictions on technology use. For adolescents and older children comfortable with technology, digital tools can significantly impact mental health care. For younger children, technology must facilitate information-gathering from various sources, including parents and teachers. Despite challenges, technology is crucial for early identification and intervention in pediatric mental health, potentially shortening the time to diagnosis and improving outcomes.

The statistics are horrifying. One third of adolescent girls have seriously thought about suicide over the past year; 13% attempt suicide. So there’s a need in the adolescent population and in the preadolescent population, too, because there’s an 8- to 10-year lag between onset of symptoms and diagnosis of mental illness. If we can shorten that lag, you see improved performance in schools; you see decreased truancy; you see greater economic achievement and so on. It makes such a profound difference. Not to mention it saves lives. So, yes, technology is critical in a pediatric population. It exists and it’s happening right now. There are challenges, but the goal can be met.

Q: A 2014 study found that 45% of people who completed suicide visited a primary care physician in the preceding month. And only 23% of people who attempt suicide have not seen a primary care physician within the past year. What does that say about the importance of screening at the primary care level?

A: The fact that a significant percentage of individuals who die by suicide have visited a primary care physician within a month or year prior to their death underscores the critical role of primary care in suicide prevention. This highlights the potential for primary care settings to identify and intervene with individuals at risk for suicide, making the case for the importance of integrating effective mental health screenings and support technologies in primary care practices.

Q: In other words, we’re not talking about a marginal benefit.

A: No, the potential benefit is huge. The United States Preventive Services Task Force did not endorse universal screening for suicide in its 2023 recommendations; they felt — and I accept that conclusion — there wasn›t enough evidence [at the time] to really support that recommendation. I think when you talk to a lot of suicide researchers, what you will hear is that providing suicide assessments as far upstream as possible is critical, especially when you start seeing more and more research showing that 20% of the population who die by suicide are not likely to have any psychiatric pathology at all. I believe the evidence base will soon support a recommendation for universal screening for adults. I believe it is especially important to screen for suicidal ideation in kids, given the high rates of suicide in this population.

Dr. Zaubler has disclosed the following relevant financial relationships: chief medical officer, NeuroFlow.

A version of this article appeared on Medscape.com.

Primary care physicians play a critical role in identifying patients at risk for serious mental health issues, including suicidality. But the ever-increasing demands on their clinical time can hinder the ability to identify emotional distress in time to intervene. Can artificial intelligence (AI) help?

This news organization spoke with Tom Zaubler, MD, a psychiatrist and chief medical officer of NeuroFlow, about how AI can improve the ability of primary care physicians and other clinicians to screen their patients for suicidal ideation and boost rates of treatment for mental health issues in their patients. This interview has been edited for clarity and length.

Question: How can AI help in suicide prevention and mental health screening in primary care?

Answer: Recent studies have demonstrated the potential of AI in mental health screening and suicide prevention. One method is natural language processing (NLP), which can analyze patients› journal entries for signs of suicidal thoughts or behaviors. This technology has shown promise in detecting suicidal ideation in patients who may not report such thoughts on traditional screening tools like the Patient Health Questionnaire-9 (PHQ-9). AI can be part of an integrated approach to identify and provide support to individuals at risk for suicide or those without a psychiatric history but who may still be at risk.

Q: A recent study by [Maria] Oquendo and colleagues found that one fifth of patients who attempt suicide do not meet the criteria for a mental health disorder.

Improved screening is obviously important, but in some ways it’s not the most important part of the problem. The lack of accessibility to specialized mental health care is a critical obstacle to treating patients with acute psychiatric needs.

How can primary care doctors effectively connect patients with mental health support, given the scarcity of mental health professionals?

A: Primary care doctors can leverage technology to extend mental health support. This includes using platforms for safety screening and providing patients with immediate access to local and national resources and digital interventions. Alerts can be sent to professionals within the practice or employed by technology companies to offer immediate support, including suicide safety planning and counseling. Users can hit a button to “Find a Therapist.” Also, if they acknowledge feelings of self-harm, these keywords are detected within the app by NLP. “Urgent alerts” are then sent to clinicians who are overseeing patient care. If someone is flagged, a social worker or member of a response services team intervenes and calls the person at risk to tailor care. These interventions do not always require a psychiatrist or masters-prepared clinician but can be effectively managed by trained paraprofessionals. These staff members can provide suicide safety planning and lethal-means-restriction counseling, and can assess the need for escalation of care.

Q: How is technology likely to manifest in physician practices in the near future to support mental health care?

A: Automated screening platforms for depression and anxiety, alerts for physicians when patients screen positively, and integration with collaborative care models are a few of the ways technology will become part of clinical practice. Additionally, advanced data analytics and predictive modeling using electronic health records and claims data will help identify high-risk patients. Technologies like voice recognition and machine learning can analyze patient journals and possibly, in the future, social media feeds to detect mental health issues. These technologies aim to extend and augment the capabilities of healthcare practices, improving the identification and management of patients at risk for mental health issues.

Q: Are these technologies as effective in pediatric populations, and are there any specific challenges?

A: Technologies for mental health screening and support are effective in pediatric populations, with certain age-specific considerations and legal restrictions on technology use. For adolescents and older children comfortable with technology, digital tools can significantly impact mental health care. For younger children, technology must facilitate information-gathering from various sources, including parents and teachers. Despite challenges, technology is crucial for early identification and intervention in pediatric mental health, potentially shortening the time to diagnosis and improving outcomes.

The statistics are horrifying. One third of adolescent girls have seriously thought about suicide over the past year; 13% attempt suicide. So there’s a need in the adolescent population and in the preadolescent population, too, because there’s an 8- to 10-year lag between onset of symptoms and diagnosis of mental illness. If we can shorten that lag, you see improved performance in schools; you see decreased truancy; you see greater economic achievement and so on. It makes such a profound difference. Not to mention it saves lives. So, yes, technology is critical in a pediatric population. It exists and it’s happening right now. There are challenges, but the goal can be met.

Q: A 2014 study found that 45% of people who completed suicide visited a primary care physician in the preceding month. And only 23% of people who attempt suicide have not seen a primary care physician within the past year. What does that say about the importance of screening at the primary care level?

A: The fact that a significant percentage of individuals who die by suicide have visited a primary care physician within a month or year prior to their death underscores the critical role of primary care in suicide prevention. This highlights the potential for primary care settings to identify and intervene with individuals at risk for suicide, making the case for the importance of integrating effective mental health screenings and support technologies in primary care practices.

Q: In other words, we’re not talking about a marginal benefit.

A: No, the potential benefit is huge. The United States Preventive Services Task Force did not endorse universal screening for suicide in its 2023 recommendations; they felt — and I accept that conclusion — there wasn›t enough evidence [at the time] to really support that recommendation. I think when you talk to a lot of suicide researchers, what you will hear is that providing suicide assessments as far upstream as possible is critical, especially when you start seeing more and more research showing that 20% of the population who die by suicide are not likely to have any psychiatric pathology at all. I believe the evidence base will soon support a recommendation for universal screening for adults. I believe it is especially important to screen for suicidal ideation in kids, given the high rates of suicide in this population.

Dr. Zaubler has disclosed the following relevant financial relationships: chief medical officer, NeuroFlow.

A version of this article appeared on Medscape.com.

Adverse childhood experiences (ACEs) are associated with a significantly increased risk for adult depressive, anxiety, and stress-related disorders, new data from a large registry study of twins showed.

Researchers found that each additional adverse event placed children at a 52% greater risk for a psychiatric disorder as an adult, with sexual abuse associated with the greatest risk.

The findings showed that the association held even after controlling for shared genetic and environmental factors.

The results suggested that “interventions targeting ACEs, including primary prevention and enhanced access to evidence-based trauma therapies to individuals who experienced ACEs, may be associated with reduced risk of future psychopathology,” the investigators, with first author Hilda Björk Daníelsdóttir, MSc, of the University of Iceland, Reykjavik, Iceland, wrote.

The findings were published online on March 6 in JAMA Psychiatry.
 

Dose-Dependent Effect

Previous research has shown a robust link between childhood abuse and an increased risk for psychiatric disorders in adulthood, but evidence of this association in studies that adjust for familial confounding is “completely lacking,” the investigators wrote.

To learn more about how genetic factors may affect the relationship between ACEs and later psychiatric diagnoses, the investigators used data from the nationwide Swedish Twin Registry, which includes data on more than 25,000 identical and nonidentical twins.

The twin registry is linked to the Swedish National Patient Registry, which includes information on inpatient or outpatient psychiatric diagnoses after age 19.

The twins responded to a large web-based questionnaire about past-week depressive symptoms as a measure of current mental health and distinct types of ACEs including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime.

Three birth cohorts from the twin registry were surveyed between 2005 and 2016 and followed up in the national registry from age 19 until the end of 2016.

Among the sample of 25,000 twin pairs (15,000 female; mean age at assessment, 29 years), 9750 (39%) participants reported exposure to at least one ACE, while 2000 (8%) reported exposure to three or more ACEs. Most respondents — 61% — reported no ACE exposure.

More than 2300 participants received a psychiatric diagnosis as an adult. The incidence of any psychiatric disorder increased from 503 individuals (6.4%) among participants without any ACEs to 993 individuals (24.6%) among those reporting three or more.

At the cohort level, a greater number of ACEs was associated with increased odds of any psychiatric disorder in a dose-dependent manner, the investigators noted (odds ratio [OR], 1.52; 95% CI, 1.48-1.57).
 

Untangling Genes and Environment

To determine how much of the increased risk for adult mental illness is due to ACEs and how much can be attributed to genetics and environment, the researchers focused on twin pairs where one had exposure to one type of ACEs and the other did not. This analysis revealed that the association remained but was attenuated. In identical twins, the effect of each ACE raised the odds of having a psychiatric condition by 20% (1.20; 95% CI, 1.02-1.40), and for nonidentical twins, the odds increased by 29% (1.29; 95% CI, 1.14-1.47).

The weakening of the risk “suggests that familial confounding contributed to the association between ACEs and adult mental health outcomes,” the authors wrote.

Of all the ACEs, sexual abuse carried the highest risk for adult psychiatric disorders. Children who were exposed to sexual abuse, compared with those who were not, had up to a 200% higher risk for any psychiatric disorder in the following comparisons: Full cohort (OR, 3.09; 95% CI, 2.68-3.56), dizygotic twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and monozygotic twin pairs (1.80; 95% CI, 1.04-3.11).

“Our results demonstrated that familial factors contributed to a lesser extent to the association between sexual abuse and adult psychiatric disorders,” the authors wrote.

One major limitation of the study was that ACEs were based on retrospective report and thus may be subject to recall bias. Also, the findings cannot be generalized to other countries or cultures.

The study was funded by the European Research Council, the Icelandic Center for Research, and the European Union Horizon 2020. Disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

Adverse childhood experiences (ACEs) are associated with a significantly increased risk for adult depressive, anxiety, and stress-related disorders, new data from a large registry study of twins showed.

Researchers found that each additional adverse event placed children at a 52% greater risk for a psychiatric disorder as an adult, with sexual abuse associated with the greatest risk.

The findings showed that the association held even after controlling for shared genetic and environmental factors.

The results suggested that “interventions targeting ACEs, including primary prevention and enhanced access to evidence-based trauma therapies to individuals who experienced ACEs, may be associated with reduced risk of future psychopathology,” the investigators, with first author Hilda Björk Daníelsdóttir, MSc, of the University of Iceland, Reykjavik, Iceland, wrote.

The findings were published online on March 6 in JAMA Psychiatry.
 

Dose-Dependent Effect

Previous research has shown a robust link between childhood abuse and an increased risk for psychiatric disorders in adulthood, but evidence of this association in studies that adjust for familial confounding is “completely lacking,” the investigators wrote.

To learn more about how genetic factors may affect the relationship between ACEs and later psychiatric diagnoses, the investigators used data from the nationwide Swedish Twin Registry, which includes data on more than 25,000 identical and nonidentical twins.

The twin registry is linked to the Swedish National Patient Registry, which includes information on inpatient or outpatient psychiatric diagnoses after age 19.

The twins responded to a large web-based questionnaire about past-week depressive symptoms as a measure of current mental health and distinct types of ACEs including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime.

Three birth cohorts from the twin registry were surveyed between 2005 and 2016 and followed up in the national registry from age 19 until the end of 2016.

Among the sample of 25,000 twin pairs (15,000 female; mean age at assessment, 29 years), 9750 (39%) participants reported exposure to at least one ACE, while 2000 (8%) reported exposure to three or more ACEs. Most respondents — 61% — reported no ACE exposure.

More than 2300 participants received a psychiatric diagnosis as an adult. The incidence of any psychiatric disorder increased from 503 individuals (6.4%) among participants without any ACEs to 993 individuals (24.6%) among those reporting three or more.

At the cohort level, a greater number of ACEs was associated with increased odds of any psychiatric disorder in a dose-dependent manner, the investigators noted (odds ratio [OR], 1.52; 95% CI, 1.48-1.57).
 

Untangling Genes and Environment

To determine how much of the increased risk for adult mental illness is due to ACEs and how much can be attributed to genetics and environment, the researchers focused on twin pairs where one had exposure to one type of ACEs and the other did not. This analysis revealed that the association remained but was attenuated. In identical twins, the effect of each ACE raised the odds of having a psychiatric condition by 20% (1.20; 95% CI, 1.02-1.40), and for nonidentical twins, the odds increased by 29% (1.29; 95% CI, 1.14-1.47).

The weakening of the risk “suggests that familial confounding contributed to the association between ACEs and adult mental health outcomes,” the authors wrote.

Of all the ACEs, sexual abuse carried the highest risk for adult psychiatric disorders. Children who were exposed to sexual abuse, compared with those who were not, had up to a 200% higher risk for any psychiatric disorder in the following comparisons: Full cohort (OR, 3.09; 95% CI, 2.68-3.56), dizygotic twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and monozygotic twin pairs (1.80; 95% CI, 1.04-3.11).

“Our results demonstrated that familial factors contributed to a lesser extent to the association between sexual abuse and adult psychiatric disorders,” the authors wrote.

One major limitation of the study was that ACEs were based on retrospective report and thus may be subject to recall bias. Also, the findings cannot be generalized to other countries or cultures.

The study was funded by the European Research Council, the Icelandic Center for Research, and the European Union Horizon 2020. Disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

Adverse childhood experiences (ACEs) are associated with a significantly increased risk for adult depressive, anxiety, and stress-related disorders, new data from a large registry study of twins showed.

Researchers found that each additional adverse event placed children at a 52% greater risk for a psychiatric disorder as an adult, with sexual abuse associated with the greatest risk.

The findings showed that the association held even after controlling for shared genetic and environmental factors.

The results suggested that “interventions targeting ACEs, including primary prevention and enhanced access to evidence-based trauma therapies to individuals who experienced ACEs, may be associated with reduced risk of future psychopathology,” the investigators, with first author Hilda Björk Daníelsdóttir, MSc, of the University of Iceland, Reykjavik, Iceland, wrote.

The findings were published online on March 6 in JAMA Psychiatry.
 

Dose-Dependent Effect

Previous research has shown a robust link between childhood abuse and an increased risk for psychiatric disorders in adulthood, but evidence of this association in studies that adjust for familial confounding is “completely lacking,” the investigators wrote.

To learn more about how genetic factors may affect the relationship between ACEs and later psychiatric diagnoses, the investigators used data from the nationwide Swedish Twin Registry, which includes data on more than 25,000 identical and nonidentical twins.

The twin registry is linked to the Swedish National Patient Registry, which includes information on inpatient or outpatient psychiatric diagnoses after age 19.

The twins responded to a large web-based questionnaire about past-week depressive symptoms as a measure of current mental health and distinct types of ACEs including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime.

Three birth cohorts from the twin registry were surveyed between 2005 and 2016 and followed up in the national registry from age 19 until the end of 2016.

Among the sample of 25,000 twin pairs (15,000 female; mean age at assessment, 29 years), 9750 (39%) participants reported exposure to at least one ACE, while 2000 (8%) reported exposure to three or more ACEs. Most respondents — 61% — reported no ACE exposure.

More than 2300 participants received a psychiatric diagnosis as an adult. The incidence of any psychiatric disorder increased from 503 individuals (6.4%) among participants without any ACEs to 993 individuals (24.6%) among those reporting three or more.

At the cohort level, a greater number of ACEs was associated with increased odds of any psychiatric disorder in a dose-dependent manner, the investigators noted (odds ratio [OR], 1.52; 95% CI, 1.48-1.57).
 

Untangling Genes and Environment

To determine how much of the increased risk for adult mental illness is due to ACEs and how much can be attributed to genetics and environment, the researchers focused on twin pairs where one had exposure to one type of ACEs and the other did not. This analysis revealed that the association remained but was attenuated. In identical twins, the effect of each ACE raised the odds of having a psychiatric condition by 20% (1.20; 95% CI, 1.02-1.40), and for nonidentical twins, the odds increased by 29% (1.29; 95% CI, 1.14-1.47).

The weakening of the risk “suggests that familial confounding contributed to the association between ACEs and adult mental health outcomes,” the authors wrote.

Of all the ACEs, sexual abuse carried the highest risk for adult psychiatric disorders. Children who were exposed to sexual abuse, compared with those who were not, had up to a 200% higher risk for any psychiatric disorder in the following comparisons: Full cohort (OR, 3.09; 95% CI, 2.68-3.56), dizygotic twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and monozygotic twin pairs (1.80; 95% CI, 1.04-3.11).

“Our results demonstrated that familial factors contributed to a lesser extent to the association between sexual abuse and adult psychiatric disorders,” the authors wrote.

One major limitation of the study was that ACEs were based on retrospective report and thus may be subject to recall bias. Also, the findings cannot be generalized to other countries or cultures.

The study was funded by the European Research Council, the Icelandic Center for Research, and the European Union Horizon 2020. Disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Scents that trigger specific, vivid autobiographical memories (AMs) could improve deficits in memory recall in patients with major depressive disorder (MDD), new research suggests. Investigators found that odor cues may be a stronger tool than word cues for improving memory, which could help reduce MDD symptoms.

METHODOLOGY:

• Participants included 32 individuals aged 18-55 years (mean age, 30 years; 26 females) with a diagnosis of MDD recruited from the community.
• Those with psychosis, bipolar I or II, neurological disorders, or drug or alcohol abuse were excluded.
• Participants were presented with a series of 12 words and 12 odors, such as cough syrup, tobacco ash, and Vicks VapoRub, and asked to recall a specific memory in response to each cue.
• AMs were rated in terms of vividness, frequency, and whether they were associated with positive or negative emotions.

TAKEAWAY:

• Although participants only guessed correct stimulus odors 30% of the time, they recalled more specific memories from odor cues than from word cues (68% vs 52%; P < .001).
• Odor-cued recall was more arousing and vivid (P < .001) than recall responses generated by word cues.
• Compared with the population mean for responses to word cues in healthy controls, study participants recalled fewer specific memories in response to words (P < .001), but the percentage of specific memories recalled in response to odor cues did not differ from the healthy control population mean.
• Investigators hoped to further their research by investigating the mechanisms underlying odor-cued AMs, particularly to test if the amygdala and hippocampus are activated during recall.

IN PRACTICE:

“This study suggests the potential for increasing autobiographical memory specificity in individuals with MDD, with the future goal of reducing depression symptoms for this population and informing a better understanding of the neural mechanisms influencing odor-based AM recall,” the authors wrote. “We hope this initial study spurs larger studies in more diverse samples that include healthy control participants to further investigate and explain these associations.”

SOURCE:

Kymberly D. Young, PhD, of the University of Pittsburgh, Pennsylvania, led the study, which was published online on February 13, 2024, in JAMA Network Open. 

LIMITATIONS:

Study limitations included the lack of a healthy control group and the small sample size. 

DISCLOSURES:

The study was funded internally by the University of Pittsburgh School of Medicine, Pennsylvania. No disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Scents that trigger specific, vivid autobiographical memories (AMs) could improve deficits in memory recall in patients with major depressive disorder (MDD), new research suggests. Investigators found that odor cues may be a stronger tool than word cues for improving memory, which could help reduce MDD symptoms.

METHODOLOGY:

• Participants included 32 individuals aged 18-55 years (mean age, 30 years; 26 females) with a diagnosis of MDD recruited from the community.
• Those with psychosis, bipolar I or II, neurological disorders, or drug or alcohol abuse were excluded.
• Participants were presented with a series of 12 words and 12 odors, such as cough syrup, tobacco ash, and Vicks VapoRub, and asked to recall a specific memory in response to each cue.
• AMs were rated in terms of vividness, frequency, and whether they were associated with positive or negative emotions.

TAKEAWAY:

• Although participants only guessed correct stimulus odors 30% of the time, they recalled more specific memories from odor cues than from word cues (68% vs 52%; P < .001).
• Odor-cued recall was more arousing and vivid (P < .001) than recall responses generated by word cues.
• Compared with the population mean for responses to word cues in healthy controls, study participants recalled fewer specific memories in response to words (P < .001), but the percentage of specific memories recalled in response to odor cues did not differ from the healthy control population mean.
• Investigators hoped to further their research by investigating the mechanisms underlying odor-cued AMs, particularly to test if the amygdala and hippocampus are activated during recall.

IN PRACTICE:

“This study suggests the potential for increasing autobiographical memory specificity in individuals with MDD, with the future goal of reducing depression symptoms for this population and informing a better understanding of the neural mechanisms influencing odor-based AM recall,” the authors wrote. “We hope this initial study spurs larger studies in more diverse samples that include healthy control participants to further investigate and explain these associations.”

SOURCE:

Kymberly D. Young, PhD, of the University of Pittsburgh, Pennsylvania, led the study, which was published online on February 13, 2024, in JAMA Network Open. 

LIMITATIONS:

Study limitations included the lack of a healthy control group and the small sample size. 

DISCLOSURES:

The study was funded internally by the University of Pittsburgh School of Medicine, Pennsylvania. No disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Scents that trigger specific, vivid autobiographical memories (AMs) could improve deficits in memory recall in patients with major depressive disorder (MDD), new research suggests. Investigators found that odor cues may be a stronger tool than word cues for improving memory, which could help reduce MDD symptoms.

METHODOLOGY:

• Participants included 32 individuals aged 18-55 years (mean age, 30 years; 26 females) with a diagnosis of MDD recruited from the community.
• Those with psychosis, bipolar I or II, neurological disorders, or drug or alcohol abuse were excluded.
• Participants were presented with a series of 12 words and 12 odors, such as cough syrup, tobacco ash, and Vicks VapoRub, and asked to recall a specific memory in response to each cue.
• AMs were rated in terms of vividness, frequency, and whether they were associated with positive or negative emotions.

TAKEAWAY:

• Although participants only guessed correct stimulus odors 30% of the time, they recalled more specific memories from odor cues than from word cues (68% vs 52%; P < .001).
• Odor-cued recall was more arousing and vivid (P < .001) than recall responses generated by word cues.
• Compared with the population mean for responses to word cues in healthy controls, study participants recalled fewer specific memories in response to words (P < .001), but the percentage of specific memories recalled in response to odor cues did not differ from the healthy control population mean.
• Investigators hoped to further their research by investigating the mechanisms underlying odor-cued AMs, particularly to test if the amygdala and hippocampus are activated during recall.

IN PRACTICE:

“This study suggests the potential for increasing autobiographical memory specificity in individuals with MDD, with the future goal of reducing depression symptoms for this population and informing a better understanding of the neural mechanisms influencing odor-based AM recall,” the authors wrote. “We hope this initial study spurs larger studies in more diverse samples that include healthy control participants to further investigate and explain these associations.”

SOURCE:

Kymberly D. Young, PhD, of the University of Pittsburgh, Pennsylvania, led the study, which was published online on February 13, 2024, in JAMA Network Open. 

LIMITATIONS:

Study limitations included the lack of a healthy control group and the small sample size. 

DISCLOSURES:

The study was funded internally by the University of Pittsburgh School of Medicine, Pennsylvania. No disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

A single dose of psilocybin administered in a group setting with one-on-one psychological support was associated with a significant and lasting reduction in depression severity among adults with cancer and major depressive disorder, a small study shows.

METHODOLOGY:

• Depression remains common in patients with cancer, and common treatment approaches — antidepressants and psychotherapy — have demonstrated limited success.
• Researchers explored the safety, feasibility, and efficacy of psilocybin-assisted group therapy in 30 patients with major depressive disorder and cancer — about half with earlier-stage disease and half with metastatic disease.
• In this single-center, open-label, phase 2 study, participants received one-on-one and group therapy sessions before, during, and after receiving a single 25-mg psilocybin dose.
• Alongside individual therapy sessions, each cohort of three to four participants received group sessions guided by a therapist who provided educational material and worked to foster trust among participants.

TAKEAWAY:

• Participants experienced a significant reduction in depression severity, demonstrating a 19.1-point reduction in Montgomery-Asberg Depression Rating Scale scores from baseline to follow-up at week 8.
• Overall, 80% of patients showed a lasting response to psilocybin treatment and 50% showed full remission of depressive symptoms by week 1, which persisted for at least 8 weeks.
• The approach was effective for patients with curable and noncurable cancer — with almost 80% in the curable group and 62% in the noncurable group showing clinically meaningful declines in depressive symptoms. The researchers also noted improvements in patients’ anxiety, pain, demoralization, disability, and spiritual well-being.
• No suicidality or other serious treatment-related adverse events occurred; treatment-related nausea and headache were generally mild and expected.

IN PRACTICE:

“Beyond tolerability, psilocybin therapy led to clinically meaningful reductions in depressive symptoms,” the authors concluded. “To our knowledge, this is the first study to show the feasibility of a group-therapy approach for psilocybin‐assisted treatment in patients with cancer. This innovative framework offers increased scalability and dissemination of psilocybin treatment in real‐world settings.”

Among the 28 participants available for exit interviews, the authors reported that, overall, “participants described that the group/simultaneous model fostered a sense of connectedness, meaning, and transcendence through the shared psilocybin experience and group integration.”

SOURCE:

The study, led by Manish Agrawal, MD, Sunstone Therapies, Rockville, Maryland, was published online on December 21, 2023, in Cancer, along with an editorial and related article on patient acceptability of psilocybin-assisted group therapy.

LIMITATIONS:

The study lacked a control group, and the sample size was small and lacked diversity. The study was also not powered to statistically adjust efficacy measures on a possible group effect.

DISCLOSURES:

The study was funded in part by Compass Pathways. Some authors reported various relationships with Compass Pathways and Sunstone Therapies.

A version of this article appeared on Medscape.com.

TOPLINE:

A single dose of psilocybin administered in a group setting with one-on-one psychological support was associated with a significant and lasting reduction in depression severity among adults with cancer and major depressive disorder, a small study shows.

METHODOLOGY:

• Depression remains common in patients with cancer, and common treatment approaches — antidepressants and psychotherapy — have demonstrated limited success.
• Researchers explored the safety, feasibility, and efficacy of psilocybin-assisted group therapy in 30 patients with major depressive disorder and cancer — about half with earlier-stage disease and half with metastatic disease.
• In this single-center, open-label, phase 2 study, participants received one-on-one and group therapy sessions before, during, and after receiving a single 25-mg psilocybin dose.
• Alongside individual therapy sessions, each cohort of three to four participants received group sessions guided by a therapist who provided educational material and worked to foster trust among participants.

TAKEAWAY:

• Participants experienced a significant reduction in depression severity, demonstrating a 19.1-point reduction in Montgomery-Asberg Depression Rating Scale scores from baseline to follow-up at week 8.
• Overall, 80% of patients showed a lasting response to psilocybin treatment and 50% showed full remission of depressive symptoms by week 1, which persisted for at least 8 weeks.
• The approach was effective for patients with curable and noncurable cancer — with almost 80% in the curable group and 62% in the noncurable group showing clinically meaningful declines in depressive symptoms. The researchers also noted improvements in patients’ anxiety, pain, demoralization, disability, and spiritual well-being.
• No suicidality or other serious treatment-related adverse events occurred; treatment-related nausea and headache were generally mild and expected.

IN PRACTICE:

“Beyond tolerability, psilocybin therapy led to clinically meaningful reductions in depressive symptoms,” the authors concluded. “To our knowledge, this is the first study to show the feasibility of a group-therapy approach for psilocybin‐assisted treatment in patients with cancer. This innovative framework offers increased scalability and dissemination of psilocybin treatment in real‐world settings.”

Among the 28 participants available for exit interviews, the authors reported that, overall, “participants described that the group/simultaneous model fostered a sense of connectedness, meaning, and transcendence through the shared psilocybin experience and group integration.”

SOURCE:

The study, led by Manish Agrawal, MD, Sunstone Therapies, Rockville, Maryland, was published online on December 21, 2023, in Cancer, along with an editorial and related article on patient acceptability of psilocybin-assisted group therapy.

LIMITATIONS:

The study lacked a control group, and the sample size was small and lacked diversity. The study was also not powered to statistically adjust efficacy measures on a possible group effect.

DISCLOSURES:

The study was funded in part by Compass Pathways. Some authors reported various relationships with Compass Pathways and Sunstone Therapies.

A version of this article appeared on Medscape.com.

TOPLINE:

A single dose of psilocybin administered in a group setting with one-on-one psychological support was associated with a significant and lasting reduction in depression severity among adults with cancer and major depressive disorder, a small study shows.

METHODOLOGY:

• Depression remains common in patients with cancer, and common treatment approaches — antidepressants and psychotherapy — have demonstrated limited success.
• Researchers explored the safety, feasibility, and efficacy of psilocybin-assisted group therapy in 30 patients with major depressive disorder and cancer — about half with earlier-stage disease and half with metastatic disease.
• In this single-center, open-label, phase 2 study, participants received one-on-one and group therapy sessions before, during, and after receiving a single 25-mg psilocybin dose.
• Alongside individual therapy sessions, each cohort of three to four participants received group sessions guided by a therapist who provided educational material and worked to foster trust among participants.

TAKEAWAY:

• Participants experienced a significant reduction in depression severity, demonstrating a 19.1-point reduction in Montgomery-Asberg Depression Rating Scale scores from baseline to follow-up at week 8.
• Overall, 80% of patients showed a lasting response to psilocybin treatment and 50% showed full remission of depressive symptoms by week 1, which persisted for at least 8 weeks.
• The approach was effective for patients with curable and noncurable cancer — with almost 80% in the curable group and 62% in the noncurable group showing clinically meaningful declines in depressive symptoms. The researchers also noted improvements in patients’ anxiety, pain, demoralization, disability, and spiritual well-being.
• No suicidality or other serious treatment-related adverse events occurred; treatment-related nausea and headache were generally mild and expected.

IN PRACTICE:

“Beyond tolerability, psilocybin therapy led to clinically meaningful reductions in depressive symptoms,” the authors concluded. “To our knowledge, this is the first study to show the feasibility of a group-therapy approach for psilocybin‐assisted treatment in patients with cancer. This innovative framework offers increased scalability and dissemination of psilocybin treatment in real‐world settings.”

Among the 28 participants available for exit interviews, the authors reported that, overall, “participants described that the group/simultaneous model fostered a sense of connectedness, meaning, and transcendence through the shared psilocybin experience and group integration.”

SOURCE:

The study, led by Manish Agrawal, MD, Sunstone Therapies, Rockville, Maryland, was published online on December 21, 2023, in Cancer, along with an editorial and related article on patient acceptability of psilocybin-assisted group therapy.

LIMITATIONS:

The study lacked a control group, and the sample size was small and lacked diversity. The study was also not powered to statistically adjust efficacy measures on a possible group effect.

DISCLOSURES:

The study was funded in part by Compass Pathways. Some authors reported various relationships with Compass Pathways and Sunstone Therapies.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Stephen M. Strakowski, MD: Hello. Thank you all for joining us today. I’m very excited to have some great guests to talk about what I consider an active controversy. I’m Stephen M. Strakowski. I’m a professor and vice chair of psychiatry at Indiana University, and professor and associate vice president at University of Texas in Austin.

Today we’re going to talk about cannabis. As all of you are aware, everyone’s talking about cannabis. We hear constantly on social media and in interviews, particularly with relevance to psychiatric disorders, that everyone should be thinking about using cannabis. That seems to be the common conversation.

Last week, I had a patient who said, “All my friends tell me I need to be on cannabis.” That was their solution to her problems. With that in mind, let me introduce our guests, who are both experts on this, to talk about the role of cannabis in psychiatric disorders today.

First, I want to welcome Dr. Leslie Hulvershorn. Dr. Hulvershorn is an associate professor and chair at Indiana University in Indianapolis. Dr. Christopher Hammond is an assistant professor and the director of the co-occurring disorders program at Johns Hopkins. Welcome!

Leslie A. Hulvershorn, MD, MSc: Thank you.

Christopher J. Hammond, MD, PhD: Thank you.

Dr. Strakowski: Leslie, as I mentioned, many people are talking about how cannabis could be a good treatment for psychiatric disorders. Is that true?

Dr. Hulvershorn: If you look at what defines a good treatment, what you’re looking for is clinical trials, ideally randomized, placebo-controlled clinical trials.

When we look at research related to cannabis, we see very few of those trials, and we see that the cannabis plant is actually quite complicated and there are many different compounds that come from it. So we need to look at all the different compounds.

If you think about THC, delta 9 or delta 8, depending on the version, that’s the active ingredient that we most often think about when we say “cannabis.” If you look at THC studies, there really is no evidence that I could find that it helps psychiatric disorders.

What we do find is an enormous literature, many hunDr.eds of studies, actually, that show that THC actually worsens or even brings on psychiatric disorders. There’s a separate conversation about other compounds within the cannabis plant, like CBD, cannabidiol, where there’s maybe a signal that certain anxiety disorders might be improved by a compound like that.

Certainly, rare forms of epilepsy have been found to be improved with that compound. It really depends on what you’re looking at within the cannabis plant, but if we’re thinking about THC, the answer really is no, this is not a helpful thing. In fact, it’s probably a harmful thing to be ingesting in terms of psychiatric disorders.

Dr. Strakowski: Thank you, Leslie. Chris, what would you add to that? Do we know anything about the use of cannabis in any psychiatric condition?

Dr. Hammond: I definitely would echo what Leslie said. The popular opinion, that the media and the state legislatures have really, in many ways, put the cart before the horse — they speak about cannabis as a medication for the treatment of psychiatric conditions before we have sufficient evidence to say that it’s safe or effective for these conditions. Most of the evidence that we have, particularly in regard to the cannabinoid compound, delta 9, tetrahyDr.ocannabinol, or THC, suggests that that cannabinoid is associated with adverse mental health outcomes across different categories.

Dr. Strakowski: Our group, a long time ago, conducted a study looking at first episode of mania, and found that regular cannabis use increases the risk for subsequent manic episodes. I’m not aware of many other studies like that.

You referred, Chris, to the safety aspect. If you look at social media, the press, and the conversations where cannabis is talked about, there’s no risk, right? This is something anybody can use. There are no negative consequences. Is that true? I mean, is it really risk free?

Dr. Hammond: Research shows that that’s an inaccurate framing of the safety profile of cannabis. Again, as Leslie put it very well, cannabis is many different compounds. Using this catchall phrase of «cannabis» is not very helpful.

In regard to the main bioactive compounds of the cannabis plant, THC and cannabidiol, or CBD, what we know from studies of THC administration and from medications that have been designed to mimic THC and act on receptors that THC acts on is that those medications have clear side effects and adverse events in a percentage of patients who take them, particularly in regard to precipitating panic attacks, dysphoric episodes, and psychosis in some individuals.

Dr. Hulvershorn: I would add that it really depends on the age of the person that you’re talking about and when they’re first exposed to cannabis. If you’re talking about a person, say, under the age of 14 who uses cannabis, there’s a large amount of concern about the worsening of psychosis and mental health symptoms, but also cognitive features like memory.

There’s a very good study that was conducted in New Zealand that followed a large number of kids over time and showed significant decreases in working memory capacity for kids who used quite heavily.

Then you think about pregnant women. That’s very interesting literature, where people are finding that cannabis not only affects brain development but also a host of other systems in the body. For example, I think the risk for asthma is increased. If you look at the genes in the placenta that are affected, it has much to do with the immune system.

Women who are using cannabis during pregnancy are really exposing their fetus to a range of potential risks that we certainly don’t understand well enough, but there’s enough science that suggests this is really concerning.

If you take a step back and look at animal models, even with things like CBD products, which, again, everybody seems to be buying and they’re viewed as very safe — it’s almost hard to find things without CBD these days.

There we find, for example, in developing rats that testicular development seems to be affected with high doses of CBD. There’s just a huge array of effects, even outside of the psychiatric world, that make me very nervous about anyone using, especially a pregnant woman or a young person.

Then there’s a whole separate literature on adults. It’s hard to find studies that suggest this is a great idea. You’re going to find on the mental health side of things, and the cognitive side of things, many effects as well.

I, personally, am agnostic one way or the other. If cannabis turns out to be helpful, great. We love things that are helpful in medicine. We don’t really care where they come from. I’m not biased politically one way or the other. It’s just when you look at the totality of the literature, it’s hard to feel excited about people using cannabis at any age.

Dr. Hammond: It’s difficult to interpret the literature because of some biases there. It speaks to the importance of thoughtful research being done in this space that takes a neutral approach to assessing cannabis and looking for evidence of both potential benefit and potential harm.

The other piece that I think is of value that builds off what Leslie mentioned is the effects of cannabis and THC. The risk for harm appears to be greater in pregnant women and in young people. For adults, I think, we’re also still trying to understand what the effects are.

The other way of parsing out effects and thinking about them is in terms of the acute effects and the acute response in the moment right after one ingests cannabis vs the long-term effects.

After acute ingestion of cannabis, it can precipitate a psychotic episode, dysphoria or severe depressive symptoms, or severe anxiety, and can cause one to be disoriented, have delayed response time, and affect the ability to Dr.ive. In that capacity, it is related to a higher risk for motor vehicle crashes.

Dr. Strakowski: That’s very interesting. In my practice, and maybe it’s atypical, but half to two thirds of my patients, particularly the younger ones, are using cannabis in some form or another. In my experience, if they’re under 21, they’re more likely to use cannabis than alcohol.

What do we tell our patients? Is there a safe level of use? Do we say to never touch it? How do we manage the social pressure and environment that our patients have to live in?

Dr. Hulvershorn: I think about what we call motivational interviewing and the substance use disorder field, which is a style of interacting with someone that’s very neutral to discuss the pros and the cons. In my practice, people are usually coming to us because of problems related to their substance use.

Not everyone is experiencing those, but for those people, it’s a pretty easy discussion. It sounds like you’re getting into trouble. Your athletic performance is suffering. Your scholastic performance is suffering.

You walk them toward understanding that, wait a minute, if I smoked less weed or no weed, I would probably be doing better in this or that domain of my life. That seems to be the most helpful thing, by allowing them to come to that conclusion.

I think it is a more difficult conversation for people who don’t identify any problems related to their use. What is the right answer? Again, I just go back to saying, “Is this good for you? It’s hard to find the literature that suggests that. Is it neutral for you? Maybe, for some people. Is it harmful for some people? Absolutely.”

I think, for me, the most impactful studies have been those that showed for certain people with certain genetic makeup, cannabis is an absolutely terrible idea. Their risk for psychosis development and things like that are so high. For other people, they could smoke weed all day and never have a problem, based on their genetics — maybe. We don’t know. It’s not like we’re doing blood tests to figure out who you are.

The safest advice, I think, is no use. That’s never going to be bad advice.

Dr. Hammond: I mostly agree with Leslie on this point but feel very, very strongly that — in this era, where in the context of popular media, celebrities and other people are stating that cannabis is good and should be put in everything — clinical providers, especially pediatric providers, need to be extremely grounded in the science, and not let popular media sway our approach and strategy for working with these young people.

There’s two decades worth of data from longitudinal studies that have followed individuals from birth or from preadolescence into their thirties and forties, that show us that, for this association between cannabis use and later adverse mental health outcomes, there is a dose effect there.

The earlier an individual starts using, the more frequent they use, and more persistent their use is over time, those individuals have poorer mental health outcomes compared with individuals who choose to abstain or individuals who use just a few times and stop.

There’s also a signal for higher-THC-potency products being associated with poorer mental health outcomes, particularly when used during adolescence.

I apply a motivational interviewing approach as well to disseminate this information to both the young people and their parents about the risks, and to communicate what the data clearly show in regard to using THC-based cannabinoid products, which is that we don’t have evidence that shows that any use is healthy to the developing brain.

There’s a large amount of evidence that suggests it’s harmful to the developing brain, so the recommendation is not to use, to delay the onset of use, if you want to use, until adulthood. Many youth choose to use. For those young people, we meet them where they’re at and try to work with them on cutting down.

Dr. Strakowski: Thank you both. There’s an interesting effort in different states, with lobbying by celebrities and legislators pushing insurance companies to fund cannabis use broadly, including in a number of psychiatric indications, with no FDA approval at this point. Do you support that? Is that a good idea?

Dr. Hammond: Absolutely not.

Dr. Strakowski: Thank you.

Dr. Hammond: I think that’s a very important statement to make. For the medical and healthcare profession to stand strong related to states requiring insurance companies to cover medical cannabis really opens the door to lawsuits that would force insurance companies to cover other undertested bioactive chemicals and health supplements.

There are insufficient safety data for medical cannabis for FDA approval for any condition right now. The FDA has approved cannabinoid-based medications. Those cannabinoid-based medications have really undergone rigorous safety and efficacy testing, and have been approved for very narrow indications, none of which are psychiatric conditions.

They’ve been approved for chemotherapy-associated nausea and vomiting, treatment-resistant seizures related to two rare seizure disorders that emerge during childhood, and related to tuberous sclerosis, and one related to treating multiple sclerosis–associated spasticity and central neuropathic pain.

Dr. Hulvershorn: Steve, I think it’s important for listeners to be aware that there is a process in place for any therapeutic to become tested and reviewed. We see an industry that stands to make an enormous amount of money, and that is really the motivation for this industry.

These are not folks who are, out of the kindness of their heart, just hoping for better treatments for people. There are many ways you could channel that desire that does not include cannabis making money.

It’s really a profit-motivated industry. They’re very effective at lobbying. The public, unfortunately, has been sort of manipulated by this industry to believe that these are healthy, safe, and natural just because they grow in the ground.

Unfortunately, that’s really the issue. I think people just need to keep that in mind. Someone stands to make a large amount of money off of this. This is a very calculated, strategic approach that goes state by state but is nationally organized, and is potentially, like Chris says, for many reasons, really harmful.

I see it as sort of a bullying approach. Like if your Dr.ug works, Medicaid will pay for it. Medicaid in each state will review the studies. The FDA obviously leads the way. To cut the line without the research is really not helpful — circumventing the process that’s been in place for a long time and works well.

Dr. Hammond: Yes, it sets a dangerous precedent.

Dr. Strakowski: I was going to add the same, that it’s potentially dangerous. Thank you both, Dr.s Hulvershorn and Hammond, for a really good, lively discussion. I know we could talk for a very long time about this situation.

I do think it’s clear for listeners, most of whom are practitioners, that at this point in time, there just really does not seem to be strong evidence for the use of cannabis-based products for any psychiatric condition.

I do think we have to approach the people we’re working with around their psychiatric conditions to manage use and abuse wisely, like we would with any other substance. I appreciate everyone who’s tuned in today to watch us. I hope this is useful for your practice. Thank you.

Stephen M. Strakowski, MD, has disclosed the following relevant financial relationships:

• Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Roche; Procter & Gamble; Novartis; Sunovion
• Received income in an amount equal to or greater than $250 from: Roche; Procter & Gamble; Novartis; Sunovion; Oxford University Press

Leslie A. Hulvershorn, MD, MSc, has disclosed the following relevant financial relationships:

• Received income in an amount equal to or greater than $250 from: Greenwich Biosciences, educational grant for Summit

Christopher J. Hammond, MD, PhD, has disclosed the following relevant financial relationships:

• Received research grant from National Institutes of Health Grants; Bench to Bench Award; Substance Abuse and Mental Health Services Administration; Doris Duke.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Stephen M. Strakowski, MD: Hello. Thank you all for joining us today. I’m very excited to have some great guests to talk about what I consider an active controversy. I’m Stephen M. Strakowski. I’m a professor and vice chair of psychiatry at Indiana University, and professor and associate vice president at University of Texas in Austin.

Today we’re going to talk about cannabis. As all of you are aware, everyone’s talking about cannabis. We hear constantly on social media and in interviews, particularly with relevance to psychiatric disorders, that everyone should be thinking about using cannabis. That seems to be the common conversation.

Last week, I had a patient who said, “All my friends tell me I need to be on cannabis.” That was their solution to her problems. With that in mind, let me introduce our guests, who are both experts on this, to talk about the role of cannabis in psychiatric disorders today.

First, I want to welcome Dr. Leslie Hulvershorn. Dr. Hulvershorn is an associate professor and chair at Indiana University in Indianapolis. Dr. Christopher Hammond is an assistant professor and the director of the co-occurring disorders program at Johns Hopkins. Welcome!

Leslie A. Hulvershorn, MD, MSc: Thank you.

Christopher J. Hammond, MD, PhD: Thank you.

Dr. Strakowski: Leslie, as I mentioned, many people are talking about how cannabis could be a good treatment for psychiatric disorders. Is that true?

Dr. Hulvershorn: If you look at what defines a good treatment, what you’re looking for is clinical trials, ideally randomized, placebo-controlled clinical trials.

When we look at research related to cannabis, we see very few of those trials, and we see that the cannabis plant is actually quite complicated and there are many different compounds that come from it. So we need to look at all the different compounds.

If you think about THC, delta 9 or delta 8, depending on the version, that’s the active ingredient that we most often think about when we say “cannabis.” If you look at THC studies, there really is no evidence that I could find that it helps psychiatric disorders.

What we do find is an enormous literature, many hunDr.eds of studies, actually, that show that THC actually worsens or even brings on psychiatric disorders. There’s a separate conversation about other compounds within the cannabis plant, like CBD, cannabidiol, where there’s maybe a signal that certain anxiety disorders might be improved by a compound like that.

Certainly, rare forms of epilepsy have been found to be improved with that compound. It really depends on what you’re looking at within the cannabis plant, but if we’re thinking about THC, the answer really is no, this is not a helpful thing. In fact, it’s probably a harmful thing to be ingesting in terms of psychiatric disorders.

Dr. Strakowski: Thank you, Leslie. Chris, what would you add to that? Do we know anything about the use of cannabis in any psychiatric condition?

Dr. Hammond: I definitely would echo what Leslie said. The popular opinion, that the media and the state legislatures have really, in many ways, put the cart before the horse — they speak about cannabis as a medication for the treatment of psychiatric conditions before we have sufficient evidence to say that it’s safe or effective for these conditions. Most of the evidence that we have, particularly in regard to the cannabinoid compound, delta 9, tetrahyDr.ocannabinol, or THC, suggests that that cannabinoid is associated with adverse mental health outcomes across different categories.

Dr. Strakowski: Our group, a long time ago, conducted a study looking at first episode of mania, and found that regular cannabis use increases the risk for subsequent manic episodes. I’m not aware of many other studies like that.

You referred, Chris, to the safety aspect. If you look at social media, the press, and the conversations where cannabis is talked about, there’s no risk, right? This is something anybody can use. There are no negative consequences. Is that true? I mean, is it really risk free?

Dr. Hammond: Research shows that that’s an inaccurate framing of the safety profile of cannabis. Again, as Leslie put it very well, cannabis is many different compounds. Using this catchall phrase of «cannabis» is not very helpful.

In regard to the main bioactive compounds of the cannabis plant, THC and cannabidiol, or CBD, what we know from studies of THC administration and from medications that have been designed to mimic THC and act on receptors that THC acts on is that those medications have clear side effects and adverse events in a percentage of patients who take them, particularly in regard to precipitating panic attacks, dysphoric episodes, and psychosis in some individuals.

Dr. Hulvershorn: I would add that it really depends on the age of the person that you’re talking about and when they’re first exposed to cannabis. If you’re talking about a person, say, under the age of 14 who uses cannabis, there’s a large amount of concern about the worsening of psychosis and mental health symptoms, but also cognitive features like memory.

There’s a very good study that was conducted in New Zealand that followed a large number of kids over time and showed significant decreases in working memory capacity for kids who used quite heavily.

Then you think about pregnant women. That’s very interesting literature, where people are finding that cannabis not only affects brain development but also a host of other systems in the body. For example, I think the risk for asthma is increased. If you look at the genes in the placenta that are affected, it has much to do with the immune system.

Women who are using cannabis during pregnancy are really exposing their fetus to a range of potential risks that we certainly don’t understand well enough, but there’s enough science that suggests this is really concerning.

If you take a step back and look at animal models, even with things like CBD products, which, again, everybody seems to be buying and they’re viewed as very safe — it’s almost hard to find things without CBD these days.

There we find, for example, in developing rats that testicular development seems to be affected with high doses of CBD. There’s just a huge array of effects, even outside of the psychiatric world, that make me very nervous about anyone using, especially a pregnant woman or a young person.

Then there’s a whole separate literature on adults. It’s hard to find studies that suggest this is a great idea. You’re going to find on the mental health side of things, and the cognitive side of things, many effects as well.

I, personally, am agnostic one way or the other. If cannabis turns out to be helpful, great. We love things that are helpful in medicine. We don’t really care where they come from. I’m not biased politically one way or the other. It’s just when you look at the totality of the literature, it’s hard to feel excited about people using cannabis at any age.

Dr. Hammond: It’s difficult to interpret the literature because of some biases there. It speaks to the importance of thoughtful research being done in this space that takes a neutral approach to assessing cannabis and looking for evidence of both potential benefit and potential harm.

The other piece that I think is of value that builds off what Leslie mentioned is the effects of cannabis and THC. The risk for harm appears to be greater in pregnant women and in young people. For adults, I think, we’re also still trying to understand what the effects are.

The other way of parsing out effects and thinking about them is in terms of the acute effects and the acute response in the moment right after one ingests cannabis vs the long-term effects.

After acute ingestion of cannabis, it can precipitate a psychotic episode, dysphoria or severe depressive symptoms, or severe anxiety, and can cause one to be disoriented, have delayed response time, and affect the ability to Dr.ive. In that capacity, it is related to a higher risk for motor vehicle crashes.

Dr. Strakowski: That’s very interesting. In my practice, and maybe it’s atypical, but half to two thirds of my patients, particularly the younger ones, are using cannabis in some form or another. In my experience, if they’re under 21, they’re more likely to use cannabis than alcohol.

What do we tell our patients? Is there a safe level of use? Do we say to never touch it? How do we manage the social pressure and environment that our patients have to live in?

Dr. Hulvershorn: I think about what we call motivational interviewing and the substance use disorder field, which is a style of interacting with someone that’s very neutral to discuss the pros and the cons. In my practice, people are usually coming to us because of problems related to their substance use.

Not everyone is experiencing those, but for those people, it’s a pretty easy discussion. It sounds like you’re getting into trouble. Your athletic performance is suffering. Your scholastic performance is suffering.

You walk them toward understanding that, wait a minute, if I smoked less weed or no weed, I would probably be doing better in this or that domain of my life. That seems to be the most helpful thing, by allowing them to come to that conclusion.

I think it is a more difficult conversation for people who don’t identify any problems related to their use. What is the right answer? Again, I just go back to saying, “Is this good for you? It’s hard to find the literature that suggests that. Is it neutral for you? Maybe, for some people. Is it harmful for some people? Absolutely.”

I think, for me, the most impactful studies have been those that showed for certain people with certain genetic makeup, cannabis is an absolutely terrible idea. Their risk for psychosis development and things like that are so high. For other people, they could smoke weed all day and never have a problem, based on their genetics — maybe. We don’t know. It’s not like we’re doing blood tests to figure out who you are.

The safest advice, I think, is no use. That’s never going to be bad advice.

Dr. Hammond: I mostly agree with Leslie on this point but feel very, very strongly that — in this era, where in the context of popular media, celebrities and other people are stating that cannabis is good and should be put in everything — clinical providers, especially pediatric providers, need to be extremely grounded in the science, and not let popular media sway our approach and strategy for working with these young people.

There’s two decades worth of data from longitudinal studies that have followed individuals from birth or from preadolescence into their thirties and forties, that show us that, for this association between cannabis use and later adverse mental health outcomes, there is a dose effect there.

The earlier an individual starts using, the more frequent they use, and more persistent their use is over time, those individuals have poorer mental health outcomes compared with individuals who choose to abstain or individuals who use just a few times and stop.

There’s also a signal for higher-THC-potency products being associated with poorer mental health outcomes, particularly when used during adolescence.

I apply a motivational interviewing approach as well to disseminate this information to both the young people and their parents about the risks, and to communicate what the data clearly show in regard to using THC-based cannabinoid products, which is that we don’t have evidence that shows that any use is healthy to the developing brain.

There’s a large amount of evidence that suggests it’s harmful to the developing brain, so the recommendation is not to use, to delay the onset of use, if you want to use, until adulthood. Many youth choose to use. For those young people, we meet them where they’re at and try to work with them on cutting down.

Dr. Strakowski: Thank you both. There’s an interesting effort in different states, with lobbying by celebrities and legislators pushing insurance companies to fund cannabis use broadly, including in a number of psychiatric indications, with no FDA approval at this point. Do you support that? Is that a good idea?

Dr. Hammond: Absolutely not.

Dr. Strakowski: Thank you.

Dr. Hammond: I think that’s a very important statement to make. For the medical and healthcare profession to stand strong related to states requiring insurance companies to cover medical cannabis really opens the door to lawsuits that would force insurance companies to cover other undertested bioactive chemicals and health supplements.

There are insufficient safety data for medical cannabis for FDA approval for any condition right now. The FDA has approved cannabinoid-based medications. Those cannabinoid-based medications have really undergone rigorous safety and efficacy testing, and have been approved for very narrow indications, none of which are psychiatric conditions.

They’ve been approved for chemotherapy-associated nausea and vomiting, treatment-resistant seizures related to two rare seizure disorders that emerge during childhood, and related to tuberous sclerosis, and one related to treating multiple sclerosis–associated spasticity and central neuropathic pain.

Dr. Hulvershorn: Steve, I think it’s important for listeners to be aware that there is a process in place for any therapeutic to become tested and reviewed. We see an industry that stands to make an enormous amount of money, and that is really the motivation for this industry.

These are not folks who are, out of the kindness of their heart, just hoping for better treatments for people. There are many ways you could channel that desire that does not include cannabis making money.

It’s really a profit-motivated industry. They’re very effective at lobbying. The public, unfortunately, has been sort of manipulated by this industry to believe that these are healthy, safe, and natural just because they grow in the ground.

Unfortunately, that’s really the issue. I think people just need to keep that in mind. Someone stands to make a large amount of money off of this. This is a very calculated, strategic approach that goes state by state but is nationally organized, and is potentially, like Chris says, for many reasons, really harmful.

I see it as sort of a bullying approach. Like if your Dr.ug works, Medicaid will pay for it. Medicaid in each state will review the studies. The FDA obviously leads the way. To cut the line without the research is really not helpful — circumventing the process that’s been in place for a long time and works well.

Dr. Hammond: Yes, it sets a dangerous precedent.

Dr. Strakowski: I was going to add the same, that it’s potentially dangerous. Thank you both, Dr.s Hulvershorn and Hammond, for a really good, lively discussion. I know we could talk for a very long time about this situation.

I do think it’s clear for listeners, most of whom are practitioners, that at this point in time, there just really does not seem to be strong evidence for the use of cannabis-based products for any psychiatric condition.

I do think we have to approach the people we’re working with around their psychiatric conditions to manage use and abuse wisely, like we would with any other substance. I appreciate everyone who’s tuned in today to watch us. I hope this is useful for your practice. Thank you.

Stephen M. Strakowski, MD, has disclosed the following relevant financial relationships:

• Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Roche; Procter & Gamble; Novartis; Sunovion
• Received income in an amount equal to or greater than $250 from: Roche; Procter & Gamble; Novartis; Sunovion; Oxford University Press

Leslie A. Hulvershorn, MD, MSc, has disclosed the following relevant financial relationships:

• Received income in an amount equal to or greater than $250 from: Greenwich Biosciences, educational grant for Summit

Christopher J. Hammond, MD, PhD, has disclosed the following relevant financial relationships:

• Received research grant from National Institutes of Health Grants; Bench to Bench Award; Substance Abuse and Mental Health Services Administration; Doris Duke.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Stephen M. Strakowski, MD: Hello. Thank you all for joining us today. I’m very excited to have some great guests to talk about what I consider an active controversy. I’m Stephen M. Strakowski. I’m a professor and vice chair of psychiatry at Indiana University, and professor and associate vice president at University of Texas in Austin.

Today we’re going to talk about cannabis. As all of you are aware, everyone’s talking about cannabis. We hear constantly on social media and in interviews, particularly with relevance to psychiatric disorders, that everyone should be thinking about using cannabis. That seems to be the common conversation.

Last week, I had a patient who said, “All my friends tell me I need to be on cannabis.” That was their solution to her problems. With that in mind, let me introduce our guests, who are both experts on this, to talk about the role of cannabis in psychiatric disorders today.

First, I want to welcome Dr. Leslie Hulvershorn. Dr. Hulvershorn is an associate professor and chair at Indiana University in Indianapolis. Dr. Christopher Hammond is an assistant professor and the director of the co-occurring disorders program at Johns Hopkins. Welcome!

Leslie A. Hulvershorn, MD, MSc: Thank you.

Christopher J. Hammond, MD, PhD: Thank you.

Dr. Strakowski: Leslie, as I mentioned, many people are talking about how cannabis could be a good treatment for psychiatric disorders. Is that true?

Dr. Hulvershorn: If you look at what defines a good treatment, what you’re looking for is clinical trials, ideally randomized, placebo-controlled clinical trials.

When we look at research related to cannabis, we see very few of those trials, and we see that the cannabis plant is actually quite complicated and there are many different compounds that come from it. So we need to look at all the different compounds.

If you think about THC, delta 9 or delta 8, depending on the version, that’s the active ingredient that we most often think about when we say “cannabis.” If you look at THC studies, there really is no evidence that I could find that it helps psychiatric disorders.

What we do find is an enormous literature, many hunDr.eds of studies, actually, that show that THC actually worsens or even brings on psychiatric disorders. There’s a separate conversation about other compounds within the cannabis plant, like CBD, cannabidiol, where there’s maybe a signal that certain anxiety disorders might be improved by a compound like that.

Certainly, rare forms of epilepsy have been found to be improved with that compound. It really depends on what you’re looking at within the cannabis plant, but if we’re thinking about THC, the answer really is no, this is not a helpful thing. In fact, it’s probably a harmful thing to be ingesting in terms of psychiatric disorders.

Dr. Strakowski: Thank you, Leslie. Chris, what would you add to that? Do we know anything about the use of cannabis in any psychiatric condition?

Dr. Hammond: I definitely would echo what Leslie said. The popular opinion, that the media and the state legislatures have really, in many ways, put the cart before the horse — they speak about cannabis as a medication for the treatment of psychiatric conditions before we have sufficient evidence to say that it’s safe or effective for these conditions. Most of the evidence that we have, particularly in regard to the cannabinoid compound, delta 9, tetrahyDr.ocannabinol, or THC, suggests that that cannabinoid is associated with adverse mental health outcomes across different categories.

Dr. Strakowski: Our group, a long time ago, conducted a study looking at first episode of mania, and found that regular cannabis use increases the risk for subsequent manic episodes. I’m not aware of many other studies like that.

You referred, Chris, to the safety aspect. If you look at social media, the press, and the conversations where cannabis is talked about, there’s no risk, right? This is something anybody can use. There are no negative consequences. Is that true? I mean, is it really risk free?

Dr. Hammond: Research shows that that’s an inaccurate framing of the safety profile of cannabis. Again, as Leslie put it very well, cannabis is many different compounds. Using this catchall phrase of «cannabis» is not very helpful.

In regard to the main bioactive compounds of the cannabis plant, THC and cannabidiol, or CBD, what we know from studies of THC administration and from medications that have been designed to mimic THC and act on receptors that THC acts on is that those medications have clear side effects and adverse events in a percentage of patients who take them, particularly in regard to precipitating panic attacks, dysphoric episodes, and psychosis in some individuals.

Dr. Hulvershorn: I would add that it really depends on the age of the person that you’re talking about and when they’re first exposed to cannabis. If you’re talking about a person, say, under the age of 14 who uses cannabis, there’s a large amount of concern about the worsening of psychosis and mental health symptoms, but also cognitive features like memory.

There’s a very good study that was conducted in New Zealand that followed a large number of kids over time and showed significant decreases in working memory capacity for kids who used quite heavily.

Then you think about pregnant women. That’s very interesting literature, where people are finding that cannabis not only affects brain development but also a host of other systems in the body. For example, I think the risk for asthma is increased. If you look at the genes in the placenta that are affected, it has much to do with the immune system.

Women who are using cannabis during pregnancy are really exposing their fetus to a range of potential risks that we certainly don’t understand well enough, but there’s enough science that suggests this is really concerning.

If you take a step back and look at animal models, even with things like CBD products, which, again, everybody seems to be buying and they’re viewed as very safe — it’s almost hard to find things without CBD these days.

There we find, for example, in developing rats that testicular development seems to be affected with high doses of CBD. There’s just a huge array of effects, even outside of the psychiatric world, that make me very nervous about anyone using, especially a pregnant woman or a young person.

Then there’s a whole separate literature on adults. It’s hard to find studies that suggest this is a great idea. You’re going to find on the mental health side of things, and the cognitive side of things, many effects as well.

I, personally, am agnostic one way or the other. If cannabis turns out to be helpful, great. We love things that are helpful in medicine. We don’t really care where they come from. I’m not biased politically one way or the other. It’s just when you look at the totality of the literature, it’s hard to feel excited about people using cannabis at any age.

Dr. Hammond: It’s difficult to interpret the literature because of some biases there. It speaks to the importance of thoughtful research being done in this space that takes a neutral approach to assessing cannabis and looking for evidence of both potential benefit and potential harm.

The other piece that I think is of value that builds off what Leslie mentioned is the effects of cannabis and THC. The risk for harm appears to be greater in pregnant women and in young people. For adults, I think, we’re also still trying to understand what the effects are.

The other way of parsing out effects and thinking about them is in terms of the acute effects and the acute response in the moment right after one ingests cannabis vs the long-term effects.

After acute ingestion of cannabis, it can precipitate a psychotic episode, dysphoria or severe depressive symptoms, or severe anxiety, and can cause one to be disoriented, have delayed response time, and affect the ability to Dr.ive. In that capacity, it is related to a higher risk for motor vehicle crashes.

Dr. Strakowski: That’s very interesting. In my practice, and maybe it’s atypical, but half to two thirds of my patients, particularly the younger ones, are using cannabis in some form or another. In my experience, if they’re under 21, they’re more likely to use cannabis than alcohol.

What do we tell our patients? Is there a safe level of use? Do we say to never touch it? How do we manage the social pressure and environment that our patients have to live in?

Dr. Hulvershorn: I think about what we call motivational interviewing and the substance use disorder field, which is a style of interacting with someone that’s very neutral to discuss the pros and the cons. In my practice, people are usually coming to us because of problems related to their substance use.

Not everyone is experiencing those, but for those people, it’s a pretty easy discussion. It sounds like you’re getting into trouble. Your athletic performance is suffering. Your scholastic performance is suffering.

You walk them toward understanding that, wait a minute, if I smoked less weed or no weed, I would probably be doing better in this or that domain of my life. That seems to be the most helpful thing, by allowing them to come to that conclusion.

I think it is a more difficult conversation for people who don’t identify any problems related to their use. What is the right answer? Again, I just go back to saying, “Is this good for you? It’s hard to find the literature that suggests that. Is it neutral for you? Maybe, for some people. Is it harmful for some people? Absolutely.”

I think, for me, the most impactful studies have been those that showed for certain people with certain genetic makeup, cannabis is an absolutely terrible idea. Their risk for psychosis development and things like that are so high. For other people, they could smoke weed all day and never have a problem, based on their genetics — maybe. We don’t know. It’s not like we’re doing blood tests to figure out who you are.

The safest advice, I think, is no use. That’s never going to be bad advice.

Dr. Hammond: I mostly agree with Leslie on this point but feel very, very strongly that — in this era, where in the context of popular media, celebrities and other people are stating that cannabis is good and should be put in everything — clinical providers, especially pediatric providers, need to be extremely grounded in the science, and not let popular media sway our approach and strategy for working with these young people.

There’s two decades worth of data from longitudinal studies that have followed individuals from birth or from preadolescence into their thirties and forties, that show us that, for this association between cannabis use and later adverse mental health outcomes, there is a dose effect there.

The earlier an individual starts using, the more frequent they use, and more persistent their use is over time, those individuals have poorer mental health outcomes compared with individuals who choose to abstain or individuals who use just a few times and stop.

There’s also a signal for higher-THC-potency products being associated with poorer mental health outcomes, particularly when used during adolescence.

I apply a motivational interviewing approach as well to disseminate this information to both the young people and their parents about the risks, and to communicate what the data clearly show in regard to using THC-based cannabinoid products, which is that we don’t have evidence that shows that any use is healthy to the developing brain.

There’s a large amount of evidence that suggests it’s harmful to the developing brain, so the recommendation is not to use, to delay the onset of use, if you want to use, until adulthood. Many youth choose to use. For those young people, we meet them where they’re at and try to work with them on cutting down.

Dr. Strakowski: Thank you both. There’s an interesting effort in different states, with lobbying by celebrities and legislators pushing insurance companies to fund cannabis use broadly, including in a number of psychiatric indications, with no FDA approval at this point. Do you support that? Is that a good idea?

Dr. Hammond: Absolutely not.

Dr. Strakowski: Thank you.

Dr. Hammond: I think that’s a very important statement to make. For the medical and healthcare profession to stand strong related to states requiring insurance companies to cover medical cannabis really opens the door to lawsuits that would force insurance companies to cover other undertested bioactive chemicals and health supplements.

There are insufficient safety data for medical cannabis for FDA approval for any condition right now. The FDA has approved cannabinoid-based medications. Those cannabinoid-based medications have really undergone rigorous safety and efficacy testing, and have been approved for very narrow indications, none of which are psychiatric conditions.

They’ve been approved for chemotherapy-associated nausea and vomiting, treatment-resistant seizures related to two rare seizure disorders that emerge during childhood, and related to tuberous sclerosis, and one related to treating multiple sclerosis–associated spasticity and central neuropathic pain.

Dr. Hulvershorn: Steve, I think it’s important for listeners to be aware that there is a process in place for any therapeutic to become tested and reviewed. We see an industry that stands to make an enormous amount of money, and that is really the motivation for this industry.

These are not folks who are, out of the kindness of their heart, just hoping for better treatments for people. There are many ways you could channel that desire that does not include cannabis making money.

It’s really a profit-motivated industry. They’re very effective at lobbying. The public, unfortunately, has been sort of manipulated by this industry to believe that these are healthy, safe, and natural just because they grow in the ground.

Unfortunately, that’s really the issue. I think people just need to keep that in mind. Someone stands to make a large amount of money off of this. This is a very calculated, strategic approach that goes state by state but is nationally organized, and is potentially, like Chris says, for many reasons, really harmful.

I see it as sort of a bullying approach. Like if your Dr.ug works, Medicaid will pay for it. Medicaid in each state will review the studies. The FDA obviously leads the way. To cut the line without the research is really not helpful — circumventing the process that’s been in place for a long time and works well.

Dr. Hammond: Yes, it sets a dangerous precedent.

Dr. Strakowski: I was going to add the same, that it’s potentially dangerous. Thank you both, Dr.s Hulvershorn and Hammond, for a really good, lively discussion. I know we could talk for a very long time about this situation.

I do think it’s clear for listeners, most of whom are practitioners, that at this point in time, there just really does not seem to be strong evidence for the use of cannabis-based products for any psychiatric condition.

I do think we have to approach the people we’re working with around their psychiatric conditions to manage use and abuse wisely, like we would with any other substance. I appreciate everyone who’s tuned in today to watch us. I hope this is useful for your practice. Thank you.

Stephen M. Strakowski, MD, has disclosed the following relevant financial relationships:

• Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Roche; Procter & Gamble; Novartis; Sunovion
• Received income in an amount equal to or greater than $250 from: Roche; Procter & Gamble; Novartis; Sunovion; Oxford University Press

Leslie A. Hulvershorn, MD, MSc, has disclosed the following relevant financial relationships:

• Received income in an amount equal to or greater than $250 from: Greenwich Biosciences, educational grant for Summit

Christopher J. Hammond, MD, PhD, has disclosed the following relevant financial relationships:

• Received research grant from National Institutes of Health Grants; Bench to Bench Award; Substance Abuse and Mental Health Services Administration; Doris Duke.

A version of this article appeared on Medscape.com.

TOPLINE:

Hypochondriasis is linked to an 84% higher risk for death for those with the disorder and a fourfold increased risk for suicide, new population-based data show. These findings, investigators noted, suggest the need for more clinical screening and treatment of hypochondriasis, also known as health anxiety disorder.

METHODOLOGY:

• Investigators used several Swedish population-based registers to identify people who received a diagnosis of hypochondriasis between January 1997 and December 2020.
• Each individual diagnosed with hypochondriasis (n = 4129; 2342 women; median 34.5 years at diagnosis) was age- and sex-matched with 10 individuals without the disorder (n = 41,290).
• For those who died during the study period, cause of death was categorized as natural (neoplasms; diseases of the nervous system, circulatory system, or respiratory system) or unnatural (primarily suicide).
• Investigators age- and sex-matched 4129 individuals with hypochondriasis to 41,290 individuals without hypochondriasis.

TAKEAWAY:

• Individuals with hypochondriasis had an 84% higher risk for all-cause mortality during the study period than those without it (adjusted hazard ratio [aHR], 1.84; 95% CI, 1.60-2.10), including a higher risk for both natural (aHR, 1.60; 95% CI, 1.38-1.85) and unnatural death (aHR, 2.43; 95% CI, 1.61-3.68).
• The majority of individuals with hypochondriasis were diagnosed with at least one additional psychiatric disorder (primarily anxiety-related and depressive disorders) vs the group without hypochondriasis (86% vs 20%, respectively; P < .001).
• The risk for suicide — the most common unnatural cause of death — was four times higher in those with hypochondriasis (aHR, 4.14; 95% CI, 2.44-7.03).
• When investigators limited analyses to include only psychiatric comorbidities recorded before the first diagnosis of hypochondriasis, suicide risk was attenuated but remained statistically significant.

IN PRACTICE:

“Taken together, these findings illustrate a paradox, whereby individuals with hypochondriasis have an increased risk for death despite their pervasive fears of illness and death. In this study, most deaths could be classified as potentially preventable. Dismissing these individuals’ somatic symptoms as imaginary may have dire consequences,” the authors wrote.

SOURCE:

David Mataix-Cols, PhD, of the Karolinska Institutet, Stockholm, Sweden, led the study, which was published online on December 13, 2023, in JAMA Psychiatry.

LIMITATIONS:

Hypochondriasis is thought to be underdiagnosed in Sweden, with only approximately 4000 cases registered within two decades. Study investigators also noted that they did not obtain data from primary care, the setting where the majority of hypochondriasis cases are diagnosed.

DISCLOSURES:

The study was funded by the Swedish Research Council for Health, Working Life and Welfare, Stockholm; the Swedish Society of Medicine, Stockholm; and Karolinska Institutet, Stockholm. Dr. Mataix-Cols reported receiving personal fees from UpToDate Inc. Author disclosures can be found in the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

Hypochondriasis is linked to an 84% higher risk for death for those with the disorder and a fourfold increased risk for suicide, new population-based data show. These findings, investigators noted, suggest the need for more clinical screening and treatment of hypochondriasis, also known as health anxiety disorder.

METHODOLOGY:

• Investigators used several Swedish population-based registers to identify people who received a diagnosis of hypochondriasis between January 1997 and December 2020.
• Each individual diagnosed with hypochondriasis (n = 4129; 2342 women; median 34.5 years at diagnosis) was age- and sex-matched with 10 individuals without the disorder (n = 41,290).
• For those who died during the study period, cause of death was categorized as natural (neoplasms; diseases of the nervous system, circulatory system, or respiratory system) or unnatural (primarily suicide).
• Investigators age- and sex-matched 4129 individuals with hypochondriasis to 41,290 individuals without hypochondriasis.

TAKEAWAY:

• Individuals with hypochondriasis had an 84% higher risk for all-cause mortality during the study period than those without it (adjusted hazard ratio [aHR], 1.84; 95% CI, 1.60-2.10), including a higher risk for both natural (aHR, 1.60; 95% CI, 1.38-1.85) and unnatural death (aHR, 2.43; 95% CI, 1.61-3.68).
• The majority of individuals with hypochondriasis were diagnosed with at least one additional psychiatric disorder (primarily anxiety-related and depressive disorders) vs the group without hypochondriasis (86% vs 20%, respectively; P < .001).
• The risk for suicide — the most common unnatural cause of death — was four times higher in those with hypochondriasis (aHR, 4.14; 95% CI, 2.44-7.03).
• When investigators limited analyses to include only psychiatric comorbidities recorded before the first diagnosis of hypochondriasis, suicide risk was attenuated but remained statistically significant.

IN PRACTICE:

“Taken together, these findings illustrate a paradox, whereby individuals with hypochondriasis have an increased risk for death despite their pervasive fears of illness and death. In this study, most deaths could be classified as potentially preventable. Dismissing these individuals’ somatic symptoms as imaginary may have dire consequences,” the authors wrote.

SOURCE:

David Mataix-Cols, PhD, of the Karolinska Institutet, Stockholm, Sweden, led the study, which was published online on December 13, 2023, in JAMA Psychiatry.

LIMITATIONS:

Hypochondriasis is thought to be underdiagnosed in Sweden, with only approximately 4000 cases registered within two decades. Study investigators also noted that they did not obtain data from primary care, the setting where the majority of hypochondriasis cases are diagnosed.

DISCLOSURES:

The study was funded by the Swedish Research Council for Health, Working Life and Welfare, Stockholm; the Swedish Society of Medicine, Stockholm; and Karolinska Institutet, Stockholm. Dr. Mataix-Cols reported receiving personal fees from UpToDate Inc. Author disclosures can be found in the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

Hypochondriasis is linked to an 84% higher risk for death for those with the disorder and a fourfold increased risk for suicide, new population-based data show. These findings, investigators noted, suggest the need for more clinical screening and treatment of hypochondriasis, also known as health anxiety disorder.

METHODOLOGY:

• Investigators used several Swedish population-based registers to identify people who received a diagnosis of hypochondriasis between January 1997 and December 2020.
• Each individual diagnosed with hypochondriasis (n = 4129; 2342 women; median 34.5 years at diagnosis) was age- and sex-matched with 10 individuals without the disorder (n = 41,290).
• For those who died during the study period, cause of death was categorized as natural (neoplasms; diseases of the nervous system, circulatory system, or respiratory system) or unnatural (primarily suicide).
• Investigators age- and sex-matched 4129 individuals with hypochondriasis to 41,290 individuals without hypochondriasis.

TAKEAWAY:

• Individuals with hypochondriasis had an 84% higher risk for all-cause mortality during the study period than those without it (adjusted hazard ratio [aHR], 1.84; 95% CI, 1.60-2.10), including a higher risk for both natural (aHR, 1.60; 95% CI, 1.38-1.85) and unnatural death (aHR, 2.43; 95% CI, 1.61-3.68).
• The majority of individuals with hypochondriasis were diagnosed with at least one additional psychiatric disorder (primarily anxiety-related and depressive disorders) vs the group without hypochondriasis (86% vs 20%, respectively; P < .001).
• The risk for suicide — the most common unnatural cause of death — was four times higher in those with hypochondriasis (aHR, 4.14; 95% CI, 2.44-7.03).
• When investigators limited analyses to include only psychiatric comorbidities recorded before the first diagnosis of hypochondriasis, suicide risk was attenuated but remained statistically significant.

IN PRACTICE:

“Taken together, these findings illustrate a paradox, whereby individuals with hypochondriasis have an increased risk for death despite their pervasive fears of illness and death. In this study, most deaths could be classified as potentially preventable. Dismissing these individuals’ somatic symptoms as imaginary may have dire consequences,” the authors wrote.

SOURCE:

David Mataix-Cols, PhD, of the Karolinska Institutet, Stockholm, Sweden, led the study, which was published online on December 13, 2023, in JAMA Psychiatry.

LIMITATIONS:

Hypochondriasis is thought to be underdiagnosed in Sweden, with only approximately 4000 cases registered within two decades. Study investigators also noted that they did not obtain data from primary care, the setting where the majority of hypochondriasis cases are diagnosed.

DISCLOSURES:

The study was funded by the Swedish Research Council for Health, Working Life and Welfare, Stockholm; the Swedish Society of Medicine, Stockholm; and Karolinska Institutet, Stockholm. Dr. Mataix-Cols reported receiving personal fees from UpToDate Inc. Author disclosures can be found in the original article.

A version of this article appeared on Medscape.com.

One dose of synthetic psilocybin in combination with psychotherapy significantly reduces treatment-resistant depression associated with bipolar II disorder (BDII), a small, nonrandomized clinical trial shows. However, the investigators and other outside experts warn these results should not be overinterpreted.

Three weeks after receiving psilocybin and psychotherapy, all 15 participants’ depression scores dropped by an average of 24 points. Twelve met criteria for response and 11 for remission.

This benefit lasted until the 12-week mark, with 12 participants (80%) meeting criteria for both response and remission. There were no reports of mixed or manic symptoms, psychotic symptoms, or suicidal ideation.

Given the study’s small, open-label design, the findings should be interpreted cautiously, but the investigators say the results are promising.

“The results we saw from this trial are encouraging and further support the clinical study of psychedelics in patients with treatment-resistant bipolar II,” lead investigator Scott T. Aaronson, MD, chief science officer of the Institute for Advanced Diagnostics and Therapeutics at Sheppard Pratt Health System in Baltimore, Maryland, remarked in a press release. “One participant compared the transformation she experienced to taking a deep breath after breathing through a straw for years.”

The findings were published online on December 6, 2023, in JAMA Psychiatry.

Underserved Population

Previous studies show that psilocybin is effective in reducing the symptoms of treatment-resistant depression, major depressive disorder, and anorexia nervosa, most with only mild to moderate adverse effects.

Individuals with bipolar disorder (BPD) have been excluded from psilocybin studies in the last two decades. Investigators attribute this to anecdotal evidence that psychedelics may result in manic episodes in patients with BPD, even though empirical evidence of those effects is limited.

This study included 15 participants (9 female; mean age, 37.8 years) with BDII who had experienced an episode for more than 3 months and failed at least two medications within the current episode.

Participants stopped all psychotropic medications at least 2 weeks prior to the trial and received 25 mg of synthetic COMP360 psilocybin in a controlled setting. Psychotherapy included three sessions before dosing, one during the 8-hour dosing day, and three integration sessions posttreatment.

Depression was measured with the Montgomery Ǻsberg Depression Rating Scale (MADRS) at six points during the 12-week study.

By week 3, all 15 participants had lower MADRS scores, with a mean decrease of 24 points (P < .001). Twelve participants met the response criteria of ≥ 50% reduction in MADRS scores, and 11 met the criteria for remission of a MADRS score of ≤ 10 (both P < .001).

MADRS scores at each posttreatment time point were significantly lower than they were at baseline and the improvement persisted at 12 weeks.

Participants were also monitored for mania and suicidality at various time points during the study, and no significant changes were found from baseline.

“As a first open-label foray into this underserved and treatment-resistant population, care should be taken not to overinterpret the findings,” the authors note, adding that the findings may not apply to patients with BDI or BDII in a mixed or hypomanic phase of their illness.

No Definitive Conclusion

In an accompanying editorial, David B. Yaden, PhD, Johns Hopkins University School of Medicine, Baltimore, Maryland, and colleagues write that the findings are “tantalizingly suggestive,” but ultimately say nothing definitive about the efficacy of psilocybin for BDII.

“The danger is that some individuals will see the large (yet uncontrolled) effect size and believe that a new treatment of bipolar II has been discovered that is substantially better than all other treatments, while neglecting to mention the lack of control condition and substantial psychosocial support included in the study,” Dr. Yaden and colleagues wrote.

They also cautioned that due to the study’s limitations, which include its small sample size and lack of a control group, “it is imperative that the large effect size before to after the study is not overinterpreted.”

However, Dr. Yaden and colleagues also characterized the safety data as “compelling,” noting the safety profile could affect exclusion criteria in future studies involving people with BPD.

“The results of the present study provide preliminary evidence that perhaps those with bipolar II can be safely included in study samples without undue risk of triggering hypomanic episodes,” they wrote. “It also suggests re-evaluation of the need to exclude individuals with mere family history of bipolar II, which several studies do.”

The study was funded by COMPASS Pathways, who provided the study drug. Dr. Aaronson reported grants and nonfinancial support (supply of drug) from COMPASS Pathways during the conduct of the study and personal fees from LivaNova, Neuronetics, Genomind, and Sage Therapeutics outside the submitted work. Other disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

One dose of synthetic psilocybin in combination with psychotherapy significantly reduces treatment-resistant depression associated with bipolar II disorder (BDII), a small, nonrandomized clinical trial shows. However, the investigators and other outside experts warn these results should not be overinterpreted.

Three weeks after receiving psilocybin and psychotherapy, all 15 participants’ depression scores dropped by an average of 24 points. Twelve met criteria for response and 11 for remission.

This benefit lasted until the 12-week mark, with 12 participants (80%) meeting criteria for both response and remission. There were no reports of mixed or manic symptoms, psychotic symptoms, or suicidal ideation.

Given the study’s small, open-label design, the findings should be interpreted cautiously, but the investigators say the results are promising.

“The results we saw from this trial are encouraging and further support the clinical study of psychedelics in patients with treatment-resistant bipolar II,” lead investigator Scott T. Aaronson, MD, chief science officer of the Institute for Advanced Diagnostics and Therapeutics at Sheppard Pratt Health System in Baltimore, Maryland, remarked in a press release. “One participant compared the transformation she experienced to taking a deep breath after breathing through a straw for years.”

The findings were published online on December 6, 2023, in JAMA Psychiatry.

Underserved Population

Previous studies show that psilocybin is effective in reducing the symptoms of treatment-resistant depression, major depressive disorder, and anorexia nervosa, most with only mild to moderate adverse effects.

Individuals with bipolar disorder (BPD) have been excluded from psilocybin studies in the last two decades. Investigators attribute this to anecdotal evidence that psychedelics may result in manic episodes in patients with BPD, even though empirical evidence of those effects is limited.

This study included 15 participants (9 female; mean age, 37.8 years) with BDII who had experienced an episode for more than 3 months and failed at least two medications within the current episode.

Participants stopped all psychotropic medications at least 2 weeks prior to the trial and received 25 mg of synthetic COMP360 psilocybin in a controlled setting. Psychotherapy included three sessions before dosing, one during the 8-hour dosing day, and three integration sessions posttreatment.

Depression was measured with the Montgomery Ǻsberg Depression Rating Scale (MADRS) at six points during the 12-week study.

By week 3, all 15 participants had lower MADRS scores, with a mean decrease of 24 points (P < .001). Twelve participants met the response criteria of ≥ 50% reduction in MADRS scores, and 11 met the criteria for remission of a MADRS score of ≤ 10 (both P < .001).

MADRS scores at each posttreatment time point were significantly lower than they were at baseline and the improvement persisted at 12 weeks.

Participants were also monitored for mania and suicidality at various time points during the study, and no significant changes were found from baseline.

“As a first open-label foray into this underserved and treatment-resistant population, care should be taken not to overinterpret the findings,” the authors note, adding that the findings may not apply to patients with BDI or BDII in a mixed or hypomanic phase of their illness.

No Definitive Conclusion

In an accompanying editorial, David B. Yaden, PhD, Johns Hopkins University School of Medicine, Baltimore, Maryland, and colleagues write that the findings are “tantalizingly suggestive,” but ultimately say nothing definitive about the efficacy of psilocybin for BDII.

“The danger is that some individuals will see the large (yet uncontrolled) effect size and believe that a new treatment of bipolar II has been discovered that is substantially better than all other treatments, while neglecting to mention the lack of control condition and substantial psychosocial support included in the study,” Dr. Yaden and colleagues wrote.

They also cautioned that due to the study’s limitations, which include its small sample size and lack of a control group, “it is imperative that the large effect size before to after the study is not overinterpreted.”

However, Dr. Yaden and colleagues also characterized the safety data as “compelling,” noting the safety profile could affect exclusion criteria in future studies involving people with BPD.

“The results of the present study provide preliminary evidence that perhaps those with bipolar II can be safely included in study samples without undue risk of triggering hypomanic episodes,” they wrote. “It also suggests re-evaluation of the need to exclude individuals with mere family history of bipolar II, which several studies do.”

The study was funded by COMPASS Pathways, who provided the study drug. Dr. Aaronson reported grants and nonfinancial support (supply of drug) from COMPASS Pathways during the conduct of the study and personal fees from LivaNova, Neuronetics, Genomind, and Sage Therapeutics outside the submitted work. Other disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

One dose of synthetic psilocybin in combination with psychotherapy significantly reduces treatment-resistant depression associated with bipolar II disorder (BDII), a small, nonrandomized clinical trial shows. However, the investigators and other outside experts warn these results should not be overinterpreted.

Three weeks after receiving psilocybin and psychotherapy, all 15 participants’ depression scores dropped by an average of 24 points. Twelve met criteria for response and 11 for remission.

This benefit lasted until the 12-week mark, with 12 participants (80%) meeting criteria for both response and remission. There were no reports of mixed or manic symptoms, psychotic symptoms, or suicidal ideation.

Given the study’s small, open-label design, the findings should be interpreted cautiously, but the investigators say the results are promising.

“The results we saw from this trial are encouraging and further support the clinical study of psychedelics in patients with treatment-resistant bipolar II,” lead investigator Scott T. Aaronson, MD, chief science officer of the Institute for Advanced Diagnostics and Therapeutics at Sheppard Pratt Health System in Baltimore, Maryland, remarked in a press release. “One participant compared the transformation she experienced to taking a deep breath after breathing through a straw for years.”

The findings were published online on December 6, 2023, in JAMA Psychiatry.

Underserved Population

Previous studies show that psilocybin is effective in reducing the symptoms of treatment-resistant depression, major depressive disorder, and anorexia nervosa, most with only mild to moderate adverse effects.

Individuals with bipolar disorder (BPD) have been excluded from psilocybin studies in the last two decades. Investigators attribute this to anecdotal evidence that psychedelics may result in manic episodes in patients with BPD, even though empirical evidence of those effects is limited.

This study included 15 participants (9 female; mean age, 37.8 years) with BDII who had experienced an episode for more than 3 months and failed at least two medications within the current episode.

Participants stopped all psychotropic medications at least 2 weeks prior to the trial and received 25 mg of synthetic COMP360 psilocybin in a controlled setting. Psychotherapy included three sessions before dosing, one during the 8-hour dosing day, and three integration sessions posttreatment.

Depression was measured with the Montgomery Ǻsberg Depression Rating Scale (MADRS) at six points during the 12-week study.

By week 3, all 15 participants had lower MADRS scores, with a mean decrease of 24 points (P < .001). Twelve participants met the response criteria of ≥ 50% reduction in MADRS scores, and 11 met the criteria for remission of a MADRS score of ≤ 10 (both P < .001).

MADRS scores at each posttreatment time point were significantly lower than they were at baseline and the improvement persisted at 12 weeks.

Participants were also monitored for mania and suicidality at various time points during the study, and no significant changes were found from baseline.

“As a first open-label foray into this underserved and treatment-resistant population, care should be taken not to overinterpret the findings,” the authors note, adding that the findings may not apply to patients with BDI or BDII in a mixed or hypomanic phase of their illness.

No Definitive Conclusion

In an accompanying editorial, David B. Yaden, PhD, Johns Hopkins University School of Medicine, Baltimore, Maryland, and colleagues write that the findings are “tantalizingly suggestive,” but ultimately say nothing definitive about the efficacy of psilocybin for BDII.

“The danger is that some individuals will see the large (yet uncontrolled) effect size and believe that a new treatment of bipolar II has been discovered that is substantially better than all other treatments, while neglecting to mention the lack of control condition and substantial psychosocial support included in the study,” Dr. Yaden and colleagues wrote.

They also cautioned that due to the study’s limitations, which include its small sample size and lack of a control group, “it is imperative that the large effect size before to after the study is not overinterpreted.”

However, Dr. Yaden and colleagues also characterized the safety data as “compelling,” noting the safety profile could affect exclusion criteria in future studies involving people with BPD.

“The results of the present study provide preliminary evidence that perhaps those with bipolar II can be safely included in study samples without undue risk of triggering hypomanic episodes,” they wrote. “It also suggests re-evaluation of the need to exclude individuals with mere family history of bipolar II, which several studies do.”

The study was funded by COMPASS Pathways, who provided the study drug. Dr. Aaronson reported grants and nonfinancial support (supply of drug) from COMPASS Pathways during the conduct of the study and personal fees from LivaNova, Neuronetics, Genomind, and Sage Therapeutics outside the submitted work. Other disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.

With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.

Cohen_Lee_S_BOSTON_web.jpg

When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.

It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.

Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.

FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.

Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.

The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.

Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
 

Looking ahead

While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.

In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.

To come out on the “other side” of the PLLR, we will need to find a way to accelerate our ability to identify signals of risk or information that is reassuring (or not reassuring) so that clinicians and patients are not left waiting for the next paper to come out, which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.

With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.

Cohen_Lee_S_BOSTON_web.jpg

When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.

It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.

Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.

FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.

Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.

The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.

Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
 

Looking ahead

While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.

In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.

To come out on the “other side” of the PLLR, we will need to find a way to accelerate our ability to identify signals of risk or information that is reassuring (or not reassuring) so that clinicians and patients are not left waiting for the next paper to come out, which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.

With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.

Cohen_Lee_S_BOSTON_web.jpg

When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.

It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.

Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.

FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.

Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.

The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.

Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
 

Looking ahead

While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.

In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.

To come out on the “other side” of the PLLR, we will need to find a way to accelerate our ability to identify signals of risk or information that is reassuring (or not reassuring) so that clinicians and patients are not left waiting for the next paper to come out, which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

TOPLINE:

A meta-analysis supports the use of mobile mental health apps, both as a standalone and added to conventional treatment, for adults with moderate to severe depression.

METHODOLOGY:

Mobile mental health apps have proliferated but data on their effectiveness in different patient populations is lacking.

To investigate, researchers conducted a systematic review and meta-analysis of 13 randomized clinical trials assessing treatment efficacy of mobile mental health apps in 1470 adults with moderate to severe depression.

The primary outcome was change in depression symptoms from pre- to post-treatment; secondary outcomes included patient-level factors associated with app efficacy.

TAKEAWAY: 

Mobile app interventions were associated with significantly reduced depressive symptoms vs both active and inactive control groups, with a medium effect size (standardized mean difference [SMD] 0.50).

App interventions delivered for < 8 weeks had a significantly greater effect size than those delivered for 8+ weeks (SMD 0.77 vs 0.43). Apps were more effective in patients not on medication or in therapy. Apps offering rewards or incentives also appeared to be more effective.

Interventions with in-app notifications were associated with significantly lower treatment outcomes (SMD 0.45) than interventions without (SMD 0.45 vs 0.71).

IN PRACTICE:

“The significant treatment efficacy of app-based interventions compared with active and inactive controls suggests the potential of mobile app interventions as an alternative to conventional psychotherapy, with further merits in accessibility, financial affordability, and safety from stigma,” the authors write.

SOURCE:

The study, with first author Hayoung Bae, BA, with Korea University School of Psychology, Seoul, South Korea, was published online November 20 in JAMA Network Open .

LIMITATIONS:

The findings are based on a small number of trials, with significant heterogeneity among the included trials. The analysis included only English-language publications. Using summary data for the subgroup analyses might have prevented a detailed understanding of the moderating associations of individual participant characteristics.

DISCLOSURES:

The study was supported by a grant from the National Research Foundation funded by the Korean government. The authors report no relevant financial relationships.

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

TOPLINE:

A meta-analysis supports the use of mobile mental health apps, both as a standalone and added to conventional treatment, for adults with moderate to severe depression.

METHODOLOGY:

Mobile mental health apps have proliferated but data on their effectiveness in different patient populations is lacking.

To investigate, researchers conducted a systematic review and meta-analysis of 13 randomized clinical trials assessing treatment efficacy of mobile mental health apps in 1470 adults with moderate to severe depression.

The primary outcome was change in depression symptoms from pre- to post-treatment; secondary outcomes included patient-level factors associated with app efficacy.

TAKEAWAY: 

Mobile app interventions were associated with significantly reduced depressive symptoms vs both active and inactive control groups, with a medium effect size (standardized mean difference [SMD] 0.50).

App interventions delivered for < 8 weeks had a significantly greater effect size than those delivered for 8+ weeks (SMD 0.77 vs 0.43). Apps were more effective in patients not on medication or in therapy. Apps offering rewards or incentives also appeared to be more effective.

Interventions with in-app notifications were associated with significantly lower treatment outcomes (SMD 0.45) than interventions without (SMD 0.45 vs 0.71).

IN PRACTICE:

“The significant treatment efficacy of app-based interventions compared with active and inactive controls suggests the potential of mobile app interventions as an alternative to conventional psychotherapy, with further merits in accessibility, financial affordability, and safety from stigma,” the authors write.

SOURCE:

The study, with first author Hayoung Bae, BA, with Korea University School of Psychology, Seoul, South Korea, was published online November 20 in JAMA Network Open .

LIMITATIONS:

The findings are based on a small number of trials, with significant heterogeneity among the included trials. The analysis included only English-language publications. Using summary data for the subgroup analyses might have prevented a detailed understanding of the moderating associations of individual participant characteristics.

DISCLOSURES:

The study was supported by a grant from the National Research Foundation funded by the Korean government. The authors report no relevant financial relationships.

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

TOPLINE:

A meta-analysis supports the use of mobile mental health apps, both as a standalone and added to conventional treatment, for adults with moderate to severe depression.

METHODOLOGY:

Mobile mental health apps have proliferated but data on their effectiveness in different patient populations is lacking.

To investigate, researchers conducted a systematic review and meta-analysis of 13 randomized clinical trials assessing treatment efficacy of mobile mental health apps in 1470 adults with moderate to severe depression.

The primary outcome was change in depression symptoms from pre- to post-treatment; secondary outcomes included patient-level factors associated with app efficacy.

TAKEAWAY: 

Mobile app interventions were associated with significantly reduced depressive symptoms vs both active and inactive control groups, with a medium effect size (standardized mean difference [SMD] 0.50).

App interventions delivered for < 8 weeks had a significantly greater effect size than those delivered for 8+ weeks (SMD 0.77 vs 0.43). Apps were more effective in patients not on medication or in therapy. Apps offering rewards or incentives also appeared to be more effective.

Interventions with in-app notifications were associated with significantly lower treatment outcomes (SMD 0.45) than interventions without (SMD 0.45 vs 0.71).

IN PRACTICE:

“The significant treatment efficacy of app-based interventions compared with active and inactive controls suggests the potential of mobile app interventions as an alternative to conventional psychotherapy, with further merits in accessibility, financial affordability, and safety from stigma,” the authors write.

SOURCE:

The study, with first author Hayoung Bae, BA, with Korea University School of Psychology, Seoul, South Korea, was published online November 20 in JAMA Network Open .

LIMITATIONS:

The findings are based on a small number of trials, with significant heterogeneity among the included trials. The analysis included only English-language publications. Using summary data for the subgroup analyses might have prevented a detailed understanding of the moderating associations of individual participant characteristics.

DISCLOSURES:

The study was supported by a grant from the National Research Foundation funded by the Korean government. The authors report no relevant financial relationships.

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