Clinical Psychiatry News

Bullying, heavy social media use, experimentation with drugs and alcohol: These are the well-described hazards of adolescence. We have growing knowledge of the risks associated with these experiences and which youth are more vulnerable to these risks. Developmentally, adolescence is a time of critical brain development marked by heightened sensitivity to social approval and limited impulse control. Adolescents also have growing autonomy from parents alongside a stronger need for time with friends (the new peer home away from the parental home). These factors alone make adolescence a period of heightened sensitivity to these experiences, but some youth have greater vulnerability to develop psychopathology such as anxiety, depression, eating disorders, or addiction after exposure to these common experiences. Pediatricians can assess these broader vulnerabilities during well child visits of pre- and early teens and offer patients and their parents strategies for minimizing risk and cultivating resilience.

Bullying

Bullying, both verbal and physical, has long been an unwelcome part of youth. Cellphones and social media have brought bullying into the 21st century. Cyberbullying has meant that targeted youth are no longer safe after school and it carries higher risk of self-harm and suicidality than the analog version. No child benefits from bullying, but some children are more vulnerable to develop an anxiety or mood disorder, self-injury, or suicidality, whereas others experience stress and distress, but are able to adaptively seek support from friends and adults and stay on track developmentally, even to flourish. There is evidence that girls and LGBTQ youth are more commonly bullied and at higher risk for depression, self-harm, and suicidality as a consequence of cyberbullying. Youth already suffering from a psychiatric illness or substance abuse who are bullied are at higher risk for self-harm and suicidality than that of their bullied peers. Youth whose parents score high on measures of distress and family dysfunction also face higher risk of self-harm and suicidality after bullying.¹

Social Media

Unlike bullying, social media has been a force only in 21st century life, with Facebook starting in 2004 and cellphones in common use by adolescents in the past 2 decades. While there are potential benefits of social media use, such as stronger connections to supportive peers for isolated LGBTQ youth or youth who live in rural areas, there are also risks. Of course, social media carries the risk of cyberbullying. It also carries the risk for very heavy patterns of use that can interfere with physical activity, adequate sleep, academic performance, and healthy in-person social activities. There is robust emerging evidence that heavy users have higher rates of mood disorders and anxiety symptoms, although it is unclear whether social media exacerbates, or more social media use is the result of depression and/or anxiety. Adolescents’ desire for social acceptance makes them especially sensitive to the social rewards of “likes” and they are thus vulnerable to becoming heavy users. Adolescent girls who are heavy users are vulnerable to developing a disordered body image and eating disorders. Those youth with especially low levels of impulse control, such as those with ADHD, have greater risk of developing problematic use.^2-4

Substance Use and Abuse

Exploration of alcohol and drug use has been a common experience, and hazard, of adolescence for many generations. As a result, we have richer knowledge of those factors that are associated with risk of and protection against that use progressing to a use disorder. Earlier age at first experimentation appears to be independently correlated with increased risk of developing a substance use disorder. Every pediatrician should be aware of a family history of substance use disorders, especially alcohol, as they are strongly associated with higher risk. Youth with temperaments that are sensation seeking, externalizing and impulsive are at higher risk. Youth with anxiety and mood disorders and untreated attention deficit disorders are at higher risk. Youth whose parents have high levels of conflict or “permissive” parenting styles are at higher risk as are those who as children experienced abuse or neglect.^5-7

Minimizing Risk and Cultivating Resilience

Protective factors balance these risks: adequate sleep; positive relationships with friends and parents; and confidence in their academic, athletic, or social abilities all are correlated with good outcomes after bullying, drug and alcohol use, and social media use. These teenagers are meaningfully connected to caring adults and peers, have a future orientation, and typically have higher self-esteem. Youth whose parents balance attunement with rules and expectations (“authoritative” parenting) appear to be at lower risk of poor mental health outcomes associated with heavy social media use as well as other risk behaviors. These parents have clear rules and expectations, including about drugs and alcohol, and enforce rules reasonably calmly and consistently. Youth whose families eat dinner together at least three times weekly, who attend schools that offer a wide range of after-school activities, and who learn to use problem-focused coping skills rather than emotion-focused coping skills are protected against poor mental health outcomes in the face of these challenges.

While bullying is a stressor, social media and substances may seem like ways of managing stress and connecting with peers. There are youth with clear vulnerabilities to the risks associated with each of them. Shared factors include vulnerable temperaments, high conflict or permissive parenting, family history of substance use disorders or preexisting psychiatric illness. Pediatricians are in a unique position to raise teenagers’ awareness of their specific vulnerabilities. Talk about the heightened risk of experimentation with alcohol or drugs in your patients who are in treatment for an anxiety or mood disorder. Help them cultivate critical thinking — an adolescent specialty — around marketing and peer pressure. Remind them that social media companies make money from keeping them online longer. Then help them identify what strategies are in their control, such as limiting their time online. What else could they be doing with their time that they actually enjoy? Remind them about the value of protecting time for adequate sleep, regular exercise, and sitting down for dinner with their family. Ask about their nourishing relationships with peers and adults and talk about the value of protecting time for them. Ask your patients and their parents about how they face stress, emphasizing their ability to locate what is within their control. While awareness of feelings is important, learning to manage intense emotions is more connected to healthy habits of sleep and exercise and strategies to get support or pivot to engaging activities. Discussing this openly models for parents how to bear difficulty alongside their children without becoming distressed or punitive themselves. Talk with worried parents about the value of regular meals together, shared physical activities, and supporting time for their children’s emerging interests and hobbies. Equipping your patients and their parents with knowledge about their particular vulnerabilities, reminders about what is known about these risks, and all that is in their power to build resilience, may be as meaningful a public health intervention as asking them about biking with helmets and using seat belts.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Zych I et al. Protective Factors Against Bullying and Cyberbullying: A Systematic Review of Meta-Analyses. Aggress Violent Behav. 2019;45:4-19. doi: 10.1016/j.avb.2018.06.008.

2. Office of the Surgeon General. Social Media and Youth Mental Health: The U.S. Surgeon General’s Advisory. 2023. https://www.ncbi.nlm.nih.gov/books/NBK594761/.

3. Uhls Y et al. Benefits and Costs of Social Media in Adolescence. Pediatrics. 2017 Nov;140(Suppl 2):S67-S70. doi: 10.1542/peds.2016-1758E.

4. Health Advisory on Social Media Use in Adolescence. American Psychological Association (2023).

5. Sloboda Z et al. Revisiting the Concepts of Risk and Protective Factors for Understanding the Etiology and Development of Substance Use and Substance Use Disorders: Implications for Prevention, Substance Use and Misuse, Subst Use Misuse. 2012 Jun-Jul;47(8-9):944-62. doi: 10.3109/10826084.2012.663280.

6. O’Connell M et al. Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities. Washington, DC: The National Academies Press and US Department of Health and Human Services, Substance Abuse and Mental Health Administration. 2009 (https://nap.nationalacademies.org/catalog/12480/preventing-mental-emotional-and-behavioral-disorders-among-young-people-progress).

7. Staiger P et al. Can Emotion-Focused Coping Help Explain the Link Between Posttraumatic Stress Disorder Severity and Triggers for Substance Use in Young Adults? J Subst Abuse Treat. 2009 Mar;36(2):220-6. doi: 10.1016/j.jsat.2008.05.008.

Bullying, heavy social media use, experimentation with drugs and alcohol: These are the well-described hazards of adolescence. We have growing knowledge of the risks associated with these experiences and which youth are more vulnerable to these risks. Developmentally, adolescence is a time of critical brain development marked by heightened sensitivity to social approval and limited impulse control. Adolescents also have growing autonomy from parents alongside a stronger need for time with friends (the new peer home away from the parental home). These factors alone make adolescence a period of heightened sensitivity to these experiences, but some youth have greater vulnerability to develop psychopathology such as anxiety, depression, eating disorders, or addiction after exposure to these common experiences. Pediatricians can assess these broader vulnerabilities during well child visits of pre- and early teens and offer patients and their parents strategies for minimizing risk and cultivating resilience.

Bullying

Bullying, both verbal and physical, has long been an unwelcome part of youth. Cellphones and social media have brought bullying into the 21st century. Cyberbullying has meant that targeted youth are no longer safe after school and it carries higher risk of self-harm and suicidality than the analog version. No child benefits from bullying, but some children are more vulnerable to develop an anxiety or mood disorder, self-injury, or suicidality, whereas others experience stress and distress, but are able to adaptively seek support from friends and adults and stay on track developmentally, even to flourish. There is evidence that girls and LGBTQ youth are more commonly bullied and at higher risk for depression, self-harm, and suicidality as a consequence of cyberbullying. Youth already suffering from a psychiatric illness or substance abuse who are bullied are at higher risk for self-harm and suicidality than that of their bullied peers. Youth whose parents score high on measures of distress and family dysfunction also face higher risk of self-harm and suicidality after bullying.¹

Social Media

Unlike bullying, social media has been a force only in 21st century life, with Facebook starting in 2004 and cellphones in common use by adolescents in the past 2 decades. While there are potential benefits of social media use, such as stronger connections to supportive peers for isolated LGBTQ youth or youth who live in rural areas, there are also risks. Of course, social media carries the risk of cyberbullying. It also carries the risk for very heavy patterns of use that can interfere with physical activity, adequate sleep, academic performance, and healthy in-person social activities. There is robust emerging evidence that heavy users have higher rates of mood disorders and anxiety symptoms, although it is unclear whether social media exacerbates, or more social media use is the result of depression and/or anxiety. Adolescents’ desire for social acceptance makes them especially sensitive to the social rewards of “likes” and they are thus vulnerable to becoming heavy users. Adolescent girls who are heavy users are vulnerable to developing a disordered body image and eating disorders. Those youth with especially low levels of impulse control, such as those with ADHD, have greater risk of developing problematic use.^2-4

Substance Use and Abuse

Exploration of alcohol and drug use has been a common experience, and hazard, of adolescence for many generations. As a result, we have richer knowledge of those factors that are associated with risk of and protection against that use progressing to a use disorder. Earlier age at first experimentation appears to be independently correlated with increased risk of developing a substance use disorder. Every pediatrician should be aware of a family history of substance use disorders, especially alcohol, as they are strongly associated with higher risk. Youth with temperaments that are sensation seeking, externalizing and impulsive are at higher risk. Youth with anxiety and mood disorders and untreated attention deficit disorders are at higher risk. Youth whose parents have high levels of conflict or “permissive” parenting styles are at higher risk as are those who as children experienced abuse or neglect.^5-7

Minimizing Risk and Cultivating Resilience

Protective factors balance these risks: adequate sleep; positive relationships with friends and parents; and confidence in their academic, athletic, or social abilities all are correlated with good outcomes after bullying, drug and alcohol use, and social media use. These teenagers are meaningfully connected to caring adults and peers, have a future orientation, and typically have higher self-esteem. Youth whose parents balance attunement with rules and expectations (“authoritative” parenting) appear to be at lower risk of poor mental health outcomes associated with heavy social media use as well as other risk behaviors. These parents have clear rules and expectations, including about drugs and alcohol, and enforce rules reasonably calmly and consistently. Youth whose families eat dinner together at least three times weekly, who attend schools that offer a wide range of after-school activities, and who learn to use problem-focused coping skills rather than emotion-focused coping skills are protected against poor mental health outcomes in the face of these challenges.

While bullying is a stressor, social media and substances may seem like ways of managing stress and connecting with peers. There are youth with clear vulnerabilities to the risks associated with each of them. Shared factors include vulnerable temperaments, high conflict or permissive parenting, family history of substance use disorders or preexisting psychiatric illness. Pediatricians are in a unique position to raise teenagers’ awareness of their specific vulnerabilities. Talk about the heightened risk of experimentation with alcohol or drugs in your patients who are in treatment for an anxiety or mood disorder. Help them cultivate critical thinking — an adolescent specialty — around marketing and peer pressure. Remind them that social media companies make money from keeping them online longer. Then help them identify what strategies are in their control, such as limiting their time online. What else could they be doing with their time that they actually enjoy? Remind them about the value of protecting time for adequate sleep, regular exercise, and sitting down for dinner with their family. Ask about their nourishing relationships with peers and adults and talk about the value of protecting time for them. Ask your patients and their parents about how they face stress, emphasizing their ability to locate what is within their control. While awareness of feelings is important, learning to manage intense emotions is more connected to healthy habits of sleep and exercise and strategies to get support or pivot to engaging activities. Discussing this openly models for parents how to bear difficulty alongside their children without becoming distressed or punitive themselves. Talk with worried parents about the value of regular meals together, shared physical activities, and supporting time for their children’s emerging interests and hobbies. Equipping your patients and their parents with knowledge about their particular vulnerabilities, reminders about what is known about these risks, and all that is in their power to build resilience, may be as meaningful a public health intervention as asking them about biking with helmets and using seat belts.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Zych I et al. Protective Factors Against Bullying and Cyberbullying: A Systematic Review of Meta-Analyses. Aggress Violent Behav. 2019;45:4-19. doi: 10.1016/j.avb.2018.06.008.

2. Office of the Surgeon General. Social Media and Youth Mental Health: The U.S. Surgeon General’s Advisory. 2023. https://www.ncbi.nlm.nih.gov/books/NBK594761/.

3. Uhls Y et al. Benefits and Costs of Social Media in Adolescence. Pediatrics. 2017 Nov;140(Suppl 2):S67-S70. doi: 10.1542/peds.2016-1758E.

4. Health Advisory on Social Media Use in Adolescence. American Psychological Association (2023).

5. Sloboda Z et al. Revisiting the Concepts of Risk and Protective Factors for Understanding the Etiology and Development of Substance Use and Substance Use Disorders: Implications for Prevention, Substance Use and Misuse, Subst Use Misuse. 2012 Jun-Jul;47(8-9):944-62. doi: 10.3109/10826084.2012.663280.

6. O’Connell M et al. Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities. Washington, DC: The National Academies Press and US Department of Health and Human Services, Substance Abuse and Mental Health Administration. 2009 (https://nap.nationalacademies.org/catalog/12480/preventing-mental-emotional-and-behavioral-disorders-among-young-people-progress).

7. Staiger P et al. Can Emotion-Focused Coping Help Explain the Link Between Posttraumatic Stress Disorder Severity and Triggers for Substance Use in Young Adults? J Subst Abuse Treat. 2009 Mar;36(2):220-6. doi: 10.1016/j.jsat.2008.05.008.

Bullying, heavy social media use, experimentation with drugs and alcohol: These are the well-described hazards of adolescence. We have growing knowledge of the risks associated with these experiences and which youth are more vulnerable to these risks. Developmentally, adolescence is a time of critical brain development marked by heightened sensitivity to social approval and limited impulse control. Adolescents also have growing autonomy from parents alongside a stronger need for time with friends (the new peer home away from the parental home). These factors alone make adolescence a period of heightened sensitivity to these experiences, but some youth have greater vulnerability to develop psychopathology such as anxiety, depression, eating disorders, or addiction after exposure to these common experiences. Pediatricians can assess these broader vulnerabilities during well child visits of pre- and early teens and offer patients and their parents strategies for minimizing risk and cultivating resilience.

Bullying

Bullying, both verbal and physical, has long been an unwelcome part of youth. Cellphones and social media have brought bullying into the 21st century. Cyberbullying has meant that targeted youth are no longer safe after school and it carries higher risk of self-harm and suicidality than the analog version. No child benefits from bullying, but some children are more vulnerable to develop an anxiety or mood disorder, self-injury, or suicidality, whereas others experience stress and distress, but are able to adaptively seek support from friends and adults and stay on track developmentally, even to flourish. There is evidence that girls and LGBTQ youth are more commonly bullied and at higher risk for depression, self-harm, and suicidality as a consequence of cyberbullying. Youth already suffering from a psychiatric illness or substance abuse who are bullied are at higher risk for self-harm and suicidality than that of their bullied peers. Youth whose parents score high on measures of distress and family dysfunction also face higher risk of self-harm and suicidality after bullying.¹

Social Media

Unlike bullying, social media has been a force only in 21st century life, with Facebook starting in 2004 and cellphones in common use by adolescents in the past 2 decades. While there are potential benefits of social media use, such as stronger connections to supportive peers for isolated LGBTQ youth or youth who live in rural areas, there are also risks. Of course, social media carries the risk of cyberbullying. It also carries the risk for very heavy patterns of use that can interfere with physical activity, adequate sleep, academic performance, and healthy in-person social activities. There is robust emerging evidence that heavy users have higher rates of mood disorders and anxiety symptoms, although it is unclear whether social media exacerbates, or more social media use is the result of depression and/or anxiety. Adolescents’ desire for social acceptance makes them especially sensitive to the social rewards of “likes” and they are thus vulnerable to becoming heavy users. Adolescent girls who are heavy users are vulnerable to developing a disordered body image and eating disorders. Those youth with especially low levels of impulse control, such as those with ADHD, have greater risk of developing problematic use.^2-4

Substance Use and Abuse

Exploration of alcohol and drug use has been a common experience, and hazard, of adolescence for many generations. As a result, we have richer knowledge of those factors that are associated with risk of and protection against that use progressing to a use disorder. Earlier age at first experimentation appears to be independently correlated with increased risk of developing a substance use disorder. Every pediatrician should be aware of a family history of substance use disorders, especially alcohol, as they are strongly associated with higher risk. Youth with temperaments that are sensation seeking, externalizing and impulsive are at higher risk. Youth with anxiety and mood disorders and untreated attention deficit disorders are at higher risk. Youth whose parents have high levels of conflict or “permissive” parenting styles are at higher risk as are those who as children experienced abuse or neglect.^5-7

Minimizing Risk and Cultivating Resilience

Protective factors balance these risks: adequate sleep; positive relationships with friends and parents; and confidence in their academic, athletic, or social abilities all are correlated with good outcomes after bullying, drug and alcohol use, and social media use. These teenagers are meaningfully connected to caring adults and peers, have a future orientation, and typically have higher self-esteem. Youth whose parents balance attunement with rules and expectations (“authoritative” parenting) appear to be at lower risk of poor mental health outcomes associated with heavy social media use as well as other risk behaviors. These parents have clear rules and expectations, including about drugs and alcohol, and enforce rules reasonably calmly and consistently. Youth whose families eat dinner together at least three times weekly, who attend schools that offer a wide range of after-school activities, and who learn to use problem-focused coping skills rather than emotion-focused coping skills are protected against poor mental health outcomes in the face of these challenges.

While bullying is a stressor, social media and substances may seem like ways of managing stress and connecting with peers. There are youth with clear vulnerabilities to the risks associated with each of them. Shared factors include vulnerable temperaments, high conflict or permissive parenting, family history of substance use disorders or preexisting psychiatric illness. Pediatricians are in a unique position to raise teenagers’ awareness of their specific vulnerabilities. Talk about the heightened risk of experimentation with alcohol or drugs in your patients who are in treatment for an anxiety or mood disorder. Help them cultivate critical thinking — an adolescent specialty — around marketing and peer pressure. Remind them that social media companies make money from keeping them online longer. Then help them identify what strategies are in their control, such as limiting their time online. What else could they be doing with their time that they actually enjoy? Remind them about the value of protecting time for adequate sleep, regular exercise, and sitting down for dinner with their family. Ask about their nourishing relationships with peers and adults and talk about the value of protecting time for them. Ask your patients and their parents about how they face stress, emphasizing their ability to locate what is within their control. While awareness of feelings is important, learning to manage intense emotions is more connected to healthy habits of sleep and exercise and strategies to get support or pivot to engaging activities. Discussing this openly models for parents how to bear difficulty alongside their children without becoming distressed or punitive themselves. Talk with worried parents about the value of regular meals together, shared physical activities, and supporting time for their children’s emerging interests and hobbies. Equipping your patients and their parents with knowledge about their particular vulnerabilities, reminders about what is known about these risks, and all that is in their power to build resilience, may be as meaningful a public health intervention as asking them about biking with helmets and using seat belts.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

References

1. Zych I et al. Protective Factors Against Bullying and Cyberbullying: A Systematic Review of Meta-Analyses. Aggress Violent Behav. 2019;45:4-19. doi: 10.1016/j.avb.2018.06.008.

2. Office of the Surgeon General. Social Media and Youth Mental Health: The U.S. Surgeon General’s Advisory. 2023. https://www.ncbi.nlm.nih.gov/books/NBK594761/.

3. Uhls Y et al. Benefits and Costs of Social Media in Adolescence. Pediatrics. 2017 Nov;140(Suppl 2):S67-S70. doi: 10.1542/peds.2016-1758E.

4. Health Advisory on Social Media Use in Adolescence. American Psychological Association (2023).

5. Sloboda Z et al. Revisiting the Concepts of Risk and Protective Factors for Understanding the Etiology and Development of Substance Use and Substance Use Disorders: Implications for Prevention, Substance Use and Misuse, Subst Use Misuse. 2012 Jun-Jul;47(8-9):944-62. doi: 10.3109/10826084.2012.663280.

6. O’Connell M et al. Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities. Washington, DC: The National Academies Press and US Department of Health and Human Services, Substance Abuse and Mental Health Administration. 2009 (https://nap.nationalacademies.org/catalog/12480/preventing-mental-emotional-and-behavioral-disorders-among-young-people-progress).

7. Staiger P et al. Can Emotion-Focused Coping Help Explain the Link Between Posttraumatic Stress Disorder Severity and Triggers for Substance Use in Young Adults? J Subst Abuse Treat. 2009 Mar;36(2):220-6. doi: 10.1016/j.jsat.2008.05.008.

On a November morning in 2022, James Messenger opened wide and swallowed a capsule like no other.

Messenger was no stranger to taking pills.

He’d first experimented with prescription opioids as a teenager in Morgantown, West Virginia, battled addiction on-and-off since, and known more than 70 people who had fatally overdosed. So, when asked to test a new “smart pill” that could detect an overdose in progress and call for help, he didn’t hesitate to join the study.

“I’ve lost pretty much every good friend I’ve ever had to this,” said Mr. Messenger. “This pill could save a lot of lives.”

The new Vitals Monitoring capsule he tested is just one example in a growing effort to radically rethink what the humble pill is capable of.

As far back as 1965, scientists introduced the Heidelberg capsule, an electronic pill that measured acidity from within the gut. In 1994, the University of Buffalo coined the term “smart pill” with a device promising to ferry medicine to a precise spot in the intestine, “like the tiny ship in the film Fantastic Voyage.” And in 2001, the US Food and Drug Administration (FDA) approved the first video capsule endoscope, a miniature-camera-toting pill that enabled noninvasive imaging of the small intestine.

Despite these milestones, the smart pill revolution has been slow to catch on due to cost, technological limitations, and some resistance among clinicians and patients.

But now, nearly 300 iterations are in various stages of development, according to a 2022 analysis. Advances in materials, imaging, and artificial intelligence (AI) are helping address everything from sleep apnea to HIV/AIDS to gut disorders via real-time tracking and real-time help.

“These technologies could enable us to shift the paradigm from ‘Let’s wait until the patient comes to us and find out what happened’ to ‘Let’s see how things are changing in real time, intervene now, and personalize that intervention,’ ” said Peter Chai, MD, associate professor of emergency medicine and health technology researcher at Brigham and Women’s Hospital in Boston.
 

Tracking Vitals From the Inside Out

Already, overdose-reversal agents like naloxone are saving lives. But more than 60% of overdoses occur when no one is around to administer them.

“While we need to focus on treatment, we also need to come up with more acute ways to save individuals when treatment doesn’t work or relapse occurs,” said James J. Mahoney III, PhD, director of addictions research at the Rockefeller Neuroscience Institute at West Virginia University (WVU), Morgantown.

Enter Celero Systems, a Massachusetts-based digital health company that has developed a vitamin-sized capsule packed with tiny sensors, microprocessors, and a radio antenna. It can measure breathing, heart rate, and core temperature — all from deep within the gut.

Respiratory distress is a hallmark early sign of an overdose. But it can be hard to monitor from a distance, especially in populations without access to a charged smartwatch.

Dr. Mahoney imagines a day when patients at risk could be given a weekly pill like Celero’s. If their respiratory rate drops below a dangerous level, it could alert loved ones or, better yet, release an overdose-reversal drug.

“It’s early days,” stressed Dr. Mahoney, whose team has been conducting pilot tests of the pill. “But initial data look promising.”

For one study, published in the journal Device in November 2023, the research team administered an overdose of fentanyl to anesthetized pigs with the pill in their stomachs. The capsule was able to detect respiratory depression within a minute and alert researchers via their laptop in time to step in.

When they gave the pill to 10 volunteers undergoing sleep studies at WVU, they found it could detect respiration rate with an accuracy of 93% compared with external monitoring devices — a feature that could also help diagnose sleep apnea or chronic obstructive pulmonary disease without expensive, intrusive tests.

Accuracy for heart rate was nearly 97%.

In another yet-to-be published trial, Dr. Mahoney tested the device with 10 volunteers in a residential treatment center to determine how well it could be tolerated.

Among the participants was Mr. Messenger, who said the thought of being tracked didn’t bother him.

“It was simple — just like taking a multivitamin,” said Mr. Messenger, now 34, sober, and working as a peer recovery support specialist at a hospital in his hometown. “It could be a great way to keep people alive long enough for them to get their head wrapped around the idea of treatment.”
 

Boosting Medication Adherence

At Brigham and Women’s Hospital, Dr. Chai is experimenting with a different smart pill — one he believes could help curb the ongoing HIV/AIDS epidemic.

Developed by Florida-based etectRx, the ID-Cap consists of a gelatin capsule embedded with a tiny radiofrequency transmitter, similar to the kind in retail antitheft devices. The capsule can be filled with a variety of medications. When swallowed, stomach acid dissolves the gel and activates the transmitter, which sends a signal to a receiver on a smartwatch, smartphone, or wall-mounted reader to confirm the medication was taken. If it isn’t, the patient’s smartphone or smart speaker might nudge them with a reminder or a family member might be notified.

In recent trials of men at a high risk for HIV, the system improved adherence to the once-daily prevention regimen pre-exposure prophylaxis (PrEP) by double digits.

“PrEP is almost 99% effective in preventing HIV, but you have to take it,” said Dr. Chai, who led the trials. “That seems like such a simple thing, but anyone who is chronically on medication can tell you just how difficult it can be.”

The pill is not the first designed to improve adherence. In 2017, the FDA approved the first digital ingestion tracking system, Abilify MyCite, for the treatment of schizophrenia and bipolar disorder. But its maker, Proteus Digital Health, filed for bankruptcy in 2020 after struggling to recruit patients willing to be tracked. (Some expressed privacy concerns. Others disliked the uncomfortable patch that received and forwarded the signal.)

More recent designs have been streamlined to ditch the patch, said etectRx senior vice president of operations Chris Carnes, PhD. And the cost of making a pill this kind of “smart” has come down to about a dollar.

So far, said Dr. Chai, in the patients he’s worked with, perceived benefits generally outweigh privacy concerns.

Studies are now underway in patients with heart disease and tuberculosis, and the company hopes to move into the aging and memory care space where medication-adherence is a serious problem.

“For us, or any company in this space, to succeed, you have to have a strong business case,” said Dr. Carnes. “If family members can keep their loved ones at home a little longer at an additional cost of $30 a month, that’s a no-brainer.”
 

Pillcams 2.0

Twenty-three years ago, the first video capsule endoscopy made it possible to image the small intestine via a tiny camera you swallow.

Such “pillcams” offered a more patient-friendly way to diagnose small bowel disorders, such as gastrointestinal bleeding and Crohn’s disease. Rather than undergoing sedation or anesthesia, as required during tube-based endoscopy, patients can go about their day as the pill painlessly passes through their gastrointestinal (GI) tract, capturing and recording data and images.

But the pills have their downsides.

Because they move passively, driven by movement in the intestine, they can miss trouble spots. Their ability to image the esophagus, stomach, and colon has proven limited. And unlike other procedures, like colonoscopy, they can’t intervene with therapy, like removing polyps.

The pillcam “had so much promise, to sort of revolutionize endoscopy, but it never really got the adoption that it seemed like it might,” said Andrew Meltzer, MD, professor of emergency medicine at the GW School of Medicine and Health Sciences in Washington.

That could soon change, he said, thanks to advances in locomotion and AI.

In a recent study of 40 patients, Dr. Meltzer tested a new magnetically controlled capsule endoscopy. Standing at a patient’s side, he could use a joystick to steer the pill around the stomach, capturing images in real time.

The pilot study, published in June 2023, found that the pill clearly identified six key stomach landmarks accurately 95% of the time and didn’t miss any lesions caught with traditional endoscopy. Notably, 80% of the patients preferred the pillcam over the tube.

“They are awake. They can go to work as soon as they leave. And it’s easy for them to tolerate,” Dr. Meltzer said.

More research is necessary, but Dr. Meltzer believes the technology could be particularly useful in the emergency department, allowing doctors to rule out high-risk bleeds in the stomach on the spot without admitting patients unnecessarily or making them return for a traditional scope.

“It has the potential to increase screening and provide more cost-effective care in emergencies,” he said.

It could also be useful in the telemedicine space, allowing a doctor to “drive” the pill from afar to diagnose a distant patient.

Someday, AI could enable the capsule to drive itself, so a doctor could merely press a button and wait. Or it could be adapted to treat what it finds, like administering a drug or cauterizing a bleed.

“If we can come up with a Mars rover which can explore other planets, we should be able to have something that can explore the stomach remotely,” Dr. Meltzer said.
 

Swallowing the Future

At the California Institute of Technology, researchers have developed a “location-aware” smart pill that uses magnetic fields to help pinpoint its location in the twists and turns of intestines. This could be useful for monitoring food in the GI tract to determine why things aren’t moving.

Other researchers are using AI models to enhance the transmission of video from inside the body and reduce the time it takes to interpret images.

One group at the Massachusetts Institute of Technology has developed a vibrating weight loss capsule designed to stimulate receptors in the gut to signal the brain that the person is full.

Not everyone is a fan of the smart-pill revolution. Some critics have raised concerns about privacy. Others fear that doctors risk yielding too much power to technology. Even those who are excited about the pills’ possibilities temper their optimism with caution.

None of these smart pills have gone mainstream yet in clinical practice, said Vivek Kaul, MD, professor of medicine at the University of Rochester Medical Center, Rochester, New York, and secretary general of the World Gastroenterology Organization.

Clinical validation, accessibility, and insurance coverage “will be critical in shaping their role,” he said. “But overall, it would be fair to state that this technology has come of age and the future is bright.”
 

A version of this article appeared on Medscape.com.

On a November morning in 2022, James Messenger opened wide and swallowed a capsule like no other.

Messenger was no stranger to taking pills.

He’d first experimented with prescription opioids as a teenager in Morgantown, West Virginia, battled addiction on-and-off since, and known more than 70 people who had fatally overdosed. So, when asked to test a new “smart pill” that could detect an overdose in progress and call for help, he didn’t hesitate to join the study.

“I’ve lost pretty much every good friend I’ve ever had to this,” said Mr. Messenger. “This pill could save a lot of lives.”

The new Vitals Monitoring capsule he tested is just one example in a growing effort to radically rethink what the humble pill is capable of.

As far back as 1965, scientists introduced the Heidelberg capsule, an electronic pill that measured acidity from within the gut. In 1994, the University of Buffalo coined the term “smart pill” with a device promising to ferry medicine to a precise spot in the intestine, “like the tiny ship in the film Fantastic Voyage.” And in 2001, the US Food and Drug Administration (FDA) approved the first video capsule endoscope, a miniature-camera-toting pill that enabled noninvasive imaging of the small intestine.

Despite these milestones, the smart pill revolution has been slow to catch on due to cost, technological limitations, and some resistance among clinicians and patients.

But now, nearly 300 iterations are in various stages of development, according to a 2022 analysis. Advances in materials, imaging, and artificial intelligence (AI) are helping address everything from sleep apnea to HIV/AIDS to gut disorders via real-time tracking and real-time help.

“These technologies could enable us to shift the paradigm from ‘Let’s wait until the patient comes to us and find out what happened’ to ‘Let’s see how things are changing in real time, intervene now, and personalize that intervention,’ ” said Peter Chai, MD, associate professor of emergency medicine and health technology researcher at Brigham and Women’s Hospital in Boston.
 

Tracking Vitals From the Inside Out

Already, overdose-reversal agents like naloxone are saving lives. But more than 60% of overdoses occur when no one is around to administer them.

“While we need to focus on treatment, we also need to come up with more acute ways to save individuals when treatment doesn’t work or relapse occurs,” said James J. Mahoney III, PhD, director of addictions research at the Rockefeller Neuroscience Institute at West Virginia University (WVU), Morgantown.

Enter Celero Systems, a Massachusetts-based digital health company that has developed a vitamin-sized capsule packed with tiny sensors, microprocessors, and a radio antenna. It can measure breathing, heart rate, and core temperature — all from deep within the gut.

Respiratory distress is a hallmark early sign of an overdose. But it can be hard to monitor from a distance, especially in populations without access to a charged smartwatch.

Dr. Mahoney imagines a day when patients at risk could be given a weekly pill like Celero’s. If their respiratory rate drops below a dangerous level, it could alert loved ones or, better yet, release an overdose-reversal drug.

“It’s early days,” stressed Dr. Mahoney, whose team has been conducting pilot tests of the pill. “But initial data look promising.”

For one study, published in the journal Device in November 2023, the research team administered an overdose of fentanyl to anesthetized pigs with the pill in their stomachs. The capsule was able to detect respiratory depression within a minute and alert researchers via their laptop in time to step in.

When they gave the pill to 10 volunteers undergoing sleep studies at WVU, they found it could detect respiration rate with an accuracy of 93% compared with external monitoring devices — a feature that could also help diagnose sleep apnea or chronic obstructive pulmonary disease without expensive, intrusive tests.

Accuracy for heart rate was nearly 97%.

In another yet-to-be published trial, Dr. Mahoney tested the device with 10 volunteers in a residential treatment center to determine how well it could be tolerated.

Among the participants was Mr. Messenger, who said the thought of being tracked didn’t bother him.

“It was simple — just like taking a multivitamin,” said Mr. Messenger, now 34, sober, and working as a peer recovery support specialist at a hospital in his hometown. “It could be a great way to keep people alive long enough for them to get their head wrapped around the idea of treatment.”
 

Boosting Medication Adherence

At Brigham and Women’s Hospital, Dr. Chai is experimenting with a different smart pill — one he believes could help curb the ongoing HIV/AIDS epidemic.

Developed by Florida-based etectRx, the ID-Cap consists of a gelatin capsule embedded with a tiny radiofrequency transmitter, similar to the kind in retail antitheft devices. The capsule can be filled with a variety of medications. When swallowed, stomach acid dissolves the gel and activates the transmitter, which sends a signal to a receiver on a smartwatch, smartphone, or wall-mounted reader to confirm the medication was taken. If it isn’t, the patient’s smartphone or smart speaker might nudge them with a reminder or a family member might be notified.

In recent trials of men at a high risk for HIV, the system improved adherence to the once-daily prevention regimen pre-exposure prophylaxis (PrEP) by double digits.

“PrEP is almost 99% effective in preventing HIV, but you have to take it,” said Dr. Chai, who led the trials. “That seems like such a simple thing, but anyone who is chronically on medication can tell you just how difficult it can be.”

The pill is not the first designed to improve adherence. In 2017, the FDA approved the first digital ingestion tracking system, Abilify MyCite, for the treatment of schizophrenia and bipolar disorder. But its maker, Proteus Digital Health, filed for bankruptcy in 2020 after struggling to recruit patients willing to be tracked. (Some expressed privacy concerns. Others disliked the uncomfortable patch that received and forwarded the signal.)

More recent designs have been streamlined to ditch the patch, said etectRx senior vice president of operations Chris Carnes, PhD. And the cost of making a pill this kind of “smart” has come down to about a dollar.

So far, said Dr. Chai, in the patients he’s worked with, perceived benefits generally outweigh privacy concerns.

Studies are now underway in patients with heart disease and tuberculosis, and the company hopes to move into the aging and memory care space where medication-adherence is a serious problem.

“For us, or any company in this space, to succeed, you have to have a strong business case,” said Dr. Carnes. “If family members can keep their loved ones at home a little longer at an additional cost of $30 a month, that’s a no-brainer.”
 

Pillcams 2.0

Twenty-three years ago, the first video capsule endoscopy made it possible to image the small intestine via a tiny camera you swallow.

Such “pillcams” offered a more patient-friendly way to diagnose small bowel disorders, such as gastrointestinal bleeding and Crohn’s disease. Rather than undergoing sedation or anesthesia, as required during tube-based endoscopy, patients can go about their day as the pill painlessly passes through their gastrointestinal (GI) tract, capturing and recording data and images.

But the pills have their downsides.

Because they move passively, driven by movement in the intestine, they can miss trouble spots. Their ability to image the esophagus, stomach, and colon has proven limited. And unlike other procedures, like colonoscopy, they can’t intervene with therapy, like removing polyps.

The pillcam “had so much promise, to sort of revolutionize endoscopy, but it never really got the adoption that it seemed like it might,” said Andrew Meltzer, MD, professor of emergency medicine at the GW School of Medicine and Health Sciences in Washington.

That could soon change, he said, thanks to advances in locomotion and AI.

In a recent study of 40 patients, Dr. Meltzer tested a new magnetically controlled capsule endoscopy. Standing at a patient’s side, he could use a joystick to steer the pill around the stomach, capturing images in real time.

The pilot study, published in June 2023, found that the pill clearly identified six key stomach landmarks accurately 95% of the time and didn’t miss any lesions caught with traditional endoscopy. Notably, 80% of the patients preferred the pillcam over the tube.

“They are awake. They can go to work as soon as they leave. And it’s easy for them to tolerate,” Dr. Meltzer said.

More research is necessary, but Dr. Meltzer believes the technology could be particularly useful in the emergency department, allowing doctors to rule out high-risk bleeds in the stomach on the spot without admitting patients unnecessarily or making them return for a traditional scope.

“It has the potential to increase screening and provide more cost-effective care in emergencies,” he said.

It could also be useful in the telemedicine space, allowing a doctor to “drive” the pill from afar to diagnose a distant patient.

Someday, AI could enable the capsule to drive itself, so a doctor could merely press a button and wait. Or it could be adapted to treat what it finds, like administering a drug or cauterizing a bleed.

“If we can come up with a Mars rover which can explore other planets, we should be able to have something that can explore the stomach remotely,” Dr. Meltzer said.
 

Swallowing the Future

At the California Institute of Technology, researchers have developed a “location-aware” smart pill that uses magnetic fields to help pinpoint its location in the twists and turns of intestines. This could be useful for monitoring food in the GI tract to determine why things aren’t moving.

Other researchers are using AI models to enhance the transmission of video from inside the body and reduce the time it takes to interpret images.

One group at the Massachusetts Institute of Technology has developed a vibrating weight loss capsule designed to stimulate receptors in the gut to signal the brain that the person is full.

Not everyone is a fan of the smart-pill revolution. Some critics have raised concerns about privacy. Others fear that doctors risk yielding too much power to technology. Even those who are excited about the pills’ possibilities temper their optimism with caution.

None of these smart pills have gone mainstream yet in clinical practice, said Vivek Kaul, MD, professor of medicine at the University of Rochester Medical Center, Rochester, New York, and secretary general of the World Gastroenterology Organization.

Clinical validation, accessibility, and insurance coverage “will be critical in shaping their role,” he said. “But overall, it would be fair to state that this technology has come of age and the future is bright.”
 

A version of this article appeared on Medscape.com.

On a November morning in 2022, James Messenger opened wide and swallowed a capsule like no other.

Messenger was no stranger to taking pills.

He’d first experimented with prescription opioids as a teenager in Morgantown, West Virginia, battled addiction on-and-off since, and known more than 70 people who had fatally overdosed. So, when asked to test a new “smart pill” that could detect an overdose in progress and call for help, he didn’t hesitate to join the study.

“I’ve lost pretty much every good friend I’ve ever had to this,” said Mr. Messenger. “This pill could save a lot of lives.”

The new Vitals Monitoring capsule he tested is just one example in a growing effort to radically rethink what the humble pill is capable of.

As far back as 1965, scientists introduced the Heidelberg capsule, an electronic pill that measured acidity from within the gut. In 1994, the University of Buffalo coined the term “smart pill” with a device promising to ferry medicine to a precise spot in the intestine, “like the tiny ship in the film Fantastic Voyage.” And in 2001, the US Food and Drug Administration (FDA) approved the first video capsule endoscope, a miniature-camera-toting pill that enabled noninvasive imaging of the small intestine.

Despite these milestones, the smart pill revolution has been slow to catch on due to cost, technological limitations, and some resistance among clinicians and patients.

But now, nearly 300 iterations are in various stages of development, according to a 2022 analysis. Advances in materials, imaging, and artificial intelligence (AI) are helping address everything from sleep apnea to HIV/AIDS to gut disorders via real-time tracking and real-time help.

“These technologies could enable us to shift the paradigm from ‘Let’s wait until the patient comes to us and find out what happened’ to ‘Let’s see how things are changing in real time, intervene now, and personalize that intervention,’ ” said Peter Chai, MD, associate professor of emergency medicine and health technology researcher at Brigham and Women’s Hospital in Boston.
 

Tracking Vitals From the Inside Out

Already, overdose-reversal agents like naloxone are saving lives. But more than 60% of overdoses occur when no one is around to administer them.

“While we need to focus on treatment, we also need to come up with more acute ways to save individuals when treatment doesn’t work or relapse occurs,” said James J. Mahoney III, PhD, director of addictions research at the Rockefeller Neuroscience Institute at West Virginia University (WVU), Morgantown.

Enter Celero Systems, a Massachusetts-based digital health company that has developed a vitamin-sized capsule packed with tiny sensors, microprocessors, and a radio antenna. It can measure breathing, heart rate, and core temperature — all from deep within the gut.

Respiratory distress is a hallmark early sign of an overdose. But it can be hard to monitor from a distance, especially in populations without access to a charged smartwatch.

Dr. Mahoney imagines a day when patients at risk could be given a weekly pill like Celero’s. If their respiratory rate drops below a dangerous level, it could alert loved ones or, better yet, release an overdose-reversal drug.

“It’s early days,” stressed Dr. Mahoney, whose team has been conducting pilot tests of the pill. “But initial data look promising.”

For one study, published in the journal Device in November 2023, the research team administered an overdose of fentanyl to anesthetized pigs with the pill in their stomachs. The capsule was able to detect respiratory depression within a minute and alert researchers via their laptop in time to step in.

When they gave the pill to 10 volunteers undergoing sleep studies at WVU, they found it could detect respiration rate with an accuracy of 93% compared with external monitoring devices — a feature that could also help diagnose sleep apnea or chronic obstructive pulmonary disease without expensive, intrusive tests.

Accuracy for heart rate was nearly 97%.

In another yet-to-be published trial, Dr. Mahoney tested the device with 10 volunteers in a residential treatment center to determine how well it could be tolerated.

Among the participants was Mr. Messenger, who said the thought of being tracked didn’t bother him.

“It was simple — just like taking a multivitamin,” said Mr. Messenger, now 34, sober, and working as a peer recovery support specialist at a hospital in his hometown. “It could be a great way to keep people alive long enough for them to get their head wrapped around the idea of treatment.”
 

Boosting Medication Adherence

At Brigham and Women’s Hospital, Dr. Chai is experimenting with a different smart pill — one he believes could help curb the ongoing HIV/AIDS epidemic.

Developed by Florida-based etectRx, the ID-Cap consists of a gelatin capsule embedded with a tiny radiofrequency transmitter, similar to the kind in retail antitheft devices. The capsule can be filled with a variety of medications. When swallowed, stomach acid dissolves the gel and activates the transmitter, which sends a signal to a receiver on a smartwatch, smartphone, or wall-mounted reader to confirm the medication was taken. If it isn’t, the patient’s smartphone or smart speaker might nudge them with a reminder or a family member might be notified.

In recent trials of men at a high risk for HIV, the system improved adherence to the once-daily prevention regimen pre-exposure prophylaxis (PrEP) by double digits.

“PrEP is almost 99% effective in preventing HIV, but you have to take it,” said Dr. Chai, who led the trials. “That seems like such a simple thing, but anyone who is chronically on medication can tell you just how difficult it can be.”

The pill is not the first designed to improve adherence. In 2017, the FDA approved the first digital ingestion tracking system, Abilify MyCite, for the treatment of schizophrenia and bipolar disorder. But its maker, Proteus Digital Health, filed for bankruptcy in 2020 after struggling to recruit patients willing to be tracked. (Some expressed privacy concerns. Others disliked the uncomfortable patch that received and forwarded the signal.)

More recent designs have been streamlined to ditch the patch, said etectRx senior vice president of operations Chris Carnes, PhD. And the cost of making a pill this kind of “smart” has come down to about a dollar.

So far, said Dr. Chai, in the patients he’s worked with, perceived benefits generally outweigh privacy concerns.

Studies are now underway in patients with heart disease and tuberculosis, and the company hopes to move into the aging and memory care space where medication-adherence is a serious problem.

“For us, or any company in this space, to succeed, you have to have a strong business case,” said Dr. Carnes. “If family members can keep their loved ones at home a little longer at an additional cost of $30 a month, that’s a no-brainer.”
 

Pillcams 2.0

Twenty-three years ago, the first video capsule endoscopy made it possible to image the small intestine via a tiny camera you swallow.

Such “pillcams” offered a more patient-friendly way to diagnose small bowel disorders, such as gastrointestinal bleeding and Crohn’s disease. Rather than undergoing sedation or anesthesia, as required during tube-based endoscopy, patients can go about their day as the pill painlessly passes through their gastrointestinal (GI) tract, capturing and recording data and images.

But the pills have their downsides.

Because they move passively, driven by movement in the intestine, they can miss trouble spots. Their ability to image the esophagus, stomach, and colon has proven limited. And unlike other procedures, like colonoscopy, they can’t intervene with therapy, like removing polyps.

The pillcam “had so much promise, to sort of revolutionize endoscopy, but it never really got the adoption that it seemed like it might,” said Andrew Meltzer, MD, professor of emergency medicine at the GW School of Medicine and Health Sciences in Washington.

That could soon change, he said, thanks to advances in locomotion and AI.

In a recent study of 40 patients, Dr. Meltzer tested a new magnetically controlled capsule endoscopy. Standing at a patient’s side, he could use a joystick to steer the pill around the stomach, capturing images in real time.

The pilot study, published in June 2023, found that the pill clearly identified six key stomach landmarks accurately 95% of the time and didn’t miss any lesions caught with traditional endoscopy. Notably, 80% of the patients preferred the pillcam over the tube.

“They are awake. They can go to work as soon as they leave. And it’s easy for them to tolerate,” Dr. Meltzer said.

More research is necessary, but Dr. Meltzer believes the technology could be particularly useful in the emergency department, allowing doctors to rule out high-risk bleeds in the stomach on the spot without admitting patients unnecessarily or making them return for a traditional scope.

“It has the potential to increase screening and provide more cost-effective care in emergencies,” he said.

It could also be useful in the telemedicine space, allowing a doctor to “drive” the pill from afar to diagnose a distant patient.

Someday, AI could enable the capsule to drive itself, so a doctor could merely press a button and wait. Or it could be adapted to treat what it finds, like administering a drug or cauterizing a bleed.

“If we can come up with a Mars rover which can explore other planets, we should be able to have something that can explore the stomach remotely,” Dr. Meltzer said.
 

Swallowing the Future

At the California Institute of Technology, researchers have developed a “location-aware” smart pill that uses magnetic fields to help pinpoint its location in the twists and turns of intestines. This could be useful for monitoring food in the GI tract to determine why things aren’t moving.

Other researchers are using AI models to enhance the transmission of video from inside the body and reduce the time it takes to interpret images.

One group at the Massachusetts Institute of Technology has developed a vibrating weight loss capsule designed to stimulate receptors in the gut to signal the brain that the person is full.

Not everyone is a fan of the smart-pill revolution. Some critics have raised concerns about privacy. Others fear that doctors risk yielding too much power to technology. Even those who are excited about the pills’ possibilities temper their optimism with caution.

None of these smart pills have gone mainstream yet in clinical practice, said Vivek Kaul, MD, professor of medicine at the University of Rochester Medical Center, Rochester, New York, and secretary general of the World Gastroenterology Organization.

Clinical validation, accessibility, and insurance coverage “will be critical in shaping their role,” he said. “But overall, it would be fair to state that this technology has come of age and the future is bright.”
 

A version of this article appeared on Medscape.com.

They have gone by many different names over the centuries: hysteria, psychosomatic illnesses, psychogenic neurological disorders, conversion disorders, dissociative neurological symptom disorders. The terminology may change, but functional neurological disorders by any other name are still real and serious yet treatable phenomena.

Functional neurological disorders, or FNDs, live at the crossroads of neurology and psychiatry, and they are as much a product of the body as they are of the brain, say neurologists who specialize in treating these complex and clinically challenging conditions.

“Whether they’re easily recognized or not depends on someone’s training and experience in this regard,” said Mark Hallett, MD, of the Human Motor Control Section of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.

“The difficulty has been that there hasn’t been very good education about functional disorders over the last 50 years or so,” he said in an interview.

However, with training and experience, clinicians can learn to identify these common and disabling conditions, Dr. Hallett said.
 

Varying Definitions

The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) labels FND as “conversion disorder,” and lists diagnostic criteria that include “one or more symptoms of altered voluntary motor or sensory function; clinical findings provide evidence of incompatibility between the symptom and recognized neurological or medical conditions; the symptom or deficit is not better explained by another medical or mental disorder;” and “the symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation.”

Dr. Hallett offers his own definition of FND, which includes the following characteristics:

• A neurological disorder, characterized by almost any type of neurological symptom
• Not voluntarily produced
• Caused by a brain network dysfunction that does not exclude the possibility of normal function
• Sometimes due in part to a psychological cause, and not explained by other neurological pathology that may or may not be present
• Symptoms may be inconsistent (variable) or incompatible (incongruent) with other known neurological disorders or human anatomy and physiology.

The two most common types of FND are psychogenic nonepileptic seizures and functional movement disorders, but patients may also have functional sensory, visual, auditory, speech, and urologic disorders, and even functional coma.

Dr. Hallett cited studies showing that an estimated 9% of neurology hospital admission are for FNDS, and that among patients in neurology clinics 5.4% had a diagnosis of FND, and 30% had an FND as part of the diagnosis.

Women comprise between 60% and 75% of the population with FNDs.
 

Diagnosis

FND is not, as once thought, a diagnosis of exclusion, but is based on signs and symptoms, which may be either inconsistent or irreversible and may occur in the absence of a stressor, said Sara Finkelstein, MD, MSc, of the Functional Neurological Disorder Unit in the Department of Neurology at Massachusetts General Hospital in Boston.

She emphasized that there are several diagnostic pitfalls that clinicians need to be aware of.

For example, “just because a patient has a psychiatric history does not mean that they have a functional neurological disorder,” she said in an interview.

Massachusetts General Hospital

Functional seizures

A definitive diagnosis can depend on the type of disorder.

“Many functional seizures have some clinical manifestations that are apparent, but as seizures are intermittent the doctor may not see one, and it may depend upon someone taking a video of the person with the seizure perhaps, or bringing them into a hospital and watching them until they do have the seizure,” Dr. Hallett said.

There are some manifestations that indicate the likelihood that a seizure has a functional origin, and when there is uncertainty EEG can help to nail down a diagnosis, he added.

Dr. Finkelstein noted that exam signs with good reliability for functional seizures include eye closure or resistance to opening; duration longer than 2 minutes; stopping and starting; asynchronous limb movements; patient maintenance of awareness during a generalized event; and ictal weeping.

Differential diagnoses included migraine with complex aura, dissociation related to posttraumatic stress disorder, or anxiety.
 

Functional movement disorders

Dr. Finkelstein cautioned that when evaluating patients for potential functional movement disorders, it’s important to not jump to conclusions.

For example, the amplitude of tremor can vary in Parkinson’s disease and essential tremor as well as in functional tremor. The clinician should not read too much into the observation that a patient’s tremor gets worse with increasing stress as stress can exacerbate most tremor types, she said.

One sign that tremor could be functional (dystonic tremor) is irregularity of amplitude and frequency, she noted.

When assessing patients with gait disorder, it’s important to understand that there is no single sign that is specially characteristic for a given disorder, and just because a patient has a “bizarre” gait, it doesn’t necessarily signal a functional disorder.

“A dystonic gait may improve with an alternate motor pattern or be inconsistent over time,” Dr. Finkelstein said.
 

Treatment

In a comprehensive review published in The Lancet: Neurology in 2022, Dr. Hallett and colleagues said that good doctor-patient communications and understanding of each patient’s needs and goals are essential for effective treatment of all FNDs.

“Neurologists have traditionally avoided taking responsibility for people with FND, although are often most appropriate to engage patients in treatment. Explaining the diagnosis with clarity, confidence, using the principles of a ‘rule in’ process, is a key step in treatment,” they wrote.

Treatment can take several forms, depending on the FND, and may include physiotherapy for patients with functional movement disorders and psychological therapy for patients with functional seizures.

“With increasing evidence-based treatment, the diagnosis of FND should be seen as a process of looking for potentially reversible cause of disability and distress whether or not an individual has abnormalities on conventional laboratory or radiological testing,” Dr. Hallett and colleagues concluded.

This article was based on interviews and from presentations by Dr. Hallett and Dr. Finkelstein at a 2023 meeting of the Indiana Neurological Society. Dr. Hallett and Dr. Finkelstein declared no conflicts of interest.

They have gone by many different names over the centuries: hysteria, psychosomatic illnesses, psychogenic neurological disorders, conversion disorders, dissociative neurological symptom disorders. The terminology may change, but functional neurological disorders by any other name are still real and serious yet treatable phenomena.

Functional neurological disorders, or FNDs, live at the crossroads of neurology and psychiatry, and they are as much a product of the body as they are of the brain, say neurologists who specialize in treating these complex and clinically challenging conditions.

“Whether they’re easily recognized or not depends on someone’s training and experience in this regard,” said Mark Hallett, MD, of the Human Motor Control Section of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.

“The difficulty has been that there hasn’t been very good education about functional disorders over the last 50 years or so,” he said in an interview.

However, with training and experience, clinicians can learn to identify these common and disabling conditions, Dr. Hallett said.
 

Varying Definitions

The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) labels FND as “conversion disorder,” and lists diagnostic criteria that include “one or more symptoms of altered voluntary motor or sensory function; clinical findings provide evidence of incompatibility between the symptom and recognized neurological or medical conditions; the symptom or deficit is not better explained by another medical or mental disorder;” and “the symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation.”

Dr. Hallett offers his own definition of FND, which includes the following characteristics:

• A neurological disorder, characterized by almost any type of neurological symptom
• Not voluntarily produced
• Caused by a brain network dysfunction that does not exclude the possibility of normal function
• Sometimes due in part to a psychological cause, and not explained by other neurological pathology that may or may not be present
• Symptoms may be inconsistent (variable) or incompatible (incongruent) with other known neurological disorders or human anatomy and physiology.

The two most common types of FND are psychogenic nonepileptic seizures and functional movement disorders, but patients may also have functional sensory, visual, auditory, speech, and urologic disorders, and even functional coma.

Dr. Hallett cited studies showing that an estimated 9% of neurology hospital admission are for FNDS, and that among patients in neurology clinics 5.4% had a diagnosis of FND, and 30% had an FND as part of the diagnosis.

Women comprise between 60% and 75% of the population with FNDs.
 

Diagnosis

FND is not, as once thought, a diagnosis of exclusion, but is based on signs and symptoms, which may be either inconsistent or irreversible and may occur in the absence of a stressor, said Sara Finkelstein, MD, MSc, of the Functional Neurological Disorder Unit in the Department of Neurology at Massachusetts General Hospital in Boston.

She emphasized that there are several diagnostic pitfalls that clinicians need to be aware of.

For example, “just because a patient has a psychiatric history does not mean that they have a functional neurological disorder,” she said in an interview.

Massachusetts General Hospital

Functional seizures

A definitive diagnosis can depend on the type of disorder.

“Many functional seizures have some clinical manifestations that are apparent, but as seizures are intermittent the doctor may not see one, and it may depend upon someone taking a video of the person with the seizure perhaps, or bringing them into a hospital and watching them until they do have the seizure,” Dr. Hallett said.

There are some manifestations that indicate the likelihood that a seizure has a functional origin, and when there is uncertainty EEG can help to nail down a diagnosis, he added.

Dr. Finkelstein noted that exam signs with good reliability for functional seizures include eye closure or resistance to opening; duration longer than 2 minutes; stopping and starting; asynchronous limb movements; patient maintenance of awareness during a generalized event; and ictal weeping.

Differential diagnoses included migraine with complex aura, dissociation related to posttraumatic stress disorder, or anxiety.
 

Functional movement disorders

Dr. Finkelstein cautioned that when evaluating patients for potential functional movement disorders, it’s important to not jump to conclusions.

For example, the amplitude of tremor can vary in Parkinson’s disease and essential tremor as well as in functional tremor. The clinician should not read too much into the observation that a patient’s tremor gets worse with increasing stress as stress can exacerbate most tremor types, she said.

One sign that tremor could be functional (dystonic tremor) is irregularity of amplitude and frequency, she noted.

When assessing patients with gait disorder, it’s important to understand that there is no single sign that is specially characteristic for a given disorder, and just because a patient has a “bizarre” gait, it doesn’t necessarily signal a functional disorder.

“A dystonic gait may improve with an alternate motor pattern or be inconsistent over time,” Dr. Finkelstein said.
 

Treatment

In a comprehensive review published in The Lancet: Neurology in 2022, Dr. Hallett and colleagues said that good doctor-patient communications and understanding of each patient’s needs and goals are essential for effective treatment of all FNDs.

“Neurologists have traditionally avoided taking responsibility for people with FND, although are often most appropriate to engage patients in treatment. Explaining the diagnosis with clarity, confidence, using the principles of a ‘rule in’ process, is a key step in treatment,” they wrote.

Treatment can take several forms, depending on the FND, and may include physiotherapy for patients with functional movement disorders and psychological therapy for patients with functional seizures.

“With increasing evidence-based treatment, the diagnosis of FND should be seen as a process of looking for potentially reversible cause of disability and distress whether or not an individual has abnormalities on conventional laboratory or radiological testing,” Dr. Hallett and colleagues concluded.

This article was based on interviews and from presentations by Dr. Hallett and Dr. Finkelstein at a 2023 meeting of the Indiana Neurological Society. Dr. Hallett and Dr. Finkelstein declared no conflicts of interest.

They have gone by many different names over the centuries: hysteria, psychosomatic illnesses, psychogenic neurological disorders, conversion disorders, dissociative neurological symptom disorders. The terminology may change, but functional neurological disorders by any other name are still real and serious yet treatable phenomena.

Functional neurological disorders, or FNDs, live at the crossroads of neurology and psychiatry, and they are as much a product of the body as they are of the brain, say neurologists who specialize in treating these complex and clinically challenging conditions.

“Whether they’re easily recognized or not depends on someone’s training and experience in this regard,” said Mark Hallett, MD, of the Human Motor Control Section of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.

“The difficulty has been that there hasn’t been very good education about functional disorders over the last 50 years or so,” he said in an interview.

However, with training and experience, clinicians can learn to identify these common and disabling conditions, Dr. Hallett said.
 

Varying Definitions

The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) labels FND as “conversion disorder,” and lists diagnostic criteria that include “one or more symptoms of altered voluntary motor or sensory function; clinical findings provide evidence of incompatibility between the symptom and recognized neurological or medical conditions; the symptom or deficit is not better explained by another medical or mental disorder;” and “the symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation.”

Dr. Hallett offers his own definition of FND, which includes the following characteristics:

• A neurological disorder, characterized by almost any type of neurological symptom
• Not voluntarily produced
• Caused by a brain network dysfunction that does not exclude the possibility of normal function
• Sometimes due in part to a psychological cause, and not explained by other neurological pathology that may or may not be present
• Symptoms may be inconsistent (variable) or incompatible (incongruent) with other known neurological disorders or human anatomy and physiology.

The two most common types of FND are psychogenic nonepileptic seizures and functional movement disorders, but patients may also have functional sensory, visual, auditory, speech, and urologic disorders, and even functional coma.

Dr. Hallett cited studies showing that an estimated 9% of neurology hospital admission are for FNDS, and that among patients in neurology clinics 5.4% had a diagnosis of FND, and 30% had an FND as part of the diagnosis.

Women comprise between 60% and 75% of the population with FNDs.
 

Diagnosis

FND is not, as once thought, a diagnosis of exclusion, but is based on signs and symptoms, which may be either inconsistent or irreversible and may occur in the absence of a stressor, said Sara Finkelstein, MD, MSc, of the Functional Neurological Disorder Unit in the Department of Neurology at Massachusetts General Hospital in Boston.

She emphasized that there are several diagnostic pitfalls that clinicians need to be aware of.

For example, “just because a patient has a psychiatric history does not mean that they have a functional neurological disorder,” she said in an interview.

Massachusetts General Hospital

Functional seizures

A definitive diagnosis can depend on the type of disorder.

“Many functional seizures have some clinical manifestations that are apparent, but as seizures are intermittent the doctor may not see one, and it may depend upon someone taking a video of the person with the seizure perhaps, or bringing them into a hospital and watching them until they do have the seizure,” Dr. Hallett said.

There are some manifestations that indicate the likelihood that a seizure has a functional origin, and when there is uncertainty EEG can help to nail down a diagnosis, he added.

Dr. Finkelstein noted that exam signs with good reliability for functional seizures include eye closure or resistance to opening; duration longer than 2 minutes; stopping and starting; asynchronous limb movements; patient maintenance of awareness during a generalized event; and ictal weeping.

Differential diagnoses included migraine with complex aura, dissociation related to posttraumatic stress disorder, or anxiety.
 

Functional movement disorders

Dr. Finkelstein cautioned that when evaluating patients for potential functional movement disorders, it’s important to not jump to conclusions.

For example, the amplitude of tremor can vary in Parkinson’s disease and essential tremor as well as in functional tremor. The clinician should not read too much into the observation that a patient’s tremor gets worse with increasing stress as stress can exacerbate most tremor types, she said.

One sign that tremor could be functional (dystonic tremor) is irregularity of amplitude and frequency, she noted.

When assessing patients with gait disorder, it’s important to understand that there is no single sign that is specially characteristic for a given disorder, and just because a patient has a “bizarre” gait, it doesn’t necessarily signal a functional disorder.

“A dystonic gait may improve with an alternate motor pattern or be inconsistent over time,” Dr. Finkelstein said.
 

Treatment

In a comprehensive review published in The Lancet: Neurology in 2022, Dr. Hallett and colleagues said that good doctor-patient communications and understanding of each patient’s needs and goals are essential for effective treatment of all FNDs.

“Neurologists have traditionally avoided taking responsibility for people with FND, although are often most appropriate to engage patients in treatment. Explaining the diagnosis with clarity, confidence, using the principles of a ‘rule in’ process, is a key step in treatment,” they wrote.

Treatment can take several forms, depending on the FND, and may include physiotherapy for patients with functional movement disorders and psychological therapy for patients with functional seizures.

“With increasing evidence-based treatment, the diagnosis of FND should be seen as a process of looking for potentially reversible cause of disability and distress whether or not an individual has abnormalities on conventional laboratory or radiological testing,” Dr. Hallett and colleagues concluded.

This article was based on interviews and from presentations by Dr. Hallett and Dr. Finkelstein at a 2023 meeting of the Indiana Neurological Society. Dr. Hallett and Dr. Finkelstein declared no conflicts of interest.

President Joe Biden on March 9 signed into law a measure that softened — but did not completely eliminate — a 2024 cut in a key rate used to determine how physicians are paid for treating Medicare patients.

While physician groups hailed the move as partial relief, they say they’ll continue to press for broader changes in the Medicare physician fee schedule.

The Medicare provision was tucked into a larger spending package approved by the US House and Senate.

The American Academy of Family Physicians (AAFP), the American Medical Association (AMA), and other groups have lobbied Congress for months to undo a 3.4% cut in the base rate, or conversion factor, in the physician fee schedule for 2024.

The conversion factor is used in calculations to determine reimbursement for myriad other services. Federal Medicare officials said the cut would mean a 1.25% decrease in overall payments in 2024, compared with 2023.

“With the passage of this legislation, Congress has offset 2.93% of that payment cut,” said Steven P. Furr, MD, AAFP’s president in a statement. “We appreciate this temporary measure but continue to urge Congress to advance comprehensive, long-term Medicare payment reform.”

In a statement, Representative Larry Bucshon, MD (R-IN), said the payment cut could not be completely eliminated because of budget constraints.

The Medicare physician fee schedule covers much of the care clinicians provide to people older than 65 and those with disabilities. It covers about 8000 different types of services, ranging from office visits to surgical procedures, imaging, and tests, according to the Medicare Payment Advisory Commission (MedPAC).

Along with physicians, the fee schedule sets payments for nurse practitioners, physician assistants, podiatrists, physical therapists, psychologists, and other clinicians.

In 2021, the Medicare program and its beneficiaries paid $92.8 billion for services provided by almost 1.3 million clinicians, MedPAC said.
 

Larger Changes Ahead?

Rep. Bucshon is among the physicians serving in the House who are pressing for a permanent revamp of the Medicare physician fee schedule. He cosponsored a bill (HR 2474) that would peg future annual increases in the physician fee schedule to the Medicare Economic Index, which would reflect inflation’s effect.

In April, more than 120 state and national medical groups signed onto an AMA-led letter urging Congress to pass this bill.

The measure is a key priority for the AMA. The organization reached out repeatedly last year to federal officials about it through its own in-house lobbyists, this news organization found through a review of congressional lobbying forms submitted by AMA.

These required disclosure forms reveal how much AMA and other organizations spend each quarter to appeal to members of Congress and federal agencies on specific issues. The disclosure forms do not include a detailed accounting of spending on each issue.

But they do show which issues are priorities for an organization. AMA’s in-house lobbyists reported raising dozens of issues in 2024 within contacts in Congress and federal agencies. These issues included abortion access, maternal health, physician burnout, and potential for bias in clinical use of algorithms, as well as Medicare payment for physicians.

AMA reported spending estimated cost of $20.6 million. (AMA spent $6.7 million in the first quarter, $4.75 million in the second quarter, $3.42 million in the third quarter, and $5.74 million in the fourth quarter.)

In a March 6 statement, Jesse M. Ehrenfeld, MD, MPH, AMA president, urged Congress to turn to more serious consideration of Medicare physician pay beyond short-term tweaks attached to other larger bills.

“As physicians, we are trained to run toward emergencies. We urge Congress to do the same,” Dr. Ehrenfeld said. “We encourage Congress to act if this policy decision is an emergency because — in fact — it is. It is well past time to put an end to stopgap measures that fail to address the underlying causes of the continuing decline in Medicare physician payments.”

There’s bipartisan interest in a revamp of the physician fee schedule amid widespread criticism of the last such overhaul, the Medicare Access and CHIP Reauthorization Act of 2015.

For example, Senate Budget Chairman Sheldon Whitehouse (D-RI) has proposed the creation of a technical advisory committee to improve how Medicare sets the physician fee schedule. The existing fee schedule provides too little money for primary care services and primary care provider pay, contributing to shortages, Sen. Whitehouse said.

Sen. Whitehouse on March 6 held a hearing on ways to beef up US primary care. Among the experts who appeared was Amol Navathe, MD, PhD, of the University of Pennsylvania, Philadelphia, Pennsylvania.

Dr. Navathe said the current Medicare physician fee schedule tilts in favor of procedural services, leading to “underinvestment in cognitive, diagnostic, and supportive services such as primary care.”

In addition, much of what primary care clinicians do, “such as addressing social challenges, is not included in the codes of the fee schedule itself,” said Dr. Navathe, who also serves as the vice chairman of MedPAC.

It’s unclear when Congress will attempt a serious revision to the Medicare physician fee schedule. Lawmakers are unlikely to take on such a major challenge in this election year.

There would be significant opposition and challenges for lawmakers in trying to clear a bill that added an inflation adjustment for what’s already seen as an imperfect physician fee schedule, said Mark E. Miller, PhD, executive vice president of healthcare at the philanthropy Arnold Ventures, which studies how payment decisions affect medical care.

“That bill could cost a lot of money and raise a lot of questions,” Dr. Miller said.

A version of this article appeared on Medscape.com.

President Joe Biden on March 9 signed into law a measure that softened — but did not completely eliminate — a 2024 cut in a key rate used to determine how physicians are paid for treating Medicare patients.

While physician groups hailed the move as partial relief, they say they’ll continue to press for broader changes in the Medicare physician fee schedule.

The Medicare provision was tucked into a larger spending package approved by the US House and Senate.

The American Academy of Family Physicians (AAFP), the American Medical Association (AMA), and other groups have lobbied Congress for months to undo a 3.4% cut in the base rate, or conversion factor, in the physician fee schedule for 2024.

The conversion factor is used in calculations to determine reimbursement for myriad other services. Federal Medicare officials said the cut would mean a 1.25% decrease in overall payments in 2024, compared with 2023.

“With the passage of this legislation, Congress has offset 2.93% of that payment cut,” said Steven P. Furr, MD, AAFP’s president in a statement. “We appreciate this temporary measure but continue to urge Congress to advance comprehensive, long-term Medicare payment reform.”

In a statement, Representative Larry Bucshon, MD (R-IN), said the payment cut could not be completely eliminated because of budget constraints.

The Medicare physician fee schedule covers much of the care clinicians provide to people older than 65 and those with disabilities. It covers about 8000 different types of services, ranging from office visits to surgical procedures, imaging, and tests, according to the Medicare Payment Advisory Commission (MedPAC).

Along with physicians, the fee schedule sets payments for nurse practitioners, physician assistants, podiatrists, physical therapists, psychologists, and other clinicians.

In 2021, the Medicare program and its beneficiaries paid $92.8 billion for services provided by almost 1.3 million clinicians, MedPAC said.
 

Larger Changes Ahead?

Rep. Bucshon is among the physicians serving in the House who are pressing for a permanent revamp of the Medicare physician fee schedule. He cosponsored a bill (HR 2474) that would peg future annual increases in the physician fee schedule to the Medicare Economic Index, which would reflect inflation’s effect.

In April, more than 120 state and national medical groups signed onto an AMA-led letter urging Congress to pass this bill.

The measure is a key priority for the AMA. The organization reached out repeatedly last year to federal officials about it through its own in-house lobbyists, this news organization found through a review of congressional lobbying forms submitted by AMA.

These required disclosure forms reveal how much AMA and other organizations spend each quarter to appeal to members of Congress and federal agencies on specific issues. The disclosure forms do not include a detailed accounting of spending on each issue.

But they do show which issues are priorities for an organization. AMA’s in-house lobbyists reported raising dozens of issues in 2024 within contacts in Congress and federal agencies. These issues included abortion access, maternal health, physician burnout, and potential for bias in clinical use of algorithms, as well as Medicare payment for physicians.

AMA reported spending estimated cost of $20.6 million. (AMA spent $6.7 million in the first quarter, $4.75 million in the second quarter, $3.42 million in the third quarter, and $5.74 million in the fourth quarter.)

In a March 6 statement, Jesse M. Ehrenfeld, MD, MPH, AMA president, urged Congress to turn to more serious consideration of Medicare physician pay beyond short-term tweaks attached to other larger bills.

“As physicians, we are trained to run toward emergencies. We urge Congress to do the same,” Dr. Ehrenfeld said. “We encourage Congress to act if this policy decision is an emergency because — in fact — it is. It is well past time to put an end to stopgap measures that fail to address the underlying causes of the continuing decline in Medicare physician payments.”

There’s bipartisan interest in a revamp of the physician fee schedule amid widespread criticism of the last such overhaul, the Medicare Access and CHIP Reauthorization Act of 2015.

For example, Senate Budget Chairman Sheldon Whitehouse (D-RI) has proposed the creation of a technical advisory committee to improve how Medicare sets the physician fee schedule. The existing fee schedule provides too little money for primary care services and primary care provider pay, contributing to shortages, Sen. Whitehouse said.

Sen. Whitehouse on March 6 held a hearing on ways to beef up US primary care. Among the experts who appeared was Amol Navathe, MD, PhD, of the University of Pennsylvania, Philadelphia, Pennsylvania.

Dr. Navathe said the current Medicare physician fee schedule tilts in favor of procedural services, leading to “underinvestment in cognitive, diagnostic, and supportive services such as primary care.”

In addition, much of what primary care clinicians do, “such as addressing social challenges, is not included in the codes of the fee schedule itself,” said Dr. Navathe, who also serves as the vice chairman of MedPAC.

It’s unclear when Congress will attempt a serious revision to the Medicare physician fee schedule. Lawmakers are unlikely to take on such a major challenge in this election year.

There would be significant opposition and challenges for lawmakers in trying to clear a bill that added an inflation adjustment for what’s already seen as an imperfect physician fee schedule, said Mark E. Miller, PhD, executive vice president of healthcare at the philanthropy Arnold Ventures, which studies how payment decisions affect medical care.

“That bill could cost a lot of money and raise a lot of questions,” Dr. Miller said.

A version of this article appeared on Medscape.com.

President Joe Biden on March 9 signed into law a measure that softened — but did not completely eliminate — a 2024 cut in a key rate used to determine how physicians are paid for treating Medicare patients.

While physician groups hailed the move as partial relief, they say they’ll continue to press for broader changes in the Medicare physician fee schedule.

The Medicare provision was tucked into a larger spending package approved by the US House and Senate.

The American Academy of Family Physicians (AAFP), the American Medical Association (AMA), and other groups have lobbied Congress for months to undo a 3.4% cut in the base rate, or conversion factor, in the physician fee schedule for 2024.

The conversion factor is used in calculations to determine reimbursement for myriad other services. Federal Medicare officials said the cut would mean a 1.25% decrease in overall payments in 2024, compared with 2023.

“With the passage of this legislation, Congress has offset 2.93% of that payment cut,” said Steven P. Furr, MD, AAFP’s president in a statement. “We appreciate this temporary measure but continue to urge Congress to advance comprehensive, long-term Medicare payment reform.”

In a statement, Representative Larry Bucshon, MD (R-IN), said the payment cut could not be completely eliminated because of budget constraints.

The Medicare physician fee schedule covers much of the care clinicians provide to people older than 65 and those with disabilities. It covers about 8000 different types of services, ranging from office visits to surgical procedures, imaging, and tests, according to the Medicare Payment Advisory Commission (MedPAC).

Along with physicians, the fee schedule sets payments for nurse practitioners, physician assistants, podiatrists, physical therapists, psychologists, and other clinicians.

In 2021, the Medicare program and its beneficiaries paid $92.8 billion for services provided by almost 1.3 million clinicians, MedPAC said.
 

Larger Changes Ahead?

Rep. Bucshon is among the physicians serving in the House who are pressing for a permanent revamp of the Medicare physician fee schedule. He cosponsored a bill (HR 2474) that would peg future annual increases in the physician fee schedule to the Medicare Economic Index, which would reflect inflation’s effect.

In April, more than 120 state and national medical groups signed onto an AMA-led letter urging Congress to pass this bill.

The measure is a key priority for the AMA. The organization reached out repeatedly last year to federal officials about it through its own in-house lobbyists, this news organization found through a review of congressional lobbying forms submitted by AMA.

These required disclosure forms reveal how much AMA and other organizations spend each quarter to appeal to members of Congress and federal agencies on specific issues. The disclosure forms do not include a detailed accounting of spending on each issue.

But they do show which issues are priorities for an organization. AMA’s in-house lobbyists reported raising dozens of issues in 2024 within contacts in Congress and federal agencies. These issues included abortion access, maternal health, physician burnout, and potential for bias in clinical use of algorithms, as well as Medicare payment for physicians.

AMA reported spending estimated cost of $20.6 million. (AMA spent $6.7 million in the first quarter, $4.75 million in the second quarter, $3.42 million in the third quarter, and $5.74 million in the fourth quarter.)

In a March 6 statement, Jesse M. Ehrenfeld, MD, MPH, AMA president, urged Congress to turn to more serious consideration of Medicare physician pay beyond short-term tweaks attached to other larger bills.

“As physicians, we are trained to run toward emergencies. We urge Congress to do the same,” Dr. Ehrenfeld said. “We encourage Congress to act if this policy decision is an emergency because — in fact — it is. It is well past time to put an end to stopgap measures that fail to address the underlying causes of the continuing decline in Medicare physician payments.”

There’s bipartisan interest in a revamp of the physician fee schedule amid widespread criticism of the last such overhaul, the Medicare Access and CHIP Reauthorization Act of 2015.

For example, Senate Budget Chairman Sheldon Whitehouse (D-RI) has proposed the creation of a technical advisory committee to improve how Medicare sets the physician fee schedule. The existing fee schedule provides too little money for primary care services and primary care provider pay, contributing to shortages, Sen. Whitehouse said.

Sen. Whitehouse on March 6 held a hearing on ways to beef up US primary care. Among the experts who appeared was Amol Navathe, MD, PhD, of the University of Pennsylvania, Philadelphia, Pennsylvania.

Dr. Navathe said the current Medicare physician fee schedule tilts in favor of procedural services, leading to “underinvestment in cognitive, diagnostic, and supportive services such as primary care.”

In addition, much of what primary care clinicians do, “such as addressing social challenges, is not included in the codes of the fee schedule itself,” said Dr. Navathe, who also serves as the vice chairman of MedPAC.

It’s unclear when Congress will attempt a serious revision to the Medicare physician fee schedule. Lawmakers are unlikely to take on such a major challenge in this election year.

There would be significant opposition and challenges for lawmakers in trying to clear a bill that added an inflation adjustment for what’s already seen as an imperfect physician fee schedule, said Mark E. Miller, PhD, executive vice president of healthcare at the philanthropy Arnold Ventures, which studies how payment decisions affect medical care.

“That bill could cost a lot of money and raise a lot of questions,” Dr. Miller said.

A version of this article appeared on Medscape.com.

Patients diagnosed with rheumatoid arthritis (RA) and co-occurring anxiety or depression are less likely to achieve low disease activity (LDA) and better symptom control after 3 months of treatment, according to new research presented at the at the annual meeting of the Canadian Rheumatology Association.

The findings emphasized the importance of taking a multidisciplinary approach to RA treatment, said presenter Susan Bartlett, PhD, a professor in the Divisions of Clinical Epidemiology, Rheumatology, and Respiratory Epidemiology at McGill University in Montreal, Quebec, Canada.

McGill University

“In the absence of directly addressing anxiety and depression, people are not going to improve to the same extent we hope that they will,” she told this news organization.
 

Symptom Clusters in RA

In her research, presented on February 29, Dr. Bartlett explored how certain symptom clusters in RA predicted prognosis.

Symptom clusters are related symptoms that occur together and can be associated with worse outcomes than one symptom alone. Symptom science has been a growing interest in precision medicine, particularly for cancer, Dr. Bartlett noted, and this same approach could help pinpoint RA subtypes, disease trajectories, and personalized treatment.

In the study, Dr. Bartlett and colleagues used data from the Canadian Early Arthritis Cohort (CATCH), a multisite prospective research study following individuals with new-onset RA. They identified patients starting methotrexate (MTX) therapy who also had clinical and patient-reported outcome measures available. Individuals included in the analysis may have also been taking additional disease-modifying antirheumatic drugs beyond MTX.

Across the 310 selected individuals, researchers identified four key symptoms: Pain, fatigue, anxiety, and depression. Pain and fatigue were defined as physical symptoms, while anxiety and depression were classified as emotional symptoms. Results showed that the patients could be sorted into four distinct symptom clusters: Minimal symptoms (12%), mild physical and emotional symptoms (11%), moderate to severe pain and fatigue (40%), and moderate to severe physical and emotional symptoms (37%).

Researchers then followed patients during the first 6 months of treatment to evaluate if patients’ symptoms improved.

Symptom improvement mostly occurred during the first 3 months of treatment and remained consistent at 6 months. Overall, patients with moderate to severe emotional symptoms had a worse prognosis and were less likely to achieve milder symptoms than those who had only pain and fatigue or mild emotional symptoms. While 64% of patients in the moderate to severe physical symptoms group achieved minimal symptoms after 3 months of treatment, only 13% of patients with moderate to severe physical and emotional systems reported minimal symptoms during this same time frame.

The study builds on previous work that “suggests that there are different factors that we can identify around the time of diagnosis that point to how well a person is likely to respond,” Dr. Bartlett added. “What our work is showing pretty clearly [is that] the presence of anxiety and depression is one of those important markers.”
 

Patients With Depression Report Worse Disease Activity

In a related study, researchers from the University of Ottawa explored how depression in RA affected subjective and objective disease measures.

The study included patients from the Ottawa Rheumatology Comprehensive Treatment and Assessment (ORCHESTRA) clinic at The Ottawa Hospital, Ottawa, Ontario, Canada, which sees patients with inflammatory arthritis who are starting biologic therapy or switching to another biologic. The clinic is designed to take a more comprehensive approach to managing inflammatory arthritis, including addressing comorbidities such as cardiac disease, depression, and cancer. Patients seen at the clinic can opt to be included in the ORCHESTRA cohort to be a part of ongoing research.

From this cohort, researchers identified 98 patients with RA. At enrollment, patients were screened for depression using patient health questionnaire scores and asked about duration of morning stiffness and tender joint counts. Swollen joint counts, ultrasound, and clinical scores were used to evaluate disease activity.

In the study group, 47 patients had no depression, 21 patients had mild depression, and 30 patients had moderate to severe depression. Researchers found that subjective disease measures, including visual analog pain scale, health assessment questionnaire, and disease activity score in 28 joints were all higher in patients with depression; however, depression did not appear to affect objective disease measures, such as the Global OMERACT-EULAR Synovitis Score or Doppler scores.

While there is a known link between inflammation and depression, these findings suggest that depression is “a concomitant comorbidity just like cardiovascular disease, just like fibromyalgia, just like some other comorbidity that also needs to be addressed in its own right to improve the outcomes,” noted Elliot Hepworth, MD, a rheumatologist and ORCHESTRA clinic lead at The Ottawa Hospital, in an interview.

Dr. Hepworth presented the findings on March 1.

Dr. Elliot Hepworth

The data also suggested that patients with depression had poorer outcomes. For the 79 patients who had 3-month follow-up visit data, 43.9% of patients with no or mild depression achieved LDA and remission compared with 21.7% of patients with moderate to severe depression, though this difference was not statistically significant (P = .064). There was a similar trend for the 39 patients with 6-month follow-up data: Only 20% of patients with moderate to severe depression had reached LDA and remission compared with 37.9% of patients with no or mild depression (P = .445). The researchers noted this could be an issue with a smaller sample size.

“Every time more patients get added we approach closer to significance,” Dr. Hepworth added.
 

Some Disagreement, Same Takeaway

Commenting on the Ottawa study, Dr. Bartlett was skeptical of the conclusion that depression may not directly influence disease activity. “There’s just too much good evidence these days that [depression] very much coexists with worse disease activity,” she said. “It is not in the person’s head.”

Dr. Hepworth added that patient-reported outcomes are important for clinicians to address during treatment.

“There’s the tender joints, there’s the pain, there’s the fatigue, there’s the patient global assessment, which are subjective,” he said, “but that does not mean that they are not important. Those are important to the patient: That is how they’re living their life, and that is how they’re experiencing their disease.”

This is why efforts to treat depression in patients with RA such as cognitive behavioral therapy are so important, he said, to which Dr. Bartlett agreed.

“A comprehensive approach is required, which includes addressing depression,” she said. Otherwise, data show “that people just never make it to remission.”

The studies looked at different patient populations but ultimately complement each other, added Sibel Aydin, MD, a professor of medicine in the Division of Rheumatology at the University of Ottawa, Ottawa, Ontario, Canada, and senior author of the Ottawa study.

Dr. Sibel Aydin

“Two different cohorts with different patient populations still reached the same result,” she said. “If you don’t address the emotional aspect, you are not going to achieve the good outcomes.”

“It’s remarkable when you have two independent researchers coming to the same conclusion without ever talking to each other,” added Dr. Hepworth. “That really shows that this is something that’s pervasive, and it’s not just within our patient population.”

CATCH is funded by unrestricted research grants from programs with Pfizer, AbbVie, Roche, Sandoz, Fresenius Kabi, Organon, Viatris, JAMP, and Celltrion. Dr. Bartlett is president of the PROMIS Health Organization. She is a member of speakers bureaus or has consulted for Pfizer, Sandoz, Merck, Janssen, and Organon. Dr. Hepworth and Dr. Aydin declared no conflicts of interest.

A version of this article appeared on Medscape.com .

Patients diagnosed with rheumatoid arthritis (RA) and co-occurring anxiety or depression are less likely to achieve low disease activity (LDA) and better symptom control after 3 months of treatment, according to new research presented at the at the annual meeting of the Canadian Rheumatology Association.

The findings emphasized the importance of taking a multidisciplinary approach to RA treatment, said presenter Susan Bartlett, PhD, a professor in the Divisions of Clinical Epidemiology, Rheumatology, and Respiratory Epidemiology at McGill University in Montreal, Quebec, Canada.

McGill University

“In the absence of directly addressing anxiety and depression, people are not going to improve to the same extent we hope that they will,” she told this news organization.
 

Symptom Clusters in RA

In her research, presented on February 29, Dr. Bartlett explored how certain symptom clusters in RA predicted prognosis.

Symptom clusters are related symptoms that occur together and can be associated with worse outcomes than one symptom alone. Symptom science has been a growing interest in precision medicine, particularly for cancer, Dr. Bartlett noted, and this same approach could help pinpoint RA subtypes, disease trajectories, and personalized treatment.

In the study, Dr. Bartlett and colleagues used data from the Canadian Early Arthritis Cohort (CATCH), a multisite prospective research study following individuals with new-onset RA. They identified patients starting methotrexate (MTX) therapy who also had clinical and patient-reported outcome measures available. Individuals included in the analysis may have also been taking additional disease-modifying antirheumatic drugs beyond MTX.

Across the 310 selected individuals, researchers identified four key symptoms: Pain, fatigue, anxiety, and depression. Pain and fatigue were defined as physical symptoms, while anxiety and depression were classified as emotional symptoms. Results showed that the patients could be sorted into four distinct symptom clusters: Minimal symptoms (12%), mild physical and emotional symptoms (11%), moderate to severe pain and fatigue (40%), and moderate to severe physical and emotional symptoms (37%).

Researchers then followed patients during the first 6 months of treatment to evaluate if patients’ symptoms improved.

Symptom improvement mostly occurred during the first 3 months of treatment and remained consistent at 6 months. Overall, patients with moderate to severe emotional symptoms had a worse prognosis and were less likely to achieve milder symptoms than those who had only pain and fatigue or mild emotional symptoms. While 64% of patients in the moderate to severe physical symptoms group achieved minimal symptoms after 3 months of treatment, only 13% of patients with moderate to severe physical and emotional systems reported minimal symptoms during this same time frame.

The study builds on previous work that “suggests that there are different factors that we can identify around the time of diagnosis that point to how well a person is likely to respond,” Dr. Bartlett added. “What our work is showing pretty clearly [is that] the presence of anxiety and depression is one of those important markers.”
 

Patients With Depression Report Worse Disease Activity

In a related study, researchers from the University of Ottawa explored how depression in RA affected subjective and objective disease measures.

The study included patients from the Ottawa Rheumatology Comprehensive Treatment and Assessment (ORCHESTRA) clinic at The Ottawa Hospital, Ottawa, Ontario, Canada, which sees patients with inflammatory arthritis who are starting biologic therapy or switching to another biologic. The clinic is designed to take a more comprehensive approach to managing inflammatory arthritis, including addressing comorbidities such as cardiac disease, depression, and cancer. Patients seen at the clinic can opt to be included in the ORCHESTRA cohort to be a part of ongoing research.

From this cohort, researchers identified 98 patients with RA. At enrollment, patients were screened for depression using patient health questionnaire scores and asked about duration of morning stiffness and tender joint counts. Swollen joint counts, ultrasound, and clinical scores were used to evaluate disease activity.

In the study group, 47 patients had no depression, 21 patients had mild depression, and 30 patients had moderate to severe depression. Researchers found that subjective disease measures, including visual analog pain scale, health assessment questionnaire, and disease activity score in 28 joints were all higher in patients with depression; however, depression did not appear to affect objective disease measures, such as the Global OMERACT-EULAR Synovitis Score or Doppler scores.

While there is a known link between inflammation and depression, these findings suggest that depression is “a concomitant comorbidity just like cardiovascular disease, just like fibromyalgia, just like some other comorbidity that also needs to be addressed in its own right to improve the outcomes,” noted Elliot Hepworth, MD, a rheumatologist and ORCHESTRA clinic lead at The Ottawa Hospital, in an interview.

Dr. Hepworth presented the findings on March 1.

Dr. Elliot Hepworth

The data also suggested that patients with depression had poorer outcomes. For the 79 patients who had 3-month follow-up visit data, 43.9% of patients with no or mild depression achieved LDA and remission compared with 21.7% of patients with moderate to severe depression, though this difference was not statistically significant (P = .064). There was a similar trend for the 39 patients with 6-month follow-up data: Only 20% of patients with moderate to severe depression had reached LDA and remission compared with 37.9% of patients with no or mild depression (P = .445). The researchers noted this could be an issue with a smaller sample size.

“Every time more patients get added we approach closer to significance,” Dr. Hepworth added.
 

Some Disagreement, Same Takeaway

Commenting on the Ottawa study, Dr. Bartlett was skeptical of the conclusion that depression may not directly influence disease activity. “There’s just too much good evidence these days that [depression] very much coexists with worse disease activity,” she said. “It is not in the person’s head.”

Dr. Hepworth added that patient-reported outcomes are important for clinicians to address during treatment.

“There’s the tender joints, there’s the pain, there’s the fatigue, there’s the patient global assessment, which are subjective,” he said, “but that does not mean that they are not important. Those are important to the patient: That is how they’re living their life, and that is how they’re experiencing their disease.”

This is why efforts to treat depression in patients with RA such as cognitive behavioral therapy are so important, he said, to which Dr. Bartlett agreed.

“A comprehensive approach is required, which includes addressing depression,” she said. Otherwise, data show “that people just never make it to remission.”

The studies looked at different patient populations but ultimately complement each other, added Sibel Aydin, MD, a professor of medicine in the Division of Rheumatology at the University of Ottawa, Ottawa, Ontario, Canada, and senior author of the Ottawa study.

Dr. Sibel Aydin

“Two different cohorts with different patient populations still reached the same result,” she said. “If you don’t address the emotional aspect, you are not going to achieve the good outcomes.”

“It’s remarkable when you have two independent researchers coming to the same conclusion without ever talking to each other,” added Dr. Hepworth. “That really shows that this is something that’s pervasive, and it’s not just within our patient population.”

CATCH is funded by unrestricted research grants from programs with Pfizer, AbbVie, Roche, Sandoz, Fresenius Kabi, Organon, Viatris, JAMP, and Celltrion. Dr. Bartlett is president of the PROMIS Health Organization. She is a member of speakers bureaus or has consulted for Pfizer, Sandoz, Merck, Janssen, and Organon. Dr. Hepworth and Dr. Aydin declared no conflicts of interest.

A version of this article appeared on Medscape.com .

Patients diagnosed with rheumatoid arthritis (RA) and co-occurring anxiety or depression are less likely to achieve low disease activity (LDA) and better symptom control after 3 months of treatment, according to new research presented at the at the annual meeting of the Canadian Rheumatology Association.

The findings emphasized the importance of taking a multidisciplinary approach to RA treatment, said presenter Susan Bartlett, PhD, a professor in the Divisions of Clinical Epidemiology, Rheumatology, and Respiratory Epidemiology at McGill University in Montreal, Quebec, Canada.

McGill University

“In the absence of directly addressing anxiety and depression, people are not going to improve to the same extent we hope that they will,” she told this news organization.
 

Symptom Clusters in RA

In her research, presented on February 29, Dr. Bartlett explored how certain symptom clusters in RA predicted prognosis.

Symptom clusters are related symptoms that occur together and can be associated with worse outcomes than one symptom alone. Symptom science has been a growing interest in precision medicine, particularly for cancer, Dr. Bartlett noted, and this same approach could help pinpoint RA subtypes, disease trajectories, and personalized treatment.

In the study, Dr. Bartlett and colleagues used data from the Canadian Early Arthritis Cohort (CATCH), a multisite prospective research study following individuals with new-onset RA. They identified patients starting methotrexate (MTX) therapy who also had clinical and patient-reported outcome measures available. Individuals included in the analysis may have also been taking additional disease-modifying antirheumatic drugs beyond MTX.

Across the 310 selected individuals, researchers identified four key symptoms: Pain, fatigue, anxiety, and depression. Pain and fatigue were defined as physical symptoms, while anxiety and depression were classified as emotional symptoms. Results showed that the patients could be sorted into four distinct symptom clusters: Minimal symptoms (12%), mild physical and emotional symptoms (11%), moderate to severe pain and fatigue (40%), and moderate to severe physical and emotional symptoms (37%).

Researchers then followed patients during the first 6 months of treatment to evaluate if patients’ symptoms improved.

Symptom improvement mostly occurred during the first 3 months of treatment and remained consistent at 6 months. Overall, patients with moderate to severe emotional symptoms had a worse prognosis and were less likely to achieve milder symptoms than those who had only pain and fatigue or mild emotional symptoms. While 64% of patients in the moderate to severe physical symptoms group achieved minimal symptoms after 3 months of treatment, only 13% of patients with moderate to severe physical and emotional systems reported minimal symptoms during this same time frame.

The study builds on previous work that “suggests that there are different factors that we can identify around the time of diagnosis that point to how well a person is likely to respond,” Dr. Bartlett added. “What our work is showing pretty clearly [is that] the presence of anxiety and depression is one of those important markers.”
 

Patients With Depression Report Worse Disease Activity

In a related study, researchers from the University of Ottawa explored how depression in RA affected subjective and objective disease measures.

The study included patients from the Ottawa Rheumatology Comprehensive Treatment and Assessment (ORCHESTRA) clinic at The Ottawa Hospital, Ottawa, Ontario, Canada, which sees patients with inflammatory arthritis who are starting biologic therapy or switching to another biologic. The clinic is designed to take a more comprehensive approach to managing inflammatory arthritis, including addressing comorbidities such as cardiac disease, depression, and cancer. Patients seen at the clinic can opt to be included in the ORCHESTRA cohort to be a part of ongoing research.

From this cohort, researchers identified 98 patients with RA. At enrollment, patients were screened for depression using patient health questionnaire scores and asked about duration of morning stiffness and tender joint counts. Swollen joint counts, ultrasound, and clinical scores were used to evaluate disease activity.

In the study group, 47 patients had no depression, 21 patients had mild depression, and 30 patients had moderate to severe depression. Researchers found that subjective disease measures, including visual analog pain scale, health assessment questionnaire, and disease activity score in 28 joints were all higher in patients with depression; however, depression did not appear to affect objective disease measures, such as the Global OMERACT-EULAR Synovitis Score or Doppler scores.

While there is a known link between inflammation and depression, these findings suggest that depression is “a concomitant comorbidity just like cardiovascular disease, just like fibromyalgia, just like some other comorbidity that also needs to be addressed in its own right to improve the outcomes,” noted Elliot Hepworth, MD, a rheumatologist and ORCHESTRA clinic lead at The Ottawa Hospital, in an interview.

Dr. Hepworth presented the findings on March 1.

Dr. Elliot Hepworth

The data also suggested that patients with depression had poorer outcomes. For the 79 patients who had 3-month follow-up visit data, 43.9% of patients with no or mild depression achieved LDA and remission compared with 21.7% of patients with moderate to severe depression, though this difference was not statistically significant (P = .064). There was a similar trend for the 39 patients with 6-month follow-up data: Only 20% of patients with moderate to severe depression had reached LDA and remission compared with 37.9% of patients with no or mild depression (P = .445). The researchers noted this could be an issue with a smaller sample size.

“Every time more patients get added we approach closer to significance,” Dr. Hepworth added.
 

Some Disagreement, Same Takeaway

Commenting on the Ottawa study, Dr. Bartlett was skeptical of the conclusion that depression may not directly influence disease activity. “There’s just too much good evidence these days that [depression] very much coexists with worse disease activity,” she said. “It is not in the person’s head.”

Dr. Hepworth added that patient-reported outcomes are important for clinicians to address during treatment.

“There’s the tender joints, there’s the pain, there’s the fatigue, there’s the patient global assessment, which are subjective,” he said, “but that does not mean that they are not important. Those are important to the patient: That is how they’re living their life, and that is how they’re experiencing their disease.”

This is why efforts to treat depression in patients with RA such as cognitive behavioral therapy are so important, he said, to which Dr. Bartlett agreed.

“A comprehensive approach is required, which includes addressing depression,” she said. Otherwise, data show “that people just never make it to remission.”

The studies looked at different patient populations but ultimately complement each other, added Sibel Aydin, MD, a professor of medicine in the Division of Rheumatology at the University of Ottawa, Ottawa, Ontario, Canada, and senior author of the Ottawa study.

Dr. Sibel Aydin

“Two different cohorts with different patient populations still reached the same result,” she said. “If you don’t address the emotional aspect, you are not going to achieve the good outcomes.”

“It’s remarkable when you have two independent researchers coming to the same conclusion without ever talking to each other,” added Dr. Hepworth. “That really shows that this is something that’s pervasive, and it’s not just within our patient population.”

CATCH is funded by unrestricted research grants from programs with Pfizer, AbbVie, Roche, Sandoz, Fresenius Kabi, Organon, Viatris, JAMP, and Celltrion. Dr. Bartlett is president of the PROMIS Health Organization. She is a member of speakers bureaus or has consulted for Pfizer, Sandoz, Merck, Janssen, and Organon. Dr. Hepworth and Dr. Aydin declared no conflicts of interest.

A version of this article appeared on Medscape.com .

Nearly 18 months after the US Food and Drug Administration (FDA) first acknowledged a national shortage of Adderall, the most common drug used to treat attention-deficit/hyperactivity disorder (ADHD), there is now a widespread scarcity of other stimulant medications — with no end in sight. How did this crisis develop and what measures are underway to address it?

The first shortage of immediate release formulations of amphetamine mixed salts (Adderall, Adderall IR) was reported by the FDA in October 2022. Now, the list includes Focalin, Ritalin, and Vyvanse, among others.

Adding to the ongoing crisis, the FDA announced in early February that Azurity Pharmaceuticals was voluntarily withdrawing one lot of its Zenzedi (dextroamphetamine sulfate) 30 mg tablets because of contamination with the antihistamine, carbinoxamine.

For the roughly 10 million adults and 6 million children in the United States grappling with ADHD, getting a prescription filled with the exact medication ordered by a physician is dictated by geographic location, insurance formularies, and pharmacy supply chains. It’s particularly challenging for those who live in rural or underserved areas with limited access to nearby pharmacies.

“Not a day goes by when I don’t hear from a number of unfortunately struggling patients about this shortage,” said Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, Baltimore, Maryland.

The ADHD drug shortage is now well into its second year, and clinicians and advocates alike say there is no apparent end in sight.

How Did We Get Here?

Manufacturers and federal agencies blame the shortage on rising demand and each other, while clinicians say that insurers, drug distributors, and middlemen are also playing a role in keeping medications out of patients’ hands.

In August 2023, the Drug Enforcement Administration (DEA), which sets quotas for the production of controlled substances, and the FDA publicly blamed manufacturers for the shortages, claiming they were not using up their allocations.

At the time, the DEA said manufacturers made and sold only 70% of their quota, nearly 1 billion doses short of what they were allowed to produce and ship that year.

The agencies also noted a record-high number of prescriptions for stimulants from 2012 to 2021. Driven in part by telehealth, the demand intensified during the pandemic. One recent study reported a 14% increase in ADHD stimulant prescriptions between 2020 and 2022.

Insurers also play a role in the shortage, David Goodman, MD, an assistant professor of psychiatry and behavioral sciences also at Johns Hopkins University, told this news organization.

Stepped therapy — in which patients must try one, two, or three medications before they are authorized to receive a more expensive or newer drug — contributes to the problem, Dr. Goodman said. Demand for such medications is high and supply low. In addition, some insurers only provide coverage for in-network pharmacies, regardless of the ability of other providers outside such networks to fill prescriptions.

“If the insurance dictates where you get your pills, and that pharmacy doesn’t have the pills or that pharmacy chain in your area doesn’t have those pills, you’re out of luck,” Dr. Goodman said.

Patients as Detectives

To get prescriptions filled, patients must “turn into detectives,” Laurie Kulikosky, CEO of Children and Adults with Attention-Deficit/Hyperactivity Disorder, told this news organization. “It’s a huge stressor.”

Tracking which ADHD medications are available, on back order, or discontinued requires frequent checking of the FDA’s drug shortages website.

Some manufacturers of generic versions of mixed amphetamine salts are only fulfilling orders for existing contracts, while others say new product won’t be available until at least April or as late as September. All blame the delay on the shortage of active ingredients.

Teva, which makes both the brand and generic of Adderall, reported on the FDA’s site that its manufacturing and distribution is at record-high levels, but demand continues to rise.

The branded Concerta is available, but some makers of generic methylphenidate reported supplies won’t be available until July.

Lisdexamfetamine dimesylate in almost all dosages is either unavailable, available in restricted quantities, or on extended back order. However, the branded product Vyvanse is available.

Industry, Government Respond

In a November 2023 statement, the DEA reported that 17 of 18 drug manufacturers the agency contacted planned to use their full DEA quota and increase production for that year. The agency said it had made it easier for manufacturers to request changes in allocations and that periodically updating quotas was a possibility.

This news organization asked the DEA whether any manufacturers had not met their 2023 quotas, but an agency spokesperson said it would not comment.

An FDA spokesperson said it could help manufacturers ask for bigger quotas and to increase production, noting that in 2023, the DEA increased the quota for methylphenidate following an FDA request.

“The FDA is in frequent communication with the manufacturers of ADHD stimulant medications and the DEA, and we will continue to monitor supply,” the spokesperson said.

For 2024, the FDA told the DEA that it predicted a 3.1% increase in use of amphetamine, methylphenidate (including dexmethylphenidate), and lisdexamfetamine. The DEA took that into account when it issued its final quotas for 2024. Whether those amounts will be enough remains to be seen.

With many drugs — not just those for ADHD — in short supply, in February, the US Department of Health and Human Services (HHS) and the Federal Trade Commission opened an inquiry of sorts, seeking comments on how middlemen and others were influencing pricing and supply of generic drugs.

“When you’re prescribed an important medication by your doctor and you learn the drug is out of stock, your heart sinks,” HHS Secretary Xavier Becerra said in a statement. “This devastating reality is the case for too many Americans who need generic drugs for ADHD, cancer, and other conditions.”

On the comments site, which is open until April 15, many of the 4000-plus complaints filed to-date are from individuals with ADHD.

Dr. Pawar said clinicians can’t know what’s going on between the FDA, the DEA, and manufacturers, adding that, “they need to sit together and figure something out.”

Even Members of Congress have had trouble getting answers. In October, Rep. Abigail Spanberger (D-Virginia) and a dozen colleagues wrote to the FDA and DEA seeking information on how the agencies were responding to stimulant shortages. The DEA has still not replied.

Workarounds the Only Option?

In the past, physicians would prescribe the optimal medication for individual patients based on clinical factors. Now, one of the major factors in determining drug choice is the agent that has “the highest likelihood of benefit and the lowest likelihood of administrative demand or burden,” Dr. Goodman said.

With so many medications in short supply, clinicians have figured out workarounds to get prescriptions filled, but they don’t often pan out.

If a patient needs a 60-mg daily dose of a medication and the pharmacy doesn’t have any 60-mg pills, Dr. Goodman said he might write a prescription for a 30-mg pill to be taken twice a day. However, insurers often will cover only 30 pills for a month, which can thwart this strategy.

Dr. Pawar said he sometimes prescribes Journay PM in lieu of Concerta because it is often available. But insurers may deny coverage of Journay PM because it is a newer medication, he said. When prescribing ADHD medications, he also provides his patients with a list of potential substitutes so they can ask the pharmacist if any are in stock.

With no end to the shortage in sight, clinicians must often prescribe multiple medications until their patients are able to find one that’s available. In addition, patients are burdened with making calls and visits to multiple pharmacies until they find one that can fill their prescription.

Meanwhile, the ripple effects to the ADHD drug shortage continue to spread. Extended periods without treatment can lead to declining job performance or job loss, fractured relationships, and even financial distress, Dr. Goodman said.

“If you go without your pills for a month and you’re not performing, your work declines and you lose your job as a result, that’s not on you — that’s on the fact that you can’t get your treatment,” he noted. “The shortage is no longer an inconvenience.”

Dr. Goodman, Dr. Pawar, and Ms. Kulikosky reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Nearly 18 months after the US Food and Drug Administration (FDA) first acknowledged a national shortage of Adderall, the most common drug used to treat attention-deficit/hyperactivity disorder (ADHD), there is now a widespread scarcity of other stimulant medications — with no end in sight. How did this crisis develop and what measures are underway to address it?

The first shortage of immediate release formulations of amphetamine mixed salts (Adderall, Adderall IR) was reported by the FDA in October 2022. Now, the list includes Focalin, Ritalin, and Vyvanse, among others.

Adding to the ongoing crisis, the FDA announced in early February that Azurity Pharmaceuticals was voluntarily withdrawing one lot of its Zenzedi (dextroamphetamine sulfate) 30 mg tablets because of contamination with the antihistamine, carbinoxamine.

For the roughly 10 million adults and 6 million children in the United States grappling with ADHD, getting a prescription filled with the exact medication ordered by a physician is dictated by geographic location, insurance formularies, and pharmacy supply chains. It’s particularly challenging for those who live in rural or underserved areas with limited access to nearby pharmacies.

“Not a day goes by when I don’t hear from a number of unfortunately struggling patients about this shortage,” said Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, Baltimore, Maryland.

The ADHD drug shortage is now well into its second year, and clinicians and advocates alike say there is no apparent end in sight.

How Did We Get Here?

Manufacturers and federal agencies blame the shortage on rising demand and each other, while clinicians say that insurers, drug distributors, and middlemen are also playing a role in keeping medications out of patients’ hands.

In August 2023, the Drug Enforcement Administration (DEA), which sets quotas for the production of controlled substances, and the FDA publicly blamed manufacturers for the shortages, claiming they were not using up their allocations.

At the time, the DEA said manufacturers made and sold only 70% of their quota, nearly 1 billion doses short of what they were allowed to produce and ship that year.

The agencies also noted a record-high number of prescriptions for stimulants from 2012 to 2021. Driven in part by telehealth, the demand intensified during the pandemic. One recent study reported a 14% increase in ADHD stimulant prescriptions between 2020 and 2022.

Insurers also play a role in the shortage, David Goodman, MD, an assistant professor of psychiatry and behavioral sciences also at Johns Hopkins University, told this news organization.

Stepped therapy — in which patients must try one, two, or three medications before they are authorized to receive a more expensive or newer drug — contributes to the problem, Dr. Goodman said. Demand for such medications is high and supply low. In addition, some insurers only provide coverage for in-network pharmacies, regardless of the ability of other providers outside such networks to fill prescriptions.

“If the insurance dictates where you get your pills, and that pharmacy doesn’t have the pills or that pharmacy chain in your area doesn’t have those pills, you’re out of luck,” Dr. Goodman said.

Patients as Detectives

To get prescriptions filled, patients must “turn into detectives,” Laurie Kulikosky, CEO of Children and Adults with Attention-Deficit/Hyperactivity Disorder, told this news organization. “It’s a huge stressor.”

Tracking which ADHD medications are available, on back order, or discontinued requires frequent checking of the FDA’s drug shortages website.

Some manufacturers of generic versions of mixed amphetamine salts are only fulfilling orders for existing contracts, while others say new product won’t be available until at least April or as late as September. All blame the delay on the shortage of active ingredients.

Teva, which makes both the brand and generic of Adderall, reported on the FDA’s site that its manufacturing and distribution is at record-high levels, but demand continues to rise.

The branded Concerta is available, but some makers of generic methylphenidate reported supplies won’t be available until July.

Lisdexamfetamine dimesylate in almost all dosages is either unavailable, available in restricted quantities, or on extended back order. However, the branded product Vyvanse is available.

Industry, Government Respond

In a November 2023 statement, the DEA reported that 17 of 18 drug manufacturers the agency contacted planned to use their full DEA quota and increase production for that year. The agency said it had made it easier for manufacturers to request changes in allocations and that periodically updating quotas was a possibility.

This news organization asked the DEA whether any manufacturers had not met their 2023 quotas, but an agency spokesperson said it would not comment.

An FDA spokesperson said it could help manufacturers ask for bigger quotas and to increase production, noting that in 2023, the DEA increased the quota for methylphenidate following an FDA request.

“The FDA is in frequent communication with the manufacturers of ADHD stimulant medications and the DEA, and we will continue to monitor supply,” the spokesperson said.

For 2024, the FDA told the DEA that it predicted a 3.1% increase in use of amphetamine, methylphenidate (including dexmethylphenidate), and lisdexamfetamine. The DEA took that into account when it issued its final quotas for 2024. Whether those amounts will be enough remains to be seen.

With many drugs — not just those for ADHD — in short supply, in February, the US Department of Health and Human Services (HHS) and the Federal Trade Commission opened an inquiry of sorts, seeking comments on how middlemen and others were influencing pricing and supply of generic drugs.

“When you’re prescribed an important medication by your doctor and you learn the drug is out of stock, your heart sinks,” HHS Secretary Xavier Becerra said in a statement. “This devastating reality is the case for too many Americans who need generic drugs for ADHD, cancer, and other conditions.”

On the comments site, which is open until April 15, many of the 4000-plus complaints filed to-date are from individuals with ADHD.

Dr. Pawar said clinicians can’t know what’s going on between the FDA, the DEA, and manufacturers, adding that, “they need to sit together and figure something out.”

Even Members of Congress have had trouble getting answers. In October, Rep. Abigail Spanberger (D-Virginia) and a dozen colleagues wrote to the FDA and DEA seeking information on how the agencies were responding to stimulant shortages. The DEA has still not replied.

Workarounds the Only Option?

In the past, physicians would prescribe the optimal medication for individual patients based on clinical factors. Now, one of the major factors in determining drug choice is the agent that has “the highest likelihood of benefit and the lowest likelihood of administrative demand or burden,” Dr. Goodman said.

With so many medications in short supply, clinicians have figured out workarounds to get prescriptions filled, but they don’t often pan out.

If a patient needs a 60-mg daily dose of a medication and the pharmacy doesn’t have any 60-mg pills, Dr. Goodman said he might write a prescription for a 30-mg pill to be taken twice a day. However, insurers often will cover only 30 pills for a month, which can thwart this strategy.

Dr. Pawar said he sometimes prescribes Journay PM in lieu of Concerta because it is often available. But insurers may deny coverage of Journay PM because it is a newer medication, he said. When prescribing ADHD medications, he also provides his patients with a list of potential substitutes so they can ask the pharmacist if any are in stock.

With no end to the shortage in sight, clinicians must often prescribe multiple medications until their patients are able to find one that’s available. In addition, patients are burdened with making calls and visits to multiple pharmacies until they find one that can fill their prescription.

Meanwhile, the ripple effects to the ADHD drug shortage continue to spread. Extended periods without treatment can lead to declining job performance or job loss, fractured relationships, and even financial distress, Dr. Goodman said.

“If you go without your pills for a month and you’re not performing, your work declines and you lose your job as a result, that’s not on you — that’s on the fact that you can’t get your treatment,” he noted. “The shortage is no longer an inconvenience.”

Dr. Goodman, Dr. Pawar, and Ms. Kulikosky reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Nearly 18 months after the US Food and Drug Administration (FDA) first acknowledged a national shortage of Adderall, the most common drug used to treat attention-deficit/hyperactivity disorder (ADHD), there is now a widespread scarcity of other stimulant medications — with no end in sight. How did this crisis develop and what measures are underway to address it?

The first shortage of immediate release formulations of amphetamine mixed salts (Adderall, Adderall IR) was reported by the FDA in October 2022. Now, the list includes Focalin, Ritalin, and Vyvanse, among others.

Adding to the ongoing crisis, the FDA announced in early February that Azurity Pharmaceuticals was voluntarily withdrawing one lot of its Zenzedi (dextroamphetamine sulfate) 30 mg tablets because of contamination with the antihistamine, carbinoxamine.

For the roughly 10 million adults and 6 million children in the United States grappling with ADHD, getting a prescription filled with the exact medication ordered by a physician is dictated by geographic location, insurance formularies, and pharmacy supply chains. It’s particularly challenging for those who live in rural or underserved areas with limited access to nearby pharmacies.

“Not a day goes by when I don’t hear from a number of unfortunately struggling patients about this shortage,” said Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, Baltimore, Maryland.

The ADHD drug shortage is now well into its second year, and clinicians and advocates alike say there is no apparent end in sight.

How Did We Get Here?

Manufacturers and federal agencies blame the shortage on rising demand and each other, while clinicians say that insurers, drug distributors, and middlemen are also playing a role in keeping medications out of patients’ hands.

In August 2023, the Drug Enforcement Administration (DEA), which sets quotas for the production of controlled substances, and the FDA publicly blamed manufacturers for the shortages, claiming they were not using up their allocations.

At the time, the DEA said manufacturers made and sold only 70% of their quota, nearly 1 billion doses short of what they were allowed to produce and ship that year.

The agencies also noted a record-high number of prescriptions for stimulants from 2012 to 2021. Driven in part by telehealth, the demand intensified during the pandemic. One recent study reported a 14% increase in ADHD stimulant prescriptions between 2020 and 2022.

Insurers also play a role in the shortage, David Goodman, MD, an assistant professor of psychiatry and behavioral sciences also at Johns Hopkins University, told this news organization.

Stepped therapy — in which patients must try one, two, or three medications before they are authorized to receive a more expensive or newer drug — contributes to the problem, Dr. Goodman said. Demand for such medications is high and supply low. In addition, some insurers only provide coverage for in-network pharmacies, regardless of the ability of other providers outside such networks to fill prescriptions.

“If the insurance dictates where you get your pills, and that pharmacy doesn’t have the pills or that pharmacy chain in your area doesn’t have those pills, you’re out of luck,” Dr. Goodman said.

Patients as Detectives

To get prescriptions filled, patients must “turn into detectives,” Laurie Kulikosky, CEO of Children and Adults with Attention-Deficit/Hyperactivity Disorder, told this news organization. “It’s a huge stressor.”

Tracking which ADHD medications are available, on back order, or discontinued requires frequent checking of the FDA’s drug shortages website.

Some manufacturers of generic versions of mixed amphetamine salts are only fulfilling orders for existing contracts, while others say new product won’t be available until at least April or as late as September. All blame the delay on the shortage of active ingredients.

Teva, which makes both the brand and generic of Adderall, reported on the FDA’s site that its manufacturing and distribution is at record-high levels, but demand continues to rise.

The branded Concerta is available, but some makers of generic methylphenidate reported supplies won’t be available until July.

Lisdexamfetamine dimesylate in almost all dosages is either unavailable, available in restricted quantities, or on extended back order. However, the branded product Vyvanse is available.

Industry, Government Respond

In a November 2023 statement, the DEA reported that 17 of 18 drug manufacturers the agency contacted planned to use their full DEA quota and increase production for that year. The agency said it had made it easier for manufacturers to request changes in allocations and that periodically updating quotas was a possibility.

This news organization asked the DEA whether any manufacturers had not met their 2023 quotas, but an agency spokesperson said it would not comment.

An FDA spokesperson said it could help manufacturers ask for bigger quotas and to increase production, noting that in 2023, the DEA increased the quota for methylphenidate following an FDA request.

“The FDA is in frequent communication with the manufacturers of ADHD stimulant medications and the DEA, and we will continue to monitor supply,” the spokesperson said.

For 2024, the FDA told the DEA that it predicted a 3.1% increase in use of amphetamine, methylphenidate (including dexmethylphenidate), and lisdexamfetamine. The DEA took that into account when it issued its final quotas for 2024. Whether those amounts will be enough remains to be seen.

With many drugs — not just those for ADHD — in short supply, in February, the US Department of Health and Human Services (HHS) and the Federal Trade Commission opened an inquiry of sorts, seeking comments on how middlemen and others were influencing pricing and supply of generic drugs.

“When you’re prescribed an important medication by your doctor and you learn the drug is out of stock, your heart sinks,” HHS Secretary Xavier Becerra said in a statement. “This devastating reality is the case for too many Americans who need generic drugs for ADHD, cancer, and other conditions.”

On the comments site, which is open until April 15, many of the 4000-plus complaints filed to-date are from individuals with ADHD.

Dr. Pawar said clinicians can’t know what’s going on between the FDA, the DEA, and manufacturers, adding that, “they need to sit together and figure something out.”

Even Members of Congress have had trouble getting answers. In October, Rep. Abigail Spanberger (D-Virginia) and a dozen colleagues wrote to the FDA and DEA seeking information on how the agencies were responding to stimulant shortages. The DEA has still not replied.

Workarounds the Only Option?

In the past, physicians would prescribe the optimal medication for individual patients based on clinical factors. Now, one of the major factors in determining drug choice is the agent that has “the highest likelihood of benefit and the lowest likelihood of administrative demand or burden,” Dr. Goodman said.

With so many medications in short supply, clinicians have figured out workarounds to get prescriptions filled, but they don’t often pan out.

If a patient needs a 60-mg daily dose of a medication and the pharmacy doesn’t have any 60-mg pills, Dr. Goodman said he might write a prescription for a 30-mg pill to be taken twice a day. However, insurers often will cover only 30 pills for a month, which can thwart this strategy.

Dr. Pawar said he sometimes prescribes Journay PM in lieu of Concerta because it is often available. But insurers may deny coverage of Journay PM because it is a newer medication, he said. When prescribing ADHD medications, he also provides his patients with a list of potential substitutes so they can ask the pharmacist if any are in stock.

With no end to the shortage in sight, clinicians must often prescribe multiple medications until their patients are able to find one that’s available. In addition, patients are burdened with making calls and visits to multiple pharmacies until they find one that can fill their prescription.

Meanwhile, the ripple effects to the ADHD drug shortage continue to spread. Extended periods without treatment can lead to declining job performance or job loss, fractured relationships, and even financial distress, Dr. Goodman said.

“If you go without your pills for a month and you’re not performing, your work declines and you lose your job as a result, that’s not on you — that’s on the fact that you can’t get your treatment,” he noted. “The shortage is no longer an inconvenience.”

Dr. Goodman, Dr. Pawar, and Ms. Kulikosky reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A new study provides more evidence that sildenafil (Viagra), which is used to treat erectile dsysfuntion (ED), may help protect against Alzheimer’s disease.

The large real-world analysis of patient data from two databases showed a 30%-54% reduced prevalence in Alzheimer’s disease among patients who took sildenafil (Viagra) than those who did not, after adjusting for potential confounding factors.

This observation was further supported by mechanistic studies showing decreased neurotoxic protein levels in brain cells exposed to the phosphodiesterase type 5 inhibitor (PDE5i).

“Our findings provide further weight to repurposing this existing FDA-approved drug as a novel treatment for Alzheimer’s, which is in great need of new therapies,” Feixiong Cheng, PhD, director of the Cleveland Clinic Genome Center, who led the research, said in a news release. 

“We used artificial intelligence to integrate data across multiple domains which all indicated sildenafil’s potential against this devastating neurological disease,” Dr. Cheng noted. 

The study was published online in the Journal of Alzheimer’s Disease.
 

Neuroprotective?

Using real-world patient data from the MarketScan Medicare Supplemental database (2012-2017) and the Clinformatics database (2007-2020), the researchers conducted propensity score-stratified analyses after adjusting for gender, age, race, and comorbidities. 

They searched for all individuals with pharmacy claims for sildenafil or four comparator drugs — bumetanide, furosemide, spironolactone, and nifedipine. Results showed that sildenafil use was associated with reduced likelihood of Alzheimer’s disease relative to the control drugs. 

For example, sildenafil use was associated with a 54% reduced incidence of Alzheimer’s disease in MarketScan (hazard ratio [HR], 0.46; 95% CI, 0.32-0.66) and a 30% reduced prevalence of Alzheimer’s disease in Clinformatics (HR, 0.70; 95% CI, 0.49-1.00) compared with spironolactone.

The findings support a study published earlier this year that found a potential protective effect of PDE5i treatment on Alzheimer’s disease risk.

However, this research and the current study are contradicted by another paper published in Brain Communications in late 2022 which showed no such link between ED meds and reduced Alzheimer’s disease risk.

The investigators also found that sildenafil reduces tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic Alzheimer’s disease patient induced pluripotent stem cell (iPSC)-derived neurons. 

They further demonstrated through RNA-sequencing data analysis that sildenafil specifically targets Alzheimer’s disease related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in Alzheimer’s disease.

“We believe our findings provide the evidence needed for clinical trials to further examine the potential effectiveness of sildenafil in patients with Alzheimer’s disease,” Dr. Cheng said. 

The study was primarily supported by the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Cheng had no relevant disclosures. 

A version of this article appeared on Medscape.com.

A new study provides more evidence that sildenafil (Viagra), which is used to treat erectile dsysfuntion (ED), may help protect against Alzheimer’s disease.

The large real-world analysis of patient data from two databases showed a 30%-54% reduced prevalence in Alzheimer’s disease among patients who took sildenafil (Viagra) than those who did not, after adjusting for potential confounding factors.

This observation was further supported by mechanistic studies showing decreased neurotoxic protein levels in brain cells exposed to the phosphodiesterase type 5 inhibitor (PDE5i).

“Our findings provide further weight to repurposing this existing FDA-approved drug as a novel treatment for Alzheimer’s, which is in great need of new therapies,” Feixiong Cheng, PhD, director of the Cleveland Clinic Genome Center, who led the research, said in a news release. 

“We used artificial intelligence to integrate data across multiple domains which all indicated sildenafil’s potential against this devastating neurological disease,” Dr. Cheng noted. 

The study was published online in the Journal of Alzheimer’s Disease.
 

Neuroprotective?

Using real-world patient data from the MarketScan Medicare Supplemental database (2012-2017) and the Clinformatics database (2007-2020), the researchers conducted propensity score-stratified analyses after adjusting for gender, age, race, and comorbidities. 

They searched for all individuals with pharmacy claims for sildenafil or four comparator drugs — bumetanide, furosemide, spironolactone, and nifedipine. Results showed that sildenafil use was associated with reduced likelihood of Alzheimer’s disease relative to the control drugs. 

For example, sildenafil use was associated with a 54% reduced incidence of Alzheimer’s disease in MarketScan (hazard ratio [HR], 0.46; 95% CI, 0.32-0.66) and a 30% reduced prevalence of Alzheimer’s disease in Clinformatics (HR, 0.70; 95% CI, 0.49-1.00) compared with spironolactone.

The findings support a study published earlier this year that found a potential protective effect of PDE5i treatment on Alzheimer’s disease risk.

However, this research and the current study are contradicted by another paper published in Brain Communications in late 2022 which showed no such link between ED meds and reduced Alzheimer’s disease risk.

The investigators also found that sildenafil reduces tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic Alzheimer’s disease patient induced pluripotent stem cell (iPSC)-derived neurons. 

They further demonstrated through RNA-sequencing data analysis that sildenafil specifically targets Alzheimer’s disease related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in Alzheimer’s disease.

“We believe our findings provide the evidence needed for clinical trials to further examine the potential effectiveness of sildenafil in patients with Alzheimer’s disease,” Dr. Cheng said. 

The study was primarily supported by the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Cheng had no relevant disclosures. 

A version of this article appeared on Medscape.com.

A new study provides more evidence that sildenafil (Viagra), which is used to treat erectile dsysfuntion (ED), may help protect against Alzheimer’s disease.

The large real-world analysis of patient data from two databases showed a 30%-54% reduced prevalence in Alzheimer’s disease among patients who took sildenafil (Viagra) than those who did not, after adjusting for potential confounding factors.

This observation was further supported by mechanistic studies showing decreased neurotoxic protein levels in brain cells exposed to the phosphodiesterase type 5 inhibitor (PDE5i).

“Our findings provide further weight to repurposing this existing FDA-approved drug as a novel treatment for Alzheimer’s, which is in great need of new therapies,” Feixiong Cheng, PhD, director of the Cleveland Clinic Genome Center, who led the research, said in a news release. 

“We used artificial intelligence to integrate data across multiple domains which all indicated sildenafil’s potential against this devastating neurological disease,” Dr. Cheng noted. 

The study was published online in the Journal of Alzheimer’s Disease.
 

Neuroprotective?

Using real-world patient data from the MarketScan Medicare Supplemental database (2012-2017) and the Clinformatics database (2007-2020), the researchers conducted propensity score-stratified analyses after adjusting for gender, age, race, and comorbidities. 

They searched for all individuals with pharmacy claims for sildenafil or four comparator drugs — bumetanide, furosemide, spironolactone, and nifedipine. Results showed that sildenafil use was associated with reduced likelihood of Alzheimer’s disease relative to the control drugs. 

For example, sildenafil use was associated with a 54% reduced incidence of Alzheimer’s disease in MarketScan (hazard ratio [HR], 0.46; 95% CI, 0.32-0.66) and a 30% reduced prevalence of Alzheimer’s disease in Clinformatics (HR, 0.70; 95% CI, 0.49-1.00) compared with spironolactone.

The findings support a study published earlier this year that found a potential protective effect of PDE5i treatment on Alzheimer’s disease risk.

However, this research and the current study are contradicted by another paper published in Brain Communications in late 2022 which showed no such link between ED meds and reduced Alzheimer’s disease risk.

The investigators also found that sildenafil reduces tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic Alzheimer’s disease patient induced pluripotent stem cell (iPSC)-derived neurons. 

They further demonstrated through RNA-sequencing data analysis that sildenafil specifically targets Alzheimer’s disease related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in Alzheimer’s disease.

“We believe our findings provide the evidence needed for clinical trials to further examine the potential effectiveness of sildenafil in patients with Alzheimer’s disease,” Dr. Cheng said. 

The study was primarily supported by the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Cheng had no relevant disclosures. 

A version of this article appeared on Medscape.com.

While severe COVID-19 is associated with a significantly higher risk for psychiatric and neurologic disorders a year after infection, mild does not carry the same risk, a new study shows.

Hospitalized patients with COVID-19 had twice the risk for psychiatric or neurologic diagnoses during the 12 months after acute infection, compared with individuals who never tested positive for SARS-CoV-2. However, less severe COVID-19 was not linked to a higher incidence of psychiatric diagnoses and was associated with only a slightly higher risk for neurologic disorders.

The new research challenges previous findings of long-term risk for psychiatric and neurologic disorders associated with SARS-CoV-2 in patients who had not been hospitalized for the condition.

“Our study does not support previous findings of substantial post-acute neurologic and psychiatric morbidities among the general population of SARS-CoV-2-infected individuals but does corroborate an elevated risk among the most severe cases with COVID-19,” the authors wrote.

The study was published online on February 21 in Neurology.

‘Alarming’ Findings

Previous studies have reported nervous system symptoms in patients who have experienced COVID-19, which may persist for several weeks or months after the acute phase, even in milder cases.

But these findings haven’t been consistent across all studies, and few studies have addressed the potential effect of different viral variants and vaccination status on post-acute psychiatric and neurologic morbidities.

“Our study was partly motivated by our strong research interest in the associations between infectious disease and later chronic disease and partly by international studies, such as those conducted in the US Veterans Health databases, that have suggested substantial risks of psychiatric and neurological conditions associated with infection,” senior author Anders Hviid, MSc, DrMedSci, head of the department and professor of pharmacoepidemiology, Statens Serum Institut, Copenhagen, Denmark, told this news organization.

Investigators drew on data from the Danish National Patient Registry to compare the risk for neurologic and psychiatric disorders during the 12 months after acute COVID-19 infection to risk among people who never tested positive.

They examined data on all recorded hospital contacts between January 2005 and January 2023 for a discharge diagnosis of at least one of 11 psychiatric illnesses or at least one of 30 neurologic disorders.

The researchers compared the incidence of each disorder within 1-12 months after infection with those of COVID-naive individuals and stratified analyses according to time since infection, vaccination status, variant period, age, sex, and infection severity.

The final study cohort included 1.8 million individuals who tested positive during the study period and 1.5 who didn’t. Three quarters of those who tested positive were infected primarily with the Omicron variant.

Hospitalized vs Nonhospitalized

Overall, individuals who tested positive had a 24% lower risk for psychiatric disorders during the post-acute period (incident rate ratio [IRR], 0.76; 95% CI, 0.74-0.78) compared with the control group, but a 5% higher risk for any neurologic disorder (IRR, 1.05; 95% CI, 1.04-1.07).

Age, sex, and variant had less influence on risk than infection severity, where the differences between hospitalized and nonhospitalized patients were significant.

Compared with COVID-negative individuals, the risk for any psychiatric disorder was double for hospitalized patients (IRR, 2.05; 95% CI, 1.78-2.37) but was 25% lower among nonhospitalized patients (IRR, 0.75; 95% CI, 0.73-0.77).

For neurologic disorders, the IRR for hospitalized patients was 2.44 (95% CI, 2.29-2.60) compared with COVID-negative individuals vs an IRR of only 1.02 (95% CI, 1.01-1.04) among nonhospitalized patients.

“In a general population, there was little support for clinically relevant post-acute risk increases of psychiatric and neurologic disorders associated with SARS-CoV-2 infection without hospitalization. This was particularly true for vaccinated individuals and for the more recent variants,” the authors wrote, adding that the only exception was for change in sense and smell.

‘Flaws’ in Previous Studies?

The findings in hospitalized patients were in line with previous findings, but those in nonhospitalized patients stand out, they added.

Previous studies were done predominantly in older males with comorbidities and those who were more socioeconomically disadvantaged, which could lead to a bias, Dr. Hviid said.

Those other studies “had a number of fundamental flaws that we do not believe our study has,” Dr. Hviid said. “Our study was conducted in the general population, with free and universal testing and healthcare.”

Researchers stress that sequelae after infection are predominantly associated with severe illness.

“Today, a healthy vaccinated adult having an asymptomatic or mild bout of COVID-19 with the current variants shouldn’t fear developing serious psychiatric or neurologic disorders in the months or years after infection.”

One limitation is that only hospital contacts were included, omitting possible diagnoses given outside hospital settings.

‘Extreme Caution’ Required

The link between COVID-19 and brain health is “complex,” and the new findings should be viewed cautiously, said Maxime Taquet, MRCPsych, PhD, National Institute for Health and Care Research clinical lecturer and specialty registrar in Psychiatry, Oxford Health NHS Foundation Trust, England, who commented on the findings.

Previous research by Dr. Taquet, who was not involved in the current study, found an increased risk for neurologic and psychiatric diagnoses during the first 6 months after COVID-19 diagnosis.

The current study “contributes to better understanding this link by providing data from another country with a different organization of healthcare provision than the US, where most of the existing data come from,” Dr. Taquet said.

However, “some observations — for example, that COVID-19 is associated with a 50% reduction in the risk of autism, a condition present from very early in life — call for extreme caution in the interpretation of the findings, as they suggest that residual bias has not been accounted for,” Dr. Taquet continued.

Authors of an accompanying editorial, Eric Chow, MD, MS, MPH, of the Division of Allergy and Infectious Diseases, University of Washington, School of Public Health, and Anita Chopra, MD, of the post-COVID Clinic, University of Washington, Seattle, called the study a “critical contribution to the published literature.”

The association of neurologic and psychiatric diagnoses with severe disease “is a reminder of the importance of risk reduction by combining vaccinations with improved indoor ventilation and masking,” they concluded.

The study was supported by a grant from the Independent Research Fund Denmark. Dr. Hviid and coauthors, Dr. Chopra, and Dr. Taquet reported no relevant financial relationships. Dr. Chow received a travel award from the Infectious Diseases Society of America to attend ID Week 2022.
 

A version of this article appeared on Medscape.com.

While severe COVID-19 is associated with a significantly higher risk for psychiatric and neurologic disorders a year after infection, mild does not carry the same risk, a new study shows.

Hospitalized patients with COVID-19 had twice the risk for psychiatric or neurologic diagnoses during the 12 months after acute infection, compared with individuals who never tested positive for SARS-CoV-2. However, less severe COVID-19 was not linked to a higher incidence of psychiatric diagnoses and was associated with only a slightly higher risk for neurologic disorders.

The new research challenges previous findings of long-term risk for psychiatric and neurologic disorders associated with SARS-CoV-2 in patients who had not been hospitalized for the condition.

“Our study does not support previous findings of substantial post-acute neurologic and psychiatric morbidities among the general population of SARS-CoV-2-infected individuals but does corroborate an elevated risk among the most severe cases with COVID-19,” the authors wrote.

The study was published online on February 21 in Neurology.

‘Alarming’ Findings

Previous studies have reported nervous system symptoms in patients who have experienced COVID-19, which may persist for several weeks or months after the acute phase, even in milder cases.

But these findings haven’t been consistent across all studies, and few studies have addressed the potential effect of different viral variants and vaccination status on post-acute psychiatric and neurologic morbidities.

“Our study was partly motivated by our strong research interest in the associations between infectious disease and later chronic disease and partly by international studies, such as those conducted in the US Veterans Health databases, that have suggested substantial risks of psychiatric and neurological conditions associated with infection,” senior author Anders Hviid, MSc, DrMedSci, head of the department and professor of pharmacoepidemiology, Statens Serum Institut, Copenhagen, Denmark, told this news organization.

Investigators drew on data from the Danish National Patient Registry to compare the risk for neurologic and psychiatric disorders during the 12 months after acute COVID-19 infection to risk among people who never tested positive.

They examined data on all recorded hospital contacts between January 2005 and January 2023 for a discharge diagnosis of at least one of 11 psychiatric illnesses or at least one of 30 neurologic disorders.

The researchers compared the incidence of each disorder within 1-12 months after infection with those of COVID-naive individuals and stratified analyses according to time since infection, vaccination status, variant period, age, sex, and infection severity.

The final study cohort included 1.8 million individuals who tested positive during the study period and 1.5 who didn’t. Three quarters of those who tested positive were infected primarily with the Omicron variant.

Hospitalized vs Nonhospitalized

Overall, individuals who tested positive had a 24% lower risk for psychiatric disorders during the post-acute period (incident rate ratio [IRR], 0.76; 95% CI, 0.74-0.78) compared with the control group, but a 5% higher risk for any neurologic disorder (IRR, 1.05; 95% CI, 1.04-1.07).

Age, sex, and variant had less influence on risk than infection severity, where the differences between hospitalized and nonhospitalized patients were significant.

Compared with COVID-negative individuals, the risk for any psychiatric disorder was double for hospitalized patients (IRR, 2.05; 95% CI, 1.78-2.37) but was 25% lower among nonhospitalized patients (IRR, 0.75; 95% CI, 0.73-0.77).

For neurologic disorders, the IRR for hospitalized patients was 2.44 (95% CI, 2.29-2.60) compared with COVID-negative individuals vs an IRR of only 1.02 (95% CI, 1.01-1.04) among nonhospitalized patients.

“In a general population, there was little support for clinically relevant post-acute risk increases of psychiatric and neurologic disorders associated with SARS-CoV-2 infection without hospitalization. This was particularly true for vaccinated individuals and for the more recent variants,” the authors wrote, adding that the only exception was for change in sense and smell.

‘Flaws’ in Previous Studies?

The findings in hospitalized patients were in line with previous findings, but those in nonhospitalized patients stand out, they added.

Previous studies were done predominantly in older males with comorbidities and those who were more socioeconomically disadvantaged, which could lead to a bias, Dr. Hviid said.

Those other studies “had a number of fundamental flaws that we do not believe our study has,” Dr. Hviid said. “Our study was conducted in the general population, with free and universal testing and healthcare.”

Researchers stress that sequelae after infection are predominantly associated with severe illness.

“Today, a healthy vaccinated adult having an asymptomatic or mild bout of COVID-19 with the current variants shouldn’t fear developing serious psychiatric or neurologic disorders in the months or years after infection.”

One limitation is that only hospital contacts were included, omitting possible diagnoses given outside hospital settings.

‘Extreme Caution’ Required

The link between COVID-19 and brain health is “complex,” and the new findings should be viewed cautiously, said Maxime Taquet, MRCPsych, PhD, National Institute for Health and Care Research clinical lecturer and specialty registrar in Psychiatry, Oxford Health NHS Foundation Trust, England, who commented on the findings.

Previous research by Dr. Taquet, who was not involved in the current study, found an increased risk for neurologic and psychiatric diagnoses during the first 6 months after COVID-19 diagnosis.

The current study “contributes to better understanding this link by providing data from another country with a different organization of healthcare provision than the US, where most of the existing data come from,” Dr. Taquet said.

However, “some observations — for example, that COVID-19 is associated with a 50% reduction in the risk of autism, a condition present from very early in life — call for extreme caution in the interpretation of the findings, as they suggest that residual bias has not been accounted for,” Dr. Taquet continued.

Authors of an accompanying editorial, Eric Chow, MD, MS, MPH, of the Division of Allergy and Infectious Diseases, University of Washington, School of Public Health, and Anita Chopra, MD, of the post-COVID Clinic, University of Washington, Seattle, called the study a “critical contribution to the published literature.”

The association of neurologic and psychiatric diagnoses with severe disease “is a reminder of the importance of risk reduction by combining vaccinations with improved indoor ventilation and masking,” they concluded.

The study was supported by a grant from the Independent Research Fund Denmark. Dr. Hviid and coauthors, Dr. Chopra, and Dr. Taquet reported no relevant financial relationships. Dr. Chow received a travel award from the Infectious Diseases Society of America to attend ID Week 2022.
 

A version of this article appeared on Medscape.com.

While severe COVID-19 is associated with a significantly higher risk for psychiatric and neurologic disorders a year after infection, mild does not carry the same risk, a new study shows.

Hospitalized patients with COVID-19 had twice the risk for psychiatric or neurologic diagnoses during the 12 months after acute infection, compared with individuals who never tested positive for SARS-CoV-2. However, less severe COVID-19 was not linked to a higher incidence of psychiatric diagnoses and was associated with only a slightly higher risk for neurologic disorders.

The new research challenges previous findings of long-term risk for psychiatric and neurologic disorders associated with SARS-CoV-2 in patients who had not been hospitalized for the condition.

“Our study does not support previous findings of substantial post-acute neurologic and psychiatric morbidities among the general population of SARS-CoV-2-infected individuals but does corroborate an elevated risk among the most severe cases with COVID-19,” the authors wrote.

The study was published online on February 21 in Neurology.

‘Alarming’ Findings

Previous studies have reported nervous system symptoms in patients who have experienced COVID-19, which may persist for several weeks or months after the acute phase, even in milder cases.

But these findings haven’t been consistent across all studies, and few studies have addressed the potential effect of different viral variants and vaccination status on post-acute psychiatric and neurologic morbidities.

“Our study was partly motivated by our strong research interest in the associations between infectious disease and later chronic disease and partly by international studies, such as those conducted in the US Veterans Health databases, that have suggested substantial risks of psychiatric and neurological conditions associated with infection,” senior author Anders Hviid, MSc, DrMedSci, head of the department and professor of pharmacoepidemiology, Statens Serum Institut, Copenhagen, Denmark, told this news organization.

Investigators drew on data from the Danish National Patient Registry to compare the risk for neurologic and psychiatric disorders during the 12 months after acute COVID-19 infection to risk among people who never tested positive.

They examined data on all recorded hospital contacts between January 2005 and January 2023 for a discharge diagnosis of at least one of 11 psychiatric illnesses or at least one of 30 neurologic disorders.

The researchers compared the incidence of each disorder within 1-12 months after infection with those of COVID-naive individuals and stratified analyses according to time since infection, vaccination status, variant period, age, sex, and infection severity.

The final study cohort included 1.8 million individuals who tested positive during the study period and 1.5 who didn’t. Three quarters of those who tested positive were infected primarily with the Omicron variant.

Hospitalized vs Nonhospitalized

Overall, individuals who tested positive had a 24% lower risk for psychiatric disorders during the post-acute period (incident rate ratio [IRR], 0.76; 95% CI, 0.74-0.78) compared with the control group, but a 5% higher risk for any neurologic disorder (IRR, 1.05; 95% CI, 1.04-1.07).

Age, sex, and variant had less influence on risk than infection severity, where the differences between hospitalized and nonhospitalized patients were significant.

Compared with COVID-negative individuals, the risk for any psychiatric disorder was double for hospitalized patients (IRR, 2.05; 95% CI, 1.78-2.37) but was 25% lower among nonhospitalized patients (IRR, 0.75; 95% CI, 0.73-0.77).

For neurologic disorders, the IRR for hospitalized patients was 2.44 (95% CI, 2.29-2.60) compared with COVID-negative individuals vs an IRR of only 1.02 (95% CI, 1.01-1.04) among nonhospitalized patients.

“In a general population, there was little support for clinically relevant post-acute risk increases of psychiatric and neurologic disorders associated with SARS-CoV-2 infection without hospitalization. This was particularly true for vaccinated individuals and for the more recent variants,” the authors wrote, adding that the only exception was for change in sense and smell.

‘Flaws’ in Previous Studies?

The findings in hospitalized patients were in line with previous findings, but those in nonhospitalized patients stand out, they added.

Previous studies were done predominantly in older males with comorbidities and those who were more socioeconomically disadvantaged, which could lead to a bias, Dr. Hviid said.

Those other studies “had a number of fundamental flaws that we do not believe our study has,” Dr. Hviid said. “Our study was conducted in the general population, with free and universal testing and healthcare.”

Researchers stress that sequelae after infection are predominantly associated with severe illness.

“Today, a healthy vaccinated adult having an asymptomatic or mild bout of COVID-19 with the current variants shouldn’t fear developing serious psychiatric or neurologic disorders in the months or years after infection.”

One limitation is that only hospital contacts were included, omitting possible diagnoses given outside hospital settings.

‘Extreme Caution’ Required

The link between COVID-19 and brain health is “complex,” and the new findings should be viewed cautiously, said Maxime Taquet, MRCPsych, PhD, National Institute for Health and Care Research clinical lecturer and specialty registrar in Psychiatry, Oxford Health NHS Foundation Trust, England, who commented on the findings.

Previous research by Dr. Taquet, who was not involved in the current study, found an increased risk for neurologic and psychiatric diagnoses during the first 6 months after COVID-19 diagnosis.

The current study “contributes to better understanding this link by providing data from another country with a different organization of healthcare provision than the US, where most of the existing data come from,” Dr. Taquet said.

However, “some observations — for example, that COVID-19 is associated with a 50% reduction in the risk of autism, a condition present from very early in life — call for extreme caution in the interpretation of the findings, as they suggest that residual bias has not been accounted for,” Dr. Taquet continued.

Authors of an accompanying editorial, Eric Chow, MD, MS, MPH, of the Division of Allergy and Infectious Diseases, University of Washington, School of Public Health, and Anita Chopra, MD, of the post-COVID Clinic, University of Washington, Seattle, called the study a “critical contribution to the published literature.”

The association of neurologic and psychiatric diagnoses with severe disease “is a reminder of the importance of risk reduction by combining vaccinations with improved indoor ventilation and masking,” they concluded.

The study was supported by a grant from the Independent Research Fund Denmark. Dr. Hviid and coauthors, Dr. Chopra, and Dr. Taquet reported no relevant financial relationships. Dr. Chow received a travel award from the Infectious Diseases Society of America to attend ID Week 2022.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted breakthrough designation to an LSD-based treatment for generalized anxiety disorder (GAD) based on promising topline data from a phase 2b clinical trial. Mind Medicine (MindMed) Inc is developing the treatment — MM120 (lysergide d-tartrate).

In a news release, the company reports that a single oral dose of MM120 met its key secondary endpoint, maintaining “clinically and statistically significant” reductions in Hamilton Anxiety Scale (HAM-A) score, compared with placebo, at 12 weeks with a 65% clinical response rate and 48% clinical remission rate.

The company previously announced statistically significant improvements on the HAM-A compared with placebo at 4 weeks, which was the trial’s primary endpoint.

“I’ve conducted clinical research studies in psychiatry for over two decades and have seen studies of many drugs under development for the treatment of anxiety. That MM120 exhibited rapid and robust efficacy, solidly sustained for 12 weeks after a single dose, is truly remarkable,” study investigator David Feifel, MD, PhD, professor emeritus of psychiatry at the University of California, San Diego, and director of the Kadima Neuropsychiatry Institute in La Jolla, California, said in the news release.

“These results suggest the potential MM120 has in the treatment of anxiety, and those of us who struggle every day to alleviate anxiety in our patients look forward to seeing results from future phase 3 trials,” Dr. Feifel added.

MM120 was administered as a single dose in a monitored clinical setting with no additional therapeutic intervention. Prior to treatment with MM120, study participants were clinically tapered and then washed out from any anxiolytic or antidepressant treatments and did not receive any form of study-related psychotherapy for the duration of their participation in the study.

MM120 100 µg — the dose that demonstrated optimal clinical activity — produced a 7.7-point improvement over placebo at week 12 (P < .003; Cohen’s d = 0.81), with a 65% clinical response rate and a 48% clinical remission rate sustained to week 12.

Also at week 12, Clinical Global Impressions–Severity (CGI-S) scores on average improved from 4.8 to 2.2 in the 100-µg dose group, representing a two-category shift from ‘markedly ill’ to ‘borderline ill’ at week 12 (P < .004), the company reported.

Improvement was noted as early as study day 2, and durable with further improvements observed in mean HAM-A or CGI-S scores between 4 and 12 weeks.

MM120 was generally well-tolerated with most adverse events rated as mild to moderate and transient and occurred on the day of administration day, in line with the expected acute effects of the study drug.

The most common adverse events on dosing day included illusion, hallucinations, euphoric mood, anxiety, abnormal thinking, headache, paresthesia, dizziness, tremor, nausea, vomiting, feeling abnormal, mydriasis, and hyperhidrosis.

The company plans to hold an end-of-phase 2 meeting with the FDA in the first half of 2024 and start phase 3 testing in the second half of 2024.

“The FDA’s decision to designate MM120 as a breakthrough therapy for GAD and the durability data from our phase 2b study provide further validation of the important potential role this treatment can play in addressing the huge unmet need among individuals living with GAD,” Robert Barrow, director and CEO of MindMed said in the release.

The primary data analyses from the trial will be presented at the American Psychiatric Association (APA) annual meeting in May.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted breakthrough designation to an LSD-based treatment for generalized anxiety disorder (GAD) based on promising topline data from a phase 2b clinical trial. Mind Medicine (MindMed) Inc is developing the treatment — MM120 (lysergide d-tartrate).

In a news release, the company reports that a single oral dose of MM120 met its key secondary endpoint, maintaining “clinically and statistically significant” reductions in Hamilton Anxiety Scale (HAM-A) score, compared with placebo, at 12 weeks with a 65% clinical response rate and 48% clinical remission rate.

The company previously announced statistically significant improvements on the HAM-A compared with placebo at 4 weeks, which was the trial’s primary endpoint.

“I’ve conducted clinical research studies in psychiatry for over two decades and have seen studies of many drugs under development for the treatment of anxiety. That MM120 exhibited rapid and robust efficacy, solidly sustained for 12 weeks after a single dose, is truly remarkable,” study investigator David Feifel, MD, PhD, professor emeritus of psychiatry at the University of California, San Diego, and director of the Kadima Neuropsychiatry Institute in La Jolla, California, said in the news release.

“These results suggest the potential MM120 has in the treatment of anxiety, and those of us who struggle every day to alleviate anxiety in our patients look forward to seeing results from future phase 3 trials,” Dr. Feifel added.

MM120 was administered as a single dose in a monitored clinical setting with no additional therapeutic intervention. Prior to treatment with MM120, study participants were clinically tapered and then washed out from any anxiolytic or antidepressant treatments and did not receive any form of study-related psychotherapy for the duration of their participation in the study.

MM120 100 µg — the dose that demonstrated optimal clinical activity — produced a 7.7-point improvement over placebo at week 12 (P < .003; Cohen’s d = 0.81), with a 65% clinical response rate and a 48% clinical remission rate sustained to week 12.

Also at week 12, Clinical Global Impressions–Severity (CGI-S) scores on average improved from 4.8 to 2.2 in the 100-µg dose group, representing a two-category shift from ‘markedly ill’ to ‘borderline ill’ at week 12 (P < .004), the company reported.

Improvement was noted as early as study day 2, and durable with further improvements observed in mean HAM-A or CGI-S scores between 4 and 12 weeks.

MM120 was generally well-tolerated with most adverse events rated as mild to moderate and transient and occurred on the day of administration day, in line with the expected acute effects of the study drug.

The most common adverse events on dosing day included illusion, hallucinations, euphoric mood, anxiety, abnormal thinking, headache, paresthesia, dizziness, tremor, nausea, vomiting, feeling abnormal, mydriasis, and hyperhidrosis.

The company plans to hold an end-of-phase 2 meeting with the FDA in the first half of 2024 and start phase 3 testing in the second half of 2024.

“The FDA’s decision to designate MM120 as a breakthrough therapy for GAD and the durability data from our phase 2b study provide further validation of the important potential role this treatment can play in addressing the huge unmet need among individuals living with GAD,” Robert Barrow, director and CEO of MindMed said in the release.

The primary data analyses from the trial will be presented at the American Psychiatric Association (APA) annual meeting in May.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted breakthrough designation to an LSD-based treatment for generalized anxiety disorder (GAD) based on promising topline data from a phase 2b clinical trial. Mind Medicine (MindMed) Inc is developing the treatment — MM120 (lysergide d-tartrate).

In a news release, the company reports that a single oral dose of MM120 met its key secondary endpoint, maintaining “clinically and statistically significant” reductions in Hamilton Anxiety Scale (HAM-A) score, compared with placebo, at 12 weeks with a 65% clinical response rate and 48% clinical remission rate.

The company previously announced statistically significant improvements on the HAM-A compared with placebo at 4 weeks, which was the trial’s primary endpoint.

“I’ve conducted clinical research studies in psychiatry for over two decades and have seen studies of many drugs under development for the treatment of anxiety. That MM120 exhibited rapid and robust efficacy, solidly sustained for 12 weeks after a single dose, is truly remarkable,” study investigator David Feifel, MD, PhD, professor emeritus of psychiatry at the University of California, San Diego, and director of the Kadima Neuropsychiatry Institute in La Jolla, California, said in the news release.

“These results suggest the potential MM120 has in the treatment of anxiety, and those of us who struggle every day to alleviate anxiety in our patients look forward to seeing results from future phase 3 trials,” Dr. Feifel added.

MM120 was administered as a single dose in a monitored clinical setting with no additional therapeutic intervention. Prior to treatment with MM120, study participants were clinically tapered and then washed out from any anxiolytic or antidepressant treatments and did not receive any form of study-related psychotherapy for the duration of their participation in the study.

MM120 100 µg — the dose that demonstrated optimal clinical activity — produced a 7.7-point improvement over placebo at week 12 (P < .003; Cohen’s d = 0.81), with a 65% clinical response rate and a 48% clinical remission rate sustained to week 12.

Also at week 12, Clinical Global Impressions–Severity (CGI-S) scores on average improved from 4.8 to 2.2 in the 100-µg dose group, representing a two-category shift from ‘markedly ill’ to ‘borderline ill’ at week 12 (P < .004), the company reported.

Improvement was noted as early as study day 2, and durable with further improvements observed in mean HAM-A or CGI-S scores between 4 and 12 weeks.

MM120 was generally well-tolerated with most adverse events rated as mild to moderate and transient and occurred on the day of administration day, in line with the expected acute effects of the study drug.

The most common adverse events on dosing day included illusion, hallucinations, euphoric mood, anxiety, abnormal thinking, headache, paresthesia, dizziness, tremor, nausea, vomiting, feeling abnormal, mydriasis, and hyperhidrosis.

The company plans to hold an end-of-phase 2 meeting with the FDA in the first half of 2024 and start phase 3 testing in the second half of 2024.

“The FDA’s decision to designate MM120 as a breakthrough therapy for GAD and the durability data from our phase 2b study provide further validation of the important potential role this treatment can play in addressing the huge unmet need among individuals living with GAD,” Robert Barrow, director and CEO of MindMed said in the release.

The primary data analyses from the trial will be presented at the American Psychiatric Association (APA) annual meeting in May.

A version of this article appeared on Medscape.com.

Lawmakers have added a provision to raise Medicare payments to clinicians to a $460 billion bipartisan package of federal spending bills that passed in the House on March 6 and is expected to be passed in the Senate and signed by President Biden before then end of March 8, but industry groups have criticized it as paltry.

Lawmakers often tweak Medicare policy by adding provisions to other kinds of legislation, including the spending bills Congress must pass to keep the federal government running.

Physicians’ groups and some lawmakers have long pressed Congress to change Medicare payment rules with little success, even as inflation has caused physicians’ expenses to rise. Doctors now face a 3.4% cut to Medicare reimbursements in 2024, which would be only partly mitigated by the recently announced provision.

The Medical Group Management Association (MGMA) said the proposed increase would total 1.68%. The increase, part of a bipartisan package of bills released by the House and Senate Appropriations committees on March 3, would apply to the budget for fiscal 2024, which began on October 1, 2023.

“We are deeply disappointed with Congress’ half-hearted attempt to remedy the devastating blow physician practices were dealt by the 2024 Medicare Physician Fee Schedule,” Anders Gilberg, senior vice president of MGMA, said in a statement. “Anything less than a full reversal of the 3.4% cut is appallingly inadequate.”

The American Medical Association said it was “extremely disappointed” that the boost only eased, but did not fully reverse, a deeper planned cut.

The American Academy of Family Physicians (AAFP) also expressed disappointment with the proposed increase.

“The AAFP has repeatedly told Congress that the 3.4% Medicare payment reduction that went into effect on January 1 is untenable for family physicians and threatens patients’ access to primary care,” the group said in a statement.

“While we appreciate the partial relief, family physicians continue to face an annual threat of payment cuts that are detrimental to practices and patients,” AAFP said.

A version of this article appeared on Medscape.com.

Lawmakers have added a provision to raise Medicare payments to clinicians to a $460 billion bipartisan package of federal spending bills that passed in the House on March 6 and is expected to be passed in the Senate and signed by President Biden before then end of March 8, but industry groups have criticized it as paltry.

Lawmakers often tweak Medicare policy by adding provisions to other kinds of legislation, including the spending bills Congress must pass to keep the federal government running.

Physicians’ groups and some lawmakers have long pressed Congress to change Medicare payment rules with little success, even as inflation has caused physicians’ expenses to rise. Doctors now face a 3.4% cut to Medicare reimbursements in 2024, which would be only partly mitigated by the recently announced provision.

The Medical Group Management Association (MGMA) said the proposed increase would total 1.68%. The increase, part of a bipartisan package of bills released by the House and Senate Appropriations committees on March 3, would apply to the budget for fiscal 2024, which began on October 1, 2023.

“We are deeply disappointed with Congress’ half-hearted attempt to remedy the devastating blow physician practices were dealt by the 2024 Medicare Physician Fee Schedule,” Anders Gilberg, senior vice president of MGMA, said in a statement. “Anything less than a full reversal of the 3.4% cut is appallingly inadequate.”

The American Medical Association said it was “extremely disappointed” that the boost only eased, but did not fully reverse, a deeper planned cut.

The American Academy of Family Physicians (AAFP) also expressed disappointment with the proposed increase.

“The AAFP has repeatedly told Congress that the 3.4% Medicare payment reduction that went into effect on January 1 is untenable for family physicians and threatens patients’ access to primary care,” the group said in a statement.

“While we appreciate the partial relief, family physicians continue to face an annual threat of payment cuts that are detrimental to practices and patients,” AAFP said.

A version of this article appeared on Medscape.com.

Lawmakers have added a provision to raise Medicare payments to clinicians to a $460 billion bipartisan package of federal spending bills that passed in the House on March 6 and is expected to be passed in the Senate and signed by President Biden before then end of March 8, but industry groups have criticized it as paltry.

Lawmakers often tweak Medicare policy by adding provisions to other kinds of legislation, including the spending bills Congress must pass to keep the federal government running.

Physicians’ groups and some lawmakers have long pressed Congress to change Medicare payment rules with little success, even as inflation has caused physicians’ expenses to rise. Doctors now face a 3.4% cut to Medicare reimbursements in 2024, which would be only partly mitigated by the recently announced provision.

The Medical Group Management Association (MGMA) said the proposed increase would total 1.68%. The increase, part of a bipartisan package of bills released by the House and Senate Appropriations committees on March 3, would apply to the budget for fiscal 2024, which began on October 1, 2023.

“We are deeply disappointed with Congress’ half-hearted attempt to remedy the devastating blow physician practices were dealt by the 2024 Medicare Physician Fee Schedule,” Anders Gilberg, senior vice president of MGMA, said in a statement. “Anything less than a full reversal of the 3.4% cut is appallingly inadequate.”

The American Medical Association said it was “extremely disappointed” that the boost only eased, but did not fully reverse, a deeper planned cut.

The American Academy of Family Physicians (AAFP) also expressed disappointment with the proposed increase.

“The AAFP has repeatedly told Congress that the 3.4% Medicare payment reduction that went into effect on January 1 is untenable for family physicians and threatens patients’ access to primary care,” the group said in a statement.

“While we appreciate the partial relief, family physicians continue to face an annual threat of payment cuts that are detrimental to practices and patients,” AAFP said.

A version of this article appeared on Medscape.com.