Clinical Psychiatry News

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

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

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

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

For almost 2 decades, antidepressants have carried boxed warnings linking the medications to an increased risk for suicidal thoughts and behaviors in young people. Paradoxically, and for almost as long, evidence suggests these warnings may have led to fewer depression diagnoses, reduced prescriptions, and, ultimately, higher suicide rates.

With mounting evidence of these negative unintended consequences, some clinicians and researchers are urging the Food and Drug Administration (FDA) to consider revising — or even eliminating — boxed warnings on these medications.

The latest report challenging the utility of the 2005 warnings was particularly sobering. Published in October in Health Affairs, the systematic review of studies from 2003 to 2022 showed a 20%-40% decline in physician visits for depression, a 20%-50% decline in antidepressant use, and an abrupt increase in psychotropic drug poisonings and suicides — all after the warnings were added.

“FDA officials should review the totality of evidence and err on the side of caution in acknowledging possible harms of the antidepressant warnings,” lead author Stephen Soumerai, ScD, professor of population medicine at Harvard Medical School at Harvard Pilgrim Health Care Institute, Boston, Massachusetts and colleagues wrote. They called on the FDA to replace the boxed warnings with a routine warning in labeling.

While good prospective data on the risks and benefits of antidepressants in youth were limited when the boxed warnings were instituted, there is more information now, said Jeffrey Strawn, MD, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine in Ohio. Strawn, whose research on the topic has been cited frequently over the years, said the new evidence suggests it is time for the FDA to reevaluate the warnings.

“I don’t think that they’ve been useful. They’ve actually been harmful,” Strawn told this news organization. “These boxed warnings have decreased physicians’ and other clinicians’ comfort and tendency to prescribe.”

 

Decline in Diagnoses

The FDA issued its first warning about the potential for suicidal thoughts and behavior in children in 2003. After an advisory panel weighed the evidence, the agency added a boxed warning in 2005 to all antidepressants for children younger than 18 years. The warning was expanded in 2007 to include young adults through age 24.

Data suggesting that the warnings have had unintended effects can be found going back to just after they were issued. For instance, in 2009, after rising for years, the rate of new pediatric depression diagnoses fell precipitously after the warning was added, with primary care physicians diagnosing 44% fewer cases.

In 2014, citing evidence of fewer diagnoses and rising psychotropic drug poisonings, Weill Cornell Medicine Professor Richard A. Friedman, MD, called on the FDA in a perspective to remove the boxed warnings.

Strawn and colleagues reported in an often-cited 2014 systematic review and meta-analysis that, in nine trials involving 1673 patients and six medications, antidepressants were superior to placebo, with no increased risk for suicidal thoughts or behavior.

He has also studied adverse effects of the medications, reporting in Pharmacotherapy that suicidality risk might be more likely with some medications, such as paroxetine and venlafaxine, and that it could be influenced by baseline suicidality, among many other factors. A Swedish register study found that risk was highest the month before starting a medication, Strawn and colleagues wrote.

Dara Sakolsky, MD, PhD, associate professor of psychiatry and associate medical director, Services for Teens at Risk at the University of Pittsburgh School of Medicine, Pennsylvania, told this news organization that, because of “these negative unintended consequences,” the FDA should lower the temperature by putting the warnings in labeling.

“It makes sense based on the data that we have at hand now,” said Sakolsky.

 

The Dangers of Untreated Depression

Even with this new information, lingering concerns about earlier studies that pointed to increased suicidality risk may discourage prescribing by primary care physicians and pediatricians, and that worries researchers and psychiatrists.

“My concern is that the risk for suicide and suicidal behavior may be higher in untreated depression than the risk of suicidal thoughts or behaviors from antidepressants,” Jeffrey Bridge, PhD, director of the Center for Suicide Prevention and Research at Nationwide Children’s Hospital, Columbus, Ohio, told this news organization.

Bridge is the lead author of a much-cited 2007 meta-analysis in JAMA that showed that the benefits of antidepressants in children and adolescents appeared to be greater than the risks for suicidality. “The concern about antidepressants must be considered in the context of possible benefit,” wrote Bridge, who also is professor of pediatrics, psychiatry, and behavioral health at Ohio State University College of Medicine, Columbus.

Depression and suicide are a scourge for those younger than 25 years. A 2021 literature review noted that the prevalence of depression — which has been increasing for all Americans — has risen more among adolescents than adults. Depression is “strongly associated with suicide,” the authors wrote.

In 2021, the National Institute of Mental Health reported suicide was the second leading cause of death among 10- to 14-year-olds and the third leading cause of death among those aged 15-24 years.

Suicide kills more kids aged between 10 and 24 years than cancer and all other illnesses combined, John Campo, MD, director of child and adolescent psychiatry at Johns Hopkins University School of Medicine and vice president of psychiatric services at Kennedy Krieger Institute, told this news organization.

Meanwhile, he added, the medications work and clinicians balance risk and benefit in prescribing.

The landmark 2007 Treatment for Adolescents with Depression Study showed that fluoxetine, especially in combination with cognitive-behavioral therapy (CBT), was significantly better than placebo. Since that time, legions of trials have shown the drugs’ effectiveness.

The most effective treatment for teen depression is a combination of CBT and a selective serotonin reuptake inhibitor, said Sakolsky.

“We know that the evidence for that is pretty good,” she said. “On the flip side, we know the risk of having an adverse outcome is pretty low.”

Sakolsky tells patients and families that perhaps 1 in 146 will have a suicidal thought or behavior. “That’s pretty rare when we know how effective these medicines are.” 

Strawn said he always notes that no suicides took place in the trials that led to the warning and stresses that he closely monitors patients. “While the more recent prospective data are reassuring,” the suicidality risk “is something that we still talk about,” he said. He also discusses how some antidepressants seem to increase risk more than others.

For Campo, the discussion is based on his reading of the evidence, not the presence of the FDA warning.

“Based on what we know, I still think it’s fair to proceed with the idea that there is a small, but real risk,” he said. However, “at the same time, the medications might be exceptionally helpful for some kids.”

 

‘What Do We Do Now?’

When the FDA issued its warning in 2005, the agency said it identified the risk for suicidality in a combined analysis of short-term placebo-controlled trials of nine antidepressants. It ultimately included 24 trials involving more than 4400 patients. The risk was highest in the first few months. The average risk for those taking antidepressants was 4%, twice the placebo risk of 2%. There were no suicides in these trials, however.

The trials relied on spontaneous reports of adverse events, not predetermined measures, Campo said. Even so, that 2% difference is “nothing to sneeze at,” he noted.

Bridge’s meta-analysis showed a smaller difference — closer to 0.7%. “But it was still statistically significant,” Campo said. “I have trouble ignoring that.”

The unintended consequences of the warning can’t be studied in a randomized controlled trial. Studies have shown an association but not a direct cause-and-effect relationship between the warning and a decline in treatment and rise in suicides.

But the potential for suicidal thoughts and behavior with antidepressants has been studied prospectively. Some older studies found a significant risk, while more recent trials have not.

While the Health Affairs analysis “certainly makes a strong case,” it is observational data, Campo said.

“The question is, what do we do now in retrospect? Do you say, ‘Never mind. We don’t need the black box warning anymore?’ ” he said. “That would require a pretty careful look.”

The Health Affairs paper “makes me think that there are other areas of research that that need to be completed and done and updated, and then there should be an assessment, a reevaluation from the FDA,” said Bridge. A new meta-analysis “would be very informative,” he said.

 

What’s Next?

When asked about the Health Affairs paper and whether the agency would review the warnings, an FDA spokesperson told this news organization that the agency “does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

Sakolsky said the data clearly point to the damage that the warning has done over the past 2 decades, but that things might be improving. Studies conducted more recently might not have captured some changes in practice.

For instance, she noted, in 2022, the US Preventive Services Task Force recommended screening for major depressive disorder in adolescents aged 12-18 years. In turn, she has seen more patients in her office who were referred by pediatricians who had conducted the screening, said Sakolsky.

Strawn said the time for pontificating is long past due. “We’re withholding medications and other treatments that could potentially be effective for disorders that, in and of themselves, are associated with a significant increase in the risk of suicide.” 

After the FDA instituted the warning, “we were all very nervous,” about the potential fallout, said Campo, adding that a part of him wishes that the warnings had been “more mundane and less dramatic.”

Despite the unintended consequences, “it’s going to be hard to put the genie back in the bottle,” he said.

Campo and Sakolsky reported no relevant financial relationships. Strawn disclosed that his institution has received research funding from the National Institute of Child Health and Human Development, the Patient-Centered Outcomes Research Institute (PCORI), and AbbVie. Bridge reported that he received grant support from the National Institute of Mental Health, Centers for Disease Control and Prevention, and PCORI; is a scientific adviser to Clarigent Health; and is on the Scientific Council of the American Foundation for Suicide Prevention.

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

A drug that combines the atypical antipsychotic brexpiprazole and the selective serotonin reuptake inhibitor sertraline provides significantly greater relief of posttraumatic stress disorder (PTSD) symptoms than sertraline plus placebo, results of a phase 3 trial showed.

The medication is currently under review by the Food and Drug Administration (FDA) and if approved, will be the first pharmacologic option for PTSD in more than 20 years.

The trial met its primary endpoint of change in the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) (CAPS-5) total score at week 10 and secondary patient-reported outcomes of PTSD symptoms, anxiety, and depression.

“And what is really cool, what’s really impactful is the combination worked better than sertraline plus placebo on a brief inventory of psychosocial functioning,” study investigator Lori L. Davis, a senior research psychiatrist, Birmingham Veterans Affairs Health Care System in Alabama, said in an interview.

“We can treat symptoms but that’s where the rubber meets the road, in terms of are they functioning better,” added Davis, who is also an adjunct professor of psychiatry, Heersink School of Medicine, University of Alabama at Birmingham.

The findings were published online on December 18 in JAMA Psychiatry and reported in May 2024 as part of a trio of trials conducted by Otsuka Pharmaceutical and Lundbeck Pharmaceuticals, codevelopers of the drug.

 

Clinically Meaningful

The FDA accepted the companies’ supplemental new drug application in June with a decision on approval expected in early February 2025.

“This study provides promising results for a medication that may be an important new option for PTSD,” John Krystal, MD, director, Clinical Neuroscience Division, National Center for PTSD, US Department of Veterans Affairs, who was not involved in the research, said in an interview. “New PTSD treatments are a high priority.”

Currently, there are two FDA-approved medication treatments for PTSD — sertraline and paroxetine.

“They are helpful for many people, but patients are often left with residual symptoms or tolerability issues,” noted Krystal, who is also professor and chair of psychiatry, Yale University, New Haven, Connecticut.

“New medications that might address the important ‘effectiveness gap’ in PTSD could help to reduce the remaining distress, disability, and suicide risk associated with PTSD.” 

The double-blind, phase 3 trial included 416 adults aged 18-65 years with a DSM-5 diagnosis of PTSD and symptoms for at least 6 months prior to screening. Patients underwent a 1-week placebo-run in period followed by randomization to daily oral brexpiprazole 2-3 mg plus sertraline 150 mg or daily sertraline 150 mg plus placebo for 11 weeks.

Participants’ mean age was 37.4 years, 74.5% were women, and mean CAPS-5 total score was 38.4, suggesting moderate to high severity PTSD, Davis said. The average time from the index traumatic event was 4 years and three fourths had no prior exposure to PTSD prescription medications.

At week 10, the mean change in CAPS-5 score from randomization was –19.2 points in the brexpiprazole plus sertraline group and –13.6 points in the sertraline plus placebo group (95% CI, –8.79 to –2.38; P < .001).

Asked whether the 5.59-point treatment difference is clinically meaningful, Davis said there is no widely agreed definition for change in CAPS-5 total score but that a within-group reduction of more than 10-13 points is most-often cited as being clinically meaningful.

The key secondary endpoint of least square mean change in the patient-reported Brief Inventory of Psychosocial Function total score from baseline to week 12 was –33.8 with the combination vs –21.8 with sertraline plus placebo (95% CI, –19.4 to –4.62; P = .002).

“That’s clinically meaningful for me as a provider and a clinician and a researcher when you’re getting the PTSD symptom change differences in parallel with the improvement in functional outcome,” she said. “I see that as the clinically meaningful gauge.”

In terms of safety, 3.9% of the participants in the brexpiprazole/sertraline group and 10.2% of those in the sertraline/placebo group discontinued treatment because of adverse events.

In both the combination and control groups, the only treatment-emergent adverse event with an incidence of more than 10% was nausea (12.2% vs 11.7%, respectively).

At the last visit, the mean change in body weight from baseline was an increase of 1.3 kg for brexpiprazole plus sertraline vs 0 kg for sertraline alone. Rates of fatigue (6.8% vs 4.1%) and somnolence (5.4% vs 2.6%) were also higher with brexpiprazole plus sertraline.

 

A Trio of Clinical Trials

The findings are part of a larger program reported by the drug makers that includes a flexible-dose brexpiprazole phase 2 trial that met the same CAPS-5 primary endpoint and a second phase 3 trial (072 study) that did not.

“We’ve looked at that data and the sertraline/placebo response was a lot higher, so it was not due to a lack of response with the combination but due to a more robust response with the active control,” Davis said. “But we want to point out for that 072 study, there was still important separation between the combination and sertraline plus placebo on the functional outcome.”

All three trials ran for 12 weeks, so longer-term efficacy and safety data are needed, she said. Other limitations of the published phase 3 study are the patient eligibility criteria, restrictions on concomitant therapy, and lack of non-US sites, which many limit generalizability, the authors noted.

“Specifically, the exclusion of patients with a current major depressive episode is both a strength (to show a specific effect on PTSD) and a limitation (given the high prevalence of comorbid depression in PTSD),” they added.

 

Kudos, Caveats

Reached for comment, Vincent F. Capaldi, II, MD, ScM, professor and chair, department of psychiatry, Uniformed Services University of the Health Sciences School of Medicine, Bethesda, Maryland, said the exclusion of these patients is a limitation but that the study was well designed and conducted in a large sample across the United States.

“The findings suggest that brexpiprazole plus sertraline is a more effective treatment for PTSD than sertraline alone,” he said. “This finding is significant for our service members, who suffer from PTSD at higher rates than the general population.”

Additionally, the significant improvement in psychosocial functioning at week 12 “is important because PTSD is known to cause significant social and occupational disability, as well as quality-of-life issues,” he said.

Capaldi pointed out, however, that the study was conducted only at US sites and did not specifically target military/veteran persons, which may limit applicability to these unique populations.

“While subgroup analyses were generally consistent with the primary analysis, the study was not powered to detect differences between subgroups,” he added. “These subgroup analyses are quite important when considering military and veteran populations.”

Further research is needed to explore whether certain traumas are more responsive to combination treatment, the efficacy of augmenting existing sertraline therapy, and the specific mechanisms of brexpiprazole driving the improved outcomes, Capaldi said.

This study was funded by Otsuka Pharmaceutical Development & Commercialization, which was involved in the design, conduct, and data analysis. Davis reported receiving advisory board fees from Otsuka and Boehringer Ingelheim; lecture fees from Clinical Care Options; and grants from Alkermes, the Veterans Affairs, Patient-Centered Outcomes Research Institute, Department of Defense, and Social Finance. Several coauthors are employees of Otsuka. Krystal reported serving as a consultant for Otsuka America Pharmaceutical, Aptinyx, Biogen, IDEC, Bionomics, Boehringer Ingelheim International, Clearmind Medicine, Cybin IRL, Enveric Biosciences, Epiodyne, EpiVario, Janssen, Jazz Pharmaceuticals, Perception Neuroscience, Praxis Precision Medicines, Springcare, and Sunovion Pharmaceuticals. Krystal also reported serving as a scientific advisory board member for several companies and holding several patents.

A version of this article appeared on Medscape.com.

A drug that combines the atypical antipsychotic brexpiprazole and the selective serotonin reuptake inhibitor sertraline provides significantly greater relief of posttraumatic stress disorder (PTSD) symptoms than sertraline plus placebo, results of a phase 3 trial showed.

The medication is currently under review by the Food and Drug Administration (FDA) and if approved, will be the first pharmacologic option for PTSD in more than 20 years.

The trial met its primary endpoint of change in the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) (CAPS-5) total score at week 10 and secondary patient-reported outcomes of PTSD symptoms, anxiety, and depression.

“And what is really cool, what’s really impactful is the combination worked better than sertraline plus placebo on a brief inventory of psychosocial functioning,” study investigator Lori L. Davis, a senior research psychiatrist, Birmingham Veterans Affairs Health Care System in Alabama, said in an interview.

“We can treat symptoms but that’s where the rubber meets the road, in terms of are they functioning better,” added Davis, who is also an adjunct professor of psychiatry, Heersink School of Medicine, University of Alabama at Birmingham.

The findings were published online on December 18 in JAMA Psychiatry and reported in May 2024 as part of a trio of trials conducted by Otsuka Pharmaceutical and Lundbeck Pharmaceuticals, codevelopers of the drug.

 

Clinically Meaningful

The FDA accepted the companies’ supplemental new drug application in June with a decision on approval expected in early February 2025.

“This study provides promising results for a medication that may be an important new option for PTSD,” John Krystal, MD, director, Clinical Neuroscience Division, National Center for PTSD, US Department of Veterans Affairs, who was not involved in the research, said in an interview. “New PTSD treatments are a high priority.”

Currently, there are two FDA-approved medication treatments for PTSD — sertraline and paroxetine.

“They are helpful for many people, but patients are often left with residual symptoms or tolerability issues,” noted Krystal, who is also professor and chair of psychiatry, Yale University, New Haven, Connecticut.

“New medications that might address the important ‘effectiveness gap’ in PTSD could help to reduce the remaining distress, disability, and suicide risk associated with PTSD.” 

The double-blind, phase 3 trial included 416 adults aged 18-65 years with a DSM-5 diagnosis of PTSD and symptoms for at least 6 months prior to screening. Patients underwent a 1-week placebo-run in period followed by randomization to daily oral brexpiprazole 2-3 mg plus sertraline 150 mg or daily sertraline 150 mg plus placebo for 11 weeks.

Participants’ mean age was 37.4 years, 74.5% were women, and mean CAPS-5 total score was 38.4, suggesting moderate to high severity PTSD, Davis said. The average time from the index traumatic event was 4 years and three fourths had no prior exposure to PTSD prescription medications.

At week 10, the mean change in CAPS-5 score from randomization was –19.2 points in the brexpiprazole plus sertraline group and –13.6 points in the sertraline plus placebo group (95% CI, –8.79 to –2.38; P < .001).

Asked whether the 5.59-point treatment difference is clinically meaningful, Davis said there is no widely agreed definition for change in CAPS-5 total score but that a within-group reduction of more than 10-13 points is most-often cited as being clinically meaningful.

The key secondary endpoint of least square mean change in the patient-reported Brief Inventory of Psychosocial Function total score from baseline to week 12 was –33.8 with the combination vs –21.8 with sertraline plus placebo (95% CI, –19.4 to –4.62; P = .002).

“That’s clinically meaningful for me as a provider and a clinician and a researcher when you’re getting the PTSD symptom change differences in parallel with the improvement in functional outcome,” she said. “I see that as the clinically meaningful gauge.”

In terms of safety, 3.9% of the participants in the brexpiprazole/sertraline group and 10.2% of those in the sertraline/placebo group discontinued treatment because of adverse events.

In both the combination and control groups, the only treatment-emergent adverse event with an incidence of more than 10% was nausea (12.2% vs 11.7%, respectively).

At the last visit, the mean change in body weight from baseline was an increase of 1.3 kg for brexpiprazole plus sertraline vs 0 kg for sertraline alone. Rates of fatigue (6.8% vs 4.1%) and somnolence (5.4% vs 2.6%) were also higher with brexpiprazole plus sertraline.

 

A Trio of Clinical Trials

The findings are part of a larger program reported by the drug makers that includes a flexible-dose brexpiprazole phase 2 trial that met the same CAPS-5 primary endpoint and a second phase 3 trial (072 study) that did not.

“We’ve looked at that data and the sertraline/placebo response was a lot higher, so it was not due to a lack of response with the combination but due to a more robust response with the active control,” Davis said. “But we want to point out for that 072 study, there was still important separation between the combination and sertraline plus placebo on the functional outcome.”

All three trials ran for 12 weeks, so longer-term efficacy and safety data are needed, she said. Other limitations of the published phase 3 study are the patient eligibility criteria, restrictions on concomitant therapy, and lack of non-US sites, which many limit generalizability, the authors noted.

“Specifically, the exclusion of patients with a current major depressive episode is both a strength (to show a specific effect on PTSD) and a limitation (given the high prevalence of comorbid depression in PTSD),” they added.

 

Kudos, Caveats

Reached for comment, Vincent F. Capaldi, II, MD, ScM, professor and chair, department of psychiatry, Uniformed Services University of the Health Sciences School of Medicine, Bethesda, Maryland, said the exclusion of these patients is a limitation but that the study was well designed and conducted in a large sample across the United States.

“The findings suggest that brexpiprazole plus sertraline is a more effective treatment for PTSD than sertraline alone,” he said. “This finding is significant for our service members, who suffer from PTSD at higher rates than the general population.”

Additionally, the significant improvement in psychosocial functioning at week 12 “is important because PTSD is known to cause significant social and occupational disability, as well as quality-of-life issues,” he said.

Capaldi pointed out, however, that the study was conducted only at US sites and did not specifically target military/veteran persons, which may limit applicability to these unique populations.

“While subgroup analyses were generally consistent with the primary analysis, the study was not powered to detect differences between subgroups,” he added. “These subgroup analyses are quite important when considering military and veteran populations.”

Further research is needed to explore whether certain traumas are more responsive to combination treatment, the efficacy of augmenting existing sertraline therapy, and the specific mechanisms of brexpiprazole driving the improved outcomes, Capaldi said.

This study was funded by Otsuka Pharmaceutical Development & Commercialization, which was involved in the design, conduct, and data analysis. Davis reported receiving advisory board fees from Otsuka and Boehringer Ingelheim; lecture fees from Clinical Care Options; and grants from Alkermes, the Veterans Affairs, Patient-Centered Outcomes Research Institute, Department of Defense, and Social Finance. Several coauthors are employees of Otsuka. Krystal reported serving as a consultant for Otsuka America Pharmaceutical, Aptinyx, Biogen, IDEC, Bionomics, Boehringer Ingelheim International, Clearmind Medicine, Cybin IRL, Enveric Biosciences, Epiodyne, EpiVario, Janssen, Jazz Pharmaceuticals, Perception Neuroscience, Praxis Precision Medicines, Springcare, and Sunovion Pharmaceuticals. Krystal also reported serving as a scientific advisory board member for several companies and holding several patents.

A version of this article appeared on Medscape.com.

A drug that combines the atypical antipsychotic brexpiprazole and the selective serotonin reuptake inhibitor sertraline provides significantly greater relief of posttraumatic stress disorder (PTSD) symptoms than sertraline plus placebo, results of a phase 3 trial showed.

The medication is currently under review by the Food and Drug Administration (FDA) and if approved, will be the first pharmacologic option for PTSD in more than 20 years.

The trial met its primary endpoint of change in the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) (CAPS-5) total score at week 10 and secondary patient-reported outcomes of PTSD symptoms, anxiety, and depression.

“And what is really cool, what’s really impactful is the combination worked better than sertraline plus placebo on a brief inventory of psychosocial functioning,” study investigator Lori L. Davis, a senior research psychiatrist, Birmingham Veterans Affairs Health Care System in Alabama, said in an interview.

“We can treat symptoms but that’s where the rubber meets the road, in terms of are they functioning better,” added Davis, who is also an adjunct professor of psychiatry, Heersink School of Medicine, University of Alabama at Birmingham.

The findings were published online on December 18 in JAMA Psychiatry and reported in May 2024 as part of a trio of trials conducted by Otsuka Pharmaceutical and Lundbeck Pharmaceuticals, codevelopers of the drug.

 

Clinically Meaningful

The FDA accepted the companies’ supplemental new drug application in June with a decision on approval expected in early February 2025.

“This study provides promising results for a medication that may be an important new option for PTSD,” John Krystal, MD, director, Clinical Neuroscience Division, National Center for PTSD, US Department of Veterans Affairs, who was not involved in the research, said in an interview. “New PTSD treatments are a high priority.”

Currently, there are two FDA-approved medication treatments for PTSD — sertraline and paroxetine.

“They are helpful for many people, but patients are often left with residual symptoms or tolerability issues,” noted Krystal, who is also professor and chair of psychiatry, Yale University, New Haven, Connecticut.

“New medications that might address the important ‘effectiveness gap’ in PTSD could help to reduce the remaining distress, disability, and suicide risk associated with PTSD.” 

The double-blind, phase 3 trial included 416 adults aged 18-65 years with a DSM-5 diagnosis of PTSD and symptoms for at least 6 months prior to screening. Patients underwent a 1-week placebo-run in period followed by randomization to daily oral brexpiprazole 2-3 mg plus sertraline 150 mg or daily sertraline 150 mg plus placebo for 11 weeks.

Participants’ mean age was 37.4 years, 74.5% were women, and mean CAPS-5 total score was 38.4, suggesting moderate to high severity PTSD, Davis said. The average time from the index traumatic event was 4 years and three fourths had no prior exposure to PTSD prescription medications.

At week 10, the mean change in CAPS-5 score from randomization was –19.2 points in the brexpiprazole plus sertraline group and –13.6 points in the sertraline plus placebo group (95% CI, –8.79 to –2.38; P < .001).

Asked whether the 5.59-point treatment difference is clinically meaningful, Davis said there is no widely agreed definition for change in CAPS-5 total score but that a within-group reduction of more than 10-13 points is most-often cited as being clinically meaningful.

The key secondary endpoint of least square mean change in the patient-reported Brief Inventory of Psychosocial Function total score from baseline to week 12 was –33.8 with the combination vs –21.8 with sertraline plus placebo (95% CI, –19.4 to –4.62; P = .002).

“That’s clinically meaningful for me as a provider and a clinician and a researcher when you’re getting the PTSD symptom change differences in parallel with the improvement in functional outcome,” she said. “I see that as the clinically meaningful gauge.”

In terms of safety, 3.9% of the participants in the brexpiprazole/sertraline group and 10.2% of those in the sertraline/placebo group discontinued treatment because of adverse events.

In both the combination and control groups, the only treatment-emergent adverse event with an incidence of more than 10% was nausea (12.2% vs 11.7%, respectively).

At the last visit, the mean change in body weight from baseline was an increase of 1.3 kg for brexpiprazole plus sertraline vs 0 kg for sertraline alone. Rates of fatigue (6.8% vs 4.1%) and somnolence (5.4% vs 2.6%) were also higher with brexpiprazole plus sertraline.

 

A Trio of Clinical Trials

The findings are part of a larger program reported by the drug makers that includes a flexible-dose brexpiprazole phase 2 trial that met the same CAPS-5 primary endpoint and a second phase 3 trial (072 study) that did not.

“We’ve looked at that data and the sertraline/placebo response was a lot higher, so it was not due to a lack of response with the combination but due to a more robust response with the active control,” Davis said. “But we want to point out for that 072 study, there was still important separation between the combination and sertraline plus placebo on the functional outcome.”

All three trials ran for 12 weeks, so longer-term efficacy and safety data are needed, she said. Other limitations of the published phase 3 study are the patient eligibility criteria, restrictions on concomitant therapy, and lack of non-US sites, which many limit generalizability, the authors noted.

“Specifically, the exclusion of patients with a current major depressive episode is both a strength (to show a specific effect on PTSD) and a limitation (given the high prevalence of comorbid depression in PTSD),” they added.

 

Kudos, Caveats

Reached for comment, Vincent F. Capaldi, II, MD, ScM, professor and chair, department of psychiatry, Uniformed Services University of the Health Sciences School of Medicine, Bethesda, Maryland, said the exclusion of these patients is a limitation but that the study was well designed and conducted in a large sample across the United States.

“The findings suggest that brexpiprazole plus sertraline is a more effective treatment for PTSD than sertraline alone,” he said. “This finding is significant for our service members, who suffer from PTSD at higher rates than the general population.”

Additionally, the significant improvement in psychosocial functioning at week 12 “is important because PTSD is known to cause significant social and occupational disability, as well as quality-of-life issues,” he said.

Capaldi pointed out, however, that the study was conducted only at US sites and did not specifically target military/veteran persons, which may limit applicability to these unique populations.

“While subgroup analyses were generally consistent with the primary analysis, the study was not powered to detect differences between subgroups,” he added. “These subgroup analyses are quite important when considering military and veteran populations.”

Further research is needed to explore whether certain traumas are more responsive to combination treatment, the efficacy of augmenting existing sertraline therapy, and the specific mechanisms of brexpiprazole driving the improved outcomes, Capaldi said.

This study was funded by Otsuka Pharmaceutical Development & Commercialization, which was involved in the design, conduct, and data analysis. Davis reported receiving advisory board fees from Otsuka and Boehringer Ingelheim; lecture fees from Clinical Care Options; and grants from Alkermes, the Veterans Affairs, Patient-Centered Outcomes Research Institute, Department of Defense, and Social Finance. Several coauthors are employees of Otsuka. Krystal reported serving as a consultant for Otsuka America Pharmaceutical, Aptinyx, Biogen, IDEC, Bionomics, Boehringer Ingelheim International, Clearmind Medicine, Cybin IRL, Enveric Biosciences, Epiodyne, EpiVario, Janssen, Jazz Pharmaceuticals, Perception Neuroscience, Praxis Precision Medicines, Springcare, and Sunovion Pharmaceuticals. Krystal also reported serving as a scientific advisory board member for several companies and holding several patents.

A version of this article appeared on Medscape.com.

A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.

There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.

“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.” 

The guideline was published online on December 9 in Schizophrenia Bulletin.

It offers three key recommendations:

• Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
• Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
• Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.

The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.

The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.

In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.

Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.

While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.

“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.

 

Experts Weigh In

This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.

Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”

While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.

Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.

“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.

Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.

“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.

“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.

Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.

Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.

This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.

A version of this article appeared on Medscape.com.

A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.

There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.

“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.” 

The guideline was published online on December 9 in Schizophrenia Bulletin.

It offers three key recommendations:

• Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
• Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
• Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.

The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.

The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.

In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.

Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.

While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.

“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.

 

Experts Weigh In

This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.

Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”

While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.

Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.

“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.

Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.

“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.

“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.

Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.

Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.

This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.

A version of this article appeared on Medscape.com.

A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.

There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.

“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.” 

The guideline was published online on December 9 in Schizophrenia Bulletin.

It offers three key recommendations:

• Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
• Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
• Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.

The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.

The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.

In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.

Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.

While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.

“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.

 

Experts Weigh In

This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.

Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”

While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.

Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.

“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.

Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.

“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.

“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.

Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.

Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.

This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.

A version of this article appeared on Medscape.com.

The World Health Organization Regional Office for Europe (WHO/Europe) and the European Association for the Study of the Liver held a symposium on December 11 to establish the European Alcohol Health Alliance to reduce alcohol-related harms across Europe. 

Europe has the highest levels of alcohol consumption in the world. Alcohol is the continent’s leading cause of death, accounting for almost 800,000 deaths per year, or 1 in 11 deaths in the region. 

This news organization spoke with Frank Murray, MBBCh, a consultant gastroenterologist and hepatologist at Bon Secours Hospital and Beaumont Private Clinic in Dublin, Ireland, who attended the symposium. The intention is to launch the European Alcohol Health Alliance in 2025. 

“We’d like to see evidence-based policies to reduce alcohol harm, which we think would be good for individual citizens and the economy,” said Murray. 

The symposium brought together multiple professional societies to discuss problems related to alcohol use, possible solutions, and their willingness to collaborate. Murray noted that attendees were enthusiastic about forming an alliance. 

Among the alliance’s first priorities, he noted, are changing the pricing and availability of alcohol, implementing restrictions in marketing and advertising, protecting children from alcohol harm, and labeling products with health warnings. 

“It’s interesting that the most dangerous product in the supermarket is sold without any nutrition or content information and without any warnings,” he said. 

 

‘David and Goliath’ 

This news organization also spoke with Barbara Broers, MD, professor of addiction medicine at the University of Geneva in Switzerland, who did not attend the meeting. 

She noted that although methods for reducing alcohol intake are well known, little action is taken to implement them. The alcohol industry is a major reason for this, she said, because it will “do everything to keep its business going.” 

One tactic, according to Broers and Murray, is heavy governmental lobbying. The industry’s resources for lobbying and advocating greatly outweigh any counterforce in what Murray described as a “bit of a David and Goliath” situation. 

“The alcohol industry should not have any role in policy making for alcohol, because it has a conflict of interest that clearly gets in the way of giving public health advice. It wants to maximize profits, while public health requires policies to reduce alcohol consumption,” he noted. 

Among the aims of the European Alcohol Health Alliance is “to rebalance the battle between those advocating for and against alcohol,” he continued.

 

Public Misperceptions

Although alcohol’s harmful effects on the liver are well known, Broers and Murray noted that its other effects are less known. 

A 2024 study found that whereas 90% of Europeans are aware of alcohol’s causal role in liver disease, just 68% are aware of a causal role for heart diseases and 53% for cancer. And only 15% were aware of a causal link with female breast cancer, even though drinking alcohol causes up to 1 in 10 cases of breast cancer.

Adding to a general lack of public awareness, methodologically flawed research may have generated a false impression that moderate drinking is beneficial for health, according to a s ystematic review and meta-analysis of 107 longitudinal studies. 

Broers noted that more work must be done to increase public knowledge about the harmful effects of alcohol, and especially its link to cancer. “We now know that a person’s risk of cancer increases right from the first drink, but I think the people don’t know this,” she said. 

“Local context and culture have a significant impact on the prevalence of alcohol consumption within a population, as well as the pattern of alcohol consumption,” Andrew Smyth, MBBCh, PhD, professor of clinical epidemiology at the University of Galway in Ireland, told this news organization. 

“Each country, region, and area are likely to need culturally appropriate and socially acceptable solutions to overcome their own hurdles,” he added.

 

Normalizing Abstinence

“Alcohol is involved in our social lives in so many ways. Reducing it would be Sisyphus’s work,” said Bernhard Maisch, MD, professor at Philipps University of Marburg, Germany. 

Jelena Šarić Posavec, a former PhD student at the University of Ljubljana in Slovenia, said that, while numerous obstacles make addressing alcohol-related harms difficult in Europe, solutions exist, too. 

Broers noted, for example, that Germany is working to change social perceptions around not drinking. “No alcohol should be the norm and should be considered positive. People should know that they might feel much better if they don’t drink at all.” 

Short-term improvements from abstaining from alcohol may be felt in sleep and energy levels, with long-term health effects ranging from weight to liver health and cancer risk, she noted. The problem, she said, however, lies in how to communicate this message. 

Murray, Broers, Smyth, Maisch, and Posavec reported having no relevant financial relationships.

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

The World Health Organization Regional Office for Europe (WHO/Europe) and the European Association for the Study of the Liver held a symposium on December 11 to establish the European Alcohol Health Alliance to reduce alcohol-related harms across Europe. 

Europe has the highest levels of alcohol consumption in the world. Alcohol is the continent’s leading cause of death, accounting for almost 800,000 deaths per year, or 1 in 11 deaths in the region. 

This news organization spoke with Frank Murray, MBBCh, a consultant gastroenterologist and hepatologist at Bon Secours Hospital and Beaumont Private Clinic in Dublin, Ireland, who attended the symposium. The intention is to launch the European Alcohol Health Alliance in 2025. 

“We’d like to see evidence-based policies to reduce alcohol harm, which we think would be good for individual citizens and the economy,” said Murray. 

The symposium brought together multiple professional societies to discuss problems related to alcohol use, possible solutions, and their willingness to collaborate. Murray noted that attendees were enthusiastic about forming an alliance. 

Among the alliance’s first priorities, he noted, are changing the pricing and availability of alcohol, implementing restrictions in marketing and advertising, protecting children from alcohol harm, and labeling products with health warnings. 

“It’s interesting that the most dangerous product in the supermarket is sold without any nutrition or content information and without any warnings,” he said. 

 

‘David and Goliath’ 

This news organization also spoke with Barbara Broers, MD, professor of addiction medicine at the University of Geneva in Switzerland, who did not attend the meeting. 

She noted that although methods for reducing alcohol intake are well known, little action is taken to implement them. The alcohol industry is a major reason for this, she said, because it will “do everything to keep its business going.” 

One tactic, according to Broers and Murray, is heavy governmental lobbying. The industry’s resources for lobbying and advocating greatly outweigh any counterforce in what Murray described as a “bit of a David and Goliath” situation. 

“The alcohol industry should not have any role in policy making for alcohol, because it has a conflict of interest that clearly gets in the way of giving public health advice. It wants to maximize profits, while public health requires policies to reduce alcohol consumption,” he noted. 

Among the aims of the European Alcohol Health Alliance is “to rebalance the battle between those advocating for and against alcohol,” he continued.

 

Public Misperceptions

Although alcohol’s harmful effects on the liver are well known, Broers and Murray noted that its other effects are less known. 

A 2024 study found that whereas 90% of Europeans are aware of alcohol’s causal role in liver disease, just 68% are aware of a causal role for heart diseases and 53% for cancer. And only 15% were aware of a causal link with female breast cancer, even though drinking alcohol causes up to 1 in 10 cases of breast cancer.

Adding to a general lack of public awareness, methodologically flawed research may have generated a false impression that moderate drinking is beneficial for health, according to a s ystematic review and meta-analysis of 107 longitudinal studies. 

Broers noted that more work must be done to increase public knowledge about the harmful effects of alcohol, and especially its link to cancer. “We now know that a person’s risk of cancer increases right from the first drink, but I think the people don’t know this,” she said. 

“Local context and culture have a significant impact on the prevalence of alcohol consumption within a population, as well as the pattern of alcohol consumption,” Andrew Smyth, MBBCh, PhD, professor of clinical epidemiology at the University of Galway in Ireland, told this news organization. 

“Each country, region, and area are likely to need culturally appropriate and socially acceptable solutions to overcome their own hurdles,” he added.

 

Normalizing Abstinence

“Alcohol is involved in our social lives in so many ways. Reducing it would be Sisyphus’s work,” said Bernhard Maisch, MD, professor at Philipps University of Marburg, Germany. 

Jelena Šarić Posavec, a former PhD student at the University of Ljubljana in Slovenia, said that, while numerous obstacles make addressing alcohol-related harms difficult in Europe, solutions exist, too. 

Broers noted, for example, that Germany is working to change social perceptions around not drinking. “No alcohol should be the norm and should be considered positive. People should know that they might feel much better if they don’t drink at all.” 

Short-term improvements from abstaining from alcohol may be felt in sleep and energy levels, with long-term health effects ranging from weight to liver health and cancer risk, she noted. The problem, she said, however, lies in how to communicate this message. 

Murray, Broers, Smyth, Maisch, and Posavec reported having no relevant financial relationships.

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

The World Health Organization Regional Office for Europe (WHO/Europe) and the European Association for the Study of the Liver held a symposium on December 11 to establish the European Alcohol Health Alliance to reduce alcohol-related harms across Europe. 

Europe has the highest levels of alcohol consumption in the world. Alcohol is the continent’s leading cause of death, accounting for almost 800,000 deaths per year, or 1 in 11 deaths in the region. 

This news organization spoke with Frank Murray, MBBCh, a consultant gastroenterologist and hepatologist at Bon Secours Hospital and Beaumont Private Clinic in Dublin, Ireland, who attended the symposium. The intention is to launch the European Alcohol Health Alliance in 2025. 

“We’d like to see evidence-based policies to reduce alcohol harm, which we think would be good for individual citizens and the economy,” said Murray. 

The symposium brought together multiple professional societies to discuss problems related to alcohol use, possible solutions, and their willingness to collaborate. Murray noted that attendees were enthusiastic about forming an alliance. 

Among the alliance’s first priorities, he noted, are changing the pricing and availability of alcohol, implementing restrictions in marketing and advertising, protecting children from alcohol harm, and labeling products with health warnings. 

“It’s interesting that the most dangerous product in the supermarket is sold without any nutrition or content information and without any warnings,” he said. 

 

‘David and Goliath’ 

This news organization also spoke with Barbara Broers, MD, professor of addiction medicine at the University of Geneva in Switzerland, who did not attend the meeting. 

She noted that although methods for reducing alcohol intake are well known, little action is taken to implement them. The alcohol industry is a major reason for this, she said, because it will “do everything to keep its business going.” 

One tactic, according to Broers and Murray, is heavy governmental lobbying. The industry’s resources for lobbying and advocating greatly outweigh any counterforce in what Murray described as a “bit of a David and Goliath” situation. 

“The alcohol industry should not have any role in policy making for alcohol, because it has a conflict of interest that clearly gets in the way of giving public health advice. It wants to maximize profits, while public health requires policies to reduce alcohol consumption,” he noted. 

Among the aims of the European Alcohol Health Alliance is “to rebalance the battle between those advocating for and against alcohol,” he continued.

 

Public Misperceptions

Although alcohol’s harmful effects on the liver are well known, Broers and Murray noted that its other effects are less known. 

A 2024 study found that whereas 90% of Europeans are aware of alcohol’s causal role in liver disease, just 68% are aware of a causal role for heart diseases and 53% for cancer. And only 15% were aware of a causal link with female breast cancer, even though drinking alcohol causes up to 1 in 10 cases of breast cancer.

Adding to a general lack of public awareness, methodologically flawed research may have generated a false impression that moderate drinking is beneficial for health, according to a s ystematic review and meta-analysis of 107 longitudinal studies. 

Broers noted that more work must be done to increase public knowledge about the harmful effects of alcohol, and especially its link to cancer. “We now know that a person’s risk of cancer increases right from the first drink, but I think the people don’t know this,” she said. 

“Local context and culture have a significant impact on the prevalence of alcohol consumption within a population, as well as the pattern of alcohol consumption,” Andrew Smyth, MBBCh, PhD, professor of clinical epidemiology at the University of Galway in Ireland, told this news organization. 

“Each country, region, and area are likely to need culturally appropriate and socially acceptable solutions to overcome their own hurdles,” he added.

 

Normalizing Abstinence

“Alcohol is involved in our social lives in so many ways. Reducing it would be Sisyphus’s work,” said Bernhard Maisch, MD, professor at Philipps University of Marburg, Germany. 

Jelena Šarić Posavec, a former PhD student at the University of Ljubljana in Slovenia, said that, while numerous obstacles make addressing alcohol-related harms difficult in Europe, solutions exist, too. 

Broers noted, for example, that Germany is working to change social perceptions around not drinking. “No alcohol should be the norm and should be considered positive. People should know that they might feel much better if they don’t drink at all.” 

Short-term improvements from abstaining from alcohol may be felt in sleep and energy levels, with long-term health effects ranging from weight to liver health and cancer risk, she noted. The problem, she said, however, lies in how to communicate this message. 

Murray, Broers, Smyth, Maisch, and Posavec reported having no relevant financial relationships.

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

While fewer than 10% of US physicians are unionized, the number of official union drives among private-sector doctors have skyrocketed in the last 2 years, compared with 2 decades prior, according to a new study. 

Researchers counted 21 union drives in 2023 and 12 in the first 5 months of 2024, compared with 0-6 drives each year between 2000 and 2022. 

If the 2023 and 2024 drives succeed, unions will represent 3523 new physicians — nearly equal to the 3541 doctors who sought unionization between 2000 and 2022.

“We were able to document a significant uptick in union petitions and success in certification drives,” said corresponding author Hayden Rooke-Ley, JD, of the Center for Advancing Health Policy Through Research, Brown University School of Public Health, Providence, Rhode Island. “We were surprised to see such a marked shift in 2023.”

About 72,000 physicians, an estimated 8% of all US doctors, are covered by unions, including some in the public sector. Physicians who are self-employed, now comprising less than a fifth of all doctors, are not eligible to join labor unions.

The study authors launched their research to better understand trends in physician unionization in light of high-profile union drives, especially among residents. Rooke-Ley said: “We suspected that declining morale and increased corporate employment for physicians were leading them to consider unionization.”

The researchers gathered data from the National Labor Relations Board about union drives by potential bargaining units that included physicians. From 2000 to 2022, 44 union petitions were filed. The number jumped to 33 from 2023-2024. 

 

“Tip of the Iceberg”

“This is the tip of the iceberg,” said ethicist Joseph F. Kras, MD, DDS, MA, an associate professor of anesthesiology at Washington University in St. Louis, Missouri, and corresponding author of a recent Anesthesia & Analgesia report about physician unionization.

“We are independent by nature,” Kras said. “But when you put us in an employed environment and start treating us as widgets, then we will act like employees of Amazon, Starbucks, and other companies and join together to push back against the increasing emphasis on profit over all at the expense of our independent judgment on what’s best for the patient.”

Of the 66 unionization efforts between 2000 and 2024 that were decided, 62% were certified, according to the JAMA study. The drives targeted hospitals (49%), community health centers (38%), and nonhospital corporate owners (13%).

The researchers only analyzed private-sector unionization and did not include physicians who are unionized at public institutions. 

 

What’s Behind Union Drives?

Alyssa Burgart, MD, MA, an ethicist and clinical associate professor of anesthesiology and pediatrics at Stanford University in California, told this news organization that physician unionization “is a big topic with a lot of really strong opinions.” 

Many doctors wrongly assume they can’t unionize because they’re physicians, said Burgart, a coauthor of the Anesthesia & Analgesia report.

Supporters of unionization believe it’s a strategy to be “recognized not as simply as a single physician with a concern,” she said. “When you’re among clinicians who can speak as a more unified group, organizations are more likely to take that seriously.”

A union may also be able to hold employers to account in areas such as the gender wage gap, sexual harassment, and bias in hiring and firing, Burgart said. And union supporters believe they’ll make more money if they collectively bargain. 

Other factors driving interest in unions include “increasing physician burnout, increasing physician exhaustion, and immense frustration with the ways that private equity is influencing how physicians need to work in order to practice,” she said. 

Earlier in 2024, physicians in Delaware’s ChristianaCare health system voted 288-130 to be represented by Doctors Council/Service Employees International, according to the union. 

“We have still not been able to staff up enough to where us physicians can get back to just focusing on taking care of patients,” a unionization leader told WHYY. 

The JAMA study examined news reports regarding most of the 2023-2024 union drives and found that supporters claimed they were motivated by working conditions (85%), lack of voice in management (81%), patient care concerns (54%), and pay (4%).

 

Critics Worry They’ll Lose Pay Because of Unions

Skeptics of unionization worry about whether “I’m going to be required to stand by some union stance that is actually out of alignment with my values as a physician,” Burgart said. And, she said, critics such as highly paid surgeons fear that adjustments to salaries because of union contracts could cause them to lose income.

In regard to compensation, a 2024 study surveyed unionized residents — along with faculty and staff — at general surgery programs and found evidence that unionization didn’t improve resident well-being or benefits, although it “provided a mechanism for resident voice and agency.”

“It is critical to study the outcomes of those who unionized to ensure that the reasons for unionizing were realized over time,” said that study’s coauthor Karl Bilimoria, MD, MS, chair of surgery at Indiana University School of Medicine, Indianapolis. “The unintended consequences of unionization must be examined along with the potential improvements.”

Rooke-Ley discloses consulting fees from the American Economic Liberties Project, National Academy of State Health Policy, and 32BJ Funds. Kras and Burgart disclose previous union membership. Bilimoria has no disclosures.

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

While fewer than 10% of US physicians are unionized, the number of official union drives among private-sector doctors have skyrocketed in the last 2 years, compared with 2 decades prior, according to a new study. 

Researchers counted 21 union drives in 2023 and 12 in the first 5 months of 2024, compared with 0-6 drives each year between 2000 and 2022. 

If the 2023 and 2024 drives succeed, unions will represent 3523 new physicians — nearly equal to the 3541 doctors who sought unionization between 2000 and 2022.

“We were able to document a significant uptick in union petitions and success in certification drives,” said corresponding author Hayden Rooke-Ley, JD, of the Center for Advancing Health Policy Through Research, Brown University School of Public Health, Providence, Rhode Island. “We were surprised to see such a marked shift in 2023.”

About 72,000 physicians, an estimated 8% of all US doctors, are covered by unions, including some in the public sector. Physicians who are self-employed, now comprising less than a fifth of all doctors, are not eligible to join labor unions.

The study authors launched their research to better understand trends in physician unionization in light of high-profile union drives, especially among residents. Rooke-Ley said: “We suspected that declining morale and increased corporate employment for physicians were leading them to consider unionization.”

The researchers gathered data from the National Labor Relations Board about union drives by potential bargaining units that included physicians. From 2000 to 2022, 44 union petitions were filed. The number jumped to 33 from 2023-2024. 

 

“Tip of the Iceberg”

“This is the tip of the iceberg,” said ethicist Joseph F. Kras, MD, DDS, MA, an associate professor of anesthesiology at Washington University in St. Louis, Missouri, and corresponding author of a recent Anesthesia & Analgesia report about physician unionization.

“We are independent by nature,” Kras said. “But when you put us in an employed environment and start treating us as widgets, then we will act like employees of Amazon, Starbucks, and other companies and join together to push back against the increasing emphasis on profit over all at the expense of our independent judgment on what’s best for the patient.”

Of the 66 unionization efforts between 2000 and 2024 that were decided, 62% were certified, according to the JAMA study. The drives targeted hospitals (49%), community health centers (38%), and nonhospital corporate owners (13%).

The researchers only analyzed private-sector unionization and did not include physicians who are unionized at public institutions. 

 

What’s Behind Union Drives?

Alyssa Burgart, MD, MA, an ethicist and clinical associate professor of anesthesiology and pediatrics at Stanford University in California, told this news organization that physician unionization “is a big topic with a lot of really strong opinions.” 

Many doctors wrongly assume they can’t unionize because they’re physicians, said Burgart, a coauthor of the Anesthesia & Analgesia report.

Supporters of unionization believe it’s a strategy to be “recognized not as simply as a single physician with a concern,” she said. “When you’re among clinicians who can speak as a more unified group, organizations are more likely to take that seriously.”

A union may also be able to hold employers to account in areas such as the gender wage gap, sexual harassment, and bias in hiring and firing, Burgart said. And union supporters believe they’ll make more money if they collectively bargain. 

Other factors driving interest in unions include “increasing physician burnout, increasing physician exhaustion, and immense frustration with the ways that private equity is influencing how physicians need to work in order to practice,” she said. 

Earlier in 2024, physicians in Delaware’s ChristianaCare health system voted 288-130 to be represented by Doctors Council/Service Employees International, according to the union. 

“We have still not been able to staff up enough to where us physicians can get back to just focusing on taking care of patients,” a unionization leader told WHYY. 

The JAMA study examined news reports regarding most of the 2023-2024 union drives and found that supporters claimed they were motivated by working conditions (85%), lack of voice in management (81%), patient care concerns (54%), and pay (4%).

 

Critics Worry They’ll Lose Pay Because of Unions

Skeptics of unionization worry about whether “I’m going to be required to stand by some union stance that is actually out of alignment with my values as a physician,” Burgart said. And, she said, critics such as highly paid surgeons fear that adjustments to salaries because of union contracts could cause them to lose income.

In regard to compensation, a 2024 study surveyed unionized residents — along with faculty and staff — at general surgery programs and found evidence that unionization didn’t improve resident well-being or benefits, although it “provided a mechanism for resident voice and agency.”

“It is critical to study the outcomes of those who unionized to ensure that the reasons for unionizing were realized over time,” said that study’s coauthor Karl Bilimoria, MD, MS, chair of surgery at Indiana University School of Medicine, Indianapolis. “The unintended consequences of unionization must be examined along with the potential improvements.”

Rooke-Ley discloses consulting fees from the American Economic Liberties Project, National Academy of State Health Policy, and 32BJ Funds. Kras and Burgart disclose previous union membership. Bilimoria has no disclosures.

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

While fewer than 10% of US physicians are unionized, the number of official union drives among private-sector doctors have skyrocketed in the last 2 years, compared with 2 decades prior, according to a new study. 

Researchers counted 21 union drives in 2023 and 12 in the first 5 months of 2024, compared with 0-6 drives each year between 2000 and 2022. 

If the 2023 and 2024 drives succeed, unions will represent 3523 new physicians — nearly equal to the 3541 doctors who sought unionization between 2000 and 2022.

“We were able to document a significant uptick in union petitions and success in certification drives,” said corresponding author Hayden Rooke-Ley, JD, of the Center for Advancing Health Policy Through Research, Brown University School of Public Health, Providence, Rhode Island. “We were surprised to see such a marked shift in 2023.”

About 72,000 physicians, an estimated 8% of all US doctors, are covered by unions, including some in the public sector. Physicians who are self-employed, now comprising less than a fifth of all doctors, are not eligible to join labor unions.

The study authors launched their research to better understand trends in physician unionization in light of high-profile union drives, especially among residents. Rooke-Ley said: “We suspected that declining morale and increased corporate employment for physicians were leading them to consider unionization.”

The researchers gathered data from the National Labor Relations Board about union drives by potential bargaining units that included physicians. From 2000 to 2022, 44 union petitions were filed. The number jumped to 33 from 2023-2024. 

 

“Tip of the Iceberg”

“This is the tip of the iceberg,” said ethicist Joseph F. Kras, MD, DDS, MA, an associate professor of anesthesiology at Washington University in St. Louis, Missouri, and corresponding author of a recent Anesthesia & Analgesia report about physician unionization.

“We are independent by nature,” Kras said. “But when you put us in an employed environment and start treating us as widgets, then we will act like employees of Amazon, Starbucks, and other companies and join together to push back against the increasing emphasis on profit over all at the expense of our independent judgment on what’s best for the patient.”

Of the 66 unionization efforts between 2000 and 2024 that were decided, 62% were certified, according to the JAMA study. The drives targeted hospitals (49%), community health centers (38%), and nonhospital corporate owners (13%).

The researchers only analyzed private-sector unionization and did not include physicians who are unionized at public institutions. 

 

What’s Behind Union Drives?

Alyssa Burgart, MD, MA, an ethicist and clinical associate professor of anesthesiology and pediatrics at Stanford University in California, told this news organization that physician unionization “is a big topic with a lot of really strong opinions.” 

Many doctors wrongly assume they can’t unionize because they’re physicians, said Burgart, a coauthor of the Anesthesia & Analgesia report.

Supporters of unionization believe it’s a strategy to be “recognized not as simply as a single physician with a concern,” she said. “When you’re among clinicians who can speak as a more unified group, organizations are more likely to take that seriously.”

A union may also be able to hold employers to account in areas such as the gender wage gap, sexual harassment, and bias in hiring and firing, Burgart said. And union supporters believe they’ll make more money if they collectively bargain. 

Other factors driving interest in unions include “increasing physician burnout, increasing physician exhaustion, and immense frustration with the ways that private equity is influencing how physicians need to work in order to practice,” she said. 

Earlier in 2024, physicians in Delaware’s ChristianaCare health system voted 288-130 to be represented by Doctors Council/Service Employees International, according to the union. 

“We have still not been able to staff up enough to where us physicians can get back to just focusing on taking care of patients,” a unionization leader told WHYY. 

The JAMA study examined news reports regarding most of the 2023-2024 union drives and found that supporters claimed they were motivated by working conditions (85%), lack of voice in management (81%), patient care concerns (54%), and pay (4%).

 

Critics Worry They’ll Lose Pay Because of Unions

Skeptics of unionization worry about whether “I’m going to be required to stand by some union stance that is actually out of alignment with my values as a physician,” Burgart said. And, she said, critics such as highly paid surgeons fear that adjustments to salaries because of union contracts could cause them to lose income.

In regard to compensation, a 2024 study surveyed unionized residents — along with faculty and staff — at general surgery programs and found evidence that unionization didn’t improve resident well-being or benefits, although it “provided a mechanism for resident voice and agency.”

“It is critical to study the outcomes of those who unionized to ensure that the reasons for unionizing were realized over time,” said that study’s coauthor Karl Bilimoria, MD, MS, chair of surgery at Indiana University School of Medicine, Indianapolis. “The unintended consequences of unionization must be examined along with the potential improvements.”

Rooke-Ley discloses consulting fees from the American Economic Liberties Project, National Academy of State Health Policy, and 32BJ Funds. Kras and Burgart disclose previous union membership. Bilimoria has no disclosures.

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

More Americans than ever are hurting with enduring, life-restricting pain. Like obesity, this condition is on the rise, according to figures in a new National Center for Health Statistics (NCHS) Data Brief from the Centers for Disease Control and Prevention (CDC).

In 2023, 24.3% of US adults had chronic pain, and 8.5% had high-impact chronic pain (HICP) that frequently limited daily activities in the past 3 months. Both types increased with age and with decreasing urbanization level. Women were more likely than men to have HICP (23.2% vs 7.3%). 

Like obesity, chronic pain is multifactorial and is best managed with multidisciplinary intervention, said Jianguo Cheng, MD, PhD, a professor of anesthesiology and medical director of the Cleveland Clinic Consortium for Pain in Ohio. “It’s a complex mix of genetic, biological, and psychosocial dimensions that can cause ongoing pain out of proportion to the original limited injury that triggered it.”

While today’s longer lifespans are the primary driver of the increase, noted Martin Cheatle, PhD, an associate professor of psychiatry, anesthesiology, and critical care and director of behavioral medicine at the Penn Pain Medicine Center at the University of Pennsylvania’s Perelman School of Medicine, Philadelphia, another important factor is the more than 100 million Americans who suffer from obesity. “Obesity is a major risk factor for chronic pain conditions including advancing joint disease, low back pain, and diabetic neuropathies,” he said.

Age is an amplifier, agreed Beth Darnall, PhD, a professor of anesthesiology and perioperative and pain medicine and director of the Pain Relief Innovations Lab at Stanford University in Palo Alto, California, but the increases in chronic pain and HICP cut across age strata. 

“Across the board we see striking increases in chronic pain, such as a 5% increase for those 65 and older, and a nearly 2% increase in HICP in that same age group,” Darnall said, referencing the changes from 2019 data in the new NCHS Data Brief. “And an almost 4% increase was observed for the youngest adult age category,18 to 29. Some of our research is now focusing on how to best treat chronic pain in young adults.”

The rise in chronic pain is broadly linked to the overall decline in the health of the US population, as indicated by the CDC 2024’s Chronic Disease Prevalence in the US: Sociodemographic and Geographic Variations by Zip Code Tabulation Area.

 

The Opioid Crisis and COVID

Beginning in 2016, in response to the opioid crisis and CDC guidelines, opioid prescribing for chronic pain rapidly dropped, both in terms of new prescriptions and tapering of doses of long-term users. “Reduced opioid prescribing yielded benefits for some patients but created new problems and harms for other patients,” said Darnall. Cheng added that the CDC’s recommendations on opioid prescribing were widely misinterpreted and were applied to patients with painful conditions such as cancer and sickle cell disease who were not intended to be affected by the guidelines. “In addition, although medical opioid prescribing dropped by 50%, overdose deaths from non-medical opioid sources increased by more 50%.”

Currently, most opioid overdoses are related to heroin, fentanyl, and newer drugs of abuse such as xylazine. “Most pain clinicians would agree that opioids are not first-line therapy for chronic non-cancer pain, but in a select number of well-vetted patients, opioids can be very effective in improving functionality and quality of life as part of a multimodal approach to pain care,” Cheatle said. 

The impact of the opioid crisis is complex, said Cheatle, noting that only 8%-10% of pain patients on long-term opioid therapy develop a use disorder. “However, opioids were overly prescribed due to clinicians’ lack of training in core competencies of pain management and the insurance companies’ refusal to adequately cover non-opioid therapies such as acupuncture, cognitive behavioral therapy, extended physical therapy, and medical massage,” he said. 

He pointed out that in the late 1990s there were more than 1000 multidisciplinary pain centers, whereas currently there are many fewer owing to lack of insurance reimbursement. “This results in more possibly avoidable invasive surgeries, which can further contribute to the increase in chronic pain.” 

The COVID pandemic further exacerbated the pain problem and delayed access to timely medical interventions for many people. Some adopted a more sedentary lifestyle, already entrenched in today’s technology-driven society, leading in turn to weight gain and more chronic pain. “The isolation and lack of normal human connections during the pandemic could exacerbate pain and loss of autonomy,” Cheatle said. And some individuals developed painful neurologic conditions related to long-haul COVID, for which there is no effective treatment. 

 

Best Approach

“Historically, pain has been treated as a purely biomedical issue. Bringing a biopsychosocial perspective to pain care can support pain relief,” said Darnall. Multiple national clinical guidance documents have called for a comprehensive approach that considers the whole person: their circumstances, their needs, their stressors, and their environment. “And we must provide patients meaningful access to the lowest-risk, non-pharmacologic treatments first – and ideally early on,” she said.

Even effective medications rarely make a person pain free, so other approaches are needed in tandem, Darnall said. Support for stronger patient competency in self-management of chronic pain is mounting.

“It’s vitally important that we help people know how to help themselves have less pain – how to steer their mind and body toward relief by using pain relief skills,” she said. “By so doing they can cultivate a critical level of control over their pain and are less at its mercy, which supports good mood and is shown to help people be more active as the impacts of pain diminish.”

Darnall outlined a recent development in the primary care setting that involves offering patients a brief program in pain-relief skills training. Within Veterans Affairs primary care, for example, patients receive several 30-minute sessions in pain reduction techniques. Outside of the VA, primary care clinics are incorporating an evidence-based, one-session 2-hour pain relief skills class called Empowered Relief, as standard care. 

The class teaches participants three pain management skills and creates a personalized plan for each that includes a free app for ongoing daily use.

Since pain causes agitation in the central nervous system, manifested as fast heart rate, rapid breathing, muscle tension, and distress, people learn various ways to calm the central nervous system – with, for example, a sound technology known as binaural audio to deepen the relaxation response. “They also learn to identify and target worry about pain and develop self-soothing actions to interrupt unhelpful patterns,” Darnall said. 

Data from randomized chronic pain studies, including one by her group using a virtual reality training program for lower back pain, show that 3 months after the training program people report clinically meaningful reductions in pain intensity, pain interference with daily activities, and sleep disturbance, as well as pain-related distress, anxiety, and fatigue

While psychological and complementary approaches have been effective in improving function and mood, there are barriers to accessing them, said Cheatle, such as lack of insurance coverage and the stigma associated with nontraditional, especially psychological, care.

 

Prevention

Good lifestyle behaviors promote better health as people age. “Maintaining a healthy weight, staying active, prioritizing good sleep, and avoiding smoking and alcohol use can support better health and buffer against chronic diseases and pain,” Darnall said.

Cheatle noted the importance of maintaining a safe work environment and avoiding injury risks by, for example, wearing a seatbelt or a cycling helmet. 

 

The Future 

“We need to ensure all individuals have access to effective, low-burden pain treatments, including evidence-based treatments they can receive from home so as to minimize treatment disparities.” Darnall said. Also needed is better comprehensive treatment for acute and chronic pain alike. “If we treat acute pain better, we will have fewer people transitioning to the chronic pain state.”

To that end, added Cheng, healthcare professionals in every specialty from doctors and nurses to psychologists and chiropractors need to develop co-competencies in pain management. 

For Cheatle, the near future looks bleak. “There are some pioneering bioengineering approaches to reduce chronic pain and novel pharmacologic agents such as calcitonin gene-related peptide inhibitors for intractable migraines, but just changing insurance reimbursement for a comprehensive approach to chronic pain care and bolstering healthcare provider education on core pain competencies will benefit the over 50 million adults who suffer from chronic pain.” 

Cheng, however, is more sanguine. “I don’t expect miracles in 10 years’ time, but we’re making rapid progress in understanding the genetics of chronic pain and the mechanisms of disease and therapy. We’re developing biomarkers to help in prognosis and monitor disease progress.” In the meantime, he pointed to an expanding array of non-pharmaceutical options, including neuromodulatory approaches such as nerve blocks and spinal cord stimulation.

Cheng, Cheatle, and Darnall disclosed no relevant competing interests.

A version of this article appeared on Medscape.com.

More Americans than ever are hurting with enduring, life-restricting pain. Like obesity, this condition is on the rise, according to figures in a new National Center for Health Statistics (NCHS) Data Brief from the Centers for Disease Control and Prevention (CDC).

In 2023, 24.3% of US adults had chronic pain, and 8.5% had high-impact chronic pain (HICP) that frequently limited daily activities in the past 3 months. Both types increased with age and with decreasing urbanization level. Women were more likely than men to have HICP (23.2% vs 7.3%). 

Like obesity, chronic pain is multifactorial and is best managed with multidisciplinary intervention, said Jianguo Cheng, MD, PhD, a professor of anesthesiology and medical director of the Cleveland Clinic Consortium for Pain in Ohio. “It’s a complex mix of genetic, biological, and psychosocial dimensions that can cause ongoing pain out of proportion to the original limited injury that triggered it.”

While today’s longer lifespans are the primary driver of the increase, noted Martin Cheatle, PhD, an associate professor of psychiatry, anesthesiology, and critical care and director of behavioral medicine at the Penn Pain Medicine Center at the University of Pennsylvania’s Perelman School of Medicine, Philadelphia, another important factor is the more than 100 million Americans who suffer from obesity. “Obesity is a major risk factor for chronic pain conditions including advancing joint disease, low back pain, and diabetic neuropathies,” he said.

Age is an amplifier, agreed Beth Darnall, PhD, a professor of anesthesiology and perioperative and pain medicine and director of the Pain Relief Innovations Lab at Stanford University in Palo Alto, California, but the increases in chronic pain and HICP cut across age strata. 

“Across the board we see striking increases in chronic pain, such as a 5% increase for those 65 and older, and a nearly 2% increase in HICP in that same age group,” Darnall said, referencing the changes from 2019 data in the new NCHS Data Brief. “And an almost 4% increase was observed for the youngest adult age category,18 to 29. Some of our research is now focusing on how to best treat chronic pain in young adults.”

The rise in chronic pain is broadly linked to the overall decline in the health of the US population, as indicated by the CDC 2024’s Chronic Disease Prevalence in the US: Sociodemographic and Geographic Variations by Zip Code Tabulation Area.

 

The Opioid Crisis and COVID

Beginning in 2016, in response to the opioid crisis and CDC guidelines, opioid prescribing for chronic pain rapidly dropped, both in terms of new prescriptions and tapering of doses of long-term users. “Reduced opioid prescribing yielded benefits for some patients but created new problems and harms for other patients,” said Darnall. Cheng added that the CDC’s recommendations on opioid prescribing were widely misinterpreted and were applied to patients with painful conditions such as cancer and sickle cell disease who were not intended to be affected by the guidelines. “In addition, although medical opioid prescribing dropped by 50%, overdose deaths from non-medical opioid sources increased by more 50%.”

Currently, most opioid overdoses are related to heroin, fentanyl, and newer drugs of abuse such as xylazine. “Most pain clinicians would agree that opioids are not first-line therapy for chronic non-cancer pain, but in a select number of well-vetted patients, opioids can be very effective in improving functionality and quality of life as part of a multimodal approach to pain care,” Cheatle said. 

The impact of the opioid crisis is complex, said Cheatle, noting that only 8%-10% of pain patients on long-term opioid therapy develop a use disorder. “However, opioids were overly prescribed due to clinicians’ lack of training in core competencies of pain management and the insurance companies’ refusal to adequately cover non-opioid therapies such as acupuncture, cognitive behavioral therapy, extended physical therapy, and medical massage,” he said. 

He pointed out that in the late 1990s there were more than 1000 multidisciplinary pain centers, whereas currently there are many fewer owing to lack of insurance reimbursement. “This results in more possibly avoidable invasive surgeries, which can further contribute to the increase in chronic pain.” 

The COVID pandemic further exacerbated the pain problem and delayed access to timely medical interventions for many people. Some adopted a more sedentary lifestyle, already entrenched in today’s technology-driven society, leading in turn to weight gain and more chronic pain. “The isolation and lack of normal human connections during the pandemic could exacerbate pain and loss of autonomy,” Cheatle said. And some individuals developed painful neurologic conditions related to long-haul COVID, for which there is no effective treatment. 

 

Best Approach

“Historically, pain has been treated as a purely biomedical issue. Bringing a biopsychosocial perspective to pain care can support pain relief,” said Darnall. Multiple national clinical guidance documents have called for a comprehensive approach that considers the whole person: their circumstances, their needs, their stressors, and their environment. “And we must provide patients meaningful access to the lowest-risk, non-pharmacologic treatments first – and ideally early on,” she said.

Even effective medications rarely make a person pain free, so other approaches are needed in tandem, Darnall said. Support for stronger patient competency in self-management of chronic pain is mounting.

“It’s vitally important that we help people know how to help themselves have less pain – how to steer their mind and body toward relief by using pain relief skills,” she said. “By so doing they can cultivate a critical level of control over their pain and are less at its mercy, which supports good mood and is shown to help people be more active as the impacts of pain diminish.”

Darnall outlined a recent development in the primary care setting that involves offering patients a brief program in pain-relief skills training. Within Veterans Affairs primary care, for example, patients receive several 30-minute sessions in pain reduction techniques. Outside of the VA, primary care clinics are incorporating an evidence-based, one-session 2-hour pain relief skills class called Empowered Relief, as standard care. 

The class teaches participants three pain management skills and creates a personalized plan for each that includes a free app for ongoing daily use.

Since pain causes agitation in the central nervous system, manifested as fast heart rate, rapid breathing, muscle tension, and distress, people learn various ways to calm the central nervous system – with, for example, a sound technology known as binaural audio to deepen the relaxation response. “They also learn to identify and target worry about pain and develop self-soothing actions to interrupt unhelpful patterns,” Darnall said. 

Data from randomized chronic pain studies, including one by her group using a virtual reality training program for lower back pain, show that 3 months after the training program people report clinically meaningful reductions in pain intensity, pain interference with daily activities, and sleep disturbance, as well as pain-related distress, anxiety, and fatigue

While psychological and complementary approaches have been effective in improving function and mood, there are barriers to accessing them, said Cheatle, such as lack of insurance coverage and the stigma associated with nontraditional, especially psychological, care.

 

Prevention

Good lifestyle behaviors promote better health as people age. “Maintaining a healthy weight, staying active, prioritizing good sleep, and avoiding smoking and alcohol use can support better health and buffer against chronic diseases and pain,” Darnall said.

Cheatle noted the importance of maintaining a safe work environment and avoiding injury risks by, for example, wearing a seatbelt or a cycling helmet. 

 

The Future 

“We need to ensure all individuals have access to effective, low-burden pain treatments, including evidence-based treatments they can receive from home so as to minimize treatment disparities.” Darnall said. Also needed is better comprehensive treatment for acute and chronic pain alike. “If we treat acute pain better, we will have fewer people transitioning to the chronic pain state.”

To that end, added Cheng, healthcare professionals in every specialty from doctors and nurses to psychologists and chiropractors need to develop co-competencies in pain management. 

For Cheatle, the near future looks bleak. “There are some pioneering bioengineering approaches to reduce chronic pain and novel pharmacologic agents such as calcitonin gene-related peptide inhibitors for intractable migraines, but just changing insurance reimbursement for a comprehensive approach to chronic pain care and bolstering healthcare provider education on core pain competencies will benefit the over 50 million adults who suffer from chronic pain.” 

Cheng, however, is more sanguine. “I don’t expect miracles in 10 years’ time, but we’re making rapid progress in understanding the genetics of chronic pain and the mechanisms of disease and therapy. We’re developing biomarkers to help in prognosis and monitor disease progress.” In the meantime, he pointed to an expanding array of non-pharmaceutical options, including neuromodulatory approaches such as nerve blocks and spinal cord stimulation.

Cheng, Cheatle, and Darnall disclosed no relevant competing interests.

A version of this article appeared on Medscape.com.

More Americans than ever are hurting with enduring, life-restricting pain. Like obesity, this condition is on the rise, according to figures in a new National Center for Health Statistics (NCHS) Data Brief from the Centers for Disease Control and Prevention (CDC).

In 2023, 24.3% of US adults had chronic pain, and 8.5% had high-impact chronic pain (HICP) that frequently limited daily activities in the past 3 months. Both types increased with age and with decreasing urbanization level. Women were more likely than men to have HICP (23.2% vs 7.3%). 

Like obesity, chronic pain is multifactorial and is best managed with multidisciplinary intervention, said Jianguo Cheng, MD, PhD, a professor of anesthesiology and medical director of the Cleveland Clinic Consortium for Pain in Ohio. “It’s a complex mix of genetic, biological, and psychosocial dimensions that can cause ongoing pain out of proportion to the original limited injury that triggered it.”

While today’s longer lifespans are the primary driver of the increase, noted Martin Cheatle, PhD, an associate professor of psychiatry, anesthesiology, and critical care and director of behavioral medicine at the Penn Pain Medicine Center at the University of Pennsylvania’s Perelman School of Medicine, Philadelphia, another important factor is the more than 100 million Americans who suffer from obesity. “Obesity is a major risk factor for chronic pain conditions including advancing joint disease, low back pain, and diabetic neuropathies,” he said.

Age is an amplifier, agreed Beth Darnall, PhD, a professor of anesthesiology and perioperative and pain medicine and director of the Pain Relief Innovations Lab at Stanford University in Palo Alto, California, but the increases in chronic pain and HICP cut across age strata. 

“Across the board we see striking increases in chronic pain, such as a 5% increase for those 65 and older, and a nearly 2% increase in HICP in that same age group,” Darnall said, referencing the changes from 2019 data in the new NCHS Data Brief. “And an almost 4% increase was observed for the youngest adult age category,18 to 29. Some of our research is now focusing on how to best treat chronic pain in young adults.”

The rise in chronic pain is broadly linked to the overall decline in the health of the US population, as indicated by the CDC 2024’s Chronic Disease Prevalence in the US: Sociodemographic and Geographic Variations by Zip Code Tabulation Area.

 

The Opioid Crisis and COVID

Beginning in 2016, in response to the opioid crisis and CDC guidelines, opioid prescribing for chronic pain rapidly dropped, both in terms of new prescriptions and tapering of doses of long-term users. “Reduced opioid prescribing yielded benefits for some patients but created new problems and harms for other patients,” said Darnall. Cheng added that the CDC’s recommendations on opioid prescribing were widely misinterpreted and were applied to patients with painful conditions such as cancer and sickle cell disease who were not intended to be affected by the guidelines. “In addition, although medical opioid prescribing dropped by 50%, overdose deaths from non-medical opioid sources increased by more 50%.”

Currently, most opioid overdoses are related to heroin, fentanyl, and newer drugs of abuse such as xylazine. “Most pain clinicians would agree that opioids are not first-line therapy for chronic non-cancer pain, but in a select number of well-vetted patients, opioids can be very effective in improving functionality and quality of life as part of a multimodal approach to pain care,” Cheatle said. 

The impact of the opioid crisis is complex, said Cheatle, noting that only 8%-10% of pain patients on long-term opioid therapy develop a use disorder. “However, opioids were overly prescribed due to clinicians’ lack of training in core competencies of pain management and the insurance companies’ refusal to adequately cover non-opioid therapies such as acupuncture, cognitive behavioral therapy, extended physical therapy, and medical massage,” he said. 

He pointed out that in the late 1990s there were more than 1000 multidisciplinary pain centers, whereas currently there are many fewer owing to lack of insurance reimbursement. “This results in more possibly avoidable invasive surgeries, which can further contribute to the increase in chronic pain.” 

The COVID pandemic further exacerbated the pain problem and delayed access to timely medical interventions for many people. Some adopted a more sedentary lifestyle, already entrenched in today’s technology-driven society, leading in turn to weight gain and more chronic pain. “The isolation and lack of normal human connections during the pandemic could exacerbate pain and loss of autonomy,” Cheatle said. And some individuals developed painful neurologic conditions related to long-haul COVID, for which there is no effective treatment. 

 

Best Approach

“Historically, pain has been treated as a purely biomedical issue. Bringing a biopsychosocial perspective to pain care can support pain relief,” said Darnall. Multiple national clinical guidance documents have called for a comprehensive approach that considers the whole person: their circumstances, their needs, their stressors, and their environment. “And we must provide patients meaningful access to the lowest-risk, non-pharmacologic treatments first – and ideally early on,” she said.

Even effective medications rarely make a person pain free, so other approaches are needed in tandem, Darnall said. Support for stronger patient competency in self-management of chronic pain is mounting.

“It’s vitally important that we help people know how to help themselves have less pain – how to steer their mind and body toward relief by using pain relief skills,” she said. “By so doing they can cultivate a critical level of control over their pain and are less at its mercy, which supports good mood and is shown to help people be more active as the impacts of pain diminish.”

Darnall outlined a recent development in the primary care setting that involves offering patients a brief program in pain-relief skills training. Within Veterans Affairs primary care, for example, patients receive several 30-minute sessions in pain reduction techniques. Outside of the VA, primary care clinics are incorporating an evidence-based, one-session 2-hour pain relief skills class called Empowered Relief, as standard care. 

The class teaches participants three pain management skills and creates a personalized plan for each that includes a free app for ongoing daily use.

Since pain causes agitation in the central nervous system, manifested as fast heart rate, rapid breathing, muscle tension, and distress, people learn various ways to calm the central nervous system – with, for example, a sound technology known as binaural audio to deepen the relaxation response. “They also learn to identify and target worry about pain and develop self-soothing actions to interrupt unhelpful patterns,” Darnall said. 

Data from randomized chronic pain studies, including one by her group using a virtual reality training program for lower back pain, show that 3 months after the training program people report clinically meaningful reductions in pain intensity, pain interference with daily activities, and sleep disturbance, as well as pain-related distress, anxiety, and fatigue

While psychological and complementary approaches have been effective in improving function and mood, there are barriers to accessing them, said Cheatle, such as lack of insurance coverage and the stigma associated with nontraditional, especially psychological, care.

 

Prevention

Good lifestyle behaviors promote better health as people age. “Maintaining a healthy weight, staying active, prioritizing good sleep, and avoiding smoking and alcohol use can support better health and buffer against chronic diseases and pain,” Darnall said.

Cheatle noted the importance of maintaining a safe work environment and avoiding injury risks by, for example, wearing a seatbelt or a cycling helmet. 

 

The Future 

“We need to ensure all individuals have access to effective, low-burden pain treatments, including evidence-based treatments they can receive from home so as to minimize treatment disparities.” Darnall said. Also needed is better comprehensive treatment for acute and chronic pain alike. “If we treat acute pain better, we will have fewer people transitioning to the chronic pain state.”

To that end, added Cheng, healthcare professionals in every specialty from doctors and nurses to psychologists and chiropractors need to develop co-competencies in pain management. 

For Cheatle, the near future looks bleak. “There are some pioneering bioengineering approaches to reduce chronic pain and novel pharmacologic agents such as calcitonin gene-related peptide inhibitors for intractable migraines, but just changing insurance reimbursement for a comprehensive approach to chronic pain care and bolstering healthcare provider education on core pain competencies will benefit the over 50 million adults who suffer from chronic pain.” 

Cheng, however, is more sanguine. “I don’t expect miracles in 10 years’ time, but we’re making rapid progress in understanding the genetics of chronic pain and the mechanisms of disease and therapy. We’re developing biomarkers to help in prognosis and monitor disease progress.” In the meantime, he pointed to an expanding array of non-pharmaceutical options, including neuromodulatory approaches such as nerve blocks and spinal cord stimulation.

Cheng, Cheatle, and Darnall disclosed no relevant competing interests.

A version of this article appeared on Medscape.com.

Cultural competency is one of the most important values in the practice of medicine. Defined as the “ability to collaborate effectively with individuals from different cultures,” this type of competence “improves healthcare experiences and outcomes.” But within the context of cultural familiarity, it’s equally important to “understand that each person is an individual and may or may not adhere to certain cultural beliefs or practices common in his or her culture,” according to the Agency for Healthcare Research and Quality’s (AHRQ’s) Health Literacy Universal Precautions Toolkit.

Sarah Candler, MD, MPH, an internal medicine physician specializing in primary care for older adults in Washington, DC, said that the medical code of ethics consists of several pillars, with patient autonomy as the “first and most primary of those pillars.” She calls the balance of patient autonomy and cultural respect a “complicated tightrope to walk,” but says that these ethical principles can inform medical decisions and the patient-physician relationship.

 

Cultural Familiarity

It’s important to be as familiar as possible with the patient’s culture, Santina Wheat, MD, program director, Northwestern McGaw Family Medicine Residency at Delnor Hospital, Geneva, told this news organization. “For example, we serve many Orthodox Jewish patients. We had a meeting with rabbis from the community to present to us what religious laws might affect our patients. Until recently, I was delivering babies, and there was always a 24-hour emergency rabbi on call if an Orthodox patient wanted the input of a rabbi into her decisions.”

Jay W. Lee, MD, MPH, a member of the board of directors of the American Academy of Family Physicians, also sets out to educate himself about the cultural norms of his patients if they come from populations he’s not familiar with. “For example, this comes up when a new refugee population comes to the United States — most recently, there was a population of Afghan refugees,” Lee told this news organization.

Lee spent “a lot of time trying to learn about their cultural norms,” which prepared him to “ask more targeted questions about the patient’s understanding of the tests we were ordering or treatment options we were bringing forward.”

Lee, also the medical director at Integrated Health Partners of Southern California and associate clinical professor of family medicine at the University of California, Irvine, said it might be best if the physician is “language congruent or culturally similar.” Lee is of Asian descent and also speaks Spanish fluently. “I enjoy cultural exchanges with my patients, and I encourage patients to find a physician who’s the best fit.” But being from the same culture isn’t absolutely necessary for building relationships with the patient. “The key is offering the patient autonomy” while understanding the cultural context.

 

Don’t Assume ... Always Ask

Cultural familiarity doesn’t equate with stereotyping, Wheat emphasized. “Proceeding without assumptions opens the opportunity to ask questions for clarification and understanding and to improve patient care,” said Lee.

Sara Glass, PhD, LCSW, agrees. She’s the clinical director of Soul Wellness NYC, New York City, a psychotherapy practice that specializes in treating trauma. Based on her own experiences, she knows that some physicians and other healthcare professionals confuse cultural sensitivity with cultural stereotyping.

Glass, formerly Hasidic and ultra-Orthodox, shared an example from her own life. During the delivery of her second child, she sustained a vaginal tear. At her 6-week postpartum visit, her ob/gyn said, “Just remind me when you’re in your ninth month next time, and I can sew it up right after you deliver.”

Much of this physician’s practice “consisted of Hasidic women who looked just like me, wearing the same garb — head coverings such as wigs and scarves and long skirts. Most women in that community have multiple pregnancies,” Glass told this news organization. “My sister has 10 children, and that’s not unusual. The doctor simply assumed I’d be going on to have more babies without asking if that’s what I wanted.”

Glass says she was also never given information by her physician about the range of available contraceptive options. The rabbis of the Hasidic sect to which Glass belonged allowed women to practice contraception for 6 months following childbirth, or for longer, in the setting of certain medical conditions, but only certain types of birth control were religiously permissible. Other options were not mentioned to her by her physician, and she didn’t know that they existed.

Making no assumptions applies not only to patients from other cultures but also to all patients — including members of “mainstream American culture.”

Candler recalls a young patient with a new baby, who shared “how exhausted she was and how much time, energy, and work it took to care for children,” Candler recounted. “To me, it sounded as though she didn’t want another child, and I was about to offer contraception when it occurred to me to first ask if she wanted to have more children.” Candler was surprised when the patient said that, although she wasn’t actively looking to become pregnant again, she didn’t want to take preventive measures. “I’m so glad I asked, rather than simply assuming.”

 

Culture Is Mutable

Important questions to ask patients include whether there are aspects of their culture or religion that might affect their care — which can include medications they may feel uncomfortable using — and what family members they want to have involved in clinical discussions and decisions, said Wheat.

Lee described treating a refugee from Afghanistan who was in her sixth month of pregnancy. “I quickly needed to learn about what her expectations were for her care and my presence as a male on her care team,” he recounted. Lee arranged for the patient to receive prenatal care from a different clinician and arranged for follow-up for her husband and children. “Everyone had good results.”

Candler noted that some patients choose their physician specifically because that practitioner is conversant with their culture and respectful of its mores — especially when physicians share the same culture as the patient. But that level of familiarity can make it easy to forget to ask questions about the experience of the individual patient within that culture.

Moreover, Glass suggested, some physicians who treat patients from a particular culture or religious group may be concerned about offending them or antagonizing religious leaders if they discuss medical options that aren’t accepted or practiced in that community or culture, such as vasectomy for male contraception. “But that deprives patients of knowing what choices are available and making truly informed decisions.”

This is especially important because “culture is mutable,” said Candler, and religious or cultural practices can “look one way on paper but be implemented, adopted, or executed in a completely different way by every human being who lives in that culture.” The best cultural competency “comes from continuing to build relationships with our patients. But even in a single visit, a single hospitalization, we should get to know patients as human beings, not just members of a given culture.”

There are cultures in which families want to be the liaison between the patient and the physician and to make decisions on the patient’s behalf. “I always ask patients what role they want their family members to play even if the cultural expectation is that the family will be heavily involved,” Candler said.

Sometimes, this can be awkward, and families might become upset. Candler described an elderly, frail patient who was diagnosed with end-stage cancer. She had always relied heavily on family to care for her. Concerned about overburdening them, she didn’t want them to know her diagnosis. The patient was mentally competent to make that decision.

“Usually, I would have had the family at the bedside so I could be sure everyone was appropriately informed and prepared for what lay ahead, but in this case, I couldn’t do so,” Candler said. “I had to inform her entire care team not to discuss the cancer diagnosis with any family members because this was the patient’s express wish. And when the family asked me if the diagnosis was cancer, I had to respond, ‘I’m so sorry, but your loved one doesn’t want us to discuss details of her diagnosis.’”

Other patients don’t want to know their own diagnosis and specifically ask Candler to inform a family member. “I’ve had patients request that I tell their children. They want their children to make decisions on their behalf.”

The main thing, Candler emphasized, is to “ask the patient, make sure the patient is competent to make that decision, thoroughly document the patient’s decision in the chart, and respect whatever that decision is.”

 

You Can Revisit the Questions

Having a longitudinal relationship means that the physician can revisit the same questions at different junctures because people’s perspectives sometimes change over time. “Discussing what a patient wants isn’t necessarily a one-time occurrence,” Wheat said. For example, “I’ve had situations where a patient has been a member of Jehovah’s Witnesses and won’t accept blood products — like transfusions — in treatment. I tell these patients that if an emergent situation arises, I would like to have the conversation again.”

Of course, sometimes patients are seen in the emergency department or in other situations where the physician has no prior relationship with them. “I always go into a room, especially with new patients, aiming to build rapport, communicate with a high level of respect, introduce myself, explain my approach, and understand the patient’s wishes,” Lee said. “As scenarios play out, I ask in multiple ways for the patient to confirm those wishes.”

He acknowledges that this can be time-consuming, “but it helps ensure the care that patient receives is complete, thorough, comprehensive, and respectful of the patient’s values and wishes.”

Candler disclosed paid part-time clinical work at CuraCapitol Primary Care Services, volunteer advocacy (reimbursed for travel) for the American College of Physicians, volunteer advocacy (reimbursed for travel) for the American Medical Association while serving on their Task Force to Preserve the Patient-Physician Relationship, and serving as a partner representative (reimbursed for time) for the AHRQ’s Person-Centered Care Planning Partnership, representing the American College of Physicians. Lee, Wheat, and Glass disclosed no relevant financial relationships.

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

Cultural competency is one of the most important values in the practice of medicine. Defined as the “ability to collaborate effectively with individuals from different cultures,” this type of competence “improves healthcare experiences and outcomes.” But within the context of cultural familiarity, it’s equally important to “understand that each person is an individual and may or may not adhere to certain cultural beliefs or practices common in his or her culture,” according to the Agency for Healthcare Research and Quality’s (AHRQ’s) Health Literacy Universal Precautions Toolkit.

Sarah Candler, MD, MPH, an internal medicine physician specializing in primary care for older adults in Washington, DC, said that the medical code of ethics consists of several pillars, with patient autonomy as the “first and most primary of those pillars.” She calls the balance of patient autonomy and cultural respect a “complicated tightrope to walk,” but says that these ethical principles can inform medical decisions and the patient-physician relationship.

 

Cultural Familiarity

It’s important to be as familiar as possible with the patient’s culture, Santina Wheat, MD, program director, Northwestern McGaw Family Medicine Residency at Delnor Hospital, Geneva, told this news organization. “For example, we serve many Orthodox Jewish patients. We had a meeting with rabbis from the community to present to us what religious laws might affect our patients. Until recently, I was delivering babies, and there was always a 24-hour emergency rabbi on call if an Orthodox patient wanted the input of a rabbi into her decisions.”

Jay W. Lee, MD, MPH, a member of the board of directors of the American Academy of Family Physicians, also sets out to educate himself about the cultural norms of his patients if they come from populations he’s not familiar with. “For example, this comes up when a new refugee population comes to the United States — most recently, there was a population of Afghan refugees,” Lee told this news organization.

Lee spent “a lot of time trying to learn about their cultural norms,” which prepared him to “ask more targeted questions about the patient’s understanding of the tests we were ordering or treatment options we were bringing forward.”

Lee, also the medical director at Integrated Health Partners of Southern California and associate clinical professor of family medicine at the University of California, Irvine, said it might be best if the physician is “language congruent or culturally similar.” Lee is of Asian descent and also speaks Spanish fluently. “I enjoy cultural exchanges with my patients, and I encourage patients to find a physician who’s the best fit.” But being from the same culture isn’t absolutely necessary for building relationships with the patient. “The key is offering the patient autonomy” while understanding the cultural context.

 

Don’t Assume ... Always Ask

Cultural familiarity doesn’t equate with stereotyping, Wheat emphasized. “Proceeding without assumptions opens the opportunity to ask questions for clarification and understanding and to improve patient care,” said Lee.

Sara Glass, PhD, LCSW, agrees. She’s the clinical director of Soul Wellness NYC, New York City, a psychotherapy practice that specializes in treating trauma. Based on her own experiences, she knows that some physicians and other healthcare professionals confuse cultural sensitivity with cultural stereotyping.

Glass, formerly Hasidic and ultra-Orthodox, shared an example from her own life. During the delivery of her second child, she sustained a vaginal tear. At her 6-week postpartum visit, her ob/gyn said, “Just remind me when you’re in your ninth month next time, and I can sew it up right after you deliver.”

Much of this physician’s practice “consisted of Hasidic women who looked just like me, wearing the same garb — head coverings such as wigs and scarves and long skirts. Most women in that community have multiple pregnancies,” Glass told this news organization. “My sister has 10 children, and that’s not unusual. The doctor simply assumed I’d be going on to have more babies without asking if that’s what I wanted.”

Glass says she was also never given information by her physician about the range of available contraceptive options. The rabbis of the Hasidic sect to which Glass belonged allowed women to practice contraception for 6 months following childbirth, or for longer, in the setting of certain medical conditions, but only certain types of birth control were religiously permissible. Other options were not mentioned to her by her physician, and she didn’t know that they existed.

Making no assumptions applies not only to patients from other cultures but also to all patients — including members of “mainstream American culture.”

Candler recalls a young patient with a new baby, who shared “how exhausted she was and how much time, energy, and work it took to care for children,” Candler recounted. “To me, it sounded as though she didn’t want another child, and I was about to offer contraception when it occurred to me to first ask if she wanted to have more children.” Candler was surprised when the patient said that, although she wasn’t actively looking to become pregnant again, she didn’t want to take preventive measures. “I’m so glad I asked, rather than simply assuming.”

 

Culture Is Mutable

Important questions to ask patients include whether there are aspects of their culture or religion that might affect their care — which can include medications they may feel uncomfortable using — and what family members they want to have involved in clinical discussions and decisions, said Wheat.

Lee described treating a refugee from Afghanistan who was in her sixth month of pregnancy. “I quickly needed to learn about what her expectations were for her care and my presence as a male on her care team,” he recounted. Lee arranged for the patient to receive prenatal care from a different clinician and arranged for follow-up for her husband and children. “Everyone had good results.”

Candler noted that some patients choose their physician specifically because that practitioner is conversant with their culture and respectful of its mores — especially when physicians share the same culture as the patient. But that level of familiarity can make it easy to forget to ask questions about the experience of the individual patient within that culture.

Moreover, Glass suggested, some physicians who treat patients from a particular culture or religious group may be concerned about offending them or antagonizing religious leaders if they discuss medical options that aren’t accepted or practiced in that community or culture, such as vasectomy for male contraception. “But that deprives patients of knowing what choices are available and making truly informed decisions.”

This is especially important because “culture is mutable,” said Candler, and religious or cultural practices can “look one way on paper but be implemented, adopted, or executed in a completely different way by every human being who lives in that culture.” The best cultural competency “comes from continuing to build relationships with our patients. But even in a single visit, a single hospitalization, we should get to know patients as human beings, not just members of a given culture.”

There are cultures in which families want to be the liaison between the patient and the physician and to make decisions on the patient’s behalf. “I always ask patients what role they want their family members to play even if the cultural expectation is that the family will be heavily involved,” Candler said.

Sometimes, this can be awkward, and families might become upset. Candler described an elderly, frail patient who was diagnosed with end-stage cancer. She had always relied heavily on family to care for her. Concerned about overburdening them, she didn’t want them to know her diagnosis. The patient was mentally competent to make that decision.

“Usually, I would have had the family at the bedside so I could be sure everyone was appropriately informed and prepared for what lay ahead, but in this case, I couldn’t do so,” Candler said. “I had to inform her entire care team not to discuss the cancer diagnosis with any family members because this was the patient’s express wish. And when the family asked me if the diagnosis was cancer, I had to respond, ‘I’m so sorry, but your loved one doesn’t want us to discuss details of her diagnosis.’”

Other patients don’t want to know their own diagnosis and specifically ask Candler to inform a family member. “I’ve had patients request that I tell their children. They want their children to make decisions on their behalf.”

The main thing, Candler emphasized, is to “ask the patient, make sure the patient is competent to make that decision, thoroughly document the patient’s decision in the chart, and respect whatever that decision is.”

 

You Can Revisit the Questions

Having a longitudinal relationship means that the physician can revisit the same questions at different junctures because people’s perspectives sometimes change over time. “Discussing what a patient wants isn’t necessarily a one-time occurrence,” Wheat said. For example, “I’ve had situations where a patient has been a member of Jehovah’s Witnesses and won’t accept blood products — like transfusions — in treatment. I tell these patients that if an emergent situation arises, I would like to have the conversation again.”

Of course, sometimes patients are seen in the emergency department or in other situations where the physician has no prior relationship with them. “I always go into a room, especially with new patients, aiming to build rapport, communicate with a high level of respect, introduce myself, explain my approach, and understand the patient’s wishes,” Lee said. “As scenarios play out, I ask in multiple ways for the patient to confirm those wishes.”

He acknowledges that this can be time-consuming, “but it helps ensure the care that patient receives is complete, thorough, comprehensive, and respectful of the patient’s values and wishes.”

Candler disclosed paid part-time clinical work at CuraCapitol Primary Care Services, volunteer advocacy (reimbursed for travel) for the American College of Physicians, volunteer advocacy (reimbursed for travel) for the American Medical Association while serving on their Task Force to Preserve the Patient-Physician Relationship, and serving as a partner representative (reimbursed for time) for the AHRQ’s Person-Centered Care Planning Partnership, representing the American College of Physicians. Lee, Wheat, and Glass disclosed no relevant financial relationships.

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

Cultural competency is one of the most important values in the practice of medicine. Defined as the “ability to collaborate effectively with individuals from different cultures,” this type of competence “improves healthcare experiences and outcomes.” But within the context of cultural familiarity, it’s equally important to “understand that each person is an individual and may or may not adhere to certain cultural beliefs or practices common in his or her culture,” according to the Agency for Healthcare Research and Quality’s (AHRQ’s) Health Literacy Universal Precautions Toolkit.

Sarah Candler, MD, MPH, an internal medicine physician specializing in primary care for older adults in Washington, DC, said that the medical code of ethics consists of several pillars, with patient autonomy as the “first and most primary of those pillars.” She calls the balance of patient autonomy and cultural respect a “complicated tightrope to walk,” but says that these ethical principles can inform medical decisions and the patient-physician relationship.

 

Cultural Familiarity

It’s important to be as familiar as possible with the patient’s culture, Santina Wheat, MD, program director, Northwestern McGaw Family Medicine Residency at Delnor Hospital, Geneva, told this news organization. “For example, we serve many Orthodox Jewish patients. We had a meeting with rabbis from the community to present to us what religious laws might affect our patients. Until recently, I was delivering babies, and there was always a 24-hour emergency rabbi on call if an Orthodox patient wanted the input of a rabbi into her decisions.”

Jay W. Lee, MD, MPH, a member of the board of directors of the American Academy of Family Physicians, also sets out to educate himself about the cultural norms of his patients if they come from populations he’s not familiar with. “For example, this comes up when a new refugee population comes to the United States — most recently, there was a population of Afghan refugees,” Lee told this news organization.

Lee spent “a lot of time trying to learn about their cultural norms,” which prepared him to “ask more targeted questions about the patient’s understanding of the tests we were ordering or treatment options we were bringing forward.”

Lee, also the medical director at Integrated Health Partners of Southern California and associate clinical professor of family medicine at the University of California, Irvine, said it might be best if the physician is “language congruent or culturally similar.” Lee is of Asian descent and also speaks Spanish fluently. “I enjoy cultural exchanges with my patients, and I encourage patients to find a physician who’s the best fit.” But being from the same culture isn’t absolutely necessary for building relationships with the patient. “The key is offering the patient autonomy” while understanding the cultural context.

 

Don’t Assume ... Always Ask

Cultural familiarity doesn’t equate with stereotyping, Wheat emphasized. “Proceeding without assumptions opens the opportunity to ask questions for clarification and understanding and to improve patient care,” said Lee.

Sara Glass, PhD, LCSW, agrees. She’s the clinical director of Soul Wellness NYC, New York City, a psychotherapy practice that specializes in treating trauma. Based on her own experiences, she knows that some physicians and other healthcare professionals confuse cultural sensitivity with cultural stereotyping.

Glass, formerly Hasidic and ultra-Orthodox, shared an example from her own life. During the delivery of her second child, she sustained a vaginal tear. At her 6-week postpartum visit, her ob/gyn said, “Just remind me when you’re in your ninth month next time, and I can sew it up right after you deliver.”

Much of this physician’s practice “consisted of Hasidic women who looked just like me, wearing the same garb — head coverings such as wigs and scarves and long skirts. Most women in that community have multiple pregnancies,” Glass told this news organization. “My sister has 10 children, and that’s not unusual. The doctor simply assumed I’d be going on to have more babies without asking if that’s what I wanted.”

Glass says she was also never given information by her physician about the range of available contraceptive options. The rabbis of the Hasidic sect to which Glass belonged allowed women to practice contraception for 6 months following childbirth, or for longer, in the setting of certain medical conditions, but only certain types of birth control were religiously permissible. Other options were not mentioned to her by her physician, and she didn’t know that they existed.

Making no assumptions applies not only to patients from other cultures but also to all patients — including members of “mainstream American culture.”

Candler recalls a young patient with a new baby, who shared “how exhausted she was and how much time, energy, and work it took to care for children,” Candler recounted. “To me, it sounded as though she didn’t want another child, and I was about to offer contraception when it occurred to me to first ask if she wanted to have more children.” Candler was surprised when the patient said that, although she wasn’t actively looking to become pregnant again, she didn’t want to take preventive measures. “I’m so glad I asked, rather than simply assuming.”

 

Culture Is Mutable

Important questions to ask patients include whether there are aspects of their culture or religion that might affect their care — which can include medications they may feel uncomfortable using — and what family members they want to have involved in clinical discussions and decisions, said Wheat.

Lee described treating a refugee from Afghanistan who was in her sixth month of pregnancy. “I quickly needed to learn about what her expectations were for her care and my presence as a male on her care team,” he recounted. Lee arranged for the patient to receive prenatal care from a different clinician and arranged for follow-up for her husband and children. “Everyone had good results.”

Candler noted that some patients choose their physician specifically because that practitioner is conversant with their culture and respectful of its mores — especially when physicians share the same culture as the patient. But that level of familiarity can make it easy to forget to ask questions about the experience of the individual patient within that culture.

Moreover, Glass suggested, some physicians who treat patients from a particular culture or religious group may be concerned about offending them or antagonizing religious leaders if they discuss medical options that aren’t accepted or practiced in that community or culture, such as vasectomy for male contraception. “But that deprives patients of knowing what choices are available and making truly informed decisions.”

This is especially important because “culture is mutable,” said Candler, and religious or cultural practices can “look one way on paper but be implemented, adopted, or executed in a completely different way by every human being who lives in that culture.” The best cultural competency “comes from continuing to build relationships with our patients. But even in a single visit, a single hospitalization, we should get to know patients as human beings, not just members of a given culture.”

There are cultures in which families want to be the liaison between the patient and the physician and to make decisions on the patient’s behalf. “I always ask patients what role they want their family members to play even if the cultural expectation is that the family will be heavily involved,” Candler said.

Sometimes, this can be awkward, and families might become upset. Candler described an elderly, frail patient who was diagnosed with end-stage cancer. She had always relied heavily on family to care for her. Concerned about overburdening them, she didn’t want them to know her diagnosis. The patient was mentally competent to make that decision.

“Usually, I would have had the family at the bedside so I could be sure everyone was appropriately informed and prepared for what lay ahead, but in this case, I couldn’t do so,” Candler said. “I had to inform her entire care team not to discuss the cancer diagnosis with any family members because this was the patient’s express wish. And when the family asked me if the diagnosis was cancer, I had to respond, ‘I’m so sorry, but your loved one doesn’t want us to discuss details of her diagnosis.’”

Other patients don’t want to know their own diagnosis and specifically ask Candler to inform a family member. “I’ve had patients request that I tell their children. They want their children to make decisions on their behalf.”

The main thing, Candler emphasized, is to “ask the patient, make sure the patient is competent to make that decision, thoroughly document the patient’s decision in the chart, and respect whatever that decision is.”

 

You Can Revisit the Questions

Having a longitudinal relationship means that the physician can revisit the same questions at different junctures because people’s perspectives sometimes change over time. “Discussing what a patient wants isn’t necessarily a one-time occurrence,” Wheat said. For example, “I’ve had situations where a patient has been a member of Jehovah’s Witnesses and won’t accept blood products — like transfusions — in treatment. I tell these patients that if an emergent situation arises, I would like to have the conversation again.”

Of course, sometimes patients are seen in the emergency department or in other situations where the physician has no prior relationship with them. “I always go into a room, especially with new patients, aiming to build rapport, communicate with a high level of respect, introduce myself, explain my approach, and understand the patient’s wishes,” Lee said. “As scenarios play out, I ask in multiple ways for the patient to confirm those wishes.”

He acknowledges that this can be time-consuming, “but it helps ensure the care that patient receives is complete, thorough, comprehensive, and respectful of the patient’s values and wishes.”

Candler disclosed paid part-time clinical work at CuraCapitol Primary Care Services, volunteer advocacy (reimbursed for travel) for the American College of Physicians, volunteer advocacy (reimbursed for travel) for the American Medical Association while serving on their Task Force to Preserve the Patient-Physician Relationship, and serving as a partner representative (reimbursed for time) for the AHRQ’s Person-Centered Care Planning Partnership, representing the American College of Physicians. Lee, Wheat, and Glass disclosed no relevant financial relationships.

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

The number of drug overdose deaths involving illegally manufactured fentanyl and fentanyl analogs (IMFs) dropped in the United States during the latter portion of 2023. But a new report from the Centers for Disease Control and Prevention (CDC) suggests that an increase in overdoses involving the potent fentanyl analog carfentanil threatens to undo that progress.

Overdose deaths from carfentanil rose by more than 700% in the past year, increasing from 29 between January and June 2023 to 238 in that same period in 2024. 

Carfentanil is used as a tranquilizing agent for elephants and other large mammals and is 100 times more potent than fentanyl. Just 2 mg can be lethal to humans, and a carfentanil-related overdose can require more than three shots of naloxone to reverse.

Prior to this resurgence of carfentanil, the drug “had largely disappeared after carfentanil-involved overdose death outbreaks in 2016-2017,” study authors noted, when carfentanil overdose deaths topped 1200, other data showed.

“Educational and response efforts that can rapidly adapt to the potential for increased distribution of drugs more potent than fentanyl, such as carfentanil, are needed and might avert or mitigate new increases in overdose deaths,” the authors wrote.

The findings were published online in CDC’s Morbidity and Mortality Weekly Report.

 

Carfentanil May Stall Overdose Decline

IMFs such as carfentanil were first detected in the United States illegal drug supply in 2013. A little more than a decade later, IMFs have replaced heroin as the most common opioid in the United States.

The introduction of IMFs led to a sharp rise in overdose deaths, but provisional data suggest these fatalities are on the decline. A recent re-emergence of carfentanil could stall that downward trend.

To investigate further, researchers used data from the CDC’s State Unintentional Drug Overdose Reporting System to analyze detection of IMFs and carfentanil between January 2021 and June 2024. 

The database houses information on drug overdoses obtained from death certificates, coroner and medical examiner reports, and postmortem toxicology reports from 49 states and the District of Columbia.

From January 2021 to December 2023, more than 251,000 people died from drug overdoses with unintentional and undetermined intent, 75% of which involved IMFs. 

IMF-linked deaths peaked at 16,814 in the second quarter of 2023, then declined by nearly 16% to 14,299 deaths by the end of that year.

Investigators could only speculate on the reasons for the decline in overdoses. It is possible that drug users are mixing fentanyl with other drugs, such as xylazine, which may reduce the danger of fatal overdose. It’s also possible that overdose prevention programs are partially responsible for the decline.

“Continued and expanded implementation of these programs, including naloxone distribution and increasing access to treatments for substance use disorders, might result in sustained and continued declines in drug overdose deaths,” they wrote.

 

Regional Differences

When researchers analyzed the results by region, they found that IMFs were detected in 81.5% of overdose deaths in the Northeast, 75% in the Midwest, and 75% in the Southern regions during the study period. These percentages were relatively stable until summer 2023, when declines in IMF-linked overdoses were noteworthy.

Specifically, deaths caused by IMFs decreased 11% in the Northeast (8245 to 7323), 16% in the Midwest (7160 to 6008), and 10.5% in the South (13,492 to 12,077).

In the West, however, overdoses linked to IMFs increased by 66.5% between 2021 and the second quarter of 2024. 

The researchers speculated that the surge in the western United States could be caused by fentanyl entering the drug markets in that region later than in other areas, “likely because of challenges of mixing fentanyl into the black tar heroin that was more common in the West,” they wrote.

The findings suggested that, despite overall declines in overdose deaths reported nationwide, “recent sharp increases in overdose deaths with carfentanil detected, although rare, highlight the ever-changing illegal drug supply and threaten progress in reducing overdose deaths.” 

The report authors encouraged expanding education programs for the public about the dangers of carfentanil and other IMFs, as well as harm reduction strategies, including using fentanyl test strips or drug-checking services.

No study funding information was available. There were no relevant financial relationships.

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

The number of drug overdose deaths involving illegally manufactured fentanyl and fentanyl analogs (IMFs) dropped in the United States during the latter portion of 2023. But a new report from the Centers for Disease Control and Prevention (CDC) suggests that an increase in overdoses involving the potent fentanyl analog carfentanil threatens to undo that progress.

Overdose deaths from carfentanil rose by more than 700% in the past year, increasing from 29 between January and June 2023 to 238 in that same period in 2024. 

Carfentanil is used as a tranquilizing agent for elephants and other large mammals and is 100 times more potent than fentanyl. Just 2 mg can be lethal to humans, and a carfentanil-related overdose can require more than three shots of naloxone to reverse.

Prior to this resurgence of carfentanil, the drug “had largely disappeared after carfentanil-involved overdose death outbreaks in 2016-2017,” study authors noted, when carfentanil overdose deaths topped 1200, other data showed.

“Educational and response efforts that can rapidly adapt to the potential for increased distribution of drugs more potent than fentanyl, such as carfentanil, are needed and might avert or mitigate new increases in overdose deaths,” the authors wrote.

The findings were published online in CDC’s Morbidity and Mortality Weekly Report.

 

Carfentanil May Stall Overdose Decline

IMFs such as carfentanil were first detected in the United States illegal drug supply in 2013. A little more than a decade later, IMFs have replaced heroin as the most common opioid in the United States.

The introduction of IMFs led to a sharp rise in overdose deaths, but provisional data suggest these fatalities are on the decline. A recent re-emergence of carfentanil could stall that downward trend.

To investigate further, researchers used data from the CDC’s State Unintentional Drug Overdose Reporting System to analyze detection of IMFs and carfentanil between January 2021 and June 2024. 

The database houses information on drug overdoses obtained from death certificates, coroner and medical examiner reports, and postmortem toxicology reports from 49 states and the District of Columbia.

From January 2021 to December 2023, more than 251,000 people died from drug overdoses with unintentional and undetermined intent, 75% of which involved IMFs. 

IMF-linked deaths peaked at 16,814 in the second quarter of 2023, then declined by nearly 16% to 14,299 deaths by the end of that year.

Investigators could only speculate on the reasons for the decline in overdoses. It is possible that drug users are mixing fentanyl with other drugs, such as xylazine, which may reduce the danger of fatal overdose. It’s also possible that overdose prevention programs are partially responsible for the decline.

“Continued and expanded implementation of these programs, including naloxone distribution and increasing access to treatments for substance use disorders, might result in sustained and continued declines in drug overdose deaths,” they wrote.

 

Regional Differences

When researchers analyzed the results by region, they found that IMFs were detected in 81.5% of overdose deaths in the Northeast, 75% in the Midwest, and 75% in the Southern regions during the study period. These percentages were relatively stable until summer 2023, when declines in IMF-linked overdoses were noteworthy.

Specifically, deaths caused by IMFs decreased 11% in the Northeast (8245 to 7323), 16% in the Midwest (7160 to 6008), and 10.5% in the South (13,492 to 12,077).

In the West, however, overdoses linked to IMFs increased by 66.5% between 2021 and the second quarter of 2024. 

The researchers speculated that the surge in the western United States could be caused by fentanyl entering the drug markets in that region later than in other areas, “likely because of challenges of mixing fentanyl into the black tar heroin that was more common in the West,” they wrote.

The findings suggested that, despite overall declines in overdose deaths reported nationwide, “recent sharp increases in overdose deaths with carfentanil detected, although rare, highlight the ever-changing illegal drug supply and threaten progress in reducing overdose deaths.” 

The report authors encouraged expanding education programs for the public about the dangers of carfentanil and other IMFs, as well as harm reduction strategies, including using fentanyl test strips or drug-checking services.

No study funding information was available. There were no relevant financial relationships.

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

The number of drug overdose deaths involving illegally manufactured fentanyl and fentanyl analogs (IMFs) dropped in the United States during the latter portion of 2023. But a new report from the Centers for Disease Control and Prevention (CDC) suggests that an increase in overdoses involving the potent fentanyl analog carfentanil threatens to undo that progress.

Overdose deaths from carfentanil rose by more than 700% in the past year, increasing from 29 between January and June 2023 to 238 in that same period in 2024. 

Carfentanil is used as a tranquilizing agent for elephants and other large mammals and is 100 times more potent than fentanyl. Just 2 mg can be lethal to humans, and a carfentanil-related overdose can require more than three shots of naloxone to reverse.

Prior to this resurgence of carfentanil, the drug “had largely disappeared after carfentanil-involved overdose death outbreaks in 2016-2017,” study authors noted, when carfentanil overdose deaths topped 1200, other data showed.

“Educational and response efforts that can rapidly adapt to the potential for increased distribution of drugs more potent than fentanyl, such as carfentanil, are needed and might avert or mitigate new increases in overdose deaths,” the authors wrote.

The findings were published online in CDC’s Morbidity and Mortality Weekly Report.

 

Carfentanil May Stall Overdose Decline

IMFs such as carfentanil were first detected in the United States illegal drug supply in 2013. A little more than a decade later, IMFs have replaced heroin as the most common opioid in the United States.

The introduction of IMFs led to a sharp rise in overdose deaths, but provisional data suggest these fatalities are on the decline. A recent re-emergence of carfentanil could stall that downward trend.

To investigate further, researchers used data from the CDC’s State Unintentional Drug Overdose Reporting System to analyze detection of IMFs and carfentanil between January 2021 and June 2024. 

The database houses information on drug overdoses obtained from death certificates, coroner and medical examiner reports, and postmortem toxicology reports from 49 states and the District of Columbia.

From January 2021 to December 2023, more than 251,000 people died from drug overdoses with unintentional and undetermined intent, 75% of which involved IMFs. 

IMF-linked deaths peaked at 16,814 in the second quarter of 2023, then declined by nearly 16% to 14,299 deaths by the end of that year.

Investigators could only speculate on the reasons for the decline in overdoses. It is possible that drug users are mixing fentanyl with other drugs, such as xylazine, which may reduce the danger of fatal overdose. It’s also possible that overdose prevention programs are partially responsible for the decline.

“Continued and expanded implementation of these programs, including naloxone distribution and increasing access to treatments for substance use disorders, might result in sustained and continued declines in drug overdose deaths,” they wrote.

 

Regional Differences

When researchers analyzed the results by region, they found that IMFs were detected in 81.5% of overdose deaths in the Northeast, 75% in the Midwest, and 75% in the Southern regions during the study period. These percentages were relatively stable until summer 2023, when declines in IMF-linked overdoses were noteworthy.

Specifically, deaths caused by IMFs decreased 11% in the Northeast (8245 to 7323), 16% in the Midwest (7160 to 6008), and 10.5% in the South (13,492 to 12,077).

In the West, however, overdoses linked to IMFs increased by 66.5% between 2021 and the second quarter of 2024. 

The researchers speculated that the surge in the western United States could be caused by fentanyl entering the drug markets in that region later than in other areas, “likely because of challenges of mixing fentanyl into the black tar heroin that was more common in the West,” they wrote.

The findings suggested that, despite overall declines in overdose deaths reported nationwide, “recent sharp increases in overdose deaths with carfentanil detected, although rare, highlight the ever-changing illegal drug supply and threaten progress in reducing overdose deaths.” 

The report authors encouraged expanding education programs for the public about the dangers of carfentanil and other IMFs, as well as harm reduction strategies, including using fentanyl test strips or drug-checking services.

No study funding information was available. There were no relevant financial relationships.

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

This transcript has been edited for clarity. 

Oh, insurance claim denials. When patient care or treatment is warranted by a specific diagnosis, I wish insurers would just reimburse it without any hassle. That’s not reality. Let’s talk about insurance claim denials, how they’re rising and harming patient care, and what we can do about it. That’s kind of complicated.

Rising Trend in Claim Denials and Financial Impact

First, denials are increasing. Experian Health surveyed provider revenue cycle leaders— that’s a fancy term for people who manage billing and insurance claims — and 75% said that denials are increasing. This is up from 42% a few years ago. Those surveyed also said that reimbursement times and errors in claims are also increasing, and changes in policy are happening more frequently. This all adds to the problem. 

Aside from being time-consuming and annoying, claim denials take a toll on hospitals and patients. One analysis, which made headlines everywhere, showed that hospitals and health systems spent nearly $20 billion in 2022 trying to repeal overturned claims. This analysis was done by Premier, a health insurance performance company.

 

Breakdown of Denial Rates and Costs

Let’s do some quick whiteboard math. Health insurance companies get about 3 billion claims per year. According to surveys, about 15% of those claims are denied, so that leaves us with 450 million denied claims. Hospitals spend, on average, $43.84 per denied claim in administrative fees trying to get them overturned.

That’s about $19.7 billion spent on claim denials. Here’s the gut punch: Around 54% of those claims are ultimately paid, so that leaves us with $10.7 billion that we definitely should have saved. 

 

Common Reasons for Denials

Let’s take a look at major causes and what’s going on. 

Insurance denial rates are all over the place. It depends on state and plan. According to one analysis, the average for in-network claim denials across some states was 4% to 5%. It was 40% in Mississippi. According to HealthCare.gov, in 2021, around 17% of in-network claims were denied. 

The most common reasons were excluded services, a lack of referral or preauthorization, or a medical treatment not being deemed necessary. Then there’s the black box of “other,” just some arbitrary reason to make a claim denial. 

Many times, these denials are done by an algorithm, not by individual people. 

What’s more, a Kaiser Family Foundation analysis found that private insurers, including Medicare Advantage plans, were more likely to deny claims than public options. 

When broken down, the problem was higher among employer-sponsored and marketplace insurance, and less so with Medicare and Medicaid. 

 

Impact on Patient Care

Many consumers don’t truly understand what their health insurance covers and what’s going to be out of pocket, and many people don’t know that they have appeal rights. They don’t know who to call for help either. 

The ACA set up Consumer Assistance Programs (CAPs), which are designed to help people navigate health insurance problems. By law, private insurers have to share data with CAPs. Yet, only 3% of people who had trouble with health insurance claims called a CAP for help.

We all know some of the downstream effects of this problem. Patients may skip or delay treatments if they can’t get insurance to cover it or it’s too expensive. When post-acute care, such as transfer to a skilled nursing facility or rehab center, isn’t covered and we’re trying to discharge patients from the hospital, hospital stays become lengthened, which means they’re more expensive, and this comes with its own set of complications.

 

How Can We Address This?

I’m genuinely curious about what you all have done to efficiently address this problem. I’m looking at this publication from the American Health Information Management Association about major reasons for denial. We’ve already talked about a lack of preauthorization or procedures not being covered, but there are also reasons such as missing or incorrect information, duplicate claims, and not filing within the appropriate time.

Also, if treatments or procedures are bundled, they can’t be filed separately. 

Preventing all of this would take a large effort. Healthcare systems would have to have a dedicated team, who would understand all the major reasons for denials, identify common patterns, and then fill everything out with accurate information, with referrals, with preauthorizations, high-specificity codes, and the correct modifiers — and do all of this within the filing deadline every time. 

You would need physicians on board, but also people from IT, finance, compliance, case management, registration, and probably a bunch of other people who are already stretched too thin. 

Perhaps our government can do more to hold insurers accountable and make sure plans, such as Medicare Advantage, are holding up their end of the public health bargain.

It’s an uphill $20 billion battle, but I’m optimistic. What about you? What’s your unfiltered take on claim denials? What more can we be doing?

Dr. Patel is a clinical instructor, Department of Pediatrics, Columbia University College of Physicians and Surgeons; pediatric hospitalist, Morgan Stanley Children’s Hospital of NewYork-Presbyterian, New York City, and Benioff Children’s Hospital, University of California, San Francisco. He reported a conflict of interest with Medumo.

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

This transcript has been edited for clarity. 

Oh, insurance claim denials. When patient care or treatment is warranted by a specific diagnosis, I wish insurers would just reimburse it without any hassle. That’s not reality. Let’s talk about insurance claim denials, how they’re rising and harming patient care, and what we can do about it. That’s kind of complicated.

Rising Trend in Claim Denials and Financial Impact

First, denials are increasing. Experian Health surveyed provider revenue cycle leaders— that’s a fancy term for people who manage billing and insurance claims — and 75% said that denials are increasing. This is up from 42% a few years ago. Those surveyed also said that reimbursement times and errors in claims are also increasing, and changes in policy are happening more frequently. This all adds to the problem. 

Aside from being time-consuming and annoying, claim denials take a toll on hospitals and patients. One analysis, which made headlines everywhere, showed that hospitals and health systems spent nearly $20 billion in 2022 trying to repeal overturned claims. This analysis was done by Premier, a health insurance performance company.

 

Breakdown of Denial Rates and Costs

Let’s do some quick whiteboard math. Health insurance companies get about 3 billion claims per year. According to surveys, about 15% of those claims are denied, so that leaves us with 450 million denied claims. Hospitals spend, on average, $43.84 per denied claim in administrative fees trying to get them overturned.

That’s about $19.7 billion spent on claim denials. Here’s the gut punch: Around 54% of those claims are ultimately paid, so that leaves us with $10.7 billion that we definitely should have saved. 

 

Common Reasons for Denials

Let’s take a look at major causes and what’s going on. 

Insurance denial rates are all over the place. It depends on state and plan. According to one analysis, the average for in-network claim denials across some states was 4% to 5%. It was 40% in Mississippi. According to HealthCare.gov, in 2021, around 17% of in-network claims were denied. 

The most common reasons were excluded services, a lack of referral or preauthorization, or a medical treatment not being deemed necessary. Then there’s the black box of “other,” just some arbitrary reason to make a claim denial. 

Many times, these denials are done by an algorithm, not by individual people. 

What’s more, a Kaiser Family Foundation analysis found that private insurers, including Medicare Advantage plans, were more likely to deny claims than public options. 

When broken down, the problem was higher among employer-sponsored and marketplace insurance, and less so with Medicare and Medicaid. 

 

Impact on Patient Care

Many consumers don’t truly understand what their health insurance covers and what’s going to be out of pocket, and many people don’t know that they have appeal rights. They don’t know who to call for help either. 

The ACA set up Consumer Assistance Programs (CAPs), which are designed to help people navigate health insurance problems. By law, private insurers have to share data with CAPs. Yet, only 3% of people who had trouble with health insurance claims called a CAP for help.

We all know some of the downstream effects of this problem. Patients may skip or delay treatments if they can’t get insurance to cover it or it’s too expensive. When post-acute care, such as transfer to a skilled nursing facility or rehab center, isn’t covered and we’re trying to discharge patients from the hospital, hospital stays become lengthened, which means they’re more expensive, and this comes with its own set of complications.

 

How Can We Address This?

I’m genuinely curious about what you all have done to efficiently address this problem. I’m looking at this publication from the American Health Information Management Association about major reasons for denial. We’ve already talked about a lack of preauthorization or procedures not being covered, but there are also reasons such as missing or incorrect information, duplicate claims, and not filing within the appropriate time.

Also, if treatments or procedures are bundled, they can’t be filed separately. 

Preventing all of this would take a large effort. Healthcare systems would have to have a dedicated team, who would understand all the major reasons for denials, identify common patterns, and then fill everything out with accurate information, with referrals, with preauthorizations, high-specificity codes, and the correct modifiers — and do all of this within the filing deadline every time. 

You would need physicians on board, but also people from IT, finance, compliance, case management, registration, and probably a bunch of other people who are already stretched too thin. 

Perhaps our government can do more to hold insurers accountable and make sure plans, such as Medicare Advantage, are holding up their end of the public health bargain.

It’s an uphill $20 billion battle, but I’m optimistic. What about you? What’s your unfiltered take on claim denials? What more can we be doing?

Dr. Patel is a clinical instructor, Department of Pediatrics, Columbia University College of Physicians and Surgeons; pediatric hospitalist, Morgan Stanley Children’s Hospital of NewYork-Presbyterian, New York City, and Benioff Children’s Hospital, University of California, San Francisco. He reported a conflict of interest with Medumo.

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

This transcript has been edited for clarity. 

Oh, insurance claim denials. When patient care or treatment is warranted by a specific diagnosis, I wish insurers would just reimburse it without any hassle. That’s not reality. Let’s talk about insurance claim denials, how they’re rising and harming patient care, and what we can do about it. That’s kind of complicated.

Rising Trend in Claim Denials and Financial Impact

First, denials are increasing. Experian Health surveyed provider revenue cycle leaders— that’s a fancy term for people who manage billing and insurance claims — and 75% said that denials are increasing. This is up from 42% a few years ago. Those surveyed also said that reimbursement times and errors in claims are also increasing, and changes in policy are happening more frequently. This all adds to the problem. 

Aside from being time-consuming and annoying, claim denials take a toll on hospitals and patients. One analysis, which made headlines everywhere, showed that hospitals and health systems spent nearly $20 billion in 2022 trying to repeal overturned claims. This analysis was done by Premier, a health insurance performance company.

 

Breakdown of Denial Rates and Costs

Let’s do some quick whiteboard math. Health insurance companies get about 3 billion claims per year. According to surveys, about 15% of those claims are denied, so that leaves us with 450 million denied claims. Hospitals spend, on average, $43.84 per denied claim in administrative fees trying to get them overturned.

That’s about $19.7 billion spent on claim denials. Here’s the gut punch: Around 54% of those claims are ultimately paid, so that leaves us with $10.7 billion that we definitely should have saved. 

 

Common Reasons for Denials

Let’s take a look at major causes and what’s going on. 

Insurance denial rates are all over the place. It depends on state and plan. According to one analysis, the average for in-network claim denials across some states was 4% to 5%. It was 40% in Mississippi. According to HealthCare.gov, in 2021, around 17% of in-network claims were denied. 

The most common reasons were excluded services, a lack of referral or preauthorization, or a medical treatment not being deemed necessary. Then there’s the black box of “other,” just some arbitrary reason to make a claim denial. 

Many times, these denials are done by an algorithm, not by individual people. 

What’s more, a Kaiser Family Foundation analysis found that private insurers, including Medicare Advantage plans, were more likely to deny claims than public options. 

When broken down, the problem was higher among employer-sponsored and marketplace insurance, and less so with Medicare and Medicaid. 

 

Impact on Patient Care

Many consumers don’t truly understand what their health insurance covers and what’s going to be out of pocket, and many people don’t know that they have appeal rights. They don’t know who to call for help either. 

The ACA set up Consumer Assistance Programs (CAPs), which are designed to help people navigate health insurance problems. By law, private insurers have to share data with CAPs. Yet, only 3% of people who had trouble with health insurance claims called a CAP for help.

We all know some of the downstream effects of this problem. Patients may skip or delay treatments if they can’t get insurance to cover it or it’s too expensive. When post-acute care, such as transfer to a skilled nursing facility or rehab center, isn’t covered and we’re trying to discharge patients from the hospital, hospital stays become lengthened, which means they’re more expensive, and this comes with its own set of complications.

 

How Can We Address This?

I’m genuinely curious about what you all have done to efficiently address this problem. I’m looking at this publication from the American Health Information Management Association about major reasons for denial. We’ve already talked about a lack of preauthorization or procedures not being covered, but there are also reasons such as missing or incorrect information, duplicate claims, and not filing within the appropriate time.

Also, if treatments or procedures are bundled, they can’t be filed separately. 

Preventing all of this would take a large effort. Healthcare systems would have to have a dedicated team, who would understand all the major reasons for denials, identify common patterns, and then fill everything out with accurate information, with referrals, with preauthorizations, high-specificity codes, and the correct modifiers — and do all of this within the filing deadline every time. 

You would need physicians on board, but also people from IT, finance, compliance, case management, registration, and probably a bunch of other people who are already stretched too thin. 

Perhaps our government can do more to hold insurers accountable and make sure plans, such as Medicare Advantage, are holding up their end of the public health bargain.

It’s an uphill $20 billion battle, but I’m optimistic. What about you? What’s your unfiltered take on claim denials? What more can we be doing?

Dr. Patel is a clinical instructor, Department of Pediatrics, Columbia University College of Physicians and Surgeons; pediatric hospitalist, Morgan Stanley Children’s Hospital of NewYork-Presbyterian, New York City, and Benioff Children’s Hospital, University of California, San Francisco. He reported a conflict of interest with Medumo.

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

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

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

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

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

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

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