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More evidence suicidal thoughts, behaviors are genetically based
“It’s really important for us to continue to study the genetic risk factors for suicidal behaviors so we can really understand the biology and develop better treatments,” study investigator Allison E. Ashley-Koch, PhD, professor in the department of medicine at Duke University Medical Center, Durham, N.C., told this news organization.
The findings were published online in JAMA Psychiatry).
SITB heritability
Suicide is a leading cause of death, particularly among individuals aged 15-29 years. Whereas the global rate of suicide has decreased by 36% in the past 20 years, the rate in the United States has increased by 35%, with the greatest rise in military veterans.
Twin studies suggest heritability for SITB is between 30% and 55%, but the molecular genetic basis of SITB remains elusive.
To address this research gap, investigators conducted a study of 633,778 U.S. military veterans from the Million Veteran Program (MVP) cohort. Of these, 71% had European ancestry, 19% had African ancestry, 8% were Hispanic, and 1% were Asian. Just under 10% of the sample was female.
Study participants donated a blood sample and agreed to have their genetic information linked with their electronic health record data.
From diagnostic codes and other sources, researchers identified 121,211 individuals with SITB. They classified participants with no documented lifetime history of suicidal ideation, suicide attempt, or suicide death as controls.
Rates of SITB differed significantly by ancestry – 25% in those with African or Hispanic ancestry, 21% in those with Asian ancestry, and 16.8% in those with European ancestry. Rates also differed by age and sex; those with SITB were younger and more likely to be female.
In addition to age and sex, covariates included “genetic principal components,” which Dr. Ashley-Koch said accounts for combining data of individuals with different ethnic/racial backgrounds.
Through meta-analysis, the investigators identified seven genome-wide, significant cross-ancestry risk loci.
To evaluate whether the findings could be replicated, researchers used the International Suicide Genetics Consortium (ISGC), a primarily civilian international consortium of roughly 550,000 individuals of mostly European ancestry.
The analysis showed the top replicated cross-ancestry risk locus was rs6557168, an intronic single-nucleotide variant (SNV) in the ESR1 gene that encodes an estrogen receptor. Previous work identified ESR1 as a causal genetic driver gene for development of posttraumatic stress disorder and depression, both of which are risk factors for SITB among veterans.
The second-strongest replicated cross-ancestry locus was rs12808482, an intronic variant in the DRD2 gene, which encodes the D2 dopamine-receptor subtype. The authors noted DRD2 is highly expressed in brain tissue and has been associated with numerous psychiatric phenotypes.
Research suggests DRD2 is associated with other risk factors for SITB, such as schizophrenia, mood disorders, and attention-deficit/hyperactivity disorder, but DRD2 could also contribute to suicide risk directly. The authors noted it is highly expressed in the prefrontal cortex, nucleus accumbens, substantia nigra, and hippocampus.
Outstanding candidate gene
The study revealed a cross-ancestry GWS association for rs10671545, a variant in DCC, which is “also an outstanding candidate gene,” the investigators write.
They note it is expressed in brain tissue, is involved in synaptic plasticity, axon guidance, and circadian entrainment, and has been associated with multiple psychiatric phenotypes.
Researchers also found what they called “intriguing” cross-ancestry GWS associations for the TRAF3 gene, which regulates type-1 interferon production. Many patients receiving interferon therapy develop major depressive disorder and suicidal ideation.
TRAF3 is also associated with antisocial behavior, substance use, and ADHD. Lithium – a standard treatment for bipolar disorder that reduces suicide risk – modulates the expression of TRAF3.
Dr. Ashley-Koch noted the replication of these loci (ESR1, DRD2, TRAF3, and DCC) was in a population of mostly White civilians. “This suggests to us that at least some of the risk for suicidal thoughts and behaviors does cross ancestry and also crosses military and civilian populations.”
It was “exciting” that all four genes the study focused on had previously been implicated in other psychiatric disorders, said Dr. Ashley-Koch. “What gave us a little more confidence, above and beyond the replication, was that these genes are somehow important for psychiatric disorders, and not any psychiatric disorders, but the ones that are also associated with a high risk of suicide behavior, such as depression, PTSD, schizophrenia, and ADHD.”
The findings will not have an immediate impact on clinical practice, said Dr. Ashley-Koch.
“We need to take the next step, which is to try to understand how these genetic factors may impact risk and what else is happening biologically to increase that risk. Then once we do that, hopefully we can develop some new treatments,” she added.
‘Valuable and noble’ research
Commenting on the study, Elspeth Cameron Ritchie, MD, chief of psychiatry at Medstar Washington Hospital Center, Washington, said this kind of genetic research is “valuable and noble.”
Researchers have long been interested in risk factors for suicide among military personnel and veterans, said Dr. Ritchie. Evidence to date suggests being a young male is a risk factor as is feeling excluded or not fitting into the unit, and drug or alcohol addiction.
Dr. Ritchie noted other psychiatric disorders, including schizophrenia, depression, and bipolar disorder, are at least partially inherited.
She noted the study’s findings should not be used to discriminate against those who might have the identified genetic loci without clearer evidence of their impact.
“If we were able to identify these genes, would we start screening everybody who joins the military to see if they have these genes, and how would that impact the ability to recruit or retain personnel?”
She agreed additional work is needed to determine if and how carrying these genes might impact clinical care.
In addition, she pointed out that behavior is influenced not only by genetic load but also by environment. “This study may show the impact of the genetic load a little bit more clearly; right now, we tend to look at environmental factors.”
The study was supported by an award from the Clinical Science Research and Development (CSR&D) service of the Veterans Health Administration’s Office of Research and Development. The work was also supported in part by the joint U.S. Department of Veterans Affairs and U.S. Department of Energy MVP CHAMPION program.
Dr. Ashley-Koch reported grants from Veterans Administration during the conduct of the study. Several other coauthors report relationships with industry, nonprofit organizations, and government agencies. The full list can be found with the original article. Dr. Ritchie reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“It’s really important for us to continue to study the genetic risk factors for suicidal behaviors so we can really understand the biology and develop better treatments,” study investigator Allison E. Ashley-Koch, PhD, professor in the department of medicine at Duke University Medical Center, Durham, N.C., told this news organization.
The findings were published online in JAMA Psychiatry).
SITB heritability
Suicide is a leading cause of death, particularly among individuals aged 15-29 years. Whereas the global rate of suicide has decreased by 36% in the past 20 years, the rate in the United States has increased by 35%, with the greatest rise in military veterans.
Twin studies suggest heritability for SITB is between 30% and 55%, but the molecular genetic basis of SITB remains elusive.
To address this research gap, investigators conducted a study of 633,778 U.S. military veterans from the Million Veteran Program (MVP) cohort. Of these, 71% had European ancestry, 19% had African ancestry, 8% were Hispanic, and 1% were Asian. Just under 10% of the sample was female.
Study participants donated a blood sample and agreed to have their genetic information linked with their electronic health record data.
From diagnostic codes and other sources, researchers identified 121,211 individuals with SITB. They classified participants with no documented lifetime history of suicidal ideation, suicide attempt, or suicide death as controls.
Rates of SITB differed significantly by ancestry – 25% in those with African or Hispanic ancestry, 21% in those with Asian ancestry, and 16.8% in those with European ancestry. Rates also differed by age and sex; those with SITB were younger and more likely to be female.
In addition to age and sex, covariates included “genetic principal components,” which Dr. Ashley-Koch said accounts for combining data of individuals with different ethnic/racial backgrounds.
Through meta-analysis, the investigators identified seven genome-wide, significant cross-ancestry risk loci.
To evaluate whether the findings could be replicated, researchers used the International Suicide Genetics Consortium (ISGC), a primarily civilian international consortium of roughly 550,000 individuals of mostly European ancestry.
The analysis showed the top replicated cross-ancestry risk locus was rs6557168, an intronic single-nucleotide variant (SNV) in the ESR1 gene that encodes an estrogen receptor. Previous work identified ESR1 as a causal genetic driver gene for development of posttraumatic stress disorder and depression, both of which are risk factors for SITB among veterans.
The second-strongest replicated cross-ancestry locus was rs12808482, an intronic variant in the DRD2 gene, which encodes the D2 dopamine-receptor subtype. The authors noted DRD2 is highly expressed in brain tissue and has been associated with numerous psychiatric phenotypes.
Research suggests DRD2 is associated with other risk factors for SITB, such as schizophrenia, mood disorders, and attention-deficit/hyperactivity disorder, but DRD2 could also contribute to suicide risk directly. The authors noted it is highly expressed in the prefrontal cortex, nucleus accumbens, substantia nigra, and hippocampus.
Outstanding candidate gene
The study revealed a cross-ancestry GWS association for rs10671545, a variant in DCC, which is “also an outstanding candidate gene,” the investigators write.
They note it is expressed in brain tissue, is involved in synaptic plasticity, axon guidance, and circadian entrainment, and has been associated with multiple psychiatric phenotypes.
Researchers also found what they called “intriguing” cross-ancestry GWS associations for the TRAF3 gene, which regulates type-1 interferon production. Many patients receiving interferon therapy develop major depressive disorder and suicidal ideation.
TRAF3 is also associated with antisocial behavior, substance use, and ADHD. Lithium – a standard treatment for bipolar disorder that reduces suicide risk – modulates the expression of TRAF3.
Dr. Ashley-Koch noted the replication of these loci (ESR1, DRD2, TRAF3, and DCC) was in a population of mostly White civilians. “This suggests to us that at least some of the risk for suicidal thoughts and behaviors does cross ancestry and also crosses military and civilian populations.”
It was “exciting” that all four genes the study focused on had previously been implicated in other psychiatric disorders, said Dr. Ashley-Koch. “What gave us a little more confidence, above and beyond the replication, was that these genes are somehow important for psychiatric disorders, and not any psychiatric disorders, but the ones that are also associated with a high risk of suicide behavior, such as depression, PTSD, schizophrenia, and ADHD.”
The findings will not have an immediate impact on clinical practice, said Dr. Ashley-Koch.
“We need to take the next step, which is to try to understand how these genetic factors may impact risk and what else is happening biologically to increase that risk. Then once we do that, hopefully we can develop some new treatments,” she added.
‘Valuable and noble’ research
Commenting on the study, Elspeth Cameron Ritchie, MD, chief of psychiatry at Medstar Washington Hospital Center, Washington, said this kind of genetic research is “valuable and noble.”
Researchers have long been interested in risk factors for suicide among military personnel and veterans, said Dr. Ritchie. Evidence to date suggests being a young male is a risk factor as is feeling excluded or not fitting into the unit, and drug or alcohol addiction.
Dr. Ritchie noted other psychiatric disorders, including schizophrenia, depression, and bipolar disorder, are at least partially inherited.
She noted the study’s findings should not be used to discriminate against those who might have the identified genetic loci without clearer evidence of their impact.
“If we were able to identify these genes, would we start screening everybody who joins the military to see if they have these genes, and how would that impact the ability to recruit or retain personnel?”
She agreed additional work is needed to determine if and how carrying these genes might impact clinical care.
In addition, she pointed out that behavior is influenced not only by genetic load but also by environment. “This study may show the impact of the genetic load a little bit more clearly; right now, we tend to look at environmental factors.”
The study was supported by an award from the Clinical Science Research and Development (CSR&D) service of the Veterans Health Administration’s Office of Research and Development. The work was also supported in part by the joint U.S. Department of Veterans Affairs and U.S. Department of Energy MVP CHAMPION program.
Dr. Ashley-Koch reported grants from Veterans Administration during the conduct of the study. Several other coauthors report relationships with industry, nonprofit organizations, and government agencies. The full list can be found with the original article. Dr. Ritchie reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“It’s really important for us to continue to study the genetic risk factors for suicidal behaviors so we can really understand the biology and develop better treatments,” study investigator Allison E. Ashley-Koch, PhD, professor in the department of medicine at Duke University Medical Center, Durham, N.C., told this news organization.
The findings were published online in JAMA Psychiatry).
SITB heritability
Suicide is a leading cause of death, particularly among individuals aged 15-29 years. Whereas the global rate of suicide has decreased by 36% in the past 20 years, the rate in the United States has increased by 35%, with the greatest rise in military veterans.
Twin studies suggest heritability for SITB is between 30% and 55%, but the molecular genetic basis of SITB remains elusive.
To address this research gap, investigators conducted a study of 633,778 U.S. military veterans from the Million Veteran Program (MVP) cohort. Of these, 71% had European ancestry, 19% had African ancestry, 8% were Hispanic, and 1% were Asian. Just under 10% of the sample was female.
Study participants donated a blood sample and agreed to have their genetic information linked with their electronic health record data.
From diagnostic codes and other sources, researchers identified 121,211 individuals with SITB. They classified participants with no documented lifetime history of suicidal ideation, suicide attempt, or suicide death as controls.
Rates of SITB differed significantly by ancestry – 25% in those with African or Hispanic ancestry, 21% in those with Asian ancestry, and 16.8% in those with European ancestry. Rates also differed by age and sex; those with SITB were younger and more likely to be female.
In addition to age and sex, covariates included “genetic principal components,” which Dr. Ashley-Koch said accounts for combining data of individuals with different ethnic/racial backgrounds.
Through meta-analysis, the investigators identified seven genome-wide, significant cross-ancestry risk loci.
To evaluate whether the findings could be replicated, researchers used the International Suicide Genetics Consortium (ISGC), a primarily civilian international consortium of roughly 550,000 individuals of mostly European ancestry.
The analysis showed the top replicated cross-ancestry risk locus was rs6557168, an intronic single-nucleotide variant (SNV) in the ESR1 gene that encodes an estrogen receptor. Previous work identified ESR1 as a causal genetic driver gene for development of posttraumatic stress disorder and depression, both of which are risk factors for SITB among veterans.
The second-strongest replicated cross-ancestry locus was rs12808482, an intronic variant in the DRD2 gene, which encodes the D2 dopamine-receptor subtype. The authors noted DRD2 is highly expressed in brain tissue and has been associated with numerous psychiatric phenotypes.
Research suggests DRD2 is associated with other risk factors for SITB, such as schizophrenia, mood disorders, and attention-deficit/hyperactivity disorder, but DRD2 could also contribute to suicide risk directly. The authors noted it is highly expressed in the prefrontal cortex, nucleus accumbens, substantia nigra, and hippocampus.
Outstanding candidate gene
The study revealed a cross-ancestry GWS association for rs10671545, a variant in DCC, which is “also an outstanding candidate gene,” the investigators write.
They note it is expressed in brain tissue, is involved in synaptic plasticity, axon guidance, and circadian entrainment, and has been associated with multiple psychiatric phenotypes.
Researchers also found what they called “intriguing” cross-ancestry GWS associations for the TRAF3 gene, which regulates type-1 interferon production. Many patients receiving interferon therapy develop major depressive disorder and suicidal ideation.
TRAF3 is also associated with antisocial behavior, substance use, and ADHD. Lithium – a standard treatment for bipolar disorder that reduces suicide risk – modulates the expression of TRAF3.
Dr. Ashley-Koch noted the replication of these loci (ESR1, DRD2, TRAF3, and DCC) was in a population of mostly White civilians. “This suggests to us that at least some of the risk for suicidal thoughts and behaviors does cross ancestry and also crosses military and civilian populations.”
It was “exciting” that all four genes the study focused on had previously been implicated in other psychiatric disorders, said Dr. Ashley-Koch. “What gave us a little more confidence, above and beyond the replication, was that these genes are somehow important for psychiatric disorders, and not any psychiatric disorders, but the ones that are also associated with a high risk of suicide behavior, such as depression, PTSD, schizophrenia, and ADHD.”
The findings will not have an immediate impact on clinical practice, said Dr. Ashley-Koch.
“We need to take the next step, which is to try to understand how these genetic factors may impact risk and what else is happening biologically to increase that risk. Then once we do that, hopefully we can develop some new treatments,” she added.
‘Valuable and noble’ research
Commenting on the study, Elspeth Cameron Ritchie, MD, chief of psychiatry at Medstar Washington Hospital Center, Washington, said this kind of genetic research is “valuable and noble.”
Researchers have long been interested in risk factors for suicide among military personnel and veterans, said Dr. Ritchie. Evidence to date suggests being a young male is a risk factor as is feeling excluded or not fitting into the unit, and drug or alcohol addiction.
Dr. Ritchie noted other psychiatric disorders, including schizophrenia, depression, and bipolar disorder, are at least partially inherited.
She noted the study’s findings should not be used to discriminate against those who might have the identified genetic loci without clearer evidence of their impact.
“If we were able to identify these genes, would we start screening everybody who joins the military to see if they have these genes, and how would that impact the ability to recruit or retain personnel?”
She agreed additional work is needed to determine if and how carrying these genes might impact clinical care.
In addition, she pointed out that behavior is influenced not only by genetic load but also by environment. “This study may show the impact of the genetic load a little bit more clearly; right now, we tend to look at environmental factors.”
The study was supported by an award from the Clinical Science Research and Development (CSR&D) service of the Veterans Health Administration’s Office of Research and Development. The work was also supported in part by the joint U.S. Department of Veterans Affairs and U.S. Department of Energy MVP CHAMPION program.
Dr. Ashley-Koch reported grants from Veterans Administration during the conduct of the study. Several other coauthors report relationships with industry, nonprofit organizations, and government agencies. The full list can be found with the original article. Dr. Ritchie reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY
Is the FDA serotonin syndrome warning unnecessary?
Results from a study that included more than 1,100 patients who were prescribed linezolid, about 20% of whom were also taking antidepressants, showed that serotonin syndrome occurred in fewer than 0.5% of participants – and that the percentage was actually lower among those who took antidepressants, compared with those who did not.
A comparison of participants who took antidepressants to propensity-matched patients who did not take antidepressants showed similar rates of altered mental status, hospitalization, and death between the two groups.
“In this cohort study of older patients who were prescribed linezolid, serotonin syndrome occurred rarely [and] concurrent antidepressants did not significantly increase the risk of serotonin syndrome,” Anthony Bai, MD, division of infectious diseases, department of medicine, Queen’s University, Kingston, Ont., and colleagues write.
“These findings suggested that linezolid is likely safe for patients receiving antidepressants. Nevertheless, prescribers should remain vigilant for this potential drug interaction,” they warn.
The findings were published online in JAMA Network Open.
Scarce data
Linezolid, a synthetic oxazolidinone antibiotic active against resistant gram-positive bacteria, has bioavailability of 100%, “making it ideal as first-line or step-down oral antibiotic therapy for bacteremia and pneumonia as well as skin and soft tissue infections,” the researchers write.
However, they note its use has been “limited because of concerns of drug interactions,” since it can reversibly inhibit monoamine oxidase (MAO).
Thus, “coadministration with antidepressants, such as nonselective MAO inhibitors, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and bupropion, may precipitate serotonin syndrome,” they write.
The investigators note that many patients who were taking antidepressants and who also needed linezolid for an infection “could not receive it because of this relative contraindication.” They add that data on the risk of serotonin syndrome associated with linezolid are “scarce” and are based largely on case reports or case series from passive surveillance.
Although a previous review of linezolid trials found “no conclusive evidence” that it increased risk for serotonin syndrome in patients taking serotonergic medication, data on patients outside of trials “are lacking.” In addition, an observational study suggested that an increased risk had a small sample size that “likely led to imprecise estimates with a wide CI and inconclusive results,” the researchers write.
Therefore, they sought to fill the knowledge gap by retrospectively analyzing data drawn from the ICES database, an independent nonprofit research institute funded by the Ontario Ministry of Health. This was done in order to “estimate the incidence of serotonin syndrome and how this risk changes because of concomitant antidepressant use in patients receiving linezolid treatment,” they write.
The study included a convenience sample of Ontario-based adults (n = 1,134, 52.5% men) who were dispensed oral linezolid 600 mg twice daily between Oct. 1, 2014, and Jan. 1, 2021. All patients were followed for 30 days.
Of these participants, 19% were also taking antidepressants. Close to half (47.9%) were taking an SSRI, 16.7% were taking an SNRI, 7% were taking a tricyclic antidepressant, and 3.3% were taking a norepinephrine and dopamine reuptake inhibitor.
Patients were divided into groups on the basis of age: 66-69 years (19.8%), 70-79 years (41.7%), and 80 years or older (38.4%).
Reassuring findings
Serotonin syndrome occurred in fewer than six patients (< .5%), although the exact numbers were not reported, owing to patient privacy concerns. However, on the basis of fewer than six events, the investigators calculated the risk difference for serotonin syndrome as ranging from −0.5% to 2.3%.
Fewer patients who were taking antidepressants experienced serotonin syndrome, compared with those who were not taking antidepressants.
The investigators estimated a propensity score for antidepressant use that incorporated several patient baseline characteristics, including age, sex, rural home address, Charlson Comorbidity Index, estimated glomerular filtration rate, history of substance use disorder, and days of use of linezolid and other serotonergic medications. They then matched patients who were not taking antidepressants with those who were taking antidepressants (n = 166 each).
The adjusted risk difference for serotonin syndrome was lower in the antidepressant group than in the no-antidepressant group (−1.2%; 95% confidence interval, −2.9% to 0.5%).
“Within this 95% CI, the worst-case scenario would be a 0.5% increase in the risk of serotonin syndrome due to antidepressants, which is equivalent to a number needed to harm of 200,” the researchers write.
For secondary outcomes, they found “similar rates” of altered mental status or confusion, hospitalization, and death within 30 days between the two propensity score–matched groups.
The investigators note that their findings have “limitations, due to the nature of retrospective observational studies.” Moreover, these types of studies are “not efficient because they often focus on a particular adverse event.”
Future research should move beyond observational studies to phase 4 studies, which would “prospectively monitor for all types of adverse events,” they write.
Still, “while waiting for higher-quality evidence, our study adds to the existing evidence for the safety of linezolid even in the context of concomitant antidepressants,” the researchers note.
“Based on the existing evidence, clinicians should be reassured that it appears safe to prescribe oral linezolid to patients taking antidepressants, especially if there are limited antibiotic options or alternative antibiotic options would be inferior,” they add.
‘Consequential relevance’
Commenting on the study, Ipsit Vahia, MD, associate chief of geriatric psychiatry and director of digital psychiatry translation at McLean Hospital, Boston, noted that although studies of drug interactions across age groups “may not accurately reflect the rates of risk for older adults,” the current study focused on linezolid use among older patients.
“One may expect higher rates of serotonin syndrome in older adults, who generally tend to be more sensitive to adverse reactions,” said Dr. Vahia, who is also director of the Technology and Aging Lab at McLean and was not involved with the current research.
“However, the study finds the risk to be low with a number needed to harm of 200,” Dr. Vahia said.
“This retrospective epidemiologic study does not shed light on why this number may be lower than expected, but it has consequential relevance in clinical practice for the management of severe infections among older adults using antidepressants,” he added.
The study was funded by a Queen’s University Research Initiation Grant. Dr. Bai and three of the four other investigators report no relevant financial relationships. Coinvestigator Mark Loeb, MD, reports having received personal fees from the Paladin Labs Advisory Committee, the International Centre for Professional Development in Health and Medicine Advisory Committee, and the Sunovion Advisory Committee outside the submitted work. Dr. Vahia serves as a consultant for Otsuka, has a research collaboration with Emerald Innovations, and receives honorarium as editor for The American Journal of Geriatric Psychiatry.
A version of this article first appeared on Medscape.com.
Results from a study that included more than 1,100 patients who were prescribed linezolid, about 20% of whom were also taking antidepressants, showed that serotonin syndrome occurred in fewer than 0.5% of participants – and that the percentage was actually lower among those who took antidepressants, compared with those who did not.
A comparison of participants who took antidepressants to propensity-matched patients who did not take antidepressants showed similar rates of altered mental status, hospitalization, and death between the two groups.
“In this cohort study of older patients who were prescribed linezolid, serotonin syndrome occurred rarely [and] concurrent antidepressants did not significantly increase the risk of serotonin syndrome,” Anthony Bai, MD, division of infectious diseases, department of medicine, Queen’s University, Kingston, Ont., and colleagues write.
“These findings suggested that linezolid is likely safe for patients receiving antidepressants. Nevertheless, prescribers should remain vigilant for this potential drug interaction,” they warn.
The findings were published online in JAMA Network Open.
Scarce data
Linezolid, a synthetic oxazolidinone antibiotic active against resistant gram-positive bacteria, has bioavailability of 100%, “making it ideal as first-line or step-down oral antibiotic therapy for bacteremia and pneumonia as well as skin and soft tissue infections,” the researchers write.
However, they note its use has been “limited because of concerns of drug interactions,” since it can reversibly inhibit monoamine oxidase (MAO).
Thus, “coadministration with antidepressants, such as nonselective MAO inhibitors, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and bupropion, may precipitate serotonin syndrome,” they write.
The investigators note that many patients who were taking antidepressants and who also needed linezolid for an infection “could not receive it because of this relative contraindication.” They add that data on the risk of serotonin syndrome associated with linezolid are “scarce” and are based largely on case reports or case series from passive surveillance.
Although a previous review of linezolid trials found “no conclusive evidence” that it increased risk for serotonin syndrome in patients taking serotonergic medication, data on patients outside of trials “are lacking.” In addition, an observational study suggested that an increased risk had a small sample size that “likely led to imprecise estimates with a wide CI and inconclusive results,” the researchers write.
Therefore, they sought to fill the knowledge gap by retrospectively analyzing data drawn from the ICES database, an independent nonprofit research institute funded by the Ontario Ministry of Health. This was done in order to “estimate the incidence of serotonin syndrome and how this risk changes because of concomitant antidepressant use in patients receiving linezolid treatment,” they write.
The study included a convenience sample of Ontario-based adults (n = 1,134, 52.5% men) who were dispensed oral linezolid 600 mg twice daily between Oct. 1, 2014, and Jan. 1, 2021. All patients were followed for 30 days.
Of these participants, 19% were also taking antidepressants. Close to half (47.9%) were taking an SSRI, 16.7% were taking an SNRI, 7% were taking a tricyclic antidepressant, and 3.3% were taking a norepinephrine and dopamine reuptake inhibitor.
Patients were divided into groups on the basis of age: 66-69 years (19.8%), 70-79 years (41.7%), and 80 years or older (38.4%).
Reassuring findings
Serotonin syndrome occurred in fewer than six patients (< .5%), although the exact numbers were not reported, owing to patient privacy concerns. However, on the basis of fewer than six events, the investigators calculated the risk difference for serotonin syndrome as ranging from −0.5% to 2.3%.
Fewer patients who were taking antidepressants experienced serotonin syndrome, compared with those who were not taking antidepressants.
The investigators estimated a propensity score for antidepressant use that incorporated several patient baseline characteristics, including age, sex, rural home address, Charlson Comorbidity Index, estimated glomerular filtration rate, history of substance use disorder, and days of use of linezolid and other serotonergic medications. They then matched patients who were not taking antidepressants with those who were taking antidepressants (n = 166 each).
The adjusted risk difference for serotonin syndrome was lower in the antidepressant group than in the no-antidepressant group (−1.2%; 95% confidence interval, −2.9% to 0.5%).
“Within this 95% CI, the worst-case scenario would be a 0.5% increase in the risk of serotonin syndrome due to antidepressants, which is equivalent to a number needed to harm of 200,” the researchers write.
For secondary outcomes, they found “similar rates” of altered mental status or confusion, hospitalization, and death within 30 days between the two propensity score–matched groups.
The investigators note that their findings have “limitations, due to the nature of retrospective observational studies.” Moreover, these types of studies are “not efficient because they often focus on a particular adverse event.”
Future research should move beyond observational studies to phase 4 studies, which would “prospectively monitor for all types of adverse events,” they write.
Still, “while waiting for higher-quality evidence, our study adds to the existing evidence for the safety of linezolid even in the context of concomitant antidepressants,” the researchers note.
“Based on the existing evidence, clinicians should be reassured that it appears safe to prescribe oral linezolid to patients taking antidepressants, especially if there are limited antibiotic options or alternative antibiotic options would be inferior,” they add.
‘Consequential relevance’
Commenting on the study, Ipsit Vahia, MD, associate chief of geriatric psychiatry and director of digital psychiatry translation at McLean Hospital, Boston, noted that although studies of drug interactions across age groups “may not accurately reflect the rates of risk for older adults,” the current study focused on linezolid use among older patients.
“One may expect higher rates of serotonin syndrome in older adults, who generally tend to be more sensitive to adverse reactions,” said Dr. Vahia, who is also director of the Technology and Aging Lab at McLean and was not involved with the current research.
“However, the study finds the risk to be low with a number needed to harm of 200,” Dr. Vahia said.
“This retrospective epidemiologic study does not shed light on why this number may be lower than expected, but it has consequential relevance in clinical practice for the management of severe infections among older adults using antidepressants,” he added.
The study was funded by a Queen’s University Research Initiation Grant. Dr. Bai and three of the four other investigators report no relevant financial relationships. Coinvestigator Mark Loeb, MD, reports having received personal fees from the Paladin Labs Advisory Committee, the International Centre for Professional Development in Health and Medicine Advisory Committee, and the Sunovion Advisory Committee outside the submitted work. Dr. Vahia serves as a consultant for Otsuka, has a research collaboration with Emerald Innovations, and receives honorarium as editor for The American Journal of Geriatric Psychiatry.
A version of this article first appeared on Medscape.com.
Results from a study that included more than 1,100 patients who were prescribed linezolid, about 20% of whom were also taking antidepressants, showed that serotonin syndrome occurred in fewer than 0.5% of participants – and that the percentage was actually lower among those who took antidepressants, compared with those who did not.
A comparison of participants who took antidepressants to propensity-matched patients who did not take antidepressants showed similar rates of altered mental status, hospitalization, and death between the two groups.
“In this cohort study of older patients who were prescribed linezolid, serotonin syndrome occurred rarely [and] concurrent antidepressants did not significantly increase the risk of serotonin syndrome,” Anthony Bai, MD, division of infectious diseases, department of medicine, Queen’s University, Kingston, Ont., and colleagues write.
“These findings suggested that linezolid is likely safe for patients receiving antidepressants. Nevertheless, prescribers should remain vigilant for this potential drug interaction,” they warn.
The findings were published online in JAMA Network Open.
Scarce data
Linezolid, a synthetic oxazolidinone antibiotic active against resistant gram-positive bacteria, has bioavailability of 100%, “making it ideal as first-line or step-down oral antibiotic therapy for bacteremia and pneumonia as well as skin and soft tissue infections,” the researchers write.
However, they note its use has been “limited because of concerns of drug interactions,” since it can reversibly inhibit monoamine oxidase (MAO).
Thus, “coadministration with antidepressants, such as nonselective MAO inhibitors, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and bupropion, may precipitate serotonin syndrome,” they write.
The investigators note that many patients who were taking antidepressants and who also needed linezolid for an infection “could not receive it because of this relative contraindication.” They add that data on the risk of serotonin syndrome associated with linezolid are “scarce” and are based largely on case reports or case series from passive surveillance.
Although a previous review of linezolid trials found “no conclusive evidence” that it increased risk for serotonin syndrome in patients taking serotonergic medication, data on patients outside of trials “are lacking.” In addition, an observational study suggested that an increased risk had a small sample size that “likely led to imprecise estimates with a wide CI and inconclusive results,” the researchers write.
Therefore, they sought to fill the knowledge gap by retrospectively analyzing data drawn from the ICES database, an independent nonprofit research institute funded by the Ontario Ministry of Health. This was done in order to “estimate the incidence of serotonin syndrome and how this risk changes because of concomitant antidepressant use in patients receiving linezolid treatment,” they write.
The study included a convenience sample of Ontario-based adults (n = 1,134, 52.5% men) who were dispensed oral linezolid 600 mg twice daily between Oct. 1, 2014, and Jan. 1, 2021. All patients were followed for 30 days.
Of these participants, 19% were also taking antidepressants. Close to half (47.9%) were taking an SSRI, 16.7% were taking an SNRI, 7% were taking a tricyclic antidepressant, and 3.3% were taking a norepinephrine and dopamine reuptake inhibitor.
Patients were divided into groups on the basis of age: 66-69 years (19.8%), 70-79 years (41.7%), and 80 years or older (38.4%).
Reassuring findings
Serotonin syndrome occurred in fewer than six patients (< .5%), although the exact numbers were not reported, owing to patient privacy concerns. However, on the basis of fewer than six events, the investigators calculated the risk difference for serotonin syndrome as ranging from −0.5% to 2.3%.
Fewer patients who were taking antidepressants experienced serotonin syndrome, compared with those who were not taking antidepressants.
The investigators estimated a propensity score for antidepressant use that incorporated several patient baseline characteristics, including age, sex, rural home address, Charlson Comorbidity Index, estimated glomerular filtration rate, history of substance use disorder, and days of use of linezolid and other serotonergic medications. They then matched patients who were not taking antidepressants with those who were taking antidepressants (n = 166 each).
The adjusted risk difference for serotonin syndrome was lower in the antidepressant group than in the no-antidepressant group (−1.2%; 95% confidence interval, −2.9% to 0.5%).
“Within this 95% CI, the worst-case scenario would be a 0.5% increase in the risk of serotonin syndrome due to antidepressants, which is equivalent to a number needed to harm of 200,” the researchers write.
For secondary outcomes, they found “similar rates” of altered mental status or confusion, hospitalization, and death within 30 days between the two propensity score–matched groups.
The investigators note that their findings have “limitations, due to the nature of retrospective observational studies.” Moreover, these types of studies are “not efficient because they often focus on a particular adverse event.”
Future research should move beyond observational studies to phase 4 studies, which would “prospectively monitor for all types of adverse events,” they write.
Still, “while waiting for higher-quality evidence, our study adds to the existing evidence for the safety of linezolid even in the context of concomitant antidepressants,” the researchers note.
“Based on the existing evidence, clinicians should be reassured that it appears safe to prescribe oral linezolid to patients taking antidepressants, especially if there are limited antibiotic options or alternative antibiotic options would be inferior,” they add.
‘Consequential relevance’
Commenting on the study, Ipsit Vahia, MD, associate chief of geriatric psychiatry and director of digital psychiatry translation at McLean Hospital, Boston, noted that although studies of drug interactions across age groups “may not accurately reflect the rates of risk for older adults,” the current study focused on linezolid use among older patients.
“One may expect higher rates of serotonin syndrome in older adults, who generally tend to be more sensitive to adverse reactions,” said Dr. Vahia, who is also director of the Technology and Aging Lab at McLean and was not involved with the current research.
“However, the study finds the risk to be low with a number needed to harm of 200,” Dr. Vahia said.
“This retrospective epidemiologic study does not shed light on why this number may be lower than expected, but it has consequential relevance in clinical practice for the management of severe infections among older adults using antidepressants,” he added.
The study was funded by a Queen’s University Research Initiation Grant. Dr. Bai and three of the four other investigators report no relevant financial relationships. Coinvestigator Mark Loeb, MD, reports having received personal fees from the Paladin Labs Advisory Committee, the International Centre for Professional Development in Health and Medicine Advisory Committee, and the Sunovion Advisory Committee outside the submitted work. Dr. Vahia serves as a consultant for Otsuka, has a research collaboration with Emerald Innovations, and receives honorarium as editor for The American Journal of Geriatric Psychiatry.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
FDA approves second antiamyloid for Alzheimer’s disease
Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.
Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.
“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.
“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.
Eisai has reported that lecanemab will cost $26,500 a year.
Modest benefit, adverse events
The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”
The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.
The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.
After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).
While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.
Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.
In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.
“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
Alzheimer’s Association reaction
Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.
In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.
“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.
“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.
After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”
Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”
“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
Critical issues
Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”
He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.
“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.
“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.
“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.
“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.
Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.
A version of this article first appeared on Medscape.com.
This article was updated 1/9/23.
Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.
Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.
“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.
“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.
Eisai has reported that lecanemab will cost $26,500 a year.
Modest benefit, adverse events
The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”
The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.
The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.
After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).
While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.
Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.
In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.
“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
Alzheimer’s Association reaction
Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.
In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.
“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.
“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.
After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”
Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”
“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
Critical issues
Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”
He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.
“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.
“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.
“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.
“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.
Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.
A version of this article first appeared on Medscape.com.
This article was updated 1/9/23.
Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.
Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.
“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.
“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.
Eisai has reported that lecanemab will cost $26,500 a year.
Modest benefit, adverse events
The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”
The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.
The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.
After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).
While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.
Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.
In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.
“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
Alzheimer’s Association reaction
Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.
In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.
“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.
“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.
After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”
Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”
“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
Critical issues
Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”
He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.
“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.
“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.
“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.
“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.
Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.
A version of this article first appeared on Medscape.com.
This article was updated 1/9/23.
‘Affect discrepancies’ may underlie negative symptoms in schizophrenia
Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.
Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.
In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.
The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.
Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.
Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.
The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.
However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.
The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.
Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.
Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.
In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.
The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.
Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.
Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.
The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.
However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.
The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.
Anhedonia is common in schizophrenia patients, but treatments have not been especially successful, possibly because of a lack of understanding the mechanisms behind anhedonia in these patients, Sydney H. James, a PhD candidate at the University of Georgia, Athens, and colleagues wrote.
Although many schizophrenia (SZ) patients exhibit anhedonia on diagnosis in a clinical interview setting, other recent research shows comparable response to pleasant stimuli between schizophrenic patients and healthy controls. The researchers proposed that anhedonia “reflects abnormalities in the valuation of desired affective states in individuals with SZ,” with differences between actual and ideal affect.
In a study published in the Journal of Psychiatric Research, the researchers identified 32 outpatients with schizophrenia and 29 healthy controls. The SZ participants were recruited from community outpatient mental health services in Georgia. All participants completed Structured Clinical Interview for DSM-5 Disorders and the SCID-5 Personality Disorders. Participants then completed the Affect Valuation Index and measures of negative symptom severity. Negative symptom severity was measured using the Negative Symptom Inventory-Self-Report, an 11-item questionnaire assessing three specific experiential and behavioral components (anhedonia, avolition, and asociality) over the past week.
The average age of the SZ patients and controls was approximately 40 years, and 10 SZ patients and 5 controls were male.
Overall, the researchers found a significant main effect of group, a significant main effect of arousal, and a significant group X arousal interaction for positive affect discrepancy scores. For negative affect discrepancy scores, they found a significant main effect on group, nonsignificant main effect of arousal, and significant group X arousal interaction.
Individuals with SZ showed greater positive and negative emotion discrepancy scores, compared with controls, in contrast to the researchers’ hypothesis. “Those diagnosed with SZ were more likely to want to feel less negative than they actually did,” they wrote. The negative affect discrepancy scores were positively associated with negative symptoms. The discrepancies between actual and ideal affect may be impacted by social interactions and the perceived expectations of others for levels of negative affect.
The study findings were limited by the small sample size and inability to test the relationship between ideal and actual affect as related to low-pleasure beliefs, which merits further study, the researchers noted. Other limitations include the focus on an outpatient population with mild to moderate SZ, and the use of a trait format to measure affect rather than experiential emotion knowledge.
However, the results have practical implications for treatment and suggest that, “given the positive associations between negative symptom and affect discrepancy scores, psychosocial treatments could target expectations for future positive and negative emotional experience,” and ecological momentary assessment could be used to track affect through a period of treatment and prompt conversations between SZ patients and therapists about discrepancies, they concluded.
The study participants were compensated by the National Institute of Mental Health through a grant to a corresponding author. Ms. James had no financial conflicts to disclose.
FROM THE JOURNAL OF PSYCHIATRIC RESEARCH
IV ketamine a promising option for resistant depression in older adults
Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).
“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.
Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”
The findings were published online in the American Journal of Geriatric Psychiatry.
Lack of data in seniors
Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.
“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.
She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”
Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).
Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.
Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.
They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.
At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
Larger plans
Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).
At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.
After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.
Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.
Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.
“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.
“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
Multiple mechanisms
In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.
Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.
“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.
“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.
He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”
Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.
A version of this article first appeared on Medscape.com.
Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).
“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.
Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”
The findings were published online in the American Journal of Geriatric Psychiatry.
Lack of data in seniors
Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.
“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.
She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”
Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).
Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.
Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.
They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.
At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
Larger plans
Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).
At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.
After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.
Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.
Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.
“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.
“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
Multiple mechanisms
In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.
Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.
“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.
“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.
He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”
Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.
A version of this article first appeared on Medscape.com.
Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).
“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.
Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”
The findings were published online in the American Journal of Geriatric Psychiatry.
Lack of data in seniors
Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.
“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.
She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”
Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).
Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.
Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.
They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.
At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
Larger plans
Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).
At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.
After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.
Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.
Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.
“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.
“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
Multiple mechanisms
In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.
Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.
“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.
“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.
He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”
Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
Treatment-resistant depression ups risk for comorbidities, death
In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.
Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.
In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.
“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.
“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.
The findings were published online in JAMA Psychiatry.
More anxiety, sleep disorders, substance use
Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.
Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.
Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.
Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.
This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).
Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.
The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
Not generalizable?
Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).
Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.
“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.
Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.
“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.
“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
Quality over quantity
In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”
Dr. Zisook has independently researched TRD but was not involved with the current study.
He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”
However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.
“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.
Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.
“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.
The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.
A version of this article first appeared on Medscape.com.
In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.
Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.
In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.
“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.
“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.
The findings were published online in JAMA Psychiatry.
More anxiety, sleep disorders, substance use
Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.
Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.
Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.
Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.
This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).
Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.
The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
Not generalizable?
Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).
Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.
“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.
Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.
“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.
“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
Quality over quantity
In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”
Dr. Zisook has independently researched TRD but was not involved with the current study.
He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”
However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.
“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.
Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.
“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.
The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.
A version of this article first appeared on Medscape.com.
In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.
Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.
In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.
“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.
“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.
The findings were published online in JAMA Psychiatry.
More anxiety, sleep disorders, substance use
Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.
Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.
Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.
Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.
This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).
Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.
The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
Not generalizable?
Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).
Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.
“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.
Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.
“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.
“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
Quality over quantity
In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”
Dr. Zisook has independently researched TRD but was not involved with the current study.
He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”
However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.
“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.
Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.
“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.
The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.
A version of this article first appeared on Medscape.com.
FROM PSYCHIATRY
Physical activity eases depressive symptoms in young people
Intervening with physical activity appears to mitigate depressive symptoms in children and adolescents, a systematic review and meta-analysis of almost 2,500 participants found. Greater reductions were observed for children older than 13 years and those having a diagnosis of mental illness and/or depression versus other conditions, according to Hong Kong researchers reporting in JAMA Pediatrics.
“There is an urgent need to explore novel treatment approaches that can be safely, feasibly, and widely implemented in the daily routine of depressed children and adolescents,” said study coauthor Parco M. Siu, PhD, exercise physiologist and associate professor in the school of public health at the University of Hong Kong, in an interview. “Given the observed association with significant reductions in symptoms, clinical practice guidelines should consider the role of physical activity for improving the mental health of young populations.”
Dr. Siu further noted that while current guidelines suggest psychotherapy and/or pharmacotherapy for children with this common mood disorder, adherence to these can be problematic, and surveys show that nearly 80% do not receive appropriate disorder-specific medical care.
The analysis
Dr. Siu’s team drew on 21 international studies, including 17 randomized controlled trials, published from 1987 to 2021 and comprising 2,444 young participants, mean age 14, 53% girls. Eligible studies compared the effect of exercise on depression versus a control condition.
In 12 studies, participants had a somatic or psychiatric disorder such as obesity, diabetes, depression, and attention-deficit/hyperactivity disorder. The mean duration of the prescribed physical activity program was 22 weeks (6-144 weeks), while the frequency of weekly sessions ranged from 2 to 5 days, with 3 days per week most common and mean duration of 50 minutes (30-120 minutes). Regimens ranged from aerobic exercise on fitness equipment such as treadmills, stationary bikes, and ellipticals, to running, swimming, dancing, sports, and exercise games.
In meta-analysis of postintervention differences, physical activity was associated with a significant reduction in the pooled estimate of depressive symptoms compared with the control condition (Hedges g statistic [effect size] = −0.29; 95% confidence interval, −0.47 to −0.10; P = .004). This was driven by moderate to large effect sizes in adolescents (g = −0.44) and children with diagnosed depression (g = −0.75).The differences, however, were not detectable after a mean follow-up of 21 weeks, possibly owing to the limited number of studies with follow-up outcomes, the authors conceded.
Despite the strong association, the mechanisms underlying the antidepressant properties of physical activity remain uncertain. “Potential pathways include the activation of the endocannabinoid system to stimulate the release of endorphins, an increase in the bioavailability of brain neurotransmitters such as serotonin, dopamine, and noradrenaline, which are reduced in depression, as well as long-term changes in brain plasticity,” Dr. Siu said.
In addition, psychosocial and behavioral hypotheses suggest that physical activity can lead to improvements in self-perception, social interactions, and self-confidence. However, he added, depressive phenomenology is multifaceted and individual, so isolating the effects that physical activity have on specific symptoms may not be possible.
Physical activity appears to enhance the treatment of cognitive and affective symptoms in depression, Dr. Siu continued, and a combination of physical activity and pharmacotherapy may also reduce relapse risk, improve adherence to antidepressants, and promote better management of adverse effects, compared with pharmacotherapy alone. “More research is warranted to explain if and how these mechanisms moderate the effect of physical activity, and whether these changes are also present in younger populations,” he said.
Still unanswered is the question of how vigorous activity has to be in order to have an effect, Dr. Siu said. “Future studies should investigate the influence of parameters such as frequency, duration, and supervision of exercise sessions to determine the optimal dose and mode of delivery of the intervention for depressive symptom management.”
But would group activity likely have broader benefits than solitary exercise? “It is still unclear whether there’s a difference between the effect of solitary activities and team sports,” Dr. Siu said.
In an accompanying editorial on the meta-analysis, Eduardo E. Bustamante, PhD, an exercise psychologist in the department of kinesiology and nutrition at the University of Illinois at Chicago, and colleagues called the meta-analysis “part of a potential watershed moment” in the field of exercise as therapy for psychological disorders. “The work is timely, aligning with the rise of mental health disorders in adolescents, and the methods are rigorous (e.g., random-effects models, risk-of-bias assessment, sensitivity analyses).”
Dr. Bustamante said the literature on physical activity in children has lagged behind that for adults, so this meta-analysis provides a welcome “critical mass” of evidence of benefit in children, in an interview. “Though the benefit is relatively small, it’s exciting to see the results come in positive specifically to depression.” In his view, the effect of exercise is likely to be less pronounced in children than in adults, especially older ones, as they have fewer inflammatory and other systemic health problems that might improve with exercise. “And we tend to see bigger effects in children with a diagnosis like ADHD or clinical depression.”
But the bottom line is clear: “The evidence that physical activity is effective medicine for mental health is robust; now we need to find ways to get people to take it.”
This work was supported by the Health and Medical Research Fund of the Food and Health Bureau, Hong Kong Special Administrative Region Government, and the Seed Fund for Basic Research of the University of Hong Kong. The authors and editorial commentators disclosed no conflicts of interest.
Intervening with physical activity appears to mitigate depressive symptoms in children and adolescents, a systematic review and meta-analysis of almost 2,500 participants found. Greater reductions were observed for children older than 13 years and those having a diagnosis of mental illness and/or depression versus other conditions, according to Hong Kong researchers reporting in JAMA Pediatrics.
“There is an urgent need to explore novel treatment approaches that can be safely, feasibly, and widely implemented in the daily routine of depressed children and adolescents,” said study coauthor Parco M. Siu, PhD, exercise physiologist and associate professor in the school of public health at the University of Hong Kong, in an interview. “Given the observed association with significant reductions in symptoms, clinical practice guidelines should consider the role of physical activity for improving the mental health of young populations.”
Dr. Siu further noted that while current guidelines suggest psychotherapy and/or pharmacotherapy for children with this common mood disorder, adherence to these can be problematic, and surveys show that nearly 80% do not receive appropriate disorder-specific medical care.
The analysis
Dr. Siu’s team drew on 21 international studies, including 17 randomized controlled trials, published from 1987 to 2021 and comprising 2,444 young participants, mean age 14, 53% girls. Eligible studies compared the effect of exercise on depression versus a control condition.
In 12 studies, participants had a somatic or psychiatric disorder such as obesity, diabetes, depression, and attention-deficit/hyperactivity disorder. The mean duration of the prescribed physical activity program was 22 weeks (6-144 weeks), while the frequency of weekly sessions ranged from 2 to 5 days, with 3 days per week most common and mean duration of 50 minutes (30-120 minutes). Regimens ranged from aerobic exercise on fitness equipment such as treadmills, stationary bikes, and ellipticals, to running, swimming, dancing, sports, and exercise games.
In meta-analysis of postintervention differences, physical activity was associated with a significant reduction in the pooled estimate of depressive symptoms compared with the control condition (Hedges g statistic [effect size] = −0.29; 95% confidence interval, −0.47 to −0.10; P = .004). This was driven by moderate to large effect sizes in adolescents (g = −0.44) and children with diagnosed depression (g = −0.75).The differences, however, were not detectable after a mean follow-up of 21 weeks, possibly owing to the limited number of studies with follow-up outcomes, the authors conceded.
Despite the strong association, the mechanisms underlying the antidepressant properties of physical activity remain uncertain. “Potential pathways include the activation of the endocannabinoid system to stimulate the release of endorphins, an increase in the bioavailability of brain neurotransmitters such as serotonin, dopamine, and noradrenaline, which are reduced in depression, as well as long-term changes in brain plasticity,” Dr. Siu said.
In addition, psychosocial and behavioral hypotheses suggest that physical activity can lead to improvements in self-perception, social interactions, and self-confidence. However, he added, depressive phenomenology is multifaceted and individual, so isolating the effects that physical activity have on specific symptoms may not be possible.
Physical activity appears to enhance the treatment of cognitive and affective symptoms in depression, Dr. Siu continued, and a combination of physical activity and pharmacotherapy may also reduce relapse risk, improve adherence to antidepressants, and promote better management of adverse effects, compared with pharmacotherapy alone. “More research is warranted to explain if and how these mechanisms moderate the effect of physical activity, and whether these changes are also present in younger populations,” he said.
Still unanswered is the question of how vigorous activity has to be in order to have an effect, Dr. Siu said. “Future studies should investigate the influence of parameters such as frequency, duration, and supervision of exercise sessions to determine the optimal dose and mode of delivery of the intervention for depressive symptom management.”
But would group activity likely have broader benefits than solitary exercise? “It is still unclear whether there’s a difference between the effect of solitary activities and team sports,” Dr. Siu said.
In an accompanying editorial on the meta-analysis, Eduardo E. Bustamante, PhD, an exercise psychologist in the department of kinesiology and nutrition at the University of Illinois at Chicago, and colleagues called the meta-analysis “part of a potential watershed moment” in the field of exercise as therapy for psychological disorders. “The work is timely, aligning with the rise of mental health disorders in adolescents, and the methods are rigorous (e.g., random-effects models, risk-of-bias assessment, sensitivity analyses).”
Dr. Bustamante said the literature on physical activity in children has lagged behind that for adults, so this meta-analysis provides a welcome “critical mass” of evidence of benefit in children, in an interview. “Though the benefit is relatively small, it’s exciting to see the results come in positive specifically to depression.” In his view, the effect of exercise is likely to be less pronounced in children than in adults, especially older ones, as they have fewer inflammatory and other systemic health problems that might improve with exercise. “And we tend to see bigger effects in children with a diagnosis like ADHD or clinical depression.”
But the bottom line is clear: “The evidence that physical activity is effective medicine for mental health is robust; now we need to find ways to get people to take it.”
This work was supported by the Health and Medical Research Fund of the Food and Health Bureau, Hong Kong Special Administrative Region Government, and the Seed Fund for Basic Research of the University of Hong Kong. The authors and editorial commentators disclosed no conflicts of interest.
Intervening with physical activity appears to mitigate depressive symptoms in children and adolescents, a systematic review and meta-analysis of almost 2,500 participants found. Greater reductions were observed for children older than 13 years and those having a diagnosis of mental illness and/or depression versus other conditions, according to Hong Kong researchers reporting in JAMA Pediatrics.
“There is an urgent need to explore novel treatment approaches that can be safely, feasibly, and widely implemented in the daily routine of depressed children and adolescents,” said study coauthor Parco M. Siu, PhD, exercise physiologist and associate professor in the school of public health at the University of Hong Kong, in an interview. “Given the observed association with significant reductions in symptoms, clinical practice guidelines should consider the role of physical activity for improving the mental health of young populations.”
Dr. Siu further noted that while current guidelines suggest psychotherapy and/or pharmacotherapy for children with this common mood disorder, adherence to these can be problematic, and surveys show that nearly 80% do not receive appropriate disorder-specific medical care.
The analysis
Dr. Siu’s team drew on 21 international studies, including 17 randomized controlled trials, published from 1987 to 2021 and comprising 2,444 young participants, mean age 14, 53% girls. Eligible studies compared the effect of exercise on depression versus a control condition.
In 12 studies, participants had a somatic or psychiatric disorder such as obesity, diabetes, depression, and attention-deficit/hyperactivity disorder. The mean duration of the prescribed physical activity program was 22 weeks (6-144 weeks), while the frequency of weekly sessions ranged from 2 to 5 days, with 3 days per week most common and mean duration of 50 minutes (30-120 minutes). Regimens ranged from aerobic exercise on fitness equipment such as treadmills, stationary bikes, and ellipticals, to running, swimming, dancing, sports, and exercise games.
In meta-analysis of postintervention differences, physical activity was associated with a significant reduction in the pooled estimate of depressive symptoms compared with the control condition (Hedges g statistic [effect size] = −0.29; 95% confidence interval, −0.47 to −0.10; P = .004). This was driven by moderate to large effect sizes in adolescents (g = −0.44) and children with diagnosed depression (g = −0.75).The differences, however, were not detectable after a mean follow-up of 21 weeks, possibly owing to the limited number of studies with follow-up outcomes, the authors conceded.
Despite the strong association, the mechanisms underlying the antidepressant properties of physical activity remain uncertain. “Potential pathways include the activation of the endocannabinoid system to stimulate the release of endorphins, an increase in the bioavailability of brain neurotransmitters such as serotonin, dopamine, and noradrenaline, which are reduced in depression, as well as long-term changes in brain plasticity,” Dr. Siu said.
In addition, psychosocial and behavioral hypotheses suggest that physical activity can lead to improvements in self-perception, social interactions, and self-confidence. However, he added, depressive phenomenology is multifaceted and individual, so isolating the effects that physical activity have on specific symptoms may not be possible.
Physical activity appears to enhance the treatment of cognitive and affective symptoms in depression, Dr. Siu continued, and a combination of physical activity and pharmacotherapy may also reduce relapse risk, improve adherence to antidepressants, and promote better management of adverse effects, compared with pharmacotherapy alone. “More research is warranted to explain if and how these mechanisms moderate the effect of physical activity, and whether these changes are also present in younger populations,” he said.
Still unanswered is the question of how vigorous activity has to be in order to have an effect, Dr. Siu said. “Future studies should investigate the influence of parameters such as frequency, duration, and supervision of exercise sessions to determine the optimal dose and mode of delivery of the intervention for depressive symptom management.”
But would group activity likely have broader benefits than solitary exercise? “It is still unclear whether there’s a difference between the effect of solitary activities and team sports,” Dr. Siu said.
In an accompanying editorial on the meta-analysis, Eduardo E. Bustamante, PhD, an exercise psychologist in the department of kinesiology and nutrition at the University of Illinois at Chicago, and colleagues called the meta-analysis “part of a potential watershed moment” in the field of exercise as therapy for psychological disorders. “The work is timely, aligning with the rise of mental health disorders in adolescents, and the methods are rigorous (e.g., random-effects models, risk-of-bias assessment, sensitivity analyses).”
Dr. Bustamante said the literature on physical activity in children has lagged behind that for adults, so this meta-analysis provides a welcome “critical mass” of evidence of benefit in children, in an interview. “Though the benefit is relatively small, it’s exciting to see the results come in positive specifically to depression.” In his view, the effect of exercise is likely to be less pronounced in children than in adults, especially older ones, as they have fewer inflammatory and other systemic health problems that might improve with exercise. “And we tend to see bigger effects in children with a diagnosis like ADHD or clinical depression.”
But the bottom line is clear: “The evidence that physical activity is effective medicine for mental health is robust; now we need to find ways to get people to take it.”
This work was supported by the Health and Medical Research Fund of the Food and Health Bureau, Hong Kong Special Administrative Region Government, and the Seed Fund for Basic Research of the University of Hong Kong. The authors and editorial commentators disclosed no conflicts of interest.
FROM JAMA PEDIATRICS
Five thoughts on the Damar Hamlin collapse
The obvious first statement is that it’s neither wise nor appropriate to speculate on the specifics of Damar Hamlin’s cardiac event during a football game on Jan. 2 (including the possibility of commotio cordis) or his ongoing care. The public nature of his collapse induces intense curiosity but people with illness deserve privacy. Privacy in health care is in short supply. I disagree strongly with those who say his doctors ought to be giving public updates. That’s up to the family.
But there are important general concepts to consider about this incident. These include ...
Cardiac arrest can happen to anyone
People with structural heart disease or other chronic illnesses have a higher risk of arrhythmia, but the notion that athletes are immune from cardiac arrest is wrong. This sentence almost seems too obvious to write, but to this day, I hear clinicians express surprise that an athletic person has heart disease.
Survival turns on rapid and effective intervention
In the old days of electrophysiology, we used to test implantable cardioverter-defibrillators during an implant procedure by inducing ventricular fibrillation (VF) and watching the device convert it. Thankfully, trials have shown that this is no longer necessary for most implants.
When you induce VF In the EP lab, you learn quickly that a) it causes loss of consciousness in a matter of seconds, b) rapid defibrillation restores consciousness, often without the patients knowing or remembering they passed out, and c) the failure of the shock to terminate VF results in deterioration in a matter of 1-2 minutes. Even 1 minute in VF feels so long.
Need is an appropriate word in VF treatment
Clinicians often use the verb need. As in, this patient needs this pill or this procedure. It’s rarely appropriate.
But in the case of treating VF, patients truly need rapid defibrillation. Survival of out-of-hospital cardiac arrest is low because there just aren’t enough automated external defibrillators (AEDs) or people trained to use them. A study of patients who had out-of-hospital cardiac arrest in Denmark found that 30-day survival almost doubled (28.8% vs. 16.4%), when the nearest AED was accessible.
Bystanders must act
The public messages are simple: If a person loses consciousness in front of you, and is not breathing normally, assume it is a cardiac arrest, call 911 to get professional help, and start hands-only chest compressions. Don’t spend time checking for a pulse or trying to wake the person. If this is not a cardiac arrest, they will soon tell you to stop compressing their chest. Seconds matter.
Chest compressions are important but what is really needed is defibrillation. A crucial step in CPR is to send someone to get an AED and get the pads attached. If this is a shockable rhythm, deliver the shock. Hamlin’s collapse emphasizes the importance of the AED; without it, his survival to the hospital would have been unlikely.
Widespread preparticipation screening of young athletes remains a bad idea
Whenever cardiac arrest occurs in an athlete, in such a public way, people think about prevention. Surely it is better to prevent such an event than react to it, goes the thinking. The argument against this idea has four prongs:
The incidence of cardiac disease in a young athlete is extremely low, which sets up a situation where most “positive” tests are false positive. A false positive screening ECG or echocardiogram can create harm in multiple ways. One is the risk from downstream procedures, but worse is the inappropriate disqualification from sport. Healthwise, few harms could be greater than creating long-term fear of exercise in someone.
There is also the problem of false-negative screening tests. An ECG may be normal in the setting of hypertrophic cardiomyopathy. And a normal echocardiogram does not exclude arrhythmogenic right ventricular cardiomyopathy or other genetic causes of cardiac arrest. In a 2018 study from a major sports cardiology center in London, 6 of the 8 sudden cardiac deaths in their series were in athletes who had no detectable abnormalities on screening.
Even when disease is found, it’s not clear that prohibiting participation in sports prevents sudden death. Many previous class III recommendations against participation in sport now carry class II – may be considered – designations.
Finally, screening for any disease loses value as treatments improve. Public education regarding rapid intervention with CPR and AED use is the best treatment option. A great example is the case of Christian Erikson, a Danish soccer player who suffered cardiac arrest during a match at the European Championships in 2021 and was rapidly defibrillated on the field. Therapy was so effective that he was conscious and able to wave to fans on his way out of the stadium. He has now returned to elite competition.
Proponents of screening might oppose my take by saying that National Football League players are intensely screened. But this is different from widespread screening of high school and college athletes. It might sound harsh to say, but professional teams have dualities of interests in the health of their athletes given the million-dollar contracts.
What’s more, professional teams can afford to hire expert cardiologists to perform the testing. This would likely reduce the rate of false-positive findings, compared with screening in the community setting. I often have young people referred to me because of asymptomatic bradycardia found during athletic screening – an obviously normal finding.
Conclusions
As long as there are sports, there will be athletes who suffer cardiac arrest.
We can both hope for Hamlin’s full recovery and learn lessons to help reduce the rate of death from out-of-hospital cardiac arrest. This mostly involves education on how to help fellow humans and a public health commitment to access to AEDs.
John Mandrola, MD, practices cardiac electrophysiology in Louisville, Ky. and is a writer and podcaster for Medscape. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.
The obvious first statement is that it’s neither wise nor appropriate to speculate on the specifics of Damar Hamlin’s cardiac event during a football game on Jan. 2 (including the possibility of commotio cordis) or his ongoing care. The public nature of his collapse induces intense curiosity but people with illness deserve privacy. Privacy in health care is in short supply. I disagree strongly with those who say his doctors ought to be giving public updates. That’s up to the family.
But there are important general concepts to consider about this incident. These include ...
Cardiac arrest can happen to anyone
People with structural heart disease or other chronic illnesses have a higher risk of arrhythmia, but the notion that athletes are immune from cardiac arrest is wrong. This sentence almost seems too obvious to write, but to this day, I hear clinicians express surprise that an athletic person has heart disease.
Survival turns on rapid and effective intervention
In the old days of electrophysiology, we used to test implantable cardioverter-defibrillators during an implant procedure by inducing ventricular fibrillation (VF) and watching the device convert it. Thankfully, trials have shown that this is no longer necessary for most implants.
When you induce VF In the EP lab, you learn quickly that a) it causes loss of consciousness in a matter of seconds, b) rapid defibrillation restores consciousness, often without the patients knowing or remembering they passed out, and c) the failure of the shock to terminate VF results in deterioration in a matter of 1-2 minutes. Even 1 minute in VF feels so long.
Need is an appropriate word in VF treatment
Clinicians often use the verb need. As in, this patient needs this pill or this procedure. It’s rarely appropriate.
But in the case of treating VF, patients truly need rapid defibrillation. Survival of out-of-hospital cardiac arrest is low because there just aren’t enough automated external defibrillators (AEDs) or people trained to use them. A study of patients who had out-of-hospital cardiac arrest in Denmark found that 30-day survival almost doubled (28.8% vs. 16.4%), when the nearest AED was accessible.
Bystanders must act
The public messages are simple: If a person loses consciousness in front of you, and is not breathing normally, assume it is a cardiac arrest, call 911 to get professional help, and start hands-only chest compressions. Don’t spend time checking for a pulse or trying to wake the person. If this is not a cardiac arrest, they will soon tell you to stop compressing their chest. Seconds matter.
Chest compressions are important but what is really needed is defibrillation. A crucial step in CPR is to send someone to get an AED and get the pads attached. If this is a shockable rhythm, deliver the shock. Hamlin’s collapse emphasizes the importance of the AED; without it, his survival to the hospital would have been unlikely.
Widespread preparticipation screening of young athletes remains a bad idea
Whenever cardiac arrest occurs in an athlete, in such a public way, people think about prevention. Surely it is better to prevent such an event than react to it, goes the thinking. The argument against this idea has four prongs:
The incidence of cardiac disease in a young athlete is extremely low, which sets up a situation where most “positive” tests are false positive. A false positive screening ECG or echocardiogram can create harm in multiple ways. One is the risk from downstream procedures, but worse is the inappropriate disqualification from sport. Healthwise, few harms could be greater than creating long-term fear of exercise in someone.
There is also the problem of false-negative screening tests. An ECG may be normal in the setting of hypertrophic cardiomyopathy. And a normal echocardiogram does not exclude arrhythmogenic right ventricular cardiomyopathy or other genetic causes of cardiac arrest. In a 2018 study from a major sports cardiology center in London, 6 of the 8 sudden cardiac deaths in their series were in athletes who had no detectable abnormalities on screening.
Even when disease is found, it’s not clear that prohibiting participation in sports prevents sudden death. Many previous class III recommendations against participation in sport now carry class II – may be considered – designations.
Finally, screening for any disease loses value as treatments improve. Public education regarding rapid intervention with CPR and AED use is the best treatment option. A great example is the case of Christian Erikson, a Danish soccer player who suffered cardiac arrest during a match at the European Championships in 2021 and was rapidly defibrillated on the field. Therapy was so effective that he was conscious and able to wave to fans on his way out of the stadium. He has now returned to elite competition.
Proponents of screening might oppose my take by saying that National Football League players are intensely screened. But this is different from widespread screening of high school and college athletes. It might sound harsh to say, but professional teams have dualities of interests in the health of their athletes given the million-dollar contracts.
What’s more, professional teams can afford to hire expert cardiologists to perform the testing. This would likely reduce the rate of false-positive findings, compared with screening in the community setting. I often have young people referred to me because of asymptomatic bradycardia found during athletic screening – an obviously normal finding.
Conclusions
As long as there are sports, there will be athletes who suffer cardiac arrest.
We can both hope for Hamlin’s full recovery and learn lessons to help reduce the rate of death from out-of-hospital cardiac arrest. This mostly involves education on how to help fellow humans and a public health commitment to access to AEDs.
John Mandrola, MD, practices cardiac electrophysiology in Louisville, Ky. and is a writer and podcaster for Medscape. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.
The obvious first statement is that it’s neither wise nor appropriate to speculate on the specifics of Damar Hamlin’s cardiac event during a football game on Jan. 2 (including the possibility of commotio cordis) or his ongoing care. The public nature of his collapse induces intense curiosity but people with illness deserve privacy. Privacy in health care is in short supply. I disagree strongly with those who say his doctors ought to be giving public updates. That’s up to the family.
But there are important general concepts to consider about this incident. These include ...
Cardiac arrest can happen to anyone
People with structural heart disease or other chronic illnesses have a higher risk of arrhythmia, but the notion that athletes are immune from cardiac arrest is wrong. This sentence almost seems too obvious to write, but to this day, I hear clinicians express surprise that an athletic person has heart disease.
Survival turns on rapid and effective intervention
In the old days of electrophysiology, we used to test implantable cardioverter-defibrillators during an implant procedure by inducing ventricular fibrillation (VF) and watching the device convert it. Thankfully, trials have shown that this is no longer necessary for most implants.
When you induce VF In the EP lab, you learn quickly that a) it causes loss of consciousness in a matter of seconds, b) rapid defibrillation restores consciousness, often without the patients knowing or remembering they passed out, and c) the failure of the shock to terminate VF results in deterioration in a matter of 1-2 minutes. Even 1 minute in VF feels so long.
Need is an appropriate word in VF treatment
Clinicians often use the verb need. As in, this patient needs this pill or this procedure. It’s rarely appropriate.
But in the case of treating VF, patients truly need rapid defibrillation. Survival of out-of-hospital cardiac arrest is low because there just aren’t enough automated external defibrillators (AEDs) or people trained to use them. A study of patients who had out-of-hospital cardiac arrest in Denmark found that 30-day survival almost doubled (28.8% vs. 16.4%), when the nearest AED was accessible.
Bystanders must act
The public messages are simple: If a person loses consciousness in front of you, and is not breathing normally, assume it is a cardiac arrest, call 911 to get professional help, and start hands-only chest compressions. Don’t spend time checking for a pulse or trying to wake the person. If this is not a cardiac arrest, they will soon tell you to stop compressing their chest. Seconds matter.
Chest compressions are important but what is really needed is defibrillation. A crucial step in CPR is to send someone to get an AED and get the pads attached. If this is a shockable rhythm, deliver the shock. Hamlin’s collapse emphasizes the importance of the AED; without it, his survival to the hospital would have been unlikely.
Widespread preparticipation screening of young athletes remains a bad idea
Whenever cardiac arrest occurs in an athlete, in such a public way, people think about prevention. Surely it is better to prevent such an event than react to it, goes the thinking. The argument against this idea has four prongs:
The incidence of cardiac disease in a young athlete is extremely low, which sets up a situation where most “positive” tests are false positive. A false positive screening ECG or echocardiogram can create harm in multiple ways. One is the risk from downstream procedures, but worse is the inappropriate disqualification from sport. Healthwise, few harms could be greater than creating long-term fear of exercise in someone.
There is also the problem of false-negative screening tests. An ECG may be normal in the setting of hypertrophic cardiomyopathy. And a normal echocardiogram does not exclude arrhythmogenic right ventricular cardiomyopathy or other genetic causes of cardiac arrest. In a 2018 study from a major sports cardiology center in London, 6 of the 8 sudden cardiac deaths in their series were in athletes who had no detectable abnormalities on screening.
Even when disease is found, it’s not clear that prohibiting participation in sports prevents sudden death. Many previous class III recommendations against participation in sport now carry class II – may be considered – designations.
Finally, screening for any disease loses value as treatments improve. Public education regarding rapid intervention with CPR and AED use is the best treatment option. A great example is the case of Christian Erikson, a Danish soccer player who suffered cardiac arrest during a match at the European Championships in 2021 and was rapidly defibrillated on the field. Therapy was so effective that he was conscious and able to wave to fans on his way out of the stadium. He has now returned to elite competition.
Proponents of screening might oppose my take by saying that National Football League players are intensely screened. But this is different from widespread screening of high school and college athletes. It might sound harsh to say, but professional teams have dualities of interests in the health of their athletes given the million-dollar contracts.
What’s more, professional teams can afford to hire expert cardiologists to perform the testing. This would likely reduce the rate of false-positive findings, compared with screening in the community setting. I often have young people referred to me because of asymptomatic bradycardia found during athletic screening – an obviously normal finding.
Conclusions
As long as there are sports, there will be athletes who suffer cardiac arrest.
We can both hope for Hamlin’s full recovery and learn lessons to help reduce the rate of death from out-of-hospital cardiac arrest. This mostly involves education on how to help fellow humans and a public health commitment to access to AEDs.
John Mandrola, MD, practices cardiac electrophysiology in Louisville, Ky. and is a writer and podcaster for Medscape. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.
One in four cardiologists worldwide report mental health issues
ranging from anxiety or anger issues to major depression or other psychiatric disorders.
Such conditions varied in prevalence by cardiology subspecialty and years in the field, were more common in women than in men, and were closely linked to enduring hostile work environments and other strains of professional life.
The survey, conducted only months before the COVID-19 pandemic and with its share of limitations, still paints a picture that’s not pretty.
For example, mental health concerns were reported by about 42% of respondents who cited a hostile work environment, defined as workplace experience of discrimination based on age, sex, religion, race or ethnicity, or emotional or sexual harassment. Conversely, the prevalence of these concerns reached only 17% among those without such workplace conditions.
The study shows substantial overlap between cardiologists reporting hostility at work and those with mental health concerns, “and that was a significant finding,” Garima Sharma, MD, Johns Hopkins University, Baltimore, said in an interview.
Still, only 31% of male and 42% of female cardiologists (P < .001) reporting mental health concerns also said they had sought professional help either within or outside their own institutions.
That means “there is a lot of silent suffering” in the field, said Dr. Sharma, who is lead author on the study, published in the Journal of the American College of Cardiology.
Bringing back the conversation
The survey findings, she added, point to at least two potential ways the cardiology community can strive to diminish what may be a major underlying cause of the mental health concerns and their consequences.
“If you work towards reducing hostility at work and making mental health a priority for your workforce, then those experiencing these types of egregious conditions based on age, gender, race, ethnicity, or sexual orientation are less likely to be harmed.”
Mental health concerns among cardiologists are seldom openly discussed, so the current study can be “a way to bring them back into the conversation,” Dr. Sharma said. Clinician mental health “is extremely important because it directly impacts patient care and productivity.”
The survey’s reported mental health conditions “are an issue across the board in medicine, and amongst our medical students as well,” senior author Laxmi S. Mehta, MD, professor of internal medicine at Ohio State University, Columbus, said in an interview. The current study provides new details about their prevalence and predictors in cardiology and, she hopes, may improve the field’s awareness of and efforts to address the problem.
“We need to support those who have underlying mental health conditions, as well as improve the work environment to reduce contributory factors to mental illnesses. And we also need to work on reducing the stigma associated with seeking treatment and on reducing the barriers to receiving treatment,” said Dr. Mehta, who chairs the Workgroup on Clinician Well-Being of the ACC, which conducted the survey in 2019.
A global perspective
Cardiologists in Africa, the Americas, Asia, Europe, the Middle East, and Oceania – 5,890 in all – responded to mental health questions on the survey, which was novel for its global reach and insights across continents and cultures.
Respondents in South America and Central America reported the highest prevalences of mental health concerns, outliers at about 39% and 33%, respectively. Rates for most other geographic regions ranged narrowly from about 20% to 26%, the lowest reported in Asia and the Middle East.
Dr. Sharma acknowledged that the countries probably varied widely in social and cultural factors likely to influence survey responses, such as interpretation of the questionnaire’s mental health terminology or the degree to which the disorders are stigmatized.
“I think it’s hard to say how people may or may not respond culturally to a certain word or metric,” she said. But on the survey results, “whether you’re practicing in rural America, in rural India, or in the United Arab Emirates, Oceania, or Eastern Europe, there is a level of consistency, across the board, in what people are recognizing as mental health conditions.”
Junior vs. senior physicians
The global perspective “is a nice positive of the study, and the high rates in Central America and South America I think were something the field was not aware of and are an important contribution,” Srijan Sen, MD, PhD, said in an interview.
The psychological toll of hostile work environments is an issue throughout medicine, “but it seems greater in certain specialties, and cardiology may be one where it’s more of a problem,” observed Dr. Sen, who studies physician mental health at the University of Michigan, Ann Arbor, and wasn’t associated with the survey.
Mental health concerns in the survey were significantly more common among women than men (33.7% vs 26.3%), and for younger cardiologists, compared with older cardiologists (32.2% for those < 40 vs. 22.1% and 16.8% for those 55-69 and 70 or older, respectively).
Those findings seem to make sense, Dr. Sen observed. “Generally, cardiology and medicine broadly are hierarchical, so being more junior can be stressful.” And if there’s more hostility in the workplace, “it might fall on junior people.”
In other studies, moreover, “a high level of work-family conflict has been a real driver of depression and burnout, and that likely is affecting younger physicians, particularly young women physicians,” who may have smaller children and a greater burden of childcare than their seniors.
He pointed to the survey’s low response rate as an important limitation of the study. Of the 71,022 cardiologists invited to participate, only 5,890 (8.3%) responded and answered the queries on mental health.
With a response rate that low, a survey “can be biased in ways that we can’t predict,” Dr. Sen noted. Also, anyone concerned about the toxicity of their own workplace might be “more likely to respond to the survey than if they worked in a more pleasant place. That would provide a skewed sense of the overall experience of cardiologists.”
Those issues might not be a concern with the current survey, however, “because the results are consistent with other studies with higher response rates.”
‘Sobering report’
An accompanying editorial said Dr. Sharm and colleagues have provided “a sobering report on the global prevalence and potential contributors to mental health concerns” in the surveyed population.
Based on its lessons, Andrew J. Sauer, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., proposed several potential “interventions” the field could enact.
It could “selectively promote leaders who strive to mitigate implicit bias, discrimination, and harassment while advancing diversity, equity, and inclusion within the broad ranks of cardiologists.”
Also, he continued, “we must eliminate the stigmatization of mental illness among physicians. We need to handle mental health concerns with compassion and without blaming, like how we strive to treat our veterans who suffer from posttraumatic stress disorder.”
Lastly, Dr. Sauer wrote, “mentorship programs should be formalized to assist the cardiologist in transition zones from early to mid-career, with particular attention to women and those experiencing a simultaneously increased load of family burdens that compound existing workplace contributors to burnout and psychological distress.”
Years in practice
Of the cardiologists who responded to the survey’s mental health questions, 28% reported they have experienced mental health issues that could include alcohol/drug use disorder, suicidal tendencies, psychological distress (including anxiety, irritability, or anger), “other psychiatric disorders” (such as panic disorder, posttraumatic stress, or eating disorders) or major psychiatric disorders such as major depression, bipolar disorder, or schizophrenia.
Cardiologists with 5-10 years of practice post-training were more likely than cardiologists practicing for at least 20 years to have mental health concerns (31.9% vs. 22.6%, P < .001).
Mental health concerns were cited by 42% of respondents who cited “any type of discrimination” based on age, sex, race or ethnicity, or sexual orientation, the report noted.
Among those reporting any mental health concern, 2.7% considered suicide within the past year and 2.9% considered suicide more than 12 months previously. Women were more likely than men to consider suicide within the past year (3.8% vs. 2.3%) but were also more likely to seek help (42.3% vs. 31.1%; P < .001 for both differences), the authors wrote.
In multivariate analysis, predictors of mental health concerns included emotional harassment, 2.81 (odds ratio, 2.81; 95% confidence interval, 2.46-3.20), any discrimination (OR, 1.85; 95% CI, 1.61-2.12), being divorced (OR, 1.73; 95% CI, 1.26-2.36, age less than 55 years (OR, 1.43; 95% CI, 1.24-1.66), and being mid-career versus late (OR, 1.36; 95% CI, 1.14-1.62).
Because the survey was conducted from September to October 2019, before the pandemic’s traumatic effects unfolded on health care nearly everywhere, “I think there needs to be a follow-up at some point when everything has leveled out,” Dr. Sharma said. The current study is “a baseline, and not a healthy baseline,” for the field’s state of mental health that has likely grown worse during the pandemic.
But even without such a follow-up, the current study “is actionable enough that it forces us to do something about it right now.”
Dr. Sharma, Dr. Mehta, their coauthors, Dr. Sen, and Dr. Sauer reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
ranging from anxiety or anger issues to major depression or other psychiatric disorders.
Such conditions varied in prevalence by cardiology subspecialty and years in the field, were more common in women than in men, and were closely linked to enduring hostile work environments and other strains of professional life.
The survey, conducted only months before the COVID-19 pandemic and with its share of limitations, still paints a picture that’s not pretty.
For example, mental health concerns were reported by about 42% of respondents who cited a hostile work environment, defined as workplace experience of discrimination based on age, sex, religion, race or ethnicity, or emotional or sexual harassment. Conversely, the prevalence of these concerns reached only 17% among those without such workplace conditions.
The study shows substantial overlap between cardiologists reporting hostility at work and those with mental health concerns, “and that was a significant finding,” Garima Sharma, MD, Johns Hopkins University, Baltimore, said in an interview.
Still, only 31% of male and 42% of female cardiologists (P < .001) reporting mental health concerns also said they had sought professional help either within or outside their own institutions.
That means “there is a lot of silent suffering” in the field, said Dr. Sharma, who is lead author on the study, published in the Journal of the American College of Cardiology.
Bringing back the conversation
The survey findings, she added, point to at least two potential ways the cardiology community can strive to diminish what may be a major underlying cause of the mental health concerns and their consequences.
“If you work towards reducing hostility at work and making mental health a priority for your workforce, then those experiencing these types of egregious conditions based on age, gender, race, ethnicity, or sexual orientation are less likely to be harmed.”
Mental health concerns among cardiologists are seldom openly discussed, so the current study can be “a way to bring them back into the conversation,” Dr. Sharma said. Clinician mental health “is extremely important because it directly impacts patient care and productivity.”
The survey’s reported mental health conditions “are an issue across the board in medicine, and amongst our medical students as well,” senior author Laxmi S. Mehta, MD, professor of internal medicine at Ohio State University, Columbus, said in an interview. The current study provides new details about their prevalence and predictors in cardiology and, she hopes, may improve the field’s awareness of and efforts to address the problem.
“We need to support those who have underlying mental health conditions, as well as improve the work environment to reduce contributory factors to mental illnesses. And we also need to work on reducing the stigma associated with seeking treatment and on reducing the barriers to receiving treatment,” said Dr. Mehta, who chairs the Workgroup on Clinician Well-Being of the ACC, which conducted the survey in 2019.
A global perspective
Cardiologists in Africa, the Americas, Asia, Europe, the Middle East, and Oceania – 5,890 in all – responded to mental health questions on the survey, which was novel for its global reach and insights across continents and cultures.
Respondents in South America and Central America reported the highest prevalences of mental health concerns, outliers at about 39% and 33%, respectively. Rates for most other geographic regions ranged narrowly from about 20% to 26%, the lowest reported in Asia and the Middle East.
Dr. Sharma acknowledged that the countries probably varied widely in social and cultural factors likely to influence survey responses, such as interpretation of the questionnaire’s mental health terminology or the degree to which the disorders are stigmatized.
“I think it’s hard to say how people may or may not respond culturally to a certain word or metric,” she said. But on the survey results, “whether you’re practicing in rural America, in rural India, or in the United Arab Emirates, Oceania, or Eastern Europe, there is a level of consistency, across the board, in what people are recognizing as mental health conditions.”
Junior vs. senior physicians
The global perspective “is a nice positive of the study, and the high rates in Central America and South America I think were something the field was not aware of and are an important contribution,” Srijan Sen, MD, PhD, said in an interview.
The psychological toll of hostile work environments is an issue throughout medicine, “but it seems greater in certain specialties, and cardiology may be one where it’s more of a problem,” observed Dr. Sen, who studies physician mental health at the University of Michigan, Ann Arbor, and wasn’t associated with the survey.
Mental health concerns in the survey were significantly more common among women than men (33.7% vs 26.3%), and for younger cardiologists, compared with older cardiologists (32.2% for those < 40 vs. 22.1% and 16.8% for those 55-69 and 70 or older, respectively).
Those findings seem to make sense, Dr. Sen observed. “Generally, cardiology and medicine broadly are hierarchical, so being more junior can be stressful.” And if there’s more hostility in the workplace, “it might fall on junior people.”
In other studies, moreover, “a high level of work-family conflict has been a real driver of depression and burnout, and that likely is affecting younger physicians, particularly young women physicians,” who may have smaller children and a greater burden of childcare than their seniors.
He pointed to the survey’s low response rate as an important limitation of the study. Of the 71,022 cardiologists invited to participate, only 5,890 (8.3%) responded and answered the queries on mental health.
With a response rate that low, a survey “can be biased in ways that we can’t predict,” Dr. Sen noted. Also, anyone concerned about the toxicity of their own workplace might be “more likely to respond to the survey than if they worked in a more pleasant place. That would provide a skewed sense of the overall experience of cardiologists.”
Those issues might not be a concern with the current survey, however, “because the results are consistent with other studies with higher response rates.”
‘Sobering report’
An accompanying editorial said Dr. Sharm and colleagues have provided “a sobering report on the global prevalence and potential contributors to mental health concerns” in the surveyed population.
Based on its lessons, Andrew J. Sauer, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., proposed several potential “interventions” the field could enact.
It could “selectively promote leaders who strive to mitigate implicit bias, discrimination, and harassment while advancing diversity, equity, and inclusion within the broad ranks of cardiologists.”
Also, he continued, “we must eliminate the stigmatization of mental illness among physicians. We need to handle mental health concerns with compassion and without blaming, like how we strive to treat our veterans who suffer from posttraumatic stress disorder.”
Lastly, Dr. Sauer wrote, “mentorship programs should be formalized to assist the cardiologist in transition zones from early to mid-career, with particular attention to women and those experiencing a simultaneously increased load of family burdens that compound existing workplace contributors to burnout and psychological distress.”
Years in practice
Of the cardiologists who responded to the survey’s mental health questions, 28% reported they have experienced mental health issues that could include alcohol/drug use disorder, suicidal tendencies, psychological distress (including anxiety, irritability, or anger), “other psychiatric disorders” (such as panic disorder, posttraumatic stress, or eating disorders) or major psychiatric disorders such as major depression, bipolar disorder, or schizophrenia.
Cardiologists with 5-10 years of practice post-training were more likely than cardiologists practicing for at least 20 years to have mental health concerns (31.9% vs. 22.6%, P < .001).
Mental health concerns were cited by 42% of respondents who cited “any type of discrimination” based on age, sex, race or ethnicity, or sexual orientation, the report noted.
Among those reporting any mental health concern, 2.7% considered suicide within the past year and 2.9% considered suicide more than 12 months previously. Women were more likely than men to consider suicide within the past year (3.8% vs. 2.3%) but were also more likely to seek help (42.3% vs. 31.1%; P < .001 for both differences), the authors wrote.
In multivariate analysis, predictors of mental health concerns included emotional harassment, 2.81 (odds ratio, 2.81; 95% confidence interval, 2.46-3.20), any discrimination (OR, 1.85; 95% CI, 1.61-2.12), being divorced (OR, 1.73; 95% CI, 1.26-2.36, age less than 55 years (OR, 1.43; 95% CI, 1.24-1.66), and being mid-career versus late (OR, 1.36; 95% CI, 1.14-1.62).
Because the survey was conducted from September to October 2019, before the pandemic’s traumatic effects unfolded on health care nearly everywhere, “I think there needs to be a follow-up at some point when everything has leveled out,” Dr. Sharma said. The current study is “a baseline, and not a healthy baseline,” for the field’s state of mental health that has likely grown worse during the pandemic.
But even without such a follow-up, the current study “is actionable enough that it forces us to do something about it right now.”
Dr. Sharma, Dr. Mehta, their coauthors, Dr. Sen, and Dr. Sauer reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
ranging from anxiety or anger issues to major depression or other psychiatric disorders.
Such conditions varied in prevalence by cardiology subspecialty and years in the field, were more common in women than in men, and were closely linked to enduring hostile work environments and other strains of professional life.
The survey, conducted only months before the COVID-19 pandemic and with its share of limitations, still paints a picture that’s not pretty.
For example, mental health concerns were reported by about 42% of respondents who cited a hostile work environment, defined as workplace experience of discrimination based on age, sex, religion, race or ethnicity, or emotional or sexual harassment. Conversely, the prevalence of these concerns reached only 17% among those without such workplace conditions.
The study shows substantial overlap between cardiologists reporting hostility at work and those with mental health concerns, “and that was a significant finding,” Garima Sharma, MD, Johns Hopkins University, Baltimore, said in an interview.
Still, only 31% of male and 42% of female cardiologists (P < .001) reporting mental health concerns also said they had sought professional help either within or outside their own institutions.
That means “there is a lot of silent suffering” in the field, said Dr. Sharma, who is lead author on the study, published in the Journal of the American College of Cardiology.
Bringing back the conversation
The survey findings, she added, point to at least two potential ways the cardiology community can strive to diminish what may be a major underlying cause of the mental health concerns and their consequences.
“If you work towards reducing hostility at work and making mental health a priority for your workforce, then those experiencing these types of egregious conditions based on age, gender, race, ethnicity, or sexual orientation are less likely to be harmed.”
Mental health concerns among cardiologists are seldom openly discussed, so the current study can be “a way to bring them back into the conversation,” Dr. Sharma said. Clinician mental health “is extremely important because it directly impacts patient care and productivity.”
The survey’s reported mental health conditions “are an issue across the board in medicine, and amongst our medical students as well,” senior author Laxmi S. Mehta, MD, professor of internal medicine at Ohio State University, Columbus, said in an interview. The current study provides new details about their prevalence and predictors in cardiology and, she hopes, may improve the field’s awareness of and efforts to address the problem.
“We need to support those who have underlying mental health conditions, as well as improve the work environment to reduce contributory factors to mental illnesses. And we also need to work on reducing the stigma associated with seeking treatment and on reducing the barriers to receiving treatment,” said Dr. Mehta, who chairs the Workgroup on Clinician Well-Being of the ACC, which conducted the survey in 2019.
A global perspective
Cardiologists in Africa, the Americas, Asia, Europe, the Middle East, and Oceania – 5,890 in all – responded to mental health questions on the survey, which was novel for its global reach and insights across continents and cultures.
Respondents in South America and Central America reported the highest prevalences of mental health concerns, outliers at about 39% and 33%, respectively. Rates for most other geographic regions ranged narrowly from about 20% to 26%, the lowest reported in Asia and the Middle East.
Dr. Sharma acknowledged that the countries probably varied widely in social and cultural factors likely to influence survey responses, such as interpretation of the questionnaire’s mental health terminology or the degree to which the disorders are stigmatized.
“I think it’s hard to say how people may or may not respond culturally to a certain word or metric,” she said. But on the survey results, “whether you’re practicing in rural America, in rural India, or in the United Arab Emirates, Oceania, or Eastern Europe, there is a level of consistency, across the board, in what people are recognizing as mental health conditions.”
Junior vs. senior physicians
The global perspective “is a nice positive of the study, and the high rates in Central America and South America I think were something the field was not aware of and are an important contribution,” Srijan Sen, MD, PhD, said in an interview.
The psychological toll of hostile work environments is an issue throughout medicine, “but it seems greater in certain specialties, and cardiology may be one where it’s more of a problem,” observed Dr. Sen, who studies physician mental health at the University of Michigan, Ann Arbor, and wasn’t associated with the survey.
Mental health concerns in the survey were significantly more common among women than men (33.7% vs 26.3%), and for younger cardiologists, compared with older cardiologists (32.2% for those < 40 vs. 22.1% and 16.8% for those 55-69 and 70 or older, respectively).
Those findings seem to make sense, Dr. Sen observed. “Generally, cardiology and medicine broadly are hierarchical, so being more junior can be stressful.” And if there’s more hostility in the workplace, “it might fall on junior people.”
In other studies, moreover, “a high level of work-family conflict has been a real driver of depression and burnout, and that likely is affecting younger physicians, particularly young women physicians,” who may have smaller children and a greater burden of childcare than their seniors.
He pointed to the survey’s low response rate as an important limitation of the study. Of the 71,022 cardiologists invited to participate, only 5,890 (8.3%) responded and answered the queries on mental health.
With a response rate that low, a survey “can be biased in ways that we can’t predict,” Dr. Sen noted. Also, anyone concerned about the toxicity of their own workplace might be “more likely to respond to the survey than if they worked in a more pleasant place. That would provide a skewed sense of the overall experience of cardiologists.”
Those issues might not be a concern with the current survey, however, “because the results are consistent with other studies with higher response rates.”
‘Sobering report’
An accompanying editorial said Dr. Sharm and colleagues have provided “a sobering report on the global prevalence and potential contributors to mental health concerns” in the surveyed population.
Based on its lessons, Andrew J. Sauer, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., proposed several potential “interventions” the field could enact.
It could “selectively promote leaders who strive to mitigate implicit bias, discrimination, and harassment while advancing diversity, equity, and inclusion within the broad ranks of cardiologists.”
Also, he continued, “we must eliminate the stigmatization of mental illness among physicians. We need to handle mental health concerns with compassion and without blaming, like how we strive to treat our veterans who suffer from posttraumatic stress disorder.”
Lastly, Dr. Sauer wrote, “mentorship programs should be formalized to assist the cardiologist in transition zones from early to mid-career, with particular attention to women and those experiencing a simultaneously increased load of family burdens that compound existing workplace contributors to burnout and psychological distress.”
Years in practice
Of the cardiologists who responded to the survey’s mental health questions, 28% reported they have experienced mental health issues that could include alcohol/drug use disorder, suicidal tendencies, psychological distress (including anxiety, irritability, or anger), “other psychiatric disorders” (such as panic disorder, posttraumatic stress, or eating disorders) or major psychiatric disorders such as major depression, bipolar disorder, or schizophrenia.
Cardiologists with 5-10 years of practice post-training were more likely than cardiologists practicing for at least 20 years to have mental health concerns (31.9% vs. 22.6%, P < .001).
Mental health concerns were cited by 42% of respondents who cited “any type of discrimination” based on age, sex, race or ethnicity, or sexual orientation, the report noted.
Among those reporting any mental health concern, 2.7% considered suicide within the past year and 2.9% considered suicide more than 12 months previously. Women were more likely than men to consider suicide within the past year (3.8% vs. 2.3%) but were also more likely to seek help (42.3% vs. 31.1%; P < .001 for both differences), the authors wrote.
In multivariate analysis, predictors of mental health concerns included emotional harassment, 2.81 (odds ratio, 2.81; 95% confidence interval, 2.46-3.20), any discrimination (OR, 1.85; 95% CI, 1.61-2.12), being divorced (OR, 1.73; 95% CI, 1.26-2.36, age less than 55 years (OR, 1.43; 95% CI, 1.24-1.66), and being mid-career versus late (OR, 1.36; 95% CI, 1.14-1.62).
Because the survey was conducted from September to October 2019, before the pandemic’s traumatic effects unfolded on health care nearly everywhere, “I think there needs to be a follow-up at some point when everything has leveled out,” Dr. Sharma said. The current study is “a baseline, and not a healthy baseline,” for the field’s state of mental health that has likely grown worse during the pandemic.
But even without such a follow-up, the current study “is actionable enough that it forces us to do something about it right now.”
Dr. Sharma, Dr. Mehta, their coauthors, Dr. Sen, and Dr. Sauer reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Compulsively checking social media linked with altered brain patterns in teens
Teens who compulsively checked social media networks showed different development patterns in parts of the brain that involve reward and punishment than did those who didn’t check their platforms as often, new research suggests.
Results were published online in JAMA Pediatrics.
Researchers, led by Maria T. Maza, of the department of psychology and neuroscience at University of North Carolina at Chapel Hill, included 169 6th- and 7th-grade students recruited from three public middle schools in rural North Carolina in a 3-year longitudinal cohort.
Participants reported how frequently they checked Facebook, Instagram, and Snapchat. Answers were grouped into eight score groups depending on their per-day check times: less than 1; 1; 2-3; 4-5; 6-10; 11-15; 16-20; or more than 20 times. Those groups were then broken into three categories: low (nonhabitual); moderate; and high (habitual).
Imaging shows reactions
Researchers used functional magnetic resonance imaging (fMRI) to see how different areas of the brain react when participants looked at a series of indicators, such as happy and angry faces, which mimic social media rewards, punishments, or neutral feedback.
The research team focused on adolescents, for whom social media participation and neural sensitivity to social feedback from peers are high.
They found that participants who frequently checked social media showed distinct brain patterns when anticipating social feedback compared with those who had moderate or low use, “suggesting that habitual social media checking early in adolescence is associated with divergent brain development over time.”
The affected regions of the brain included the networks that respond to motivation and cognitive control.
However, the study was not able to determine whether the differences are a good or bad thing.
“While for some individuals with habitual checking behaviors, an initial hyposensitivity to potential social rewards and punishments followed by hypersensitivity may contribute to checking behaviors on social media becoming compulsive and problematic, for others, this change in sensitivity may reflect an adaptive behavior that allows them to better navigate their increasingly digital environment,” the authors wrote.
Chicken-and-egg questions
David Rettew, MD, a child and adolescent psychiatrist at the Oregon Health & Science University in Portland, who was not part of this research, said in an interview that it’s not clear from this study which came first – different brain development in the teens prior to this study that caused compulsive checking, or checking behaviors that caused different brain development. The authors acknowledge this is a limitation of the study.
“Hopefully, someday researchers will look at some of these brain activation patterns before kids have been exposed to social media to help us sort some of these questions out,” Dr. Rettew said.
“It wasn’t as though the groups looked the same at baseline and then diverged as they used more and more social media,” Dr. Rettew said. “It looked like there were some baseline differences that could be traced back maybe years before the study even started.”
People hear “divergent brain development” associated with social media and naturally get alarmed, he acknowledged.
“I get that, but the study isn’t really equipped to tell us what should be happening in the brain and what changes may have implications for other parts of an adolescent’s life,” Dr. Rettew said, “In the end, what we have is an association between heavy social media use and certain brain activation patterns which is cool to see and measure.”
He agrees with the authors, however, that overuse of social media is concerning and studying its effects is important.
Seventy-eight percent of early adolescents check every hour
According to the paper, 78% of 13- to 17-year-olds report checking their devices at least every hour and 46% check “almost constantly.”
“Regardless of which brain regions light up when looking at various emoji responses to their Instagram post, I think it is valid already to have some concerns about youth who can’t stay off their phone for more than 10 minutes,” Dr. Rettew said. “Technology is here to stay, but how we can learn to use it rather than have it use us is probably the more pressing question at this point.”
One coauthor reports grants from the National Institute on Drug Abuse (NIDA) during the conduct of the study and grants from NIDA and the National Science Foundation outside the submitted work; a coauthor reports grants from the Winston Family Foundation; and a coauthor reports a grant from NIDA and funds from the Winston Family Foundation – both during the conduct of the study. No other disclosures were reported. Dr. Rettew is author of the book, “Parenting Made Complicated: What Science Really Knows about the Greatest Debates of Early Childhood.”
Teens who compulsively checked social media networks showed different development patterns in parts of the brain that involve reward and punishment than did those who didn’t check their platforms as often, new research suggests.
Results were published online in JAMA Pediatrics.
Researchers, led by Maria T. Maza, of the department of psychology and neuroscience at University of North Carolina at Chapel Hill, included 169 6th- and 7th-grade students recruited from three public middle schools in rural North Carolina in a 3-year longitudinal cohort.
Participants reported how frequently they checked Facebook, Instagram, and Snapchat. Answers were grouped into eight score groups depending on their per-day check times: less than 1; 1; 2-3; 4-5; 6-10; 11-15; 16-20; or more than 20 times. Those groups were then broken into three categories: low (nonhabitual); moderate; and high (habitual).
Imaging shows reactions
Researchers used functional magnetic resonance imaging (fMRI) to see how different areas of the brain react when participants looked at a series of indicators, such as happy and angry faces, which mimic social media rewards, punishments, or neutral feedback.
The research team focused on adolescents, for whom social media participation and neural sensitivity to social feedback from peers are high.
They found that participants who frequently checked social media showed distinct brain patterns when anticipating social feedback compared with those who had moderate or low use, “suggesting that habitual social media checking early in adolescence is associated with divergent brain development over time.”
The affected regions of the brain included the networks that respond to motivation and cognitive control.
However, the study was not able to determine whether the differences are a good or bad thing.
“While for some individuals with habitual checking behaviors, an initial hyposensitivity to potential social rewards and punishments followed by hypersensitivity may contribute to checking behaviors on social media becoming compulsive and problematic, for others, this change in sensitivity may reflect an adaptive behavior that allows them to better navigate their increasingly digital environment,” the authors wrote.
Chicken-and-egg questions
David Rettew, MD, a child and adolescent psychiatrist at the Oregon Health & Science University in Portland, who was not part of this research, said in an interview that it’s not clear from this study which came first – different brain development in the teens prior to this study that caused compulsive checking, or checking behaviors that caused different brain development. The authors acknowledge this is a limitation of the study.
“Hopefully, someday researchers will look at some of these brain activation patterns before kids have been exposed to social media to help us sort some of these questions out,” Dr. Rettew said.
“It wasn’t as though the groups looked the same at baseline and then diverged as they used more and more social media,” Dr. Rettew said. “It looked like there were some baseline differences that could be traced back maybe years before the study even started.”
People hear “divergent brain development” associated with social media and naturally get alarmed, he acknowledged.
“I get that, but the study isn’t really equipped to tell us what should be happening in the brain and what changes may have implications for other parts of an adolescent’s life,” Dr. Rettew said, “In the end, what we have is an association between heavy social media use and certain brain activation patterns which is cool to see and measure.”
He agrees with the authors, however, that overuse of social media is concerning and studying its effects is important.
Seventy-eight percent of early adolescents check every hour
According to the paper, 78% of 13- to 17-year-olds report checking their devices at least every hour and 46% check “almost constantly.”
“Regardless of which brain regions light up when looking at various emoji responses to their Instagram post, I think it is valid already to have some concerns about youth who can’t stay off their phone for more than 10 minutes,” Dr. Rettew said. “Technology is here to stay, but how we can learn to use it rather than have it use us is probably the more pressing question at this point.”
One coauthor reports grants from the National Institute on Drug Abuse (NIDA) during the conduct of the study and grants from NIDA and the National Science Foundation outside the submitted work; a coauthor reports grants from the Winston Family Foundation; and a coauthor reports a grant from NIDA and funds from the Winston Family Foundation – both during the conduct of the study. No other disclosures were reported. Dr. Rettew is author of the book, “Parenting Made Complicated: What Science Really Knows about the Greatest Debates of Early Childhood.”
Teens who compulsively checked social media networks showed different development patterns in parts of the brain that involve reward and punishment than did those who didn’t check their platforms as often, new research suggests.
Results were published online in JAMA Pediatrics.
Researchers, led by Maria T. Maza, of the department of psychology and neuroscience at University of North Carolina at Chapel Hill, included 169 6th- and 7th-grade students recruited from three public middle schools in rural North Carolina in a 3-year longitudinal cohort.
Participants reported how frequently they checked Facebook, Instagram, and Snapchat. Answers were grouped into eight score groups depending on their per-day check times: less than 1; 1; 2-3; 4-5; 6-10; 11-15; 16-20; or more than 20 times. Those groups were then broken into three categories: low (nonhabitual); moderate; and high (habitual).
Imaging shows reactions
Researchers used functional magnetic resonance imaging (fMRI) to see how different areas of the brain react when participants looked at a series of indicators, such as happy and angry faces, which mimic social media rewards, punishments, or neutral feedback.
The research team focused on adolescents, for whom social media participation and neural sensitivity to social feedback from peers are high.
They found that participants who frequently checked social media showed distinct brain patterns when anticipating social feedback compared with those who had moderate or low use, “suggesting that habitual social media checking early in adolescence is associated with divergent brain development over time.”
The affected regions of the brain included the networks that respond to motivation and cognitive control.
However, the study was not able to determine whether the differences are a good or bad thing.
“While for some individuals with habitual checking behaviors, an initial hyposensitivity to potential social rewards and punishments followed by hypersensitivity may contribute to checking behaviors on social media becoming compulsive and problematic, for others, this change in sensitivity may reflect an adaptive behavior that allows them to better navigate their increasingly digital environment,” the authors wrote.
Chicken-and-egg questions
David Rettew, MD, a child and adolescent psychiatrist at the Oregon Health & Science University in Portland, who was not part of this research, said in an interview that it’s not clear from this study which came first – different brain development in the teens prior to this study that caused compulsive checking, or checking behaviors that caused different brain development. The authors acknowledge this is a limitation of the study.
“Hopefully, someday researchers will look at some of these brain activation patterns before kids have been exposed to social media to help us sort some of these questions out,” Dr. Rettew said.
“It wasn’t as though the groups looked the same at baseline and then diverged as they used more and more social media,” Dr. Rettew said. “It looked like there were some baseline differences that could be traced back maybe years before the study even started.”
People hear “divergent brain development” associated with social media and naturally get alarmed, he acknowledged.
“I get that, but the study isn’t really equipped to tell us what should be happening in the brain and what changes may have implications for other parts of an adolescent’s life,” Dr. Rettew said, “In the end, what we have is an association between heavy social media use and certain brain activation patterns which is cool to see and measure.”
He agrees with the authors, however, that overuse of social media is concerning and studying its effects is important.
Seventy-eight percent of early adolescents check every hour
According to the paper, 78% of 13- to 17-year-olds report checking their devices at least every hour and 46% check “almost constantly.”
“Regardless of which brain regions light up when looking at various emoji responses to their Instagram post, I think it is valid already to have some concerns about youth who can’t stay off their phone for more than 10 minutes,” Dr. Rettew said. “Technology is here to stay, but how we can learn to use it rather than have it use us is probably the more pressing question at this point.”
One coauthor reports grants from the National Institute on Drug Abuse (NIDA) during the conduct of the study and grants from NIDA and the National Science Foundation outside the submitted work; a coauthor reports grants from the Winston Family Foundation; and a coauthor reports a grant from NIDA and funds from the Winston Family Foundation – both during the conduct of the study. No other disclosures were reported. Dr. Rettew is author of the book, “Parenting Made Complicated: What Science Really Knows about the Greatest Debates of Early Childhood.”
FROM JAMA PEDIATRICS