Depression

TOPLINE:

A study found that patients who die by suicide within a year after discharge from inpatient mental health care are less likely to have primary care consultation in the first 2 weeks, highlighting a gap during the high-risk transition period.

METHODOLOGY:

• Researchers used a nested case-control study design, analyzing the records of 613 people who died by suicide within a year of being discharged from an inpatient psychiatric facility in England between 2001 and 2019.
• Of these, 93 (15.4%) died within 2 weeks of discharge.
• Each patient was matched with up to 20 control individuals who were discharged at a similar time but were living.
• Researchers evaluated primary care consultations after discharge.

TAKEAWAY:

• People who died by suicide within a year were less likely to have had a primary care consultation within 2 weeks of discharge (adjusted odds ratio [aOR], 0.61; P = .01).
• Those who died by suicide had higher odds for a consultation in the week preceding their death (aOR, 1.71; P < .001) and the prescription of three or more psychotropic medications (aOR, 1.73; P < .001).
• Evidence of discharge communication between the facility and primary care clinician was infrequent, highlighting a gap in continuity of care.
• Approximately 40% of people who died within 2 weeks of discharge had a documented visit with a primary care clinician during that period.

IN PRACTICE:

“Primary care clinicians have opportunities to intervene and should prioritize patients experiencing transition from inpatient care,” the authors wrote.

SOURCE:

The study was led by Rebecca Musgrove, PhD, of the Centre for Mental Health and Safety at The University of Manchester in England, and published online on June 12 in BJGP Open.

LIMITATIONS:

The study’s reliance on individuals registered with the Clinical Practice Research Datalink may have caused some suicide cases to be excluded, limiting generalizability. Lack of linked up-to-date mental health records may have led to the omission of significant post-discharge care data. Incomplete discharge documentation may undercount informational continuity, affecting multivariable analysis.

DISCLOSURES:

The study was supported by the National Institute of Health and Care Research. Some authors declared serving as members of advisory groups and receiving grants and personal fees from various sources.

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

TOPLINE:

A study found that patients who die by suicide within a year after discharge from inpatient mental health care are less likely to have primary care consultation in the first 2 weeks, highlighting a gap during the high-risk transition period.

METHODOLOGY:

• Researchers used a nested case-control study design, analyzing the records of 613 people who died by suicide within a year of being discharged from an inpatient psychiatric facility in England between 2001 and 2019.
• Of these, 93 (15.4%) died within 2 weeks of discharge.
• Each patient was matched with up to 20 control individuals who were discharged at a similar time but were living.
• Researchers evaluated primary care consultations after discharge.

TAKEAWAY:

• People who died by suicide within a year were less likely to have had a primary care consultation within 2 weeks of discharge (adjusted odds ratio [aOR], 0.61; P = .01).
• Those who died by suicide had higher odds for a consultation in the week preceding their death (aOR, 1.71; P < .001) and the prescription of three or more psychotropic medications (aOR, 1.73; P < .001).
• Evidence of discharge communication between the facility and primary care clinician was infrequent, highlighting a gap in continuity of care.
• Approximately 40% of people who died within 2 weeks of discharge had a documented visit with a primary care clinician during that period.

IN PRACTICE:

“Primary care clinicians have opportunities to intervene and should prioritize patients experiencing transition from inpatient care,” the authors wrote.

SOURCE:

The study was led by Rebecca Musgrove, PhD, of the Centre for Mental Health and Safety at The University of Manchester in England, and published online on June 12 in BJGP Open.

LIMITATIONS:

The study’s reliance on individuals registered with the Clinical Practice Research Datalink may have caused some suicide cases to be excluded, limiting generalizability. Lack of linked up-to-date mental health records may have led to the omission of significant post-discharge care data. Incomplete discharge documentation may undercount informational continuity, affecting multivariable analysis.

DISCLOSURES:

The study was supported by the National Institute of Health and Care Research. Some authors declared serving as members of advisory groups and receiving grants and personal fees from various sources.

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

TOPLINE:

A study found that patients who die by suicide within a year after discharge from inpatient mental health care are less likely to have primary care consultation in the first 2 weeks, highlighting a gap during the high-risk transition period.

METHODOLOGY:

• Researchers used a nested case-control study design, analyzing the records of 613 people who died by suicide within a year of being discharged from an inpatient psychiatric facility in England between 2001 and 2019.
• Of these, 93 (15.4%) died within 2 weeks of discharge.
• Each patient was matched with up to 20 control individuals who were discharged at a similar time but were living.
• Researchers evaluated primary care consultations after discharge.

TAKEAWAY:

• People who died by suicide within a year were less likely to have had a primary care consultation within 2 weeks of discharge (adjusted odds ratio [aOR], 0.61; P = .01).
• Those who died by suicide had higher odds for a consultation in the week preceding their death (aOR, 1.71; P < .001) and the prescription of three or more psychotropic medications (aOR, 1.73; P < .001).
• Evidence of discharge communication between the facility and primary care clinician was infrequent, highlighting a gap in continuity of care.
• Approximately 40% of people who died within 2 weeks of discharge had a documented visit with a primary care clinician during that period.

IN PRACTICE:

“Primary care clinicians have opportunities to intervene and should prioritize patients experiencing transition from inpatient care,” the authors wrote.

SOURCE:

The study was led by Rebecca Musgrove, PhD, of the Centre for Mental Health and Safety at The University of Manchester in England, and published online on June 12 in BJGP Open.

LIMITATIONS:

The study’s reliance on individuals registered with the Clinical Practice Research Datalink may have caused some suicide cases to be excluded, limiting generalizability. Lack of linked up-to-date mental health records may have led to the omission of significant post-discharge care data. Incomplete discharge documentation may undercount informational continuity, affecting multivariable analysis.

DISCLOSURES:

The study was supported by the National Institute of Health and Care Research. Some authors declared serving as members of advisory groups and receiving grants and personal fees from various sources.

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

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

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

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

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

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

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

Brain imaging combined with artificial intelligence has identified six distinct “biotypes” of depression and anxiety that may lead to more personalized and effective treatment.

This research has “immediate clinical implications,” study investigator Leanne Williams, PhD, director of the Stanford Medicine Center for Precision Mental Health and Wellness, told this news organization.

“At Stanford, we have started translating the imaging technology into use in a new precision mental health clinic. The technology is being actively developed for wider use in clinical settings, and we hope to make it accessible to more clinicians and patients,” Dr. Williams said.

The study was published online in Nature Medicine.

 

No More Trial and Error?

Depression is a highly heterogeneous disease, with individual patients having different symptoms and treatment responses. About 30% of patients with major depression are resistant to treatment, and about half of patients with generalized anxiety disorder do not respond to first-line treatment.

“The dominant ‘one-size-fits-all’ diagnostic approach in psychiatry leads to cycling through treatment options by trial and error, which is lengthy, expensive, and frustrating, with 30%-40% of patients not achieving remission after trying one treatment,” the authors noted.

“The goal of our work is figuring out how we can get it right the first time,” Dr. Williams said in a news release, and that requires a better understanding of the neurobiology of depression.

To that end, 801 adults diagnosed with depression and anxiety underwent functional MRI to measure brain activity at rest and when engaged in tasks designed to test cognitive and emotional functioning.

Researchers probed six brain circuits previously associated with depression: the default mode circuit, salience circuit, attention circuit, negative affect circuit, positive affect circuit, and the cognitive control circuit.

Using a machine learning technique known as cluster analysis to group the patients’ brain images, they identified six clinically distinct biotypes of depression and anxiety defined by specific profiles of dysfunction within both task-free and task-evoked brain circuits.

“Importantly for clinical translation, these biotypes predict response to different pharmacological and behavioral interventions,” investigators wrote.

For example, patients with a biotype characterized by overactivity in cognitive regions of the brain experienced the best response to the antidepressant venlafaxine, compared with patients with other biotypes.

Patients with a different biotype, characterized by higher at-rest levels of activity in three regions associated with depression and problem-solving, responded better to behavioral therapy.

In addition, those with a third biotype, who had lower levels of activity at rest in the brain circuit that controls attention, were less apt to see improvement of their symptoms with behavioral therapy than those with other biotypes. The various biotypes also correlated with differences in symptoms and task performance.

For example, individuals with overactive cognitive regions of the brain had higher levels of anhedonia than those with other biotypes, and they also performed worse on tasks measuring executive function. Those with the biotype that responded best to behavioral therapy also made errors on executive function tasks but performed well on cognitive tasks.
 

A Work in Progress

The findings provide a deeper understanding of the neurobiological underpinnings of depression and anxiety and could lead to improved diagnostic accuracy and more tailored treatment approaches, the researchers noted.

Naming the biotypes is a work in progress, Dr. Williams said.

“We have thought a lot about the naming. In the Nature Medicine paper, we use a technical convention to name the biotypes based on which brain circuit problems define each of them,” she explained.

“For example, the first biotype is called DC+SC+AC+ because it is defined by connectivity increases [C+] on three resting circuits — default mode [D], salience [S], and frontoparietal attention [A]. We are working with collaborators to generate biotype names that could be convergent across findings and labs. In the near future, we anticipate generating more descriptive medical names that clinicians could refer to alongside the technical names,” Dr. Williams said.

Commenting on the research for this news organization, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai, New York, called it “super exciting.”

“The work from this research group is an excellent example of where precision psychiatry research is right now, particularly with regard to the use of brain imaging to personalize treatment, and this paper gives us a glimpse of where we could be in the not-too-distant future,” Dr. Murrough said.

However, he cautioned that at this point, “we’re far from realizing the dream of precision psychiatry. We just don’t have robust evidence that brain imaging markers can really guide clinical decision-making currently.”

Funding for the study was provided by the National Institutes of Health and by Brain Resource Ltd. Dr. Williams declared US patent applications numbered 10/034,645 and 15/820,338: “Systems and methods for detecting complex networks in MRI data.” Dr. Murrough had no relevant disclosures.

A version of this article appeared on Medscape.com.

Brain imaging combined with artificial intelligence has identified six distinct “biotypes” of depression and anxiety that may lead to more personalized and effective treatment.

This research has “immediate clinical implications,” study investigator Leanne Williams, PhD, director of the Stanford Medicine Center for Precision Mental Health and Wellness, told this news organization.

“At Stanford, we have started translating the imaging technology into use in a new precision mental health clinic. The technology is being actively developed for wider use in clinical settings, and we hope to make it accessible to more clinicians and patients,” Dr. Williams said.

The study was published online in Nature Medicine.

 

No More Trial and Error?

Depression is a highly heterogeneous disease, with individual patients having different symptoms and treatment responses. About 30% of patients with major depression are resistant to treatment, and about half of patients with generalized anxiety disorder do not respond to first-line treatment.

“The dominant ‘one-size-fits-all’ diagnostic approach in psychiatry leads to cycling through treatment options by trial and error, which is lengthy, expensive, and frustrating, with 30%-40% of patients not achieving remission after trying one treatment,” the authors noted.

“The goal of our work is figuring out how we can get it right the first time,” Dr. Williams said in a news release, and that requires a better understanding of the neurobiology of depression.

To that end, 801 adults diagnosed with depression and anxiety underwent functional MRI to measure brain activity at rest and when engaged in tasks designed to test cognitive and emotional functioning.

Researchers probed six brain circuits previously associated with depression: the default mode circuit, salience circuit, attention circuit, negative affect circuit, positive affect circuit, and the cognitive control circuit.

Using a machine learning technique known as cluster analysis to group the patients’ brain images, they identified six clinically distinct biotypes of depression and anxiety defined by specific profiles of dysfunction within both task-free and task-evoked brain circuits.

“Importantly for clinical translation, these biotypes predict response to different pharmacological and behavioral interventions,” investigators wrote.

For example, patients with a biotype characterized by overactivity in cognitive regions of the brain experienced the best response to the antidepressant venlafaxine, compared with patients with other biotypes.

Patients with a different biotype, characterized by higher at-rest levels of activity in three regions associated with depression and problem-solving, responded better to behavioral therapy.

In addition, those with a third biotype, who had lower levels of activity at rest in the brain circuit that controls attention, were less apt to see improvement of their symptoms with behavioral therapy than those with other biotypes. The various biotypes also correlated with differences in symptoms and task performance.

For example, individuals with overactive cognitive regions of the brain had higher levels of anhedonia than those with other biotypes, and they also performed worse on tasks measuring executive function. Those with the biotype that responded best to behavioral therapy also made errors on executive function tasks but performed well on cognitive tasks.
 

A Work in Progress

The findings provide a deeper understanding of the neurobiological underpinnings of depression and anxiety and could lead to improved diagnostic accuracy and more tailored treatment approaches, the researchers noted.

Naming the biotypes is a work in progress, Dr. Williams said.

“We have thought a lot about the naming. In the Nature Medicine paper, we use a technical convention to name the biotypes based on which brain circuit problems define each of them,” she explained.

“For example, the first biotype is called DC+SC+AC+ because it is defined by connectivity increases [C+] on three resting circuits — default mode [D], salience [S], and frontoparietal attention [A]. We are working with collaborators to generate biotype names that could be convergent across findings and labs. In the near future, we anticipate generating more descriptive medical names that clinicians could refer to alongside the technical names,” Dr. Williams said.

Commenting on the research for this news organization, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai, New York, called it “super exciting.”

“The work from this research group is an excellent example of where precision psychiatry research is right now, particularly with regard to the use of brain imaging to personalize treatment, and this paper gives us a glimpse of where we could be in the not-too-distant future,” Dr. Murrough said.

However, he cautioned that at this point, “we’re far from realizing the dream of precision psychiatry. We just don’t have robust evidence that brain imaging markers can really guide clinical decision-making currently.”

Funding for the study was provided by the National Institutes of Health and by Brain Resource Ltd. Dr. Williams declared US patent applications numbered 10/034,645 and 15/820,338: “Systems and methods for detecting complex networks in MRI data.” Dr. Murrough had no relevant disclosures.

A version of this article appeared on Medscape.com.

Brain imaging combined with artificial intelligence has identified six distinct “biotypes” of depression and anxiety that may lead to more personalized and effective treatment.

This research has “immediate clinical implications,” study investigator Leanne Williams, PhD, director of the Stanford Medicine Center for Precision Mental Health and Wellness, told this news organization.

“At Stanford, we have started translating the imaging technology into use in a new precision mental health clinic. The technology is being actively developed for wider use in clinical settings, and we hope to make it accessible to more clinicians and patients,” Dr. Williams said.

The study was published online in Nature Medicine.

 

No More Trial and Error?

Depression is a highly heterogeneous disease, with individual patients having different symptoms and treatment responses. About 30% of patients with major depression are resistant to treatment, and about half of patients with generalized anxiety disorder do not respond to first-line treatment.

“The dominant ‘one-size-fits-all’ diagnostic approach in psychiatry leads to cycling through treatment options by trial and error, which is lengthy, expensive, and frustrating, with 30%-40% of patients not achieving remission after trying one treatment,” the authors noted.

“The goal of our work is figuring out how we can get it right the first time,” Dr. Williams said in a news release, and that requires a better understanding of the neurobiology of depression.

To that end, 801 adults diagnosed with depression and anxiety underwent functional MRI to measure brain activity at rest and when engaged in tasks designed to test cognitive and emotional functioning.

Researchers probed six brain circuits previously associated with depression: the default mode circuit, salience circuit, attention circuit, negative affect circuit, positive affect circuit, and the cognitive control circuit.

Using a machine learning technique known as cluster analysis to group the patients’ brain images, they identified six clinically distinct biotypes of depression and anxiety defined by specific profiles of dysfunction within both task-free and task-evoked brain circuits.

“Importantly for clinical translation, these biotypes predict response to different pharmacological and behavioral interventions,” investigators wrote.

For example, patients with a biotype characterized by overactivity in cognitive regions of the brain experienced the best response to the antidepressant venlafaxine, compared with patients with other biotypes.

Patients with a different biotype, characterized by higher at-rest levels of activity in three regions associated with depression and problem-solving, responded better to behavioral therapy.

In addition, those with a third biotype, who had lower levels of activity at rest in the brain circuit that controls attention, were less apt to see improvement of their symptoms with behavioral therapy than those with other biotypes. The various biotypes also correlated with differences in symptoms and task performance.

For example, individuals with overactive cognitive regions of the brain had higher levels of anhedonia than those with other biotypes, and they also performed worse on tasks measuring executive function. Those with the biotype that responded best to behavioral therapy also made errors on executive function tasks but performed well on cognitive tasks.
 

A Work in Progress

The findings provide a deeper understanding of the neurobiological underpinnings of depression and anxiety and could lead to improved diagnostic accuracy and more tailored treatment approaches, the researchers noted.

Naming the biotypes is a work in progress, Dr. Williams said.

“We have thought a lot about the naming. In the Nature Medicine paper, we use a technical convention to name the biotypes based on which brain circuit problems define each of them,” she explained.

“For example, the first biotype is called DC+SC+AC+ because it is defined by connectivity increases [C+] on three resting circuits — default mode [D], salience [S], and frontoparietal attention [A]. We are working with collaborators to generate biotype names that could be convergent across findings and labs. In the near future, we anticipate generating more descriptive medical names that clinicians could refer to alongside the technical names,” Dr. Williams said.

Commenting on the research for this news organization, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai, New York, called it “super exciting.”

“The work from this research group is an excellent example of where precision psychiatry research is right now, particularly with regard to the use of brain imaging to personalize treatment, and this paper gives us a glimpse of where we could be in the not-too-distant future,” Dr. Murrough said.

However, he cautioned that at this point, “we’re far from realizing the dream of precision psychiatry. We just don’t have robust evidence that brain imaging markers can really guide clinical decision-making currently.”

Funding for the study was provided by the National Institutes of Health and by Brain Resource Ltd. Dr. Williams declared US patent applications numbered 10/034,645 and 15/820,338: “Systems and methods for detecting complex networks in MRI data.” Dr. Murrough had no relevant disclosures.

A version of this article appeared on Medscape.com.

HOUSTON — Sleep may have a role in driving down rates of loneliness, especially among younger adults.

A study of nearly 2300 participants showed that better sleep health is associated with significantly lower levels of loneliness across ages and that the association is particularly strong in younger individuals.

The US Surgeon General has identified loneliness as “a major public health concern, linked to high rates of negative physical and mental health outcomes,” lead researcher Joseph Dzierzewski, PhD, vice president for research and scientific affairs at the National Sleep Foundation, told this news organization.

“Loneliness is an urgent public health crisis, and there is a pressing need for providers to better understand and treat it,” Dr. Dzierzewski said in a statement.

“Better sleep health might be connected to lower feelings of loneliness by empowering people to engage in social activities, reducing feelings of negative emotions and increasing the likelihood that people interpret interactions in a positive way,” he added.

The findings were presented at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies and recently published in an online supplement of the journal Sleep.
 

Rested, Connected

An American Psychiatric Association poll conducted earlier this year showed 30% of US adults reported feelings of loneliness at least once a week over the past year, and 10% reported feeling lonely every day.

Younger people are more likely to report feeling lonely, with 30% of Americans, aged 18-34 years, feeling lonely every day or several times a week.

While there is growing research identifying a relationship between loneliness and poor sleep in different age groups, few studies have explored ties between social and emotional loneliness and sleep health across the adult lifespan.

In the current study led by Dr. Dzierzewski, 2297 adults (mean age, 44 years; 51% male) completed a validated sleep health questionnaire and loneliness scale.

Linear regression analyses were used to examine the direct associations between sleep health, age, and loneliness. Moderation analyses tested whether the link between sleep health and loneliness differed by age.

On average, the total sleep score was 7.7 (range, 0-12), with higher scores indicating better multidimensional sleep health, and total loneliness scale score was 8.9 (out of 11), indicating moderate levels of loneliness.

Better sleep health and younger age were associated with significantly lower loneliness total scores and social and emotional loneliness subscale scores (all P < .001).

Age significantly moderated the association between sleep health and total (P < .001) and emotional loneliness scores (P < .001) but did not moderate the association between sleep health and social loneliness (P = .034). Better sleep health was associated with lower loneliness across ages, and this association was stronger at younger ages.

“Why younger adults might experience more sleep-related benefits to loneliness than older adults is unknown and intriguing — certainly worth further investigation,” Dr. Dzierzewski said in a conference statement.
 

Untapped Avenue

Promoting sleep health may be an “untapped avenue” to support efforts and programs that aim to reduce loneliness and increase engagement in all age groups but especially in younger ages, the researchers noted.

Future research should consider monitoring sleep health in programs or interventions that address loneliness, they added.

“Healthcare providers should be aware of the important link between sleep health and loneliness as both sleep and social connections are essential to health and well-being. When sitting across from patients, asking about both sleep health and loneliness might yield important insights into avenues for health promotion,” said Dr. Dzierzewski.

Michael Breus, PhD, clinical psychologist and founder of SleepDoctor.com, who wasn’t involved in the study, is not surprised by the results.

It makes sense that better sleep would lead to less feelings of loneliness, he told this news organization.

Research has shown that when someone is not sleeping well, they “give others a sense of unhappiness, which socially deflects new encounters or even encounters with friends. So social awareness and social initiation would appear to both be affected by sleep quality, therefore potentially leading, at least in part, to loneliness,” he said.

Support for the study was provided by the National Institute on Aging. Dr. Dzierzewski and Dr. Breus had no relevant disclosures.

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

HOUSTON — Sleep may have a role in driving down rates of loneliness, especially among younger adults.

A study of nearly 2300 participants showed that better sleep health is associated with significantly lower levels of loneliness across ages and that the association is particularly strong in younger individuals.

The US Surgeon General has identified loneliness as “a major public health concern, linked to high rates of negative physical and mental health outcomes,” lead researcher Joseph Dzierzewski, PhD, vice president for research and scientific affairs at the National Sleep Foundation, told this news organization.

“Loneliness is an urgent public health crisis, and there is a pressing need for providers to better understand and treat it,” Dr. Dzierzewski said in a statement.

“Better sleep health might be connected to lower feelings of loneliness by empowering people to engage in social activities, reducing feelings of negative emotions and increasing the likelihood that people interpret interactions in a positive way,” he added.

The findings were presented at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies and recently published in an online supplement of the journal Sleep.
 

Rested, Connected

An American Psychiatric Association poll conducted earlier this year showed 30% of US adults reported feelings of loneliness at least once a week over the past year, and 10% reported feeling lonely every day.

Younger people are more likely to report feeling lonely, with 30% of Americans, aged 18-34 years, feeling lonely every day or several times a week.

While there is growing research identifying a relationship between loneliness and poor sleep in different age groups, few studies have explored ties between social and emotional loneliness and sleep health across the adult lifespan.

In the current study led by Dr. Dzierzewski, 2297 adults (mean age, 44 years; 51% male) completed a validated sleep health questionnaire and loneliness scale.

Linear regression analyses were used to examine the direct associations between sleep health, age, and loneliness. Moderation analyses tested whether the link between sleep health and loneliness differed by age.

On average, the total sleep score was 7.7 (range, 0-12), with higher scores indicating better multidimensional sleep health, and total loneliness scale score was 8.9 (out of 11), indicating moderate levels of loneliness.

Better sleep health and younger age were associated with significantly lower loneliness total scores and social and emotional loneliness subscale scores (all P < .001).

Age significantly moderated the association between sleep health and total (P < .001) and emotional loneliness scores (P < .001) but did not moderate the association between sleep health and social loneliness (P = .034). Better sleep health was associated with lower loneliness across ages, and this association was stronger at younger ages.

“Why younger adults might experience more sleep-related benefits to loneliness than older adults is unknown and intriguing — certainly worth further investigation,” Dr. Dzierzewski said in a conference statement.
 

Untapped Avenue

Promoting sleep health may be an “untapped avenue” to support efforts and programs that aim to reduce loneliness and increase engagement in all age groups but especially in younger ages, the researchers noted.

Future research should consider monitoring sleep health in programs or interventions that address loneliness, they added.

“Healthcare providers should be aware of the important link between sleep health and loneliness as both sleep and social connections are essential to health and well-being. When sitting across from patients, asking about both sleep health and loneliness might yield important insights into avenues for health promotion,” said Dr. Dzierzewski.

Michael Breus, PhD, clinical psychologist and founder of SleepDoctor.com, who wasn’t involved in the study, is not surprised by the results.

It makes sense that better sleep would lead to less feelings of loneliness, he told this news organization.

Research has shown that when someone is not sleeping well, they “give others a sense of unhappiness, which socially deflects new encounters or even encounters with friends. So social awareness and social initiation would appear to both be affected by sleep quality, therefore potentially leading, at least in part, to loneliness,” he said.

Support for the study was provided by the National Institute on Aging. Dr. Dzierzewski and Dr. Breus had no relevant disclosures.

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

HOUSTON — Sleep may have a role in driving down rates of loneliness, especially among younger adults.

A study of nearly 2300 participants showed that better sleep health is associated with significantly lower levels of loneliness across ages and that the association is particularly strong in younger individuals.

The US Surgeon General has identified loneliness as “a major public health concern, linked to high rates of negative physical and mental health outcomes,” lead researcher Joseph Dzierzewski, PhD, vice president for research and scientific affairs at the National Sleep Foundation, told this news organization.

“Loneliness is an urgent public health crisis, and there is a pressing need for providers to better understand and treat it,” Dr. Dzierzewski said in a statement.

“Better sleep health might be connected to lower feelings of loneliness by empowering people to engage in social activities, reducing feelings of negative emotions and increasing the likelihood that people interpret interactions in a positive way,” he added.

The findings were presented at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies and recently published in an online supplement of the journal Sleep.
 

Rested, Connected

An American Psychiatric Association poll conducted earlier this year showed 30% of US adults reported feelings of loneliness at least once a week over the past year, and 10% reported feeling lonely every day.

Younger people are more likely to report feeling lonely, with 30% of Americans, aged 18-34 years, feeling lonely every day or several times a week.

While there is growing research identifying a relationship between loneliness and poor sleep in different age groups, few studies have explored ties between social and emotional loneliness and sleep health across the adult lifespan.

In the current study led by Dr. Dzierzewski, 2297 adults (mean age, 44 years; 51% male) completed a validated sleep health questionnaire and loneliness scale.

Linear regression analyses were used to examine the direct associations between sleep health, age, and loneliness. Moderation analyses tested whether the link between sleep health and loneliness differed by age.

On average, the total sleep score was 7.7 (range, 0-12), with higher scores indicating better multidimensional sleep health, and total loneliness scale score was 8.9 (out of 11), indicating moderate levels of loneliness.

Better sleep health and younger age were associated with significantly lower loneliness total scores and social and emotional loneliness subscale scores (all P < .001).

Age significantly moderated the association between sleep health and total (P < .001) and emotional loneliness scores (P < .001) but did not moderate the association between sleep health and social loneliness (P = .034). Better sleep health was associated with lower loneliness across ages, and this association was stronger at younger ages.

“Why younger adults might experience more sleep-related benefits to loneliness than older adults is unknown and intriguing — certainly worth further investigation,” Dr. Dzierzewski said in a conference statement.
 

Untapped Avenue

Promoting sleep health may be an “untapped avenue” to support efforts and programs that aim to reduce loneliness and increase engagement in all age groups but especially in younger ages, the researchers noted.

Future research should consider monitoring sleep health in programs or interventions that address loneliness, they added.

“Healthcare providers should be aware of the important link between sleep health and loneliness as both sleep and social connections are essential to health and well-being. When sitting across from patients, asking about both sleep health and loneliness might yield important insights into avenues for health promotion,” said Dr. Dzierzewski.

Michael Breus, PhD, clinical psychologist and founder of SleepDoctor.com, who wasn’t involved in the study, is not surprised by the results.

It makes sense that better sleep would lead to less feelings of loneliness, he told this news organization.

Research has shown that when someone is not sleeping well, they “give others a sense of unhappiness, which socially deflects new encounters or even encounters with friends. So social awareness and social initiation would appear to both be affected by sleep quality, therefore potentially leading, at least in part, to loneliness,” he said.

Support for the study was provided by the National Institute on Aging. Dr. Dzierzewski and Dr. Breus had no relevant disclosures.

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

Do drugs work better if taken by the clock?

A new analysis published in The Lancet journal’s eClinicalMedicine suggests: Yes, they do — if you consider the patient’s individual body clock. The study is the first to find that timing blood pressure drugs to a person’s personal “chronotype” — that is, whether they are a night owl or an early bird — may reduce the risk for a heart attack.

The findings represent a significant advance in the field of circadian medicine or “chronotherapy” — timing drug administration to circadian rhythms. A growing stack of research suggests this approach could reduce side effects and improve the effectiveness of a wide range of therapies, including vaccines, cancer treatments, and drugs for depression, glaucoma, pain, seizures, and other conditions. Still, despite decades of research, time of day is rarely considered in writing prescriptions.

“We are really just at the beginning of an exciting new way of looking at patient care,” said Kenneth A. Dyar, PhD, whose lab at Helmholtz Zentrum München’s Institute for Diabetes and Cancer focuses on metabolic physiology. Dr. Dyar is co-lead author of the new blood pressure analysis.

“Chronotherapy is a rapidly growing field,” he said, “and I suspect we are soon going to see more and more studies focused on ‘personalized chronotherapy,’ not only in hypertension but also potentially in other clinical areas.”
 

The ‘Missing Piece’ in Chronotherapy Research

Blood pressure drugs have long been chronotherapy’s battleground. After all, blood pressure follows a circadian rhythm, peaking in the morning and dropping at night.

That healthy overnight dip can disappear in people with diabetes, kidney disease, and obstructive sleep apnea. Some physicians have suggested a bed-time dose to restore that dip. But studies have had mixed results, so “take at bedtime” has become a less common recommendation in recent years.

But the debate continued. After a large 2019 Spanish study found that bedtime doses had benefits so big that the results drew questions, an even larger, 2022 randomized, controlled trial from the University of Dundee in Dundee, Scotland — called the TIME study — aimed to settle the question.

Researchers assigned over 21,000 people to take morning or night hypertension drugs for several years and found no difference in cardiovascular outcomes.

“We did this study thinking nocturnal blood pressure tablets might be better,” said Thomas MacDonald, MD, professor emeritus of clinical pharmacology and pharmacoepidemiology at the University of Dundee and principal investigator for the TIME study and the recent chronotype analysis. “But there was no difference for heart attacks, strokes, or vascular death.”

So, the researchers then looked at participants’ chronotypes, sorting outcomes based on whether the participants were late-to-bed, late-to-rise “night owls” or early-to-bed, early-to-rise “morning larks.”

Their analysis of these 5358 TIME participants found the following results: Risk for hospitalization for a heart attack was at least 34% lower for “owls” who took their drugs at bedtime. By contrast, owls’ heart attack risk was at least 62% higher with morning doses. For “larks,” the opposite was true. Morning doses were associated with an 11% lower heart attack risk and night doses with an 11% higher risk, according to supplemental data.

The personalized approach could explain why some previous chronotherapy studies have failed to show a benefit. Those studies did not individualize drug timing as this one did. But personalization could be key to circadian medicine’s success.

“Our ‘internal personal time’ appears to be an important variable to consider when dosing antihypertensives,” said co-lead author Filippo Pigazzani, MD, PhD, clinical senior lecturer and honorary consultant cardiologist at the University of Dundee School of Medicine. “Chronotherapy research has been going on for decades. We knew there was something important with time of day. But researchers haven’t considered the internal time of individual people. I think that is the missing piece.”

The analysis has several important limitations, the researchers said. A total of 95% of participants were White. And it was an observational study, not a true randomized comparison. “We started it late in the original TIME study,” Dr. MacDonald said. “You could argue we were reporting on those who survived long enough to get into the analysis.” More research is needed, they concluded.
 

Looking Beyond Blood Pressure

What about the rest of the body? “Almost all the cells of our body contain ‘circadian clocks’ that are synchronized by daily environmental cues, including light-dark, activity-rest, and feeding-fasting cycles,” said Dr. Dyar.

An estimated 50% of prescription drugs hit targets in the body that have circadian patterns. So, experts suspect that syncing a drug with a person’s body clock might increase effectiveness of many drugs.

A handful of US Food and Drug Administration–approved drugs already have time-of-day recommendations on the label for effectiveness or to limit side effects, including bedtime or evening for the insomnia drug Ambien, the HIV antiviral Atripla, and cholesterol-lowering Zocor. Others are intended to be taken with or after your last meal of the day, such as the long-acting insulin Levemir and the cardiovascular drug Xarelto. A morning recommendation comes with the proton pump inhibitor Nexium and the attention-deficit/hyperactivity disorder drug Ritalin.

Interest is expanding. About one third of the papers published about chronotherapy in the past 25 years have come out in the past 5 years. The May 2024 meeting of the Society for Research on Biological Rhythms featured a day-long session aimed at bringing clinicians up to speed. An organization called the International Association of Circadian Health Clinics is trying to bring circadian medicine findings to clinicians and their patients and to support research.

Moreover, while recent research suggests minding the clock could have benefits for a wide range of treatments, ignoring it could cause problems.

In a Massachusetts Institute of Technology study published in April in Science Advances, researchers looked at engineered livers made from human donor cells and found more than 300 genes that operate on a circadian schedule, many with roles in drug metabolism. They also found that circadian patterns affected the toxicity of acetaminophen and atorvastatin. Identifying the time of day to take these drugs could maximize effectiveness and minimize adverse effects, the researchers said.
 

Timing and the Immune System

Circadian rhythms are also seen in immune processes. In a 2023 study in The Journal of Clinical Investigation of vaccine data from 1.5 million people in Israel, researchers found that children and older adults who got their second dose of the Pfizer mRNA COVID vaccine earlier in the day were about 36% less likely to be hospitalized with SARS-CoV-2 infection than those who got an evening shot.

“The sweet spot in our data was somewhere around late morning to late afternoon,” said lead researcher Jeffrey Haspel, MD, PhD, associate professor of medicine in the division of pulmonary and critical care medicine at Washington University School of Medicine in St. Louis.

In a multicenter, 2024 analysis of 13 studies of immunotherapy for advanced cancers in 1663 people, researchers found treatment earlier in the day was associated with longer survival time and longer survival without cancer progression.

“Patients with selected metastatic cancers seemed to largely benefit from early [time of day] infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking,” the researchers noted. But “retrospective randomized trials are needed to establish recommendations for optimal circadian timing.”

Other research suggests or is investigating possible chronotherapy benefits for depression, glaucoma, respiratory diseases, stroke treatment, epilepsy, and sedatives used in surgery. So why aren’t healthcare providers adding time of day to more prescriptions? “What’s missing is more reliable data,” Dr. Dyar said.
 

Should You Use Chronotherapy Now?

Experts emphasize that more research is needed before doctors use chronotherapy and before medical organizations include it in treatment recommendations. But for some patients, circadian dosing may be worth a try:

Night owls whose blood pressure isn’t well controlled. Dr. Dyar and Dr. Pigazzani said night-time blood pressure drugs may be helpful for people with a “late chronotype.” Of course, patients shouldn’t change their medication schedule on their own, they said. And doctors may want to consider other concerns, like more overnight bathroom visits with evening diuretics.

In their study, the researchers determined participants’ chronotype with a few questions from the Munich Chronotype Questionnaire about what time they fell asleep and woke up on workdays and days off and whether they considered themselves “morning types” or “evening types.” (The questions can be found in supplementary data for the study.)

If a physician thinks matching the timing of a dose with chronotype would help, they can consider it, Dr. Pigazzani said. “However, I must add that this was an observational study, so I would advise healthcare practitioners to wait for our data to be confirmed in new RCTs of personalized chronotherapy of hypertension.”

Children and older adults getting vaccines. Timing COVID shots and possibly other vaccines from late morning to mid-afternoon could have a small benefit for individuals and a bigger public-health benefit, Dr. Haspel said. But the most important thing is getting vaccinated. “If you can only get one in the evening, it’s still worthwhile. Timing may add oomph at a public-health level for more vulnerable groups.”
 

A version of this article appeared on Medscape.com.

Do drugs work better if taken by the clock?

A new analysis published in The Lancet journal’s eClinicalMedicine suggests: Yes, they do — if you consider the patient’s individual body clock. The study is the first to find that timing blood pressure drugs to a person’s personal “chronotype” — that is, whether they are a night owl or an early bird — may reduce the risk for a heart attack.

The findings represent a significant advance in the field of circadian medicine or “chronotherapy” — timing drug administration to circadian rhythms. A growing stack of research suggests this approach could reduce side effects and improve the effectiveness of a wide range of therapies, including vaccines, cancer treatments, and drugs for depression, glaucoma, pain, seizures, and other conditions. Still, despite decades of research, time of day is rarely considered in writing prescriptions.

“We are really just at the beginning of an exciting new way of looking at patient care,” said Kenneth A. Dyar, PhD, whose lab at Helmholtz Zentrum München’s Institute for Diabetes and Cancer focuses on metabolic physiology. Dr. Dyar is co-lead author of the new blood pressure analysis.

“Chronotherapy is a rapidly growing field,” he said, “and I suspect we are soon going to see more and more studies focused on ‘personalized chronotherapy,’ not only in hypertension but also potentially in other clinical areas.”
 

The ‘Missing Piece’ in Chronotherapy Research

Blood pressure drugs have long been chronotherapy’s battleground. After all, blood pressure follows a circadian rhythm, peaking in the morning and dropping at night.

That healthy overnight dip can disappear in people with diabetes, kidney disease, and obstructive sleep apnea. Some physicians have suggested a bed-time dose to restore that dip. But studies have had mixed results, so “take at bedtime” has become a less common recommendation in recent years.

But the debate continued. After a large 2019 Spanish study found that bedtime doses had benefits so big that the results drew questions, an even larger, 2022 randomized, controlled trial from the University of Dundee in Dundee, Scotland — called the TIME study — aimed to settle the question.

Researchers assigned over 21,000 people to take morning or night hypertension drugs for several years and found no difference in cardiovascular outcomes.

“We did this study thinking nocturnal blood pressure tablets might be better,” said Thomas MacDonald, MD, professor emeritus of clinical pharmacology and pharmacoepidemiology at the University of Dundee and principal investigator for the TIME study and the recent chronotype analysis. “But there was no difference for heart attacks, strokes, or vascular death.”

So, the researchers then looked at participants’ chronotypes, sorting outcomes based on whether the participants were late-to-bed, late-to-rise “night owls” or early-to-bed, early-to-rise “morning larks.”

Their analysis of these 5358 TIME participants found the following results: Risk for hospitalization for a heart attack was at least 34% lower for “owls” who took their drugs at bedtime. By contrast, owls’ heart attack risk was at least 62% higher with morning doses. For “larks,” the opposite was true. Morning doses were associated with an 11% lower heart attack risk and night doses with an 11% higher risk, according to supplemental data.

The personalized approach could explain why some previous chronotherapy studies have failed to show a benefit. Those studies did not individualize drug timing as this one did. But personalization could be key to circadian medicine’s success.

“Our ‘internal personal time’ appears to be an important variable to consider when dosing antihypertensives,” said co-lead author Filippo Pigazzani, MD, PhD, clinical senior lecturer and honorary consultant cardiologist at the University of Dundee School of Medicine. “Chronotherapy research has been going on for decades. We knew there was something important with time of day. But researchers haven’t considered the internal time of individual people. I think that is the missing piece.”

The analysis has several important limitations, the researchers said. A total of 95% of participants were White. And it was an observational study, not a true randomized comparison. “We started it late in the original TIME study,” Dr. MacDonald said. “You could argue we were reporting on those who survived long enough to get into the analysis.” More research is needed, they concluded.
 

Looking Beyond Blood Pressure

What about the rest of the body? “Almost all the cells of our body contain ‘circadian clocks’ that are synchronized by daily environmental cues, including light-dark, activity-rest, and feeding-fasting cycles,” said Dr. Dyar.

An estimated 50% of prescription drugs hit targets in the body that have circadian patterns. So, experts suspect that syncing a drug with a person’s body clock might increase effectiveness of many drugs.

A handful of US Food and Drug Administration–approved drugs already have time-of-day recommendations on the label for effectiveness or to limit side effects, including bedtime or evening for the insomnia drug Ambien, the HIV antiviral Atripla, and cholesterol-lowering Zocor. Others are intended to be taken with or after your last meal of the day, such as the long-acting insulin Levemir and the cardiovascular drug Xarelto. A morning recommendation comes with the proton pump inhibitor Nexium and the attention-deficit/hyperactivity disorder drug Ritalin.

Interest is expanding. About one third of the papers published about chronotherapy in the past 25 years have come out in the past 5 years. The May 2024 meeting of the Society for Research on Biological Rhythms featured a day-long session aimed at bringing clinicians up to speed. An organization called the International Association of Circadian Health Clinics is trying to bring circadian medicine findings to clinicians and their patients and to support research.

Moreover, while recent research suggests minding the clock could have benefits for a wide range of treatments, ignoring it could cause problems.

In a Massachusetts Institute of Technology study published in April in Science Advances, researchers looked at engineered livers made from human donor cells and found more than 300 genes that operate on a circadian schedule, many with roles in drug metabolism. They also found that circadian patterns affected the toxicity of acetaminophen and atorvastatin. Identifying the time of day to take these drugs could maximize effectiveness and minimize adverse effects, the researchers said.
 

Timing and the Immune System

Circadian rhythms are also seen in immune processes. In a 2023 study in The Journal of Clinical Investigation of vaccine data from 1.5 million people in Israel, researchers found that children and older adults who got their second dose of the Pfizer mRNA COVID vaccine earlier in the day were about 36% less likely to be hospitalized with SARS-CoV-2 infection than those who got an evening shot.

“The sweet spot in our data was somewhere around late morning to late afternoon,” said lead researcher Jeffrey Haspel, MD, PhD, associate professor of medicine in the division of pulmonary and critical care medicine at Washington University School of Medicine in St. Louis.

In a multicenter, 2024 analysis of 13 studies of immunotherapy for advanced cancers in 1663 people, researchers found treatment earlier in the day was associated with longer survival time and longer survival without cancer progression.

“Patients with selected metastatic cancers seemed to largely benefit from early [time of day] infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking,” the researchers noted. But “retrospective randomized trials are needed to establish recommendations for optimal circadian timing.”

Other research suggests or is investigating possible chronotherapy benefits for depression, glaucoma, respiratory diseases, stroke treatment, epilepsy, and sedatives used in surgery. So why aren’t healthcare providers adding time of day to more prescriptions? “What’s missing is more reliable data,” Dr. Dyar said.
 

Should You Use Chronotherapy Now?

Experts emphasize that more research is needed before doctors use chronotherapy and before medical organizations include it in treatment recommendations. But for some patients, circadian dosing may be worth a try:

Night owls whose blood pressure isn’t well controlled. Dr. Dyar and Dr. Pigazzani said night-time blood pressure drugs may be helpful for people with a “late chronotype.” Of course, patients shouldn’t change their medication schedule on their own, they said. And doctors may want to consider other concerns, like more overnight bathroom visits with evening diuretics.

In their study, the researchers determined participants’ chronotype with a few questions from the Munich Chronotype Questionnaire about what time they fell asleep and woke up on workdays and days off and whether they considered themselves “morning types” or “evening types.” (The questions can be found in supplementary data for the study.)

If a physician thinks matching the timing of a dose with chronotype would help, they can consider it, Dr. Pigazzani said. “However, I must add that this was an observational study, so I would advise healthcare practitioners to wait for our data to be confirmed in new RCTs of personalized chronotherapy of hypertension.”

Children and older adults getting vaccines. Timing COVID shots and possibly other vaccines from late morning to mid-afternoon could have a small benefit for individuals and a bigger public-health benefit, Dr. Haspel said. But the most important thing is getting vaccinated. “If you can only get one in the evening, it’s still worthwhile. Timing may add oomph at a public-health level for more vulnerable groups.”
 

A version of this article appeared on Medscape.com.

Do drugs work better if taken by the clock?

A new analysis published in The Lancet journal’s eClinicalMedicine suggests: Yes, they do — if you consider the patient’s individual body clock. The study is the first to find that timing blood pressure drugs to a person’s personal “chronotype” — that is, whether they are a night owl or an early bird — may reduce the risk for a heart attack.

The findings represent a significant advance in the field of circadian medicine or “chronotherapy” — timing drug administration to circadian rhythms. A growing stack of research suggests this approach could reduce side effects and improve the effectiveness of a wide range of therapies, including vaccines, cancer treatments, and drugs for depression, glaucoma, pain, seizures, and other conditions. Still, despite decades of research, time of day is rarely considered in writing prescriptions.

“We are really just at the beginning of an exciting new way of looking at patient care,” said Kenneth A. Dyar, PhD, whose lab at Helmholtz Zentrum München’s Institute for Diabetes and Cancer focuses on metabolic physiology. Dr. Dyar is co-lead author of the new blood pressure analysis.

“Chronotherapy is a rapidly growing field,” he said, “and I suspect we are soon going to see more and more studies focused on ‘personalized chronotherapy,’ not only in hypertension but also potentially in other clinical areas.”
 

The ‘Missing Piece’ in Chronotherapy Research

Blood pressure drugs have long been chronotherapy’s battleground. After all, blood pressure follows a circadian rhythm, peaking in the morning and dropping at night.

That healthy overnight dip can disappear in people with diabetes, kidney disease, and obstructive sleep apnea. Some physicians have suggested a bed-time dose to restore that dip. But studies have had mixed results, so “take at bedtime” has become a less common recommendation in recent years.

But the debate continued. After a large 2019 Spanish study found that bedtime doses had benefits so big that the results drew questions, an even larger, 2022 randomized, controlled trial from the University of Dundee in Dundee, Scotland — called the TIME study — aimed to settle the question.

Researchers assigned over 21,000 people to take morning or night hypertension drugs for several years and found no difference in cardiovascular outcomes.

“We did this study thinking nocturnal blood pressure tablets might be better,” said Thomas MacDonald, MD, professor emeritus of clinical pharmacology and pharmacoepidemiology at the University of Dundee and principal investigator for the TIME study and the recent chronotype analysis. “But there was no difference for heart attacks, strokes, or vascular death.”

So, the researchers then looked at participants’ chronotypes, sorting outcomes based on whether the participants were late-to-bed, late-to-rise “night owls” or early-to-bed, early-to-rise “morning larks.”

Their analysis of these 5358 TIME participants found the following results: Risk for hospitalization for a heart attack was at least 34% lower for “owls” who took their drugs at bedtime. By contrast, owls’ heart attack risk was at least 62% higher with morning doses. For “larks,” the opposite was true. Morning doses were associated with an 11% lower heart attack risk and night doses with an 11% higher risk, according to supplemental data.

The personalized approach could explain why some previous chronotherapy studies have failed to show a benefit. Those studies did not individualize drug timing as this one did. But personalization could be key to circadian medicine’s success.

“Our ‘internal personal time’ appears to be an important variable to consider when dosing antihypertensives,” said co-lead author Filippo Pigazzani, MD, PhD, clinical senior lecturer and honorary consultant cardiologist at the University of Dundee School of Medicine. “Chronotherapy research has been going on for decades. We knew there was something important with time of day. But researchers haven’t considered the internal time of individual people. I think that is the missing piece.”

The analysis has several important limitations, the researchers said. A total of 95% of participants were White. And it was an observational study, not a true randomized comparison. “We started it late in the original TIME study,” Dr. MacDonald said. “You could argue we were reporting on those who survived long enough to get into the analysis.” More research is needed, they concluded.
 

Looking Beyond Blood Pressure

What about the rest of the body? “Almost all the cells of our body contain ‘circadian clocks’ that are synchronized by daily environmental cues, including light-dark, activity-rest, and feeding-fasting cycles,” said Dr. Dyar.

An estimated 50% of prescription drugs hit targets in the body that have circadian patterns. So, experts suspect that syncing a drug with a person’s body clock might increase effectiveness of many drugs.

A handful of US Food and Drug Administration–approved drugs already have time-of-day recommendations on the label for effectiveness or to limit side effects, including bedtime or evening for the insomnia drug Ambien, the HIV antiviral Atripla, and cholesterol-lowering Zocor. Others are intended to be taken with or after your last meal of the day, such as the long-acting insulin Levemir and the cardiovascular drug Xarelto. A morning recommendation comes with the proton pump inhibitor Nexium and the attention-deficit/hyperactivity disorder drug Ritalin.

Interest is expanding. About one third of the papers published about chronotherapy in the past 25 years have come out in the past 5 years. The May 2024 meeting of the Society for Research on Biological Rhythms featured a day-long session aimed at bringing clinicians up to speed. An organization called the International Association of Circadian Health Clinics is trying to bring circadian medicine findings to clinicians and their patients and to support research.

Moreover, while recent research suggests minding the clock could have benefits for a wide range of treatments, ignoring it could cause problems.

In a Massachusetts Institute of Technology study published in April in Science Advances, researchers looked at engineered livers made from human donor cells and found more than 300 genes that operate on a circadian schedule, many with roles in drug metabolism. They also found that circadian patterns affected the toxicity of acetaminophen and atorvastatin. Identifying the time of day to take these drugs could maximize effectiveness and minimize adverse effects, the researchers said.
 

Timing and the Immune System

Circadian rhythms are also seen in immune processes. In a 2023 study in The Journal of Clinical Investigation of vaccine data from 1.5 million people in Israel, researchers found that children and older adults who got their second dose of the Pfizer mRNA COVID vaccine earlier in the day were about 36% less likely to be hospitalized with SARS-CoV-2 infection than those who got an evening shot.

“The sweet spot in our data was somewhere around late morning to late afternoon,” said lead researcher Jeffrey Haspel, MD, PhD, associate professor of medicine in the division of pulmonary and critical care medicine at Washington University School of Medicine in St. Louis.

In a multicenter, 2024 analysis of 13 studies of immunotherapy for advanced cancers in 1663 people, researchers found treatment earlier in the day was associated with longer survival time and longer survival without cancer progression.

“Patients with selected metastatic cancers seemed to largely benefit from early [time of day] infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking,” the researchers noted. But “retrospective randomized trials are needed to establish recommendations for optimal circadian timing.”

Other research suggests or is investigating possible chronotherapy benefits for depression, glaucoma, respiratory diseases, stroke treatment, epilepsy, and sedatives used in surgery. So why aren’t healthcare providers adding time of day to more prescriptions? “What’s missing is more reliable data,” Dr. Dyar said.
 

Should You Use Chronotherapy Now?

Experts emphasize that more research is needed before doctors use chronotherapy and before medical organizations include it in treatment recommendations. But for some patients, circadian dosing may be worth a try:

Night owls whose blood pressure isn’t well controlled. Dr. Dyar and Dr. Pigazzani said night-time blood pressure drugs may be helpful for people with a “late chronotype.” Of course, patients shouldn’t change their medication schedule on their own, they said. And doctors may want to consider other concerns, like more overnight bathroom visits with evening diuretics.

In their study, the researchers determined participants’ chronotype with a few questions from the Munich Chronotype Questionnaire about what time they fell asleep and woke up on workdays and days off and whether they considered themselves “morning types” or “evening types.” (The questions can be found in supplementary data for the study.)

If a physician thinks matching the timing of a dose with chronotype would help, they can consider it, Dr. Pigazzani said. “However, I must add that this was an observational study, so I would advise healthcare practitioners to wait for our data to be confirmed in new RCTs of personalized chronotherapy of hypertension.”

Children and older adults getting vaccines. Timing COVID shots and possibly other vaccines from late morning to mid-afternoon could have a small benefit for individuals and a bigger public-health benefit, Dr. Haspel said. But the most important thing is getting vaccinated. “If you can only get one in the evening, it’s still worthwhile. Timing may add oomph at a public-health level for more vulnerable groups.”
 

A version of this article appeared on Medscape.com.

TOPLINE:

Taking antidepressants in midlife was not associated with an increased risk of subsequent Alzheimer’s disease (AD) or AD-related dementias (ADRD), data from a large prospective study of US veterans show.

METHODOLOGY:

• Investigators analyzed data from 35,200 US veterans aged ≥ 55 years diagnosed with major depressive disorder from January 1, 2000, to June 1, 2022, and followed them for ≤ 20 years to track subsequent AD/ADRD diagnoses.
• Health information was pulled from electronic health records of the Veterans Health Administration (VHA) Corporate Data Warehouse, and veterans had to be at the VHA for ≥ 1 year before diagnosis.
• Participants were considered to be exposed to an antidepressant when a prescription lasted ≥ 3 months.

TAKEAWAY:

• A total of 32,500 individuals were diagnosed with MDD. The mean age was 65 years, and 91% were men. 17,000 patients received antidepressants for a median duration of 4 years. Median follow-up time was 3.2 years.
• There was no significant association between antidepressant exposure and the risk for AD/ADRD (events = 1056; hazard ratio, 0.93; 95% CI, 0.80-1.08) vs no exposure.
• In a subgroup analysis, investigators found no significant link between different classes of antidepressants and dementia risk. These included selective serotonin reuptake inhibitors, norepinephrine and dopamine reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors.
• Investigators emphasized the need for further research, particularly in populations with a larger representation of female patients.

IN PRACTICE:

“A possibility for the conflicting results in retrospective studies is that the heightened risk identified in participants on antidepressants may be attributed to depression itself, rather than the result of a potential pharmacological action. So, this and other clinical confounding factors need to be taken into account,” the investigators noted.

SOURCE:

The study was led by Jaime Ramos-Cejudo, PhD, VA Boston Healthcare System, Boston. It was published online May 8 in Alzheimer’s & Dementia.

LIMITATIONS:

The cohort’s relatively young age limited the number of dementia cases captured. Data from supplemental insurance, including Medicare, were not included, potentially limiting outcome capture.

DISCLOSURES:

The study was supported by the National Institutes of Health and the National Alzheimer’s Coordinating Center. The authors declared no conflicts of interest.

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

A version of this article appeared on Medscape.com.

TOPLINE:

Taking antidepressants in midlife was not associated with an increased risk of subsequent Alzheimer’s disease (AD) or AD-related dementias (ADRD), data from a large prospective study of US veterans show.

METHODOLOGY:

• Investigators analyzed data from 35,200 US veterans aged ≥ 55 years diagnosed with major depressive disorder from January 1, 2000, to June 1, 2022, and followed them for ≤ 20 years to track subsequent AD/ADRD diagnoses.
• Health information was pulled from electronic health records of the Veterans Health Administration (VHA) Corporate Data Warehouse, and veterans had to be at the VHA for ≥ 1 year before diagnosis.
• Participants were considered to be exposed to an antidepressant when a prescription lasted ≥ 3 months.

TAKEAWAY:

• A total of 32,500 individuals were diagnosed with MDD. The mean age was 65 years, and 91% were men. 17,000 patients received antidepressants for a median duration of 4 years. Median follow-up time was 3.2 years.
• There was no significant association between antidepressant exposure and the risk for AD/ADRD (events = 1056; hazard ratio, 0.93; 95% CI, 0.80-1.08) vs no exposure.
• In a subgroup analysis, investigators found no significant link between different classes of antidepressants and dementia risk. These included selective serotonin reuptake inhibitors, norepinephrine and dopamine reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors.
• Investigators emphasized the need for further research, particularly in populations with a larger representation of female patients.

IN PRACTICE:

“A possibility for the conflicting results in retrospective studies is that the heightened risk identified in participants on antidepressants may be attributed to depression itself, rather than the result of a potential pharmacological action. So, this and other clinical confounding factors need to be taken into account,” the investigators noted.

SOURCE:

The study was led by Jaime Ramos-Cejudo, PhD, VA Boston Healthcare System, Boston. It was published online May 8 in Alzheimer’s & Dementia.

LIMITATIONS:

The cohort’s relatively young age limited the number of dementia cases captured. Data from supplemental insurance, including Medicare, were not included, potentially limiting outcome capture.

DISCLOSURES:

The study was supported by the National Institutes of Health and the National Alzheimer’s Coordinating Center. The authors declared no conflicts of interest.

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

A version of this article appeared on Medscape.com.

TOPLINE:

Taking antidepressants in midlife was not associated with an increased risk of subsequent Alzheimer’s disease (AD) or AD-related dementias (ADRD), data from a large prospective study of US veterans show.

METHODOLOGY:

• Investigators analyzed data from 35,200 US veterans aged ≥ 55 years diagnosed with major depressive disorder from January 1, 2000, to June 1, 2022, and followed them for ≤ 20 years to track subsequent AD/ADRD diagnoses.
• Health information was pulled from electronic health records of the Veterans Health Administration (VHA) Corporate Data Warehouse, and veterans had to be at the VHA for ≥ 1 year before diagnosis.
• Participants were considered to be exposed to an antidepressant when a prescription lasted ≥ 3 months.

TAKEAWAY:

• A total of 32,500 individuals were diagnosed with MDD. The mean age was 65 years, and 91% were men. 17,000 patients received antidepressants for a median duration of 4 years. Median follow-up time was 3.2 years.
• There was no significant association between antidepressant exposure and the risk for AD/ADRD (events = 1056; hazard ratio, 0.93; 95% CI, 0.80-1.08) vs no exposure.
• In a subgroup analysis, investigators found no significant link between different classes of antidepressants and dementia risk. These included selective serotonin reuptake inhibitors, norepinephrine and dopamine reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors.
• Investigators emphasized the need for further research, particularly in populations with a larger representation of female patients.

IN PRACTICE:

“A possibility for the conflicting results in retrospective studies is that the heightened risk identified in participants on antidepressants may be attributed to depression itself, rather than the result of a potential pharmacological action. So, this and other clinical confounding factors need to be taken into account,” the investigators noted.

SOURCE:

The study was led by Jaime Ramos-Cejudo, PhD, VA Boston Healthcare System, Boston. It was published online May 8 in Alzheimer’s & Dementia.

LIMITATIONS:

The cohort’s relatively young age limited the number of dementia cases captured. Data from supplemental insurance, including Medicare, were not included, potentially limiting outcome capture.

DISCLOSURES:

The study was supported by the National Institutes of Health and the National Alzheimer’s Coordinating Center. The authors declared no conflicts of interest.

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

A version of this article appeared on Medscape.com.

TOPLINE:

Posttraumatic stress disorder (PTSD) rates among college students more than doubled between 2017 and 2022, new data showed. Rates of acute stress disorder (ASD) also increased during that time.

METHODOLOGY:

• Researchers conducted five waves of cross-sectional study from 2017 to 2022, involving 392,377 participants across 332 colleges and universities.
• The study utilized the Healthy Minds Study data, ensuring representativeness by applying sample weights based on institutional demographics.
• Outcome variables were diagnoses of PTSD and ASD, confirmed by healthcare practitioners, with statistical analysis assessing change in odds of estimated prevalence during 2017-2022.

TAKEAWAY:

• The prevalence of PTSD among US college students increased from 3.4% in 2017-2018 to 7.5% in 2021-2022.
• ASD diagnoses also rose from 0.2% in 2017-2018 to 0.7% in 2021-2022, with both increases remaining statistically significant after adjusting for demographic differences.
• Investigators noted that these findings underscore the need for targeted, trauma-informed intervention strategies in college settings.

IN PRACTICE:

“These trends highlight the escalating mental health challenges among college students, which is consistent with recent research reporting a surge in psychiatric diagnoses,” the authors wrote. “Factors contributing to this rise may include pandemic-related stressors (eg, loss of loved ones) and the effect of traumatic events (eg, campus shootings and racial trauma),” they added.

SOURCE:

The study was led by Yusen Zhai, PhD, University of Alabama at Birmingham. It was published online on May 30, 2024, in JAMA Network Open.

LIMITATIONS:

The study’s reliance on self-reported data and single questions for diagnosed PTSD and ASD may have limited the accuracy of the findings. The retrospective design and the absence of longitudinal follow-up may have restricted the ability to infer causality from the observed trends.

DISCLOSURES:

No disclosures were reported. No funding information was available.

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

A version of this article appeared on Medscape.com.

TOPLINE:

Posttraumatic stress disorder (PTSD) rates among college students more than doubled between 2017 and 2022, new data showed. Rates of acute stress disorder (ASD) also increased during that time.

METHODOLOGY:

• Researchers conducted five waves of cross-sectional study from 2017 to 2022, involving 392,377 participants across 332 colleges and universities.
• The study utilized the Healthy Minds Study data, ensuring representativeness by applying sample weights based on institutional demographics.
• Outcome variables were diagnoses of PTSD and ASD, confirmed by healthcare practitioners, with statistical analysis assessing change in odds of estimated prevalence during 2017-2022.

TAKEAWAY:

• The prevalence of PTSD among US college students increased from 3.4% in 2017-2018 to 7.5% in 2021-2022.
• ASD diagnoses also rose from 0.2% in 2017-2018 to 0.7% in 2021-2022, with both increases remaining statistically significant after adjusting for demographic differences.
• Investigators noted that these findings underscore the need for targeted, trauma-informed intervention strategies in college settings.

IN PRACTICE:

“These trends highlight the escalating mental health challenges among college students, which is consistent with recent research reporting a surge in psychiatric diagnoses,” the authors wrote. “Factors contributing to this rise may include pandemic-related stressors (eg, loss of loved ones) and the effect of traumatic events (eg, campus shootings and racial trauma),” they added.

SOURCE:

The study was led by Yusen Zhai, PhD, University of Alabama at Birmingham. It was published online on May 30, 2024, in JAMA Network Open.

LIMITATIONS:

The study’s reliance on self-reported data and single questions for diagnosed PTSD and ASD may have limited the accuracy of the findings. The retrospective design and the absence of longitudinal follow-up may have restricted the ability to infer causality from the observed trends.

DISCLOSURES:

No disclosures were reported. No funding information was available.

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

A version of this article appeared on Medscape.com.

TOPLINE:

Posttraumatic stress disorder (PTSD) rates among college students more than doubled between 2017 and 2022, new data showed. Rates of acute stress disorder (ASD) also increased during that time.

METHODOLOGY:

• Researchers conducted five waves of cross-sectional study from 2017 to 2022, involving 392,377 participants across 332 colleges and universities.
• The study utilized the Healthy Minds Study data, ensuring representativeness by applying sample weights based on institutional demographics.
• Outcome variables were diagnoses of PTSD and ASD, confirmed by healthcare practitioners, with statistical analysis assessing change in odds of estimated prevalence during 2017-2022.

TAKEAWAY:

• The prevalence of PTSD among US college students increased from 3.4% in 2017-2018 to 7.5% in 2021-2022.
• ASD diagnoses also rose from 0.2% in 2017-2018 to 0.7% in 2021-2022, with both increases remaining statistically significant after adjusting for demographic differences.
• Investigators noted that these findings underscore the need for targeted, trauma-informed intervention strategies in college settings.

IN PRACTICE:

“These trends highlight the escalating mental health challenges among college students, which is consistent with recent research reporting a surge in psychiatric diagnoses,” the authors wrote. “Factors contributing to this rise may include pandemic-related stressors (eg, loss of loved ones) and the effect of traumatic events (eg, campus shootings and racial trauma),” they added.

SOURCE:

The study was led by Yusen Zhai, PhD, University of Alabama at Birmingham. It was published online on May 30, 2024, in JAMA Network Open.

LIMITATIONS:

The study’s reliance on self-reported data and single questions for diagnosed PTSD and ASD may have limited the accuracy of the findings. The retrospective design and the absence of longitudinal follow-up may have restricted the ability to infer causality from the observed trends.

DISCLOSURES:

No disclosures were reported. No funding information was available.

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

A version of this article appeared on Medscape.com.

Early-life exposure to air and noise pollution is associated with a higher risk for psychosis, depression, and anxiety in adolescence and early adulthood, results from a longitudinal birth cohort study showed.

While air pollution was associated primarily with psychotic experiences and depression, noise pollution was more likely to be associated with anxiety in adolescence and early adulthood.

“Early-life exposure could be detrimental to mental health given the extensive brain development and epigenetic processes that occur in utero and during infancy,” the researchers, led by Joanne Newbury, PhD, of Bristol Medical School, University of Bristol, England, wrote, adding that “the results of this cohort study provide novel evidence that early-life exposure to particulate matter is prospectively associated with the development of psychotic experiences and depression in youth.”

The findings were published online on May 28 in JAMA Network Open.
 

Large, Longitudinal Study

To learn more about how air and noise pollution may affect the brain from an early age, the investigators used data from the Avon Longitudinal Study of Parents and Children, an ongoing longitudinal birth cohort capturing data on new births in Southwest England from 1991 to 1992.

Investigators captured levels of air pollutants, which included nitrogen dioxide and fine particulate matter with a diameter smaller than 2.5 µm (PM2.5), in the areas where expectant mothers lived and where their children lived until age 12.

They also collected decibel levels of noise pollution in neighborhoods where expectant mothers and their children lived.

Participants were assessed for psychotic experiences, depression, and anxiety when they were 13, 18, and 24 years old.

Among the 9065 participants who had mental health data, 20% reported psychotic experiences, 11% reported depression, and 10% reported anxiety. About 60% of the participants had a family history of mental illness.

When they were age 13, 13.6% of participants reported psychotic experiences; 9.2% reported them at age 18, and 12.6% at age 24.

A lower number of participants reported feeling depressed and anxious at 13 years (5.6% for depression and 3.6% for anxiety) and 18 years (7.9% for depression and 5.7% for anxiety).

After adjusting for individual and family-level variables, including family psychiatric history, maternal social class, and neighborhood deprivation, elevated PM2.5 levels during pregnancy (P = .002) and childhood (P = .04) were associated with a significantly increased risk for psychotic experiences later in life. Pregnancy PM2.5 exposure was also associated with depression (P = .01).

Participants exposed to higher noise pollution in childhood and adolescence had an increased risk for anxiety (P = .03) as teenagers.
 

Vulnerability of the Developing Brain

The investigators noted that more information is needed to understand the underlying mechanisms behind these associations but noted that early-life exposure could be detrimental to mental health given “extensive brain development and epigenetic processes that occur in utero.”

They also noted that air pollution could lead to restricted fetal growth and premature birth, both of which are risk factors for psychopathology.

Martin Clift, PhD, of Swansea University in Swansea, Wales, who was not involved in the study, said that the paper highlights the need for more consideration of health consequences related to these exposures.

“As noted by the authors, this is an area that has received a lot of recent attention, yet there remains a large void of knowledge,” Dr. Clift said in a UK Science Media Centre release. “It highlights that some of the most dominant air pollutants can impact different mental health diagnoses, but that time-of-life is particularly important as to how each individual air pollutant may impact this diagnosis.”

Study limitations included limitations to generalizability of the data — the families in the study were more affluent and less diverse than the UK population overall.

The study was funded by the UK Medical Research Council, Wellcome Trust, and University of Bristol. Disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

Early-life exposure to air and noise pollution is associated with a higher risk for psychosis, depression, and anxiety in adolescence and early adulthood, results from a longitudinal birth cohort study showed.

While air pollution was associated primarily with psychotic experiences and depression, noise pollution was more likely to be associated with anxiety in adolescence and early adulthood.

“Early-life exposure could be detrimental to mental health given the extensive brain development and epigenetic processes that occur in utero and during infancy,” the researchers, led by Joanne Newbury, PhD, of Bristol Medical School, University of Bristol, England, wrote, adding that “the results of this cohort study provide novel evidence that early-life exposure to particulate matter is prospectively associated with the development of psychotic experiences and depression in youth.”

The findings were published online on May 28 in JAMA Network Open.
 

Large, Longitudinal Study

To learn more about how air and noise pollution may affect the brain from an early age, the investigators used data from the Avon Longitudinal Study of Parents and Children, an ongoing longitudinal birth cohort capturing data on new births in Southwest England from 1991 to 1992.

Investigators captured levels of air pollutants, which included nitrogen dioxide and fine particulate matter with a diameter smaller than 2.5 µm (PM2.5), in the areas where expectant mothers lived and where their children lived until age 12.

They also collected decibel levels of noise pollution in neighborhoods where expectant mothers and their children lived.

Participants were assessed for psychotic experiences, depression, and anxiety when they were 13, 18, and 24 years old.

Among the 9065 participants who had mental health data, 20% reported psychotic experiences, 11% reported depression, and 10% reported anxiety. About 60% of the participants had a family history of mental illness.

When they were age 13, 13.6% of participants reported psychotic experiences; 9.2% reported them at age 18, and 12.6% at age 24.

A lower number of participants reported feeling depressed and anxious at 13 years (5.6% for depression and 3.6% for anxiety) and 18 years (7.9% for depression and 5.7% for anxiety).

After adjusting for individual and family-level variables, including family psychiatric history, maternal social class, and neighborhood deprivation, elevated PM2.5 levels during pregnancy (P = .002) and childhood (P = .04) were associated with a significantly increased risk for psychotic experiences later in life. Pregnancy PM2.5 exposure was also associated with depression (P = .01).

Participants exposed to higher noise pollution in childhood and adolescence had an increased risk for anxiety (P = .03) as teenagers.
 

Vulnerability of the Developing Brain

The investigators noted that more information is needed to understand the underlying mechanisms behind these associations but noted that early-life exposure could be detrimental to mental health given “extensive brain development and epigenetic processes that occur in utero.”

They also noted that air pollution could lead to restricted fetal growth and premature birth, both of which are risk factors for psychopathology.

Martin Clift, PhD, of Swansea University in Swansea, Wales, who was not involved in the study, said that the paper highlights the need for more consideration of health consequences related to these exposures.

“As noted by the authors, this is an area that has received a lot of recent attention, yet there remains a large void of knowledge,” Dr. Clift said in a UK Science Media Centre release. “It highlights that some of the most dominant air pollutants can impact different mental health diagnoses, but that time-of-life is particularly important as to how each individual air pollutant may impact this diagnosis.”

Study limitations included limitations to generalizability of the data — the families in the study were more affluent and less diverse than the UK population overall.

The study was funded by the UK Medical Research Council, Wellcome Trust, and University of Bristol. Disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

Early-life exposure to air and noise pollution is associated with a higher risk for psychosis, depression, and anxiety in adolescence and early adulthood, results from a longitudinal birth cohort study showed.

While air pollution was associated primarily with psychotic experiences and depression, noise pollution was more likely to be associated with anxiety in adolescence and early adulthood.

“Early-life exposure could be detrimental to mental health given the extensive brain development and epigenetic processes that occur in utero and during infancy,” the researchers, led by Joanne Newbury, PhD, of Bristol Medical School, University of Bristol, England, wrote, adding that “the results of this cohort study provide novel evidence that early-life exposure to particulate matter is prospectively associated with the development of psychotic experiences and depression in youth.”

The findings were published online on May 28 in JAMA Network Open.
 

Large, Longitudinal Study

To learn more about how air and noise pollution may affect the brain from an early age, the investigators used data from the Avon Longitudinal Study of Parents and Children, an ongoing longitudinal birth cohort capturing data on new births in Southwest England from 1991 to 1992.

Investigators captured levels of air pollutants, which included nitrogen dioxide and fine particulate matter with a diameter smaller than 2.5 µm (PM2.5), in the areas where expectant mothers lived and where their children lived until age 12.

They also collected decibel levels of noise pollution in neighborhoods where expectant mothers and their children lived.

Participants were assessed for psychotic experiences, depression, and anxiety when they were 13, 18, and 24 years old.

Among the 9065 participants who had mental health data, 20% reported psychotic experiences, 11% reported depression, and 10% reported anxiety. About 60% of the participants had a family history of mental illness.

When they were age 13, 13.6% of participants reported psychotic experiences; 9.2% reported them at age 18, and 12.6% at age 24.

A lower number of participants reported feeling depressed and anxious at 13 years (5.6% for depression and 3.6% for anxiety) and 18 years (7.9% for depression and 5.7% for anxiety).

After adjusting for individual and family-level variables, including family psychiatric history, maternal social class, and neighborhood deprivation, elevated PM2.5 levels during pregnancy (P = .002) and childhood (P = .04) were associated with a significantly increased risk for psychotic experiences later in life. Pregnancy PM2.5 exposure was also associated with depression (P = .01).

Participants exposed to higher noise pollution in childhood and adolescence had an increased risk for anxiety (P = .03) as teenagers.
 

Vulnerability of the Developing Brain

The investigators noted that more information is needed to understand the underlying mechanisms behind these associations but noted that early-life exposure could be detrimental to mental health given “extensive brain development and epigenetic processes that occur in utero.”

They also noted that air pollution could lead to restricted fetal growth and premature birth, both of which are risk factors for psychopathology.

Martin Clift, PhD, of Swansea University in Swansea, Wales, who was not involved in the study, said that the paper highlights the need for more consideration of health consequences related to these exposures.

“As noted by the authors, this is an area that has received a lot of recent attention, yet there remains a large void of knowledge,” Dr. Clift said in a UK Science Media Centre release. “It highlights that some of the most dominant air pollutants can impact different mental health diagnoses, but that time-of-life is particularly important as to how each individual air pollutant may impact this diagnosis.”

Study limitations included limitations to generalizability of the data — the families in the study were more affluent and less diverse than the UK population overall.

The study was funded by the UK Medical Research Council, Wellcome Trust, and University of Bristol. Disclosures were noted in the original article.

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The incidence of antidepressant discontinuation symptoms appears to be much lower than was previously thought, results from a new meta-analysis of studies assessing this issue showed.

After accounting for placebo effects, results showed that about 15% of patients who discontinue antidepressant therapy had true discontinuation symptoms, with severe symptoms occurring in about 2% of patients. 

“Considering all available data, we conservatively estimate that one out of every six to seven patients has truly pharmacologically-caused antidepressant discontinuation symptoms. This might still be an over-estimate, as it is difficult to factor in residual or re-emerging symptoms of depression or anxiety,” the researchers concluded. 

The study was published online in The Lancet.
 

More Reliable Data

“We are not saying all antidepressant discontinuation symptoms are a placebo effect. It is a real phenomenon. And we are not saying that there is no problem discontinuing antidepressants. But these findings suggest that true antidepressant discontinuation symptoms are lower than previous studies have suggested,” study investigator, Christopher Baethge, MD, University of Cologne, Germany, said at a Science Media Centre press briefing.

“Our data should de-emotionalize the debate on this issue. Yes, antidepressant discontinuation symptoms are a problem, but they should not cause undue alarm to patients or doctors,” Dr. Baethge added. 

Lead investigator, Jonathan Henssler, MD, Charité – Universitätsmedizin Berlin, Germany, noted that “previous studies on this issue have included surveys which have selection bias in that people with symptoms antidepressant discontinuation are more likely to participate. This study includes a broader range of research and excluded surveys, so we believe these are more reliable results.” 
 

A Controversial Issue

The investigators note that antidepressant discontinuation symptoms can be highly variable and nonspecific, with the most frequently reported symptoms being dizziness, headache, nausea, insomnia, and irritability. These symptoms typically occur within a few days and are usually transient but can last up to several weeks or months.

Explaining the mechanism behind the phenomenon, Dr. Baethge noted that selective serotonin reuptake inhibitor antidepressants increase the available serotonin in the brain, but the body responds by reducing the number of serotonin receptors. If the amount of available serotonin is reduced after stopping the medication, then this can lead to discontinuation symptoms. 

However, the incidence and severity of these symptoms remains controversial, the researchers noted. They point out that some estimates suggest that antidepressant discontinuation symptoms occurred in the majority of patients (56%), with almost half of cases classed as severe. 

Previous attempts at assessment have been questioned on methodologic grounds especially because of inclusion of online surveys or other studies prone to selection and dissatisfaction bias.

“Medical professionals continue to hold polarized positions on the incidence and severity of antidepressant discontinuation symptoms, and the debate continues in public media,” they wrote.

This is the first publication of a larger project on antidepressant discontinuation symptoms.

For the study, the researchers conducted a meta-analysis of 44 controlled trials and 35 observational studies assessing the incidence of antidepressant discontinuation symptoms including a total of 21,002 patients. Of these, 16,532 patients discontinued antidepressant treatment, and 4470 patients discontinued placebo. 

Incidence of at least one antidepressant discontinuation symptom occurred in 31% of patients stopping antidepressant therapy and in 17% after discontinuation of placebo, giving a true rate of pharmacologic-driven antidepressant discontinuation symptoms of 14%-15%.

The study also showed that severe discontinuation symptoms occurred in 2.8% of those stopping antidepressants and in 0.6% of those stopping placebo, giving a true rate of severe antidepressant discontinuation symptoms of around 2%. 

There was no association with treatment duration or with pharmaceutical company funding, and different statistical analyses produced similar results, suggesting the findings are robust, Dr. Baethge reported.

 

Risks by Medication

Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequency of discontinuation symptoms and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms.

Fluoxetine, sertraline, and citalopram had lower rates of discontinuation symptoms. No data were available for bupropion, mirtazapine, and amitriptyline.

As for the clinical implications of the findings, Dr. Henssler said that he does consider discontinuation symptoms when selecting a medication. “I would choose a drug with lower rate of these symptoms unless there was a specific reason to choose one with a higher rate,” he said. 

Dr. Henssler added that these data raise awareness of the placebo effect.

“Considering the placebo results, approximately half of antidepressant discontinuation symptoms could be attributable to expectation or non-specific symptoms,” the researchers noted.

“This is not to say all antidepressant discontinuation symptoms are caused by patient expectations; in practice, all patients discontinuing antidepressants need to be counseled and monitored, and patients who report antidepressant discontinuation symptoms must be helped, in particular those who develop severe antidepressant discontinuation symptoms,” they concluded.

 

Experts Weigh In

Commenting on the study at a press briefing, Oliver Howes, MD, chair of the psychopharmacology committee at the Royal College of Psychiatrists, United Kingdom, said that he welcomed “the insight that this robust study provides.”

“If someone chooses to stop taking their antidepressants, their doctor should help them to do so slowly and in a controlled manner that limits the impact of any potential withdrawal symptoms,” Dr. Howes said.

He added that the Royal College of Psychiatrists has produced a resource for patients and carers on stopping antidepressants that offers information on tapering medication at a pace that suits individual patient needs.

Also commenting, Tony Kendrick, MD, professor of primary care, University of Southampton, United Kingdom, pointed out some limitations of the new meta-analysis — in particular, that the method of assessment of discontinuation symptoms in the included studies was very variable, with specific measurement scales of discontinuation symptoms used in only six of the studies. 

“In most cases the assessment seemed to depend at least partly on the judgment of the authors of the included studies rather than being based on a systematic collection of data,” Dr. Kendrick added.

In an accompanying editorial, Glyn Lewis, PhD, and Gemma Lewis, PhD, University College London, United Kingdom, wrote that though the meta-analysis has its limitations, including the fact that many of the studies were small, often use antidepressants that are not commonly used now, and studied people who had not taken the antidepressants for a very long time, “the results here are a substantial improvement on anything that has been published before.”

They emphasize the importance of discussing the issue of a placebo effect with patients when stopping antidepressants. 

The editorialists pointed out that as antidepressants are prescribed to many millions of people, the relatively uncommon severe withdrawal symptoms will still affect a substantial number of people. However, for individual clinicians, severe withdrawal symptoms will seem uncommon, and most patients will probably not be troubled by antidepressant withdrawal, especially when medication is tapered over a few weeks.

They noted that cessation of antidepressants can lead to an increase in depressive and anxious symptoms, and distinguishing between relapsing symptoms and withdrawal is difficult. 

“Short-term symptoms that reduce quickly, without intervention, are best thought of as a form of withdrawal, even if those symptoms might be similar or identical to the symptoms of depression and anxiety. More serious and longer-term symptoms might best be managed by tapering more slowly, or even deciding to remain on the antidepressant,” the editorialists wrote.

There was no funding source for this study. The authors declare no competing interests. Dr. Kendrick led the NIHR REDUCE trial of internet and telephone support for antidepressant discontinuation and was a member of the guideline committee for the NICE 2022 Depression Guideline.

A version of this article appeared on Medscape.com.

The incidence of antidepressant discontinuation symptoms appears to be much lower than was previously thought, results from a new meta-analysis of studies assessing this issue showed.

After accounting for placebo effects, results showed that about 15% of patients who discontinue antidepressant therapy had true discontinuation symptoms, with severe symptoms occurring in about 2% of patients. 

“Considering all available data, we conservatively estimate that one out of every six to seven patients has truly pharmacologically-caused antidepressant discontinuation symptoms. This might still be an over-estimate, as it is difficult to factor in residual or re-emerging symptoms of depression or anxiety,” the researchers concluded. 

The study was published online in The Lancet.
 

More Reliable Data

“We are not saying all antidepressant discontinuation symptoms are a placebo effect. It is a real phenomenon. And we are not saying that there is no problem discontinuing antidepressants. But these findings suggest that true antidepressant discontinuation symptoms are lower than previous studies have suggested,” study investigator, Christopher Baethge, MD, University of Cologne, Germany, said at a Science Media Centre press briefing.

“Our data should de-emotionalize the debate on this issue. Yes, antidepressant discontinuation symptoms are a problem, but they should not cause undue alarm to patients or doctors,” Dr. Baethge added. 

Lead investigator, Jonathan Henssler, MD, Charité – Universitätsmedizin Berlin, Germany, noted that “previous studies on this issue have included surveys which have selection bias in that people with symptoms antidepressant discontinuation are more likely to participate. This study includes a broader range of research and excluded surveys, so we believe these are more reliable results.” 
 

A Controversial Issue

The investigators note that antidepressant discontinuation symptoms can be highly variable and nonspecific, with the most frequently reported symptoms being dizziness, headache, nausea, insomnia, and irritability. These symptoms typically occur within a few days and are usually transient but can last up to several weeks or months.

Explaining the mechanism behind the phenomenon, Dr. Baethge noted that selective serotonin reuptake inhibitor antidepressants increase the available serotonin in the brain, but the body responds by reducing the number of serotonin receptors. If the amount of available serotonin is reduced after stopping the medication, then this can lead to discontinuation symptoms. 

However, the incidence and severity of these symptoms remains controversial, the researchers noted. They point out that some estimates suggest that antidepressant discontinuation symptoms occurred in the majority of patients (56%), with almost half of cases classed as severe. 

Previous attempts at assessment have been questioned on methodologic grounds especially because of inclusion of online surveys or other studies prone to selection and dissatisfaction bias.

“Medical professionals continue to hold polarized positions on the incidence and severity of antidepressant discontinuation symptoms, and the debate continues in public media,” they wrote.

This is the first publication of a larger project on antidepressant discontinuation symptoms.

For the study, the researchers conducted a meta-analysis of 44 controlled trials and 35 observational studies assessing the incidence of antidepressant discontinuation symptoms including a total of 21,002 patients. Of these, 16,532 patients discontinued antidepressant treatment, and 4470 patients discontinued placebo. 

Incidence of at least one antidepressant discontinuation symptom occurred in 31% of patients stopping antidepressant therapy and in 17% after discontinuation of placebo, giving a true rate of pharmacologic-driven antidepressant discontinuation symptoms of 14%-15%.

The study also showed that severe discontinuation symptoms occurred in 2.8% of those stopping antidepressants and in 0.6% of those stopping placebo, giving a true rate of severe antidepressant discontinuation symptoms of around 2%. 

There was no association with treatment duration or with pharmaceutical company funding, and different statistical analyses produced similar results, suggesting the findings are robust, Dr. Baethge reported.

 

Risks by Medication

Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequency of discontinuation symptoms and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms.

Fluoxetine, sertraline, and citalopram had lower rates of discontinuation symptoms. No data were available for bupropion, mirtazapine, and amitriptyline.

As for the clinical implications of the findings, Dr. Henssler said that he does consider discontinuation symptoms when selecting a medication. “I would choose a drug with lower rate of these symptoms unless there was a specific reason to choose one with a higher rate,” he said. 

Dr. Henssler added that these data raise awareness of the placebo effect.

“Considering the placebo results, approximately half of antidepressant discontinuation symptoms could be attributable to expectation or non-specific symptoms,” the researchers noted.

“This is not to say all antidepressant discontinuation symptoms are caused by patient expectations; in practice, all patients discontinuing antidepressants need to be counseled and monitored, and patients who report antidepressant discontinuation symptoms must be helped, in particular those who develop severe antidepressant discontinuation symptoms,” they concluded.

 

Experts Weigh In

Commenting on the study at a press briefing, Oliver Howes, MD, chair of the psychopharmacology committee at the Royal College of Psychiatrists, United Kingdom, said that he welcomed “the insight that this robust study provides.”

“If someone chooses to stop taking their antidepressants, their doctor should help them to do so slowly and in a controlled manner that limits the impact of any potential withdrawal symptoms,” Dr. Howes said.

He added that the Royal College of Psychiatrists has produced a resource for patients and carers on stopping antidepressants that offers information on tapering medication at a pace that suits individual patient needs.

Also commenting, Tony Kendrick, MD, professor of primary care, University of Southampton, United Kingdom, pointed out some limitations of the new meta-analysis — in particular, that the method of assessment of discontinuation symptoms in the included studies was very variable, with specific measurement scales of discontinuation symptoms used in only six of the studies. 

“In most cases the assessment seemed to depend at least partly on the judgment of the authors of the included studies rather than being based on a systematic collection of data,” Dr. Kendrick added.

In an accompanying editorial, Glyn Lewis, PhD, and Gemma Lewis, PhD, University College London, United Kingdom, wrote that though the meta-analysis has its limitations, including the fact that many of the studies were small, often use antidepressants that are not commonly used now, and studied people who had not taken the antidepressants for a very long time, “the results here are a substantial improvement on anything that has been published before.”

They emphasize the importance of discussing the issue of a placebo effect with patients when stopping antidepressants. 

The editorialists pointed out that as antidepressants are prescribed to many millions of people, the relatively uncommon severe withdrawal symptoms will still affect a substantial number of people. However, for individual clinicians, severe withdrawal symptoms will seem uncommon, and most patients will probably not be troubled by antidepressant withdrawal, especially when medication is tapered over a few weeks.

They noted that cessation of antidepressants can lead to an increase in depressive and anxious symptoms, and distinguishing between relapsing symptoms and withdrawal is difficult. 

“Short-term symptoms that reduce quickly, without intervention, are best thought of as a form of withdrawal, even if those symptoms might be similar or identical to the symptoms of depression and anxiety. More serious and longer-term symptoms might best be managed by tapering more slowly, or even deciding to remain on the antidepressant,” the editorialists wrote.

There was no funding source for this study. The authors declare no competing interests. Dr. Kendrick led the NIHR REDUCE trial of internet and telephone support for antidepressant discontinuation and was a member of the guideline committee for the NICE 2022 Depression Guideline.

A version of this article appeared on Medscape.com.

The incidence of antidepressant discontinuation symptoms appears to be much lower than was previously thought, results from a new meta-analysis of studies assessing this issue showed.

After accounting for placebo effects, results showed that about 15% of patients who discontinue antidepressant therapy had true discontinuation symptoms, with severe symptoms occurring in about 2% of patients. 

“Considering all available data, we conservatively estimate that one out of every six to seven patients has truly pharmacologically-caused antidepressant discontinuation symptoms. This might still be an over-estimate, as it is difficult to factor in residual or re-emerging symptoms of depression or anxiety,” the researchers concluded. 

The study was published online in The Lancet.
 

More Reliable Data

“We are not saying all antidepressant discontinuation symptoms are a placebo effect. It is a real phenomenon. And we are not saying that there is no problem discontinuing antidepressants. But these findings suggest that true antidepressant discontinuation symptoms are lower than previous studies have suggested,” study investigator, Christopher Baethge, MD, University of Cologne, Germany, said at a Science Media Centre press briefing.

“Our data should de-emotionalize the debate on this issue. Yes, antidepressant discontinuation symptoms are a problem, but they should not cause undue alarm to patients or doctors,” Dr. Baethge added. 

Lead investigator, Jonathan Henssler, MD, Charité – Universitätsmedizin Berlin, Germany, noted that “previous studies on this issue have included surveys which have selection bias in that people with symptoms antidepressant discontinuation are more likely to participate. This study includes a broader range of research and excluded surveys, so we believe these are more reliable results.” 
 

A Controversial Issue

The investigators note that antidepressant discontinuation symptoms can be highly variable and nonspecific, with the most frequently reported symptoms being dizziness, headache, nausea, insomnia, and irritability. These symptoms typically occur within a few days and are usually transient but can last up to several weeks or months.

Explaining the mechanism behind the phenomenon, Dr. Baethge noted that selective serotonin reuptake inhibitor antidepressants increase the available serotonin in the brain, but the body responds by reducing the number of serotonin receptors. If the amount of available serotonin is reduced after stopping the medication, then this can lead to discontinuation symptoms. 

However, the incidence and severity of these symptoms remains controversial, the researchers noted. They point out that some estimates suggest that antidepressant discontinuation symptoms occurred in the majority of patients (56%), with almost half of cases classed as severe. 

Previous attempts at assessment have been questioned on methodologic grounds especially because of inclusion of online surveys or other studies prone to selection and dissatisfaction bias.

“Medical professionals continue to hold polarized positions on the incidence and severity of antidepressant discontinuation symptoms, and the debate continues in public media,” they wrote.

This is the first publication of a larger project on antidepressant discontinuation symptoms.

For the study, the researchers conducted a meta-analysis of 44 controlled trials and 35 observational studies assessing the incidence of antidepressant discontinuation symptoms including a total of 21,002 patients. Of these, 16,532 patients discontinued antidepressant treatment, and 4470 patients discontinued placebo. 

Incidence of at least one antidepressant discontinuation symptom occurred in 31% of patients stopping antidepressant therapy and in 17% after discontinuation of placebo, giving a true rate of pharmacologic-driven antidepressant discontinuation symptoms of 14%-15%.

The study also showed that severe discontinuation symptoms occurred in 2.8% of those stopping antidepressants and in 0.6% of those stopping placebo, giving a true rate of severe antidepressant discontinuation symptoms of around 2%. 

There was no association with treatment duration or with pharmaceutical company funding, and different statistical analyses produced similar results, suggesting the findings are robust, Dr. Baethge reported.

 

Risks by Medication

Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequency of discontinuation symptoms and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms.

Fluoxetine, sertraline, and citalopram had lower rates of discontinuation symptoms. No data were available for bupropion, mirtazapine, and amitriptyline.

As for the clinical implications of the findings, Dr. Henssler said that he does consider discontinuation symptoms when selecting a medication. “I would choose a drug with lower rate of these symptoms unless there was a specific reason to choose one with a higher rate,” he said. 

Dr. Henssler added that these data raise awareness of the placebo effect.

“Considering the placebo results, approximately half of antidepressant discontinuation symptoms could be attributable to expectation or non-specific symptoms,” the researchers noted.

“This is not to say all antidepressant discontinuation symptoms are caused by patient expectations; in practice, all patients discontinuing antidepressants need to be counseled and monitored, and patients who report antidepressant discontinuation symptoms must be helped, in particular those who develop severe antidepressant discontinuation symptoms,” they concluded.

 

Experts Weigh In

Commenting on the study at a press briefing, Oliver Howes, MD, chair of the psychopharmacology committee at the Royal College of Psychiatrists, United Kingdom, said that he welcomed “the insight that this robust study provides.”

“If someone chooses to stop taking their antidepressants, their doctor should help them to do so slowly and in a controlled manner that limits the impact of any potential withdrawal symptoms,” Dr. Howes said.

He added that the Royal College of Psychiatrists has produced a resource for patients and carers on stopping antidepressants that offers information on tapering medication at a pace that suits individual patient needs.

Also commenting, Tony Kendrick, MD, professor of primary care, University of Southampton, United Kingdom, pointed out some limitations of the new meta-analysis — in particular, that the method of assessment of discontinuation symptoms in the included studies was very variable, with specific measurement scales of discontinuation symptoms used in only six of the studies. 

“In most cases the assessment seemed to depend at least partly on the judgment of the authors of the included studies rather than being based on a systematic collection of data,” Dr. Kendrick added.

In an accompanying editorial, Glyn Lewis, PhD, and Gemma Lewis, PhD, University College London, United Kingdom, wrote that though the meta-analysis has its limitations, including the fact that many of the studies were small, often use antidepressants that are not commonly used now, and studied people who had not taken the antidepressants for a very long time, “the results here are a substantial improvement on anything that has been published before.”

They emphasize the importance of discussing the issue of a placebo effect with patients when stopping antidepressants. 

The editorialists pointed out that as antidepressants are prescribed to many millions of people, the relatively uncommon severe withdrawal symptoms will still affect a substantial number of people. However, for individual clinicians, severe withdrawal symptoms will seem uncommon, and most patients will probably not be troubled by antidepressant withdrawal, especially when medication is tapered over a few weeks.

They noted that cessation of antidepressants can lead to an increase in depressive and anxious symptoms, and distinguishing between relapsing symptoms and withdrawal is difficult. 

“Short-term symptoms that reduce quickly, without intervention, are best thought of as a form of withdrawal, even if those symptoms might be similar or identical to the symptoms of depression and anxiety. More serious and longer-term symptoms might best be managed by tapering more slowly, or even deciding to remain on the antidepressant,” the editorialists wrote.

There was no funding source for this study. The authors declare no competing interests. Dr. Kendrick led the NIHR REDUCE trial of internet and telephone support for antidepressant discontinuation and was a member of the guideline committee for the NICE 2022 Depression Guideline.

A version of this article appeared on Medscape.com.