Clinical Psychiatry News

The B vitamin, L-methylfolate (LMF) can be an effective adjunctive treatment for patients with major depressive disorder (MDD) with an inadequate response to antidepressants, new research suggests.

The investigators analyzed six studies and found support for adjunctive use of LMF with patients with MDD not responding to antidepressant monotherapy. Treatment response was highest in those with obesity and inflammatory biomarkers.

Vladimir Maletic

“If clinicians try LMF on their patients with treatment-resistant depression, the treatment is very robust in patients who have high BMI [body mass index] or inflammatory biomarkers, and it’s worth a try even in patients who don’t have these indicators, since it’s safe and well tolerated, with no downside,” study investigator Vladimir Maletic, MD, MS, clinical professor of psychiatry and behavioral science, University of South Carolina, Greenville, said in an interview.

The study was published online in the Journal of Clinical Psychiatry.
 

‘Shortcut’ to the brain

A considerable percentage of patients with MDD fail to achieve an adequate response to treatment, the authors wrote.

Previous research shows benefits of folate (vitamin B9) and other B vitamins in the pathophysiology and treatment of depression.

Folate is available in several forms, including LMF, which differs from dietary folate and synthetic folic acid supplements because it’s a reduced metabolite that readily crosses the blood-brain barrier.

“This is a ‘shortcut’ that gets directly to the brain, especially in those with higher BMI or inflammatory indicators, allowing their antidepressant to work better,” Dr. Maletic said.

LMF is available as a prescription medical food and approved for the clinical dietary management of patients with MDD.

The authors wanted to understand the potential role of LMF in treating patients with MDD with insufficient response to current antidepressant therapy.

They analyzed six studies:

• Two multicenter, randomized, double-blind, placebo-controlled sequential parallel trials for patients with SSRI-resistant MDD (n = 148 and n = 75).
• A 12-month open-label extension trial of the two randomized, controlled trials (n = 68).
• A retrospective cohort study evaluating patients previously prescribed LMF (n = 554).
• Two post hoc exploratory analyses of the second randomized, controlled trial, stratifying patients by specific biological and genetic markers (n = 74) and evaluating the effect of biomarkers on treatment effect (n = 74).

The primary endpoints were improvement on the 17-item Hamilton Depression Rating Scale (HDRS-17) or the Patient Health Questionnaire (PHQ-9).

Patients in all trials were treated with either 7.5 mg or 15 mg of LMF.

Both RCTs were divided into two 30-day phases, with patients assessed every 10 days. Response was defined as at least a 50% reduction in HDRS-17 score during treatment or a final score of 7 or less.
 

‘Salvage pathway’

In the RCTs, patients who received 7.5 mg of LMF did not achieve efficacy superior to placebo, while those receiving 15 mg/day of LMF for 30 days showed significantly greater reduction in HDRS-17 scores (–5.6 vs. –3.0; P = .05, respectively) and higher response rates (32.3% vs. 14.6%; P = .05, respectively).

The 12-month open extension trial showed that among patients who received the 15-mg dose, 61% achieved remission at any point, and 38% achieved recovery. Among initial nonresponders, 60% eventually achieved remission, with no serious adverse events.

“These results indicate that patients who respond well to shorter-term treatment are likely to maintain that response over the subsequent year and shows that those not adequately responding within the first 8 weeks of therapy may benefit from longer-term LMF treatments,” the investigators noted.

In the prospective observational study, the pooled mean change in PHQ-9 was –8.5, with response and remission rates of 67.9% and 45.7%, respectively.

“These outcomes suggest that the results seen in the controlled trial are likely to extend to patients in real-world practice,” the researchers wrote.

The post hoc analyses focusing on the findings of the two RCTs explored the differences in response to LMF, based on biomarker, BMI, and genotype.

Individuals with BMI less than 30 did not have a significant change from baseline with LMF treatment, in contrast to those with BMI of 30 or higher (pooled treatment effect, –4.66;95% CI, –7.22 to –1.98) – a difference the authors call “striking.”

Levels of inflammatory markers (tumor necrosis factor–alpha, interleukin-8, heart-specific C-reactive protein, and leptin) above the median value were associated with significantly greater treatment effect – a finding that remained significant even after adjustment for BMI.

Although BMI and cytokines all showed significant main effects, the “synergy” between them “suggests that these risk factors may interact with each other to influence response to LMF,” the authors wrote.

The mechanism by which LMF augments antidepressant treatment is tied to monoamine synthesis, since LMF promotes the synthesis of key monoamine neurotransmitters associated with MDD (serotonin, norepinephrine, and dopamine), Dr. Maletic explained.

High levels of inflammation (often tied to obesity) cause oxidative stress, which inhibits the synthesis of these neurotransmitters and depletes them more rapidly. LMF provides a “salvage pathway” that may prevent this from happening, thus increasing the antidepressant response of the monoamines, he said.
 

A ‘good addition’

In a comment, David Mischoulon, MD, PhD, Joyce R. Tedlow Professor of Psychiatry at Harvard Medical School and director of the depression clinical and research program at Massachusetts General Hospital, both in Boston, said the paper “does a good job of synthesizing what we know about LMF as an adjunctive treatment in major depression.” 

However, he recommended “caution” when interpreting the findings, since “relatively few” studies were reviewed. 

Dr. Mischoulon, who was not involved with the study, said that a “particularly interesting finding from these studies is individuals who are overweight and/or have elevation in inflammatory activity ... seemed to respond better to the addition of LMF.” This finding is similar to what his research team observed when investigating the potential role of fish oils in treating depression.

“These findings overall are not surprising, in view of the well-established multidirectional relationship between depression, inflammation, and overweight status,” he said. 

LMF “seems like a good addition to the pharmacological armamentarium for depression; and because it is safe and has minimal side effects, it can be added to the treatment regimen of patients who are depressed and not responding adequately to standard antidepressants,” he said.

This work was funded by Alfasigma USA. The authors did not receive payment for their participation. Dr. Maletic has received writing support from Alfasigma USA; consulting/advisory fees from AbbVie/Allergan, Acadia, Alfasigma USA, Alkermes, Eisai-Purdue, Intra-Cellular Therapies, Janssen, Lundbeck, Jazz, Noven, Otsuka America, Sage, Sunovion, Supernus, and Takeda; and honoraria for lectures from AbbVie, Acadia, Alkermes, Allergan, Eisai, Ironshore, Intra-Cellular, Janssen, Lundbeck, Otsuka America, Sunovion, Supernus, and Takeda. Dr. Mischoulon has received research support from Nordic Naturals and Heckel Medizintechnik. He has received honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy, PeerPoint Medical Education Institute, and Harvard blog.

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

The B vitamin, L-methylfolate (LMF) can be an effective adjunctive treatment for patients with major depressive disorder (MDD) with an inadequate response to antidepressants, new research suggests.

The investigators analyzed six studies and found support for adjunctive use of LMF with patients with MDD not responding to antidepressant monotherapy. Treatment response was highest in those with obesity and inflammatory biomarkers.

Vladimir Maletic

“If clinicians try LMF on their patients with treatment-resistant depression, the treatment is very robust in patients who have high BMI [body mass index] or inflammatory biomarkers, and it’s worth a try even in patients who don’t have these indicators, since it’s safe and well tolerated, with no downside,” study investigator Vladimir Maletic, MD, MS, clinical professor of psychiatry and behavioral science, University of South Carolina, Greenville, said in an interview.

The study was published online in the Journal of Clinical Psychiatry.
 

‘Shortcut’ to the brain

A considerable percentage of patients with MDD fail to achieve an adequate response to treatment, the authors wrote.

Previous research shows benefits of folate (vitamin B9) and other B vitamins in the pathophysiology and treatment of depression.

Folate is available in several forms, including LMF, which differs from dietary folate and synthetic folic acid supplements because it’s a reduced metabolite that readily crosses the blood-brain barrier.

“This is a ‘shortcut’ that gets directly to the brain, especially in those with higher BMI or inflammatory indicators, allowing their antidepressant to work better,” Dr. Maletic said.

LMF is available as a prescription medical food and approved for the clinical dietary management of patients with MDD.

The authors wanted to understand the potential role of LMF in treating patients with MDD with insufficient response to current antidepressant therapy.

They analyzed six studies:

• Two multicenter, randomized, double-blind, placebo-controlled sequential parallel trials for patients with SSRI-resistant MDD (n = 148 and n = 75).
• A 12-month open-label extension trial of the two randomized, controlled trials (n = 68).
• A retrospective cohort study evaluating patients previously prescribed LMF (n = 554).
• Two post hoc exploratory analyses of the second randomized, controlled trial, stratifying patients by specific biological and genetic markers (n = 74) and evaluating the effect of biomarkers on treatment effect (n = 74).

The primary endpoints were improvement on the 17-item Hamilton Depression Rating Scale (HDRS-17) or the Patient Health Questionnaire (PHQ-9).

Patients in all trials were treated with either 7.5 mg or 15 mg of LMF.

Both RCTs were divided into two 30-day phases, with patients assessed every 10 days. Response was defined as at least a 50% reduction in HDRS-17 score during treatment or a final score of 7 or less.
 

‘Salvage pathway’

In the RCTs, patients who received 7.5 mg of LMF did not achieve efficacy superior to placebo, while those receiving 15 mg/day of LMF for 30 days showed significantly greater reduction in HDRS-17 scores (–5.6 vs. –3.0; P = .05, respectively) and higher response rates (32.3% vs. 14.6%; P = .05, respectively).

The 12-month open extension trial showed that among patients who received the 15-mg dose, 61% achieved remission at any point, and 38% achieved recovery. Among initial nonresponders, 60% eventually achieved remission, with no serious adverse events.

“These results indicate that patients who respond well to shorter-term treatment are likely to maintain that response over the subsequent year and shows that those not adequately responding within the first 8 weeks of therapy may benefit from longer-term LMF treatments,” the investigators noted.

In the prospective observational study, the pooled mean change in PHQ-9 was –8.5, with response and remission rates of 67.9% and 45.7%, respectively.

“These outcomes suggest that the results seen in the controlled trial are likely to extend to patients in real-world practice,” the researchers wrote.

The post hoc analyses focusing on the findings of the two RCTs explored the differences in response to LMF, based on biomarker, BMI, and genotype.

Individuals with BMI less than 30 did not have a significant change from baseline with LMF treatment, in contrast to those with BMI of 30 or higher (pooled treatment effect, –4.66;95% CI, –7.22 to –1.98) – a difference the authors call “striking.”

Levels of inflammatory markers (tumor necrosis factor–alpha, interleukin-8, heart-specific C-reactive protein, and leptin) above the median value were associated with significantly greater treatment effect – a finding that remained significant even after adjustment for BMI.

Although BMI and cytokines all showed significant main effects, the “synergy” between them “suggests that these risk factors may interact with each other to influence response to LMF,” the authors wrote.

The mechanism by which LMF augments antidepressant treatment is tied to monoamine synthesis, since LMF promotes the synthesis of key monoamine neurotransmitters associated with MDD (serotonin, norepinephrine, and dopamine), Dr. Maletic explained.

High levels of inflammation (often tied to obesity) cause oxidative stress, which inhibits the synthesis of these neurotransmitters and depletes them more rapidly. LMF provides a “salvage pathway” that may prevent this from happening, thus increasing the antidepressant response of the monoamines, he said.
 

A ‘good addition’

In a comment, David Mischoulon, MD, PhD, Joyce R. Tedlow Professor of Psychiatry at Harvard Medical School and director of the depression clinical and research program at Massachusetts General Hospital, both in Boston, said the paper “does a good job of synthesizing what we know about LMF as an adjunctive treatment in major depression.” 

However, he recommended “caution” when interpreting the findings, since “relatively few” studies were reviewed. 

Dr. Mischoulon, who was not involved with the study, said that a “particularly interesting finding from these studies is individuals who are overweight and/or have elevation in inflammatory activity ... seemed to respond better to the addition of LMF.” This finding is similar to what his research team observed when investigating the potential role of fish oils in treating depression.

“These findings overall are not surprising, in view of the well-established multidirectional relationship between depression, inflammation, and overweight status,” he said. 

LMF “seems like a good addition to the pharmacological armamentarium for depression; and because it is safe and has minimal side effects, it can be added to the treatment regimen of patients who are depressed and not responding adequately to standard antidepressants,” he said.

This work was funded by Alfasigma USA. The authors did not receive payment for their participation. Dr. Maletic has received writing support from Alfasigma USA; consulting/advisory fees from AbbVie/Allergan, Acadia, Alfasigma USA, Alkermes, Eisai-Purdue, Intra-Cellular Therapies, Janssen, Lundbeck, Jazz, Noven, Otsuka America, Sage, Sunovion, Supernus, and Takeda; and honoraria for lectures from AbbVie, Acadia, Alkermes, Allergan, Eisai, Ironshore, Intra-Cellular, Janssen, Lundbeck, Otsuka America, Sunovion, Supernus, and Takeda. Dr. Mischoulon has received research support from Nordic Naturals and Heckel Medizintechnik. He has received honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy, PeerPoint Medical Education Institute, and Harvard blog.

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

The B vitamin, L-methylfolate (LMF) can be an effective adjunctive treatment for patients with major depressive disorder (MDD) with an inadequate response to antidepressants, new research suggests.

The investigators analyzed six studies and found support for adjunctive use of LMF with patients with MDD not responding to antidepressant monotherapy. Treatment response was highest in those with obesity and inflammatory biomarkers.

Vladimir Maletic

“If clinicians try LMF on their patients with treatment-resistant depression, the treatment is very robust in patients who have high BMI [body mass index] or inflammatory biomarkers, and it’s worth a try even in patients who don’t have these indicators, since it’s safe and well tolerated, with no downside,” study investigator Vladimir Maletic, MD, MS, clinical professor of psychiatry and behavioral science, University of South Carolina, Greenville, said in an interview.

The study was published online in the Journal of Clinical Psychiatry.
 

‘Shortcut’ to the brain

A considerable percentage of patients with MDD fail to achieve an adequate response to treatment, the authors wrote.

Previous research shows benefits of folate (vitamin B9) and other B vitamins in the pathophysiology and treatment of depression.

Folate is available in several forms, including LMF, which differs from dietary folate and synthetic folic acid supplements because it’s a reduced metabolite that readily crosses the blood-brain barrier.

“This is a ‘shortcut’ that gets directly to the brain, especially in those with higher BMI or inflammatory indicators, allowing their antidepressant to work better,” Dr. Maletic said.

LMF is available as a prescription medical food and approved for the clinical dietary management of patients with MDD.

The authors wanted to understand the potential role of LMF in treating patients with MDD with insufficient response to current antidepressant therapy.

They analyzed six studies:

• Two multicenter, randomized, double-blind, placebo-controlled sequential parallel trials for patients with SSRI-resistant MDD (n = 148 and n = 75).
• A 12-month open-label extension trial of the two randomized, controlled trials (n = 68).
• A retrospective cohort study evaluating patients previously prescribed LMF (n = 554).
• Two post hoc exploratory analyses of the second randomized, controlled trial, stratifying patients by specific biological and genetic markers (n = 74) and evaluating the effect of biomarkers on treatment effect (n = 74).

The primary endpoints were improvement on the 17-item Hamilton Depression Rating Scale (HDRS-17) or the Patient Health Questionnaire (PHQ-9).

Patients in all trials were treated with either 7.5 mg or 15 mg of LMF.

Both RCTs were divided into two 30-day phases, with patients assessed every 10 days. Response was defined as at least a 50% reduction in HDRS-17 score during treatment or a final score of 7 or less.
 

‘Salvage pathway’

In the RCTs, patients who received 7.5 mg of LMF did not achieve efficacy superior to placebo, while those receiving 15 mg/day of LMF for 30 days showed significantly greater reduction in HDRS-17 scores (–5.6 vs. –3.0; P = .05, respectively) and higher response rates (32.3% vs. 14.6%; P = .05, respectively).

The 12-month open extension trial showed that among patients who received the 15-mg dose, 61% achieved remission at any point, and 38% achieved recovery. Among initial nonresponders, 60% eventually achieved remission, with no serious adverse events.

“These results indicate that patients who respond well to shorter-term treatment are likely to maintain that response over the subsequent year and shows that those not adequately responding within the first 8 weeks of therapy may benefit from longer-term LMF treatments,” the investigators noted.

In the prospective observational study, the pooled mean change in PHQ-9 was –8.5, with response and remission rates of 67.9% and 45.7%, respectively.

“These outcomes suggest that the results seen in the controlled trial are likely to extend to patients in real-world practice,” the researchers wrote.

The post hoc analyses focusing on the findings of the two RCTs explored the differences in response to LMF, based on biomarker, BMI, and genotype.

Individuals with BMI less than 30 did not have a significant change from baseline with LMF treatment, in contrast to those with BMI of 30 or higher (pooled treatment effect, –4.66;95% CI, –7.22 to –1.98) – a difference the authors call “striking.”

Levels of inflammatory markers (tumor necrosis factor–alpha, interleukin-8, heart-specific C-reactive protein, and leptin) above the median value were associated with significantly greater treatment effect – a finding that remained significant even after adjustment for BMI.

Although BMI and cytokines all showed significant main effects, the “synergy” between them “suggests that these risk factors may interact with each other to influence response to LMF,” the authors wrote.

The mechanism by which LMF augments antidepressant treatment is tied to monoamine synthesis, since LMF promotes the synthesis of key monoamine neurotransmitters associated with MDD (serotonin, norepinephrine, and dopamine), Dr. Maletic explained.

High levels of inflammation (often tied to obesity) cause oxidative stress, which inhibits the synthesis of these neurotransmitters and depletes them more rapidly. LMF provides a “salvage pathway” that may prevent this from happening, thus increasing the antidepressant response of the monoamines, he said.
 

A ‘good addition’

In a comment, David Mischoulon, MD, PhD, Joyce R. Tedlow Professor of Psychiatry at Harvard Medical School and director of the depression clinical and research program at Massachusetts General Hospital, both in Boston, said the paper “does a good job of synthesizing what we know about LMF as an adjunctive treatment in major depression.” 

However, he recommended “caution” when interpreting the findings, since “relatively few” studies were reviewed. 

Dr. Mischoulon, who was not involved with the study, said that a “particularly interesting finding from these studies is individuals who are overweight and/or have elevation in inflammatory activity ... seemed to respond better to the addition of LMF.” This finding is similar to what his research team observed when investigating the potential role of fish oils in treating depression.

“These findings overall are not surprising, in view of the well-established multidirectional relationship between depression, inflammation, and overweight status,” he said. 

LMF “seems like a good addition to the pharmacological armamentarium for depression; and because it is safe and has minimal side effects, it can be added to the treatment regimen of patients who are depressed and not responding adequately to standard antidepressants,” he said.

This work was funded by Alfasigma USA. The authors did not receive payment for their participation. Dr. Maletic has received writing support from Alfasigma USA; consulting/advisory fees from AbbVie/Allergan, Acadia, Alfasigma USA, Alkermes, Eisai-Purdue, Intra-Cellular Therapies, Janssen, Lundbeck, Jazz, Noven, Otsuka America, Sage, Sunovion, Supernus, and Takeda; and honoraria for lectures from AbbVie, Acadia, Alkermes, Allergan, Eisai, Ironshore, Intra-Cellular, Janssen, Lundbeck, Otsuka America, Sunovion, Supernus, and Takeda. Dr. Mischoulon has received research support from Nordic Naturals and Heckel Medizintechnik. He has received honoraria for speaking from the Massachusetts General Hospital Psychiatry Academy, PeerPoint Medical Education Institute, and Harvard blog.

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

An early predictor of cardiovascular disease (CVD) has been found in youth with bipolar disorder (BD), in new findings that may explain the “excessive and premature mortality” related to heart disease in this patient population.

The investigators found that higher reactive hyperemia index (RHI) scores, a measure of endothelial function, were tied to mood severity in patients with higher mania, but not depression scores. These findings persisted even after accounting for medications, obesity, and other cardiovascular risk factors (CVRFs).

“From a clinical perspective, these findings highlight the potential value of integrating vascular health in the assessment and management of youth with BD, and from a scientific perspective, these findings call for additional research focused on shared biological mechanisms linking vascular health and mood symptoms of BD,” senior investigator Benjamin Goldstein, MD, PhD, full professor of psychiatry, pharmacology, and psychological clinical science, University of Toronto, said in an interview.

The study was published online in the Journal of Clinical Psychiatry.
 

‘Excessively present’

BD is associated with “excessive and premature cardiovascular mortality” and CVD is “excessively present” in BD, exceeding what can be explained by traditional cardiovascular risk factors, psychiatric medications, and substance use, the researchers noted.

“In adults, more severe mood symptoms increase the risk of future CVD. Our focus on endothelial function rose due to the fact that CVD is rare in youth, whereas endothelial dysfunction – considered a precursor of CVD – can be assessed in youth,” said Dr. Goldstein, who holds the RBC Investments Chair in children’s mental health and developmental psychopathology at the Centre for Addiction and Mental Health, Toronto, where he is director of the Centre for Youth Bipolar Disorder.

For this reason, he and his colleagues were “interested in researching whether endothelial dysfunction is associated with mood symptoms in youth with BD.” Ultimately, the motivation was to “inspire new therapeutic opportunities that may improve both cardiovascular and mental health simultaneously.”

To investigate the question, the researchers studied 209 youth aged 13-20 years (n = 114 with BD and 94 healthy controls [HCs]).

In the BD group, there were 34 BD-euthymia, 36 BD-depressed, and 44 BD-hypomanic/mixed; and within the groups who had depression or hypomania/mixed features, 72 were experiencing clinically significant depression. 

Participants had to be free of chronic inflammatory illness, use of medications that might be addressing traditional CVRFs, recent infectious diseases, or neurologic conditions.

Participants’ bipolar symptoms, psychosocial functioning, and family history were assessed. In addition, they were asked about treatment, physical and/or sexual abuse, smoking status, and socioeconomic status. Height, weight, waist circumference, blood pressure, and blood tests to assess CVRFs, including C-reactive protein (CRP), were also assessed. RHI was measured via pulse amplitude tonometry, with lower values indicating poorer endothelial function.
 

Positive affect beneficial?

Compared with HCs, there were fewer White participants in the BD group (78% vs. 55%; P < .001). The BD group also had higher Tanner stage development scores (stage 5: 65% vs. 35%; P = .03; V = 0.21), higher body mass index (BMI, 24.4 ± 4.6 vs. 22.0 ± 4.2; P < .001; d = 0.53), and higher CRP (1.94 ± 3.99 vs. 0.76 ± 0.86; P = .009; d = –0.40).

After controlling for age, sex, and BMI (F_3,202 = 4.47; P = .005; n_p²  = 0.06), the researchers found significant between-group differences in RHI.

Post hoc pairwise comparisons showed RHI to be significantly lower in the BD-depressed versus the HC group (P = .04; d = 0.4). Moreover, the BD-hypomanic/mixed group had significantly higher RHI, compared with the other BD groups and the HC group.

RHI was associated with higher mania scores (beta, 0.26; P = .006), but there was no similar significant association with depression mood scores (beta, 0.01; P = .90).

The mood state differences in RHI and the RHI-mania association remained significant in sensitivity analyses examining the effect of current medication use as well as CVRFs, including lipids, CRP, and blood pressure on RHI.

“We found that youth with BD experiencing a depressive episode had lower endothelial function, whereas youth with BD experiencing a hypomanic/mixed episode had higher endothelial function, as compared to healthy youth,” Dr. Goldstein said.

There are several mechanisms potentially underlying the association between endothelial function and hypomania, the investigators noted. For example, positive affect is associated with increased endothelial function in normative samples, so hypomanic symptoms, including elation, may have similar beneficial associations, although those benefits likely do not extend to mania, which has been associated with cardiovascular risk.

They also point to several limitations in the study. The cross-sectional design “precludes making inferences regarding the temporal relationship between RHI and mood.” Moreover, the study focused only on hypomania, so “we cannot draw conclusions about mania.” In addition, the HC group had a “significantly higher proportion” of White participants, and a lower Tanner stage, so it “may not be a representative control sample.”

Nevertheless, the researchers concluded that the study “adds to the existing evidence for the potential value of integrating cardiovascular-related therapeutic approaches in BD,” noting that further research is needed to elucidate the mechanisms of the association.
 

Observable changes in youth

In a comment, Jess G Fiedorowicz, MD, PhD, head and chief, department of mental health, Ottawa Hospital Research Institute, noted that individuals with BD “have a much higher risk of CVD, which tends to develop earlier and shortens life expectancy by more than a decade.” 

This cardiovascular risk “appears to be acquired over the long-term course of illness and proportionate to the persistence and severity of mood symptoms, which implies that mood syndromes, such as depression and mania, themselves may induce changes in the body relevant to CVD,” said Dr. Fiedorowicz, who is also a professor in the department of psychiatry and senior research chair in adult psychiatry at the Brain and Mind Research Institute, University of Ottawa, and was not involved with the study.

The study “adds to a growing body of evidence that mood syndromes may enact physiological changes that may be relevant to risk of CVD. One important aspect of this study is that this can even be observed in young sample,” he said.

This study was funded by the Canadian Institutes of Health Research and a Miner’s Lamp Innovation Fund from the University of Toronto. Dr. Goldstein and coauthors declare no relevant financial relationships. Dr. Fiedorowicz receives an honorarium from Elsevier for his work as editor-in-chief of the Journal of Psychosomatic Research.

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

An early predictor of cardiovascular disease (CVD) has been found in youth with bipolar disorder (BD), in new findings that may explain the “excessive and premature mortality” related to heart disease in this patient population.

The investigators found that higher reactive hyperemia index (RHI) scores, a measure of endothelial function, were tied to mood severity in patients with higher mania, but not depression scores. These findings persisted even after accounting for medications, obesity, and other cardiovascular risk factors (CVRFs).

“From a clinical perspective, these findings highlight the potential value of integrating vascular health in the assessment and management of youth with BD, and from a scientific perspective, these findings call for additional research focused on shared biological mechanisms linking vascular health and mood symptoms of BD,” senior investigator Benjamin Goldstein, MD, PhD, full professor of psychiatry, pharmacology, and psychological clinical science, University of Toronto, said in an interview.

The study was published online in the Journal of Clinical Psychiatry.
 

‘Excessively present’

BD is associated with “excessive and premature cardiovascular mortality” and CVD is “excessively present” in BD, exceeding what can be explained by traditional cardiovascular risk factors, psychiatric medications, and substance use, the researchers noted.

“In adults, more severe mood symptoms increase the risk of future CVD. Our focus on endothelial function rose due to the fact that CVD is rare in youth, whereas endothelial dysfunction – considered a precursor of CVD – can be assessed in youth,” said Dr. Goldstein, who holds the RBC Investments Chair in children’s mental health and developmental psychopathology at the Centre for Addiction and Mental Health, Toronto, where he is director of the Centre for Youth Bipolar Disorder.

For this reason, he and his colleagues were “interested in researching whether endothelial dysfunction is associated with mood symptoms in youth with BD.” Ultimately, the motivation was to “inspire new therapeutic opportunities that may improve both cardiovascular and mental health simultaneously.”

To investigate the question, the researchers studied 209 youth aged 13-20 years (n = 114 with BD and 94 healthy controls [HCs]).

In the BD group, there were 34 BD-euthymia, 36 BD-depressed, and 44 BD-hypomanic/mixed; and within the groups who had depression or hypomania/mixed features, 72 were experiencing clinically significant depression. 

Participants had to be free of chronic inflammatory illness, use of medications that might be addressing traditional CVRFs, recent infectious diseases, or neurologic conditions.

Participants’ bipolar symptoms, psychosocial functioning, and family history were assessed. In addition, they were asked about treatment, physical and/or sexual abuse, smoking status, and socioeconomic status. Height, weight, waist circumference, blood pressure, and blood tests to assess CVRFs, including C-reactive protein (CRP), were also assessed. RHI was measured via pulse amplitude tonometry, with lower values indicating poorer endothelial function.
 

Positive affect beneficial?

Compared with HCs, there were fewer White participants in the BD group (78% vs. 55%; P < .001). The BD group also had higher Tanner stage development scores (stage 5: 65% vs. 35%; P = .03; V = 0.21), higher body mass index (BMI, 24.4 ± 4.6 vs. 22.0 ± 4.2; P < .001; d = 0.53), and higher CRP (1.94 ± 3.99 vs. 0.76 ± 0.86; P = .009; d = –0.40).

After controlling for age, sex, and BMI (F_3,202 = 4.47; P = .005; n_p²  = 0.06), the researchers found significant between-group differences in RHI.

Post hoc pairwise comparisons showed RHI to be significantly lower in the BD-depressed versus the HC group (P = .04; d = 0.4). Moreover, the BD-hypomanic/mixed group had significantly higher RHI, compared with the other BD groups and the HC group.

RHI was associated with higher mania scores (beta, 0.26; P = .006), but there was no similar significant association with depression mood scores (beta, 0.01; P = .90).

The mood state differences in RHI and the RHI-mania association remained significant in sensitivity analyses examining the effect of current medication use as well as CVRFs, including lipids, CRP, and blood pressure on RHI.

“We found that youth with BD experiencing a depressive episode had lower endothelial function, whereas youth with BD experiencing a hypomanic/mixed episode had higher endothelial function, as compared to healthy youth,” Dr. Goldstein said.

There are several mechanisms potentially underlying the association between endothelial function and hypomania, the investigators noted. For example, positive affect is associated with increased endothelial function in normative samples, so hypomanic symptoms, including elation, may have similar beneficial associations, although those benefits likely do not extend to mania, which has been associated with cardiovascular risk.

They also point to several limitations in the study. The cross-sectional design “precludes making inferences regarding the temporal relationship between RHI and mood.” Moreover, the study focused only on hypomania, so “we cannot draw conclusions about mania.” In addition, the HC group had a “significantly higher proportion” of White participants, and a lower Tanner stage, so it “may not be a representative control sample.”

Nevertheless, the researchers concluded that the study “adds to the existing evidence for the potential value of integrating cardiovascular-related therapeutic approaches in BD,” noting that further research is needed to elucidate the mechanisms of the association.
 

Observable changes in youth

In a comment, Jess G Fiedorowicz, MD, PhD, head and chief, department of mental health, Ottawa Hospital Research Institute, noted that individuals with BD “have a much higher risk of CVD, which tends to develop earlier and shortens life expectancy by more than a decade.” 

This cardiovascular risk “appears to be acquired over the long-term course of illness and proportionate to the persistence and severity of mood symptoms, which implies that mood syndromes, such as depression and mania, themselves may induce changes in the body relevant to CVD,” said Dr. Fiedorowicz, who is also a professor in the department of psychiatry and senior research chair in adult psychiatry at the Brain and Mind Research Institute, University of Ottawa, and was not involved with the study.

The study “adds to a growing body of evidence that mood syndromes may enact physiological changes that may be relevant to risk of CVD. One important aspect of this study is that this can even be observed in young sample,” he said.

This study was funded by the Canadian Institutes of Health Research and a Miner’s Lamp Innovation Fund from the University of Toronto. Dr. Goldstein and coauthors declare no relevant financial relationships. Dr. Fiedorowicz receives an honorarium from Elsevier for his work as editor-in-chief of the Journal of Psychosomatic Research.

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

An early predictor of cardiovascular disease (CVD) has been found in youth with bipolar disorder (BD), in new findings that may explain the “excessive and premature mortality” related to heart disease in this patient population.

The investigators found that higher reactive hyperemia index (RHI) scores, a measure of endothelial function, were tied to mood severity in patients with higher mania, but not depression scores. These findings persisted even after accounting for medications, obesity, and other cardiovascular risk factors (CVRFs).

“From a clinical perspective, these findings highlight the potential value of integrating vascular health in the assessment and management of youth with BD, and from a scientific perspective, these findings call for additional research focused on shared biological mechanisms linking vascular health and mood symptoms of BD,” senior investigator Benjamin Goldstein, MD, PhD, full professor of psychiatry, pharmacology, and psychological clinical science, University of Toronto, said in an interview.

The study was published online in the Journal of Clinical Psychiatry.
 

‘Excessively present’

BD is associated with “excessive and premature cardiovascular mortality” and CVD is “excessively present” in BD, exceeding what can be explained by traditional cardiovascular risk factors, psychiatric medications, and substance use, the researchers noted.

“In adults, more severe mood symptoms increase the risk of future CVD. Our focus on endothelial function rose due to the fact that CVD is rare in youth, whereas endothelial dysfunction – considered a precursor of CVD – can be assessed in youth,” said Dr. Goldstein, who holds the RBC Investments Chair in children’s mental health and developmental psychopathology at the Centre for Addiction and Mental Health, Toronto, where he is director of the Centre for Youth Bipolar Disorder.

For this reason, he and his colleagues were “interested in researching whether endothelial dysfunction is associated with mood symptoms in youth with BD.” Ultimately, the motivation was to “inspire new therapeutic opportunities that may improve both cardiovascular and mental health simultaneously.”

To investigate the question, the researchers studied 209 youth aged 13-20 years (n = 114 with BD and 94 healthy controls [HCs]).

In the BD group, there were 34 BD-euthymia, 36 BD-depressed, and 44 BD-hypomanic/mixed; and within the groups who had depression or hypomania/mixed features, 72 were experiencing clinically significant depression. 

Participants had to be free of chronic inflammatory illness, use of medications that might be addressing traditional CVRFs, recent infectious diseases, or neurologic conditions.

Participants’ bipolar symptoms, psychosocial functioning, and family history were assessed. In addition, they were asked about treatment, physical and/or sexual abuse, smoking status, and socioeconomic status. Height, weight, waist circumference, blood pressure, and blood tests to assess CVRFs, including C-reactive protein (CRP), were also assessed. RHI was measured via pulse amplitude tonometry, with lower values indicating poorer endothelial function.
 

Positive affect beneficial?

Compared with HCs, there were fewer White participants in the BD group (78% vs. 55%; P < .001). The BD group also had higher Tanner stage development scores (stage 5: 65% vs. 35%; P = .03; V = 0.21), higher body mass index (BMI, 24.4 ± 4.6 vs. 22.0 ± 4.2; P < .001; d = 0.53), and higher CRP (1.94 ± 3.99 vs. 0.76 ± 0.86; P = .009; d = –0.40).

After controlling for age, sex, and BMI (F_3,202 = 4.47; P = .005; n_p²  = 0.06), the researchers found significant between-group differences in RHI.

Post hoc pairwise comparisons showed RHI to be significantly lower in the BD-depressed versus the HC group (P = .04; d = 0.4). Moreover, the BD-hypomanic/mixed group had significantly higher RHI, compared with the other BD groups and the HC group.

RHI was associated with higher mania scores (beta, 0.26; P = .006), but there was no similar significant association with depression mood scores (beta, 0.01; P = .90).

The mood state differences in RHI and the RHI-mania association remained significant in sensitivity analyses examining the effect of current medication use as well as CVRFs, including lipids, CRP, and blood pressure on RHI.

“We found that youth with BD experiencing a depressive episode had lower endothelial function, whereas youth with BD experiencing a hypomanic/mixed episode had higher endothelial function, as compared to healthy youth,” Dr. Goldstein said.

There are several mechanisms potentially underlying the association between endothelial function and hypomania, the investigators noted. For example, positive affect is associated with increased endothelial function in normative samples, so hypomanic symptoms, including elation, may have similar beneficial associations, although those benefits likely do not extend to mania, which has been associated with cardiovascular risk.

They also point to several limitations in the study. The cross-sectional design “precludes making inferences regarding the temporal relationship between RHI and mood.” Moreover, the study focused only on hypomania, so “we cannot draw conclusions about mania.” In addition, the HC group had a “significantly higher proportion” of White participants, and a lower Tanner stage, so it “may not be a representative control sample.”

Nevertheless, the researchers concluded that the study “adds to the existing evidence for the potential value of integrating cardiovascular-related therapeutic approaches in BD,” noting that further research is needed to elucidate the mechanisms of the association.
 

Observable changes in youth

In a comment, Jess G Fiedorowicz, MD, PhD, head and chief, department of mental health, Ottawa Hospital Research Institute, noted that individuals with BD “have a much higher risk of CVD, which tends to develop earlier and shortens life expectancy by more than a decade.” 

This cardiovascular risk “appears to be acquired over the long-term course of illness and proportionate to the persistence and severity of mood symptoms, which implies that mood syndromes, such as depression and mania, themselves may induce changes in the body relevant to CVD,” said Dr. Fiedorowicz, who is also a professor in the department of psychiatry and senior research chair in adult psychiatry at the Brain and Mind Research Institute, University of Ottawa, and was not involved with the study.

The study “adds to a growing body of evidence that mood syndromes may enact physiological changes that may be relevant to risk of CVD. One important aspect of this study is that this can even be observed in young sample,” he said.

This study was funded by the Canadian Institutes of Health Research and a Miner’s Lamp Innovation Fund from the University of Toronto. Dr. Goldstein and coauthors declare no relevant financial relationships. Dr. Fiedorowicz receives an honorarium from Elsevier for his work as editor-in-chief of the Journal of Psychosomatic Research.

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

Anxiety, depression, and COVID-19 can be a bad combination for your brain – and your long-term health.

Having anxiety and depression before a COVID infection increases the risk of developing long COVID, researchers have found. 

Those with long COVID who develop anxiety and depression after an infection may have brain shrinkage in areas that regulate memory, emotion, and other functions as well as disruption of brain connectivity. 

While many questions remain about these intertwined relationships, the associations aren’t a complete surprise. Experts already know that depression and anxiety are associated with inflammation and immune dysfunction, perhaps helping to explain the link between these mental health conditions, the risk of long COVID, and the changes in the brain.

Brain changes accompanying a COVID infection have concerned researchers since earlier in the pandemic, when U.K. Biobank researchers found brain atrophy, loss of grey matter, and decline in cognition in those infected with COVID, compared with those not infected.
 

Common conditions

The ramifications of the research linking anxiety, depression, and long COVID are far-reaching. According to the Centers for Disease Control and Prevention, 12.5% of U.S. adults have regular feelings of anxiety (as well as nervousness and worry), and the latest Gallup Poll found that nearly 18% of adults currently have or are being treated for depression. 

As of May 8, 10% of infected adults in the United States have long COVID, according to the CDC, and among U.S. adults ever infected, 27% have reported long COVID. Long COVID has been defined by the CDC as symptoms such as fatigue, brain fog, and cough that persist longer than 4 weeks and by the World Health Organization as symptoms persisting for 3 months or more. 

Here’s a roundup of what the research shows about mental health and long COVID risk – along with other research finding that paying attention to health habits may reduce that risk. 
 

Pre-existing depression, anxiety, and long COVID risk

A history of mental health issues – including depression, anxiety, worry, perceived stress, and loneliness – raises the risk of long COVID if infection occurs, Harvard researchers have found.

The researchers evaluated data from three large, ongoing studies including nearly 55,000 participants to determine the effects of high levels of psychological distress before a COVID infection. 

“Our study was purely survey based,” said Siwen Wang, MD, the study’s lead author and a research fellow at Harvard School of Public Health, Boston.

At the start of the survey in April 2020, none of the participants reported a current or previous COVID infection. They answered surveys about psychological distress at the start of the study, at 6 monthly time points, then quarterly until November 2021.

Over the follow up, 3,193 people reported a positive COVID test and 43% of those, or 1,403, developed long COVID. That number may seem high, but 38% of the 55,000 were active health care workers. On the final questionnaire, they reported whether their symptoms persisted for 4 weeks or longer and thus had long COVID by the standard CDC definition.

Dr. Wang’s team then looked at the infected participants’ psychological status. Anxiety raised the risk of long COVID by 42%, depression by 32%, worry about COVID by 37%, perceived stress, 46%, and loneliness, 32%.

COVID patients with a history of depression or anxiety are also more likely than others to report trouble with cognition in the weeks after a COVID infection and to develop brain fog and long COVID, UCLA researchers found. They evaluated 766 people with a confirmed COVID infection; 36% said their thinking was affected within 4 weeks of the infection. Those with anxiety and depression were more likely to report those difficulties.
 

Long COVID, then anxiety, depression, brain changes

Even mild cases of COVID infection can lead to long COVID and brain changes in those who suffer anxiety or depression after the infection, according to Clarissa Yasuda, MD, PhD, assistant professor of neurology at the University of Campinas in Sao Paulo. She has researched long COVID’s effects on the brain, even as she is coping with being a long COVID patient.

In one of her studies, presented at the 2023 annual meeting of the American Academy of Neurology, she found brain changes in people with anxiety, depression, and COVID but not in those infected who did not have either mental health issue. She evaluated 254 people, median age 41, after about 82 days from their positive PCR test for COVID.  Everyone completed a standard questionnaire for depression (the Beck Depression Inventory) and another for anxiety (the Beck Anxiety Inventory). She further divided them into two groups – the 102 with symptoms and the 152 who had no symptoms of either depression or anxiety. 

Brain scans showed those with COVID who also had anxiety and depression had shrinkage in the limbic area of the brain (which helps process emotion and memory), while those infected who didn’t have anxiety or depression did not. The researchers then scanned the brains of 148 healthy people without COVID and found no shrinkage.

The atrophy, Dr. Yasuda said, “is not something you can see with your eyes. It was only detected with computer analysis. Visualization on an MRI is normal.”

The number of people in this study with mental health issues was surprisingly high, Dr. Yasuda said. “It was intriguing for us that we noticed many individuals have both symptoms, anxiety and depression. We were not expecting it at that proportion.”

The researchers found a pattern of change not only in brain structure but in brain communication. They found those changes by using specialized software to analyze brain networks in some of the participants. Those with anxiety and depression had widespread functional changes in each of 12 networks tested. The participants without mental health symptoms showed changes in just five networks. These changes are enough to lead to problems with thinking skills and memory, Dr. Yasuda said.
 

Explaining the links

Several ideas have been proposed to explain the link between psychological distress and long COVID risk, Dr. Wang said. “The first and most mainstream mechanism for long COVID is chronic inflammation and immune dysregulation. Several mental health conditions, such as anxiety and depression, are associated with inflammation and dysfunction and that might be the link between depression, anxiety, and long COVID.”

Another less mainstream hypothesis, she said, is that “those with long COVID have more autoantibodies and they are more likely to have blood clotting issues. These have also been found in people with anxiety, depression, or other psychological distress.”

Other researchers are looking more broadly at how COVID infections affect the brain. When German researchers evaluated the brain and other body parts of 20 patients who died from non-COVID causes but had documented COVID infections, they found that 12 had accumulations of the SARS-CoV-2 spike protein in the brain tissue as well as the skull and meninges, the membranes that line the skull and spinal cord. Healthy controls did not. 

The findings suggest the persistence of the spike protein may contribute to the long-term neurologic symptoms of long COVID and may also lead to understanding of the molecular mechanisms as well as therapies for long COVID, the researchers said in their preprint report, which has not yet been peer reviewed. 

In another recent study, researchers from Germany performed neuroimaging and neuropsychological assessments of 223 people who were not vaccinated and recovered from mild to moderate COVID infections, comparing them with 223 matched healthy controls who had the same testing. In those infected, they found alterations in the cerebral white matter but no worse cognitive function in the first year after recovering. They conclude that the infection triggers a prolonged neuroinflammatory response. 

Can the brain changes reverse? “We don’t have an answer right now, but we are working on that,” Dr. Yasuda said. For now, she speculates about the return of brain volume: “I think for most it will. But I think we need to treat the symptoms. We can’t disregard the symptoms of long COVID. People are suffering a lot, and this suffering is causing some brain damage.”
 

Lifestyle habits and risk of long COVID

Meanwhile, healthy lifestyle habits in those infected can reduce the risk of long COVID, research by Dr. Wang and colleagues found. They followed nearly 2,000 women with a positive COVID test over 19 months. Of these, 44%, or 871, developed long COVID. Compared with women who followed none of the healthy lifestyle habits evaluated, those with five to six of the habits had a 49% lower risk of long COVID.

The habits included: a healthy body mass index (18.5-24.9 kg/m²), never smoking, at least 150 minutes weekly of moderate to vigorous physical activity, moderate alcohol intake (5-15 grams a day), high diet quality, and good sleep (7-9 hours nightly).
 

Long-term solutions 

Dr. Yasuda hopes that mental health care – of those infected and those not – will be taken more seriously. In a commentary on her own long COVID experience, she wrote, in part: “I fear for the numerous survivors of COVID-19 who do not have access to medical attention for their post-COVID symptoms. ... The mental health system needs to become prepared to receive survivors with different neuropsychiatric symptoms, including anxiety and depression.” 

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

Anxiety, depression, and COVID-19 can be a bad combination for your brain – and your long-term health.

Having anxiety and depression before a COVID infection increases the risk of developing long COVID, researchers have found. 

Those with long COVID who develop anxiety and depression after an infection may have brain shrinkage in areas that regulate memory, emotion, and other functions as well as disruption of brain connectivity. 

While many questions remain about these intertwined relationships, the associations aren’t a complete surprise. Experts already know that depression and anxiety are associated with inflammation and immune dysfunction, perhaps helping to explain the link between these mental health conditions, the risk of long COVID, and the changes in the brain.

Brain changes accompanying a COVID infection have concerned researchers since earlier in the pandemic, when U.K. Biobank researchers found brain atrophy, loss of grey matter, and decline in cognition in those infected with COVID, compared with those not infected.
 

Common conditions

The ramifications of the research linking anxiety, depression, and long COVID are far-reaching. According to the Centers for Disease Control and Prevention, 12.5% of U.S. adults have regular feelings of anxiety (as well as nervousness and worry), and the latest Gallup Poll found that nearly 18% of adults currently have or are being treated for depression. 

As of May 8, 10% of infected adults in the United States have long COVID, according to the CDC, and among U.S. adults ever infected, 27% have reported long COVID. Long COVID has been defined by the CDC as symptoms such as fatigue, brain fog, and cough that persist longer than 4 weeks and by the World Health Organization as symptoms persisting for 3 months or more. 

Here’s a roundup of what the research shows about mental health and long COVID risk – along with other research finding that paying attention to health habits may reduce that risk. 
 

Pre-existing depression, anxiety, and long COVID risk

A history of mental health issues – including depression, anxiety, worry, perceived stress, and loneliness – raises the risk of long COVID if infection occurs, Harvard researchers have found.

The researchers evaluated data from three large, ongoing studies including nearly 55,000 participants to determine the effects of high levels of psychological distress before a COVID infection. 

“Our study was purely survey based,” said Siwen Wang, MD, the study’s lead author and a research fellow at Harvard School of Public Health, Boston.

At the start of the survey in April 2020, none of the participants reported a current or previous COVID infection. They answered surveys about psychological distress at the start of the study, at 6 monthly time points, then quarterly until November 2021.

Over the follow up, 3,193 people reported a positive COVID test and 43% of those, or 1,403, developed long COVID. That number may seem high, but 38% of the 55,000 were active health care workers. On the final questionnaire, they reported whether their symptoms persisted for 4 weeks or longer and thus had long COVID by the standard CDC definition.

Dr. Wang’s team then looked at the infected participants’ psychological status. Anxiety raised the risk of long COVID by 42%, depression by 32%, worry about COVID by 37%, perceived stress, 46%, and loneliness, 32%.

COVID patients with a history of depression or anxiety are also more likely than others to report trouble with cognition in the weeks after a COVID infection and to develop brain fog and long COVID, UCLA researchers found. They evaluated 766 people with a confirmed COVID infection; 36% said their thinking was affected within 4 weeks of the infection. Those with anxiety and depression were more likely to report those difficulties.
 

Long COVID, then anxiety, depression, brain changes

Even mild cases of COVID infection can lead to long COVID and brain changes in those who suffer anxiety or depression after the infection, according to Clarissa Yasuda, MD, PhD, assistant professor of neurology at the University of Campinas in Sao Paulo. She has researched long COVID’s effects on the brain, even as she is coping with being a long COVID patient.

In one of her studies, presented at the 2023 annual meeting of the American Academy of Neurology, she found brain changes in people with anxiety, depression, and COVID but not in those infected who did not have either mental health issue. She evaluated 254 people, median age 41, after about 82 days from their positive PCR test for COVID.  Everyone completed a standard questionnaire for depression (the Beck Depression Inventory) and another for anxiety (the Beck Anxiety Inventory). She further divided them into two groups – the 102 with symptoms and the 152 who had no symptoms of either depression or anxiety. 

Brain scans showed those with COVID who also had anxiety and depression had shrinkage in the limbic area of the brain (which helps process emotion and memory), while those infected who didn’t have anxiety or depression did not. The researchers then scanned the brains of 148 healthy people without COVID and found no shrinkage.

The atrophy, Dr. Yasuda said, “is not something you can see with your eyes. It was only detected with computer analysis. Visualization on an MRI is normal.”

The number of people in this study with mental health issues was surprisingly high, Dr. Yasuda said. “It was intriguing for us that we noticed many individuals have both symptoms, anxiety and depression. We were not expecting it at that proportion.”

The researchers found a pattern of change not only in brain structure but in brain communication. They found those changes by using specialized software to analyze brain networks in some of the participants. Those with anxiety and depression had widespread functional changes in each of 12 networks tested. The participants without mental health symptoms showed changes in just five networks. These changes are enough to lead to problems with thinking skills and memory, Dr. Yasuda said.
 

Explaining the links

Several ideas have been proposed to explain the link between psychological distress and long COVID risk, Dr. Wang said. “The first and most mainstream mechanism for long COVID is chronic inflammation and immune dysregulation. Several mental health conditions, such as anxiety and depression, are associated with inflammation and dysfunction and that might be the link between depression, anxiety, and long COVID.”

Another less mainstream hypothesis, she said, is that “those with long COVID have more autoantibodies and they are more likely to have blood clotting issues. These have also been found in people with anxiety, depression, or other psychological distress.”

Other researchers are looking more broadly at how COVID infections affect the brain. When German researchers evaluated the brain and other body parts of 20 patients who died from non-COVID causes but had documented COVID infections, they found that 12 had accumulations of the SARS-CoV-2 spike protein in the brain tissue as well as the skull and meninges, the membranes that line the skull and spinal cord. Healthy controls did not. 

The findings suggest the persistence of the spike protein may contribute to the long-term neurologic symptoms of long COVID and may also lead to understanding of the molecular mechanisms as well as therapies for long COVID, the researchers said in their preprint report, which has not yet been peer reviewed. 

In another recent study, researchers from Germany performed neuroimaging and neuropsychological assessments of 223 people who were not vaccinated and recovered from mild to moderate COVID infections, comparing them with 223 matched healthy controls who had the same testing. In those infected, they found alterations in the cerebral white matter but no worse cognitive function in the first year after recovering. They conclude that the infection triggers a prolonged neuroinflammatory response. 

Can the brain changes reverse? “We don’t have an answer right now, but we are working on that,” Dr. Yasuda said. For now, she speculates about the return of brain volume: “I think for most it will. But I think we need to treat the symptoms. We can’t disregard the symptoms of long COVID. People are suffering a lot, and this suffering is causing some brain damage.”
 

Lifestyle habits and risk of long COVID

Meanwhile, healthy lifestyle habits in those infected can reduce the risk of long COVID, research by Dr. Wang and colleagues found. They followed nearly 2,000 women with a positive COVID test over 19 months. Of these, 44%, or 871, developed long COVID. Compared with women who followed none of the healthy lifestyle habits evaluated, those with five to six of the habits had a 49% lower risk of long COVID.

The habits included: a healthy body mass index (18.5-24.9 kg/m²), never smoking, at least 150 minutes weekly of moderate to vigorous physical activity, moderate alcohol intake (5-15 grams a day), high diet quality, and good sleep (7-9 hours nightly).
 

Long-term solutions 

Dr. Yasuda hopes that mental health care – of those infected and those not – will be taken more seriously. In a commentary on her own long COVID experience, she wrote, in part: “I fear for the numerous survivors of COVID-19 who do not have access to medical attention for their post-COVID symptoms. ... The mental health system needs to become prepared to receive survivors with different neuropsychiatric symptoms, including anxiety and depression.” 

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

Anxiety, depression, and COVID-19 can be a bad combination for your brain – and your long-term health.

Having anxiety and depression before a COVID infection increases the risk of developing long COVID, researchers have found. 

Those with long COVID who develop anxiety and depression after an infection may have brain shrinkage in areas that regulate memory, emotion, and other functions as well as disruption of brain connectivity. 

While many questions remain about these intertwined relationships, the associations aren’t a complete surprise. Experts already know that depression and anxiety are associated with inflammation and immune dysfunction, perhaps helping to explain the link between these mental health conditions, the risk of long COVID, and the changes in the brain.

Brain changes accompanying a COVID infection have concerned researchers since earlier in the pandemic, when U.K. Biobank researchers found brain atrophy, loss of grey matter, and decline in cognition in those infected with COVID, compared with those not infected.
 

Common conditions

The ramifications of the research linking anxiety, depression, and long COVID are far-reaching. According to the Centers for Disease Control and Prevention, 12.5% of U.S. adults have regular feelings of anxiety (as well as nervousness and worry), and the latest Gallup Poll found that nearly 18% of adults currently have or are being treated for depression. 

As of May 8, 10% of infected adults in the United States have long COVID, according to the CDC, and among U.S. adults ever infected, 27% have reported long COVID. Long COVID has been defined by the CDC as symptoms such as fatigue, brain fog, and cough that persist longer than 4 weeks and by the World Health Organization as symptoms persisting for 3 months or more. 

Here’s a roundup of what the research shows about mental health and long COVID risk – along with other research finding that paying attention to health habits may reduce that risk. 
 

Pre-existing depression, anxiety, and long COVID risk

A history of mental health issues – including depression, anxiety, worry, perceived stress, and loneliness – raises the risk of long COVID if infection occurs, Harvard researchers have found.

The researchers evaluated data from three large, ongoing studies including nearly 55,000 participants to determine the effects of high levels of psychological distress before a COVID infection. 

“Our study was purely survey based,” said Siwen Wang, MD, the study’s lead author and a research fellow at Harvard School of Public Health, Boston.

At the start of the survey in April 2020, none of the participants reported a current or previous COVID infection. They answered surveys about psychological distress at the start of the study, at 6 monthly time points, then quarterly until November 2021.

Over the follow up, 3,193 people reported a positive COVID test and 43% of those, or 1,403, developed long COVID. That number may seem high, but 38% of the 55,000 were active health care workers. On the final questionnaire, they reported whether their symptoms persisted for 4 weeks or longer and thus had long COVID by the standard CDC definition.

Dr. Wang’s team then looked at the infected participants’ psychological status. Anxiety raised the risk of long COVID by 42%, depression by 32%, worry about COVID by 37%, perceived stress, 46%, and loneliness, 32%.

COVID patients with a history of depression or anxiety are also more likely than others to report trouble with cognition in the weeks after a COVID infection and to develop brain fog and long COVID, UCLA researchers found. They evaluated 766 people with a confirmed COVID infection; 36% said their thinking was affected within 4 weeks of the infection. Those with anxiety and depression were more likely to report those difficulties.
 

Long COVID, then anxiety, depression, brain changes

Even mild cases of COVID infection can lead to long COVID and brain changes in those who suffer anxiety or depression after the infection, according to Clarissa Yasuda, MD, PhD, assistant professor of neurology at the University of Campinas in Sao Paulo. She has researched long COVID’s effects on the brain, even as she is coping with being a long COVID patient.

In one of her studies, presented at the 2023 annual meeting of the American Academy of Neurology, she found brain changes in people with anxiety, depression, and COVID but not in those infected who did not have either mental health issue. She evaluated 254 people, median age 41, after about 82 days from their positive PCR test for COVID.  Everyone completed a standard questionnaire for depression (the Beck Depression Inventory) and another for anxiety (the Beck Anxiety Inventory). She further divided them into two groups – the 102 with symptoms and the 152 who had no symptoms of either depression or anxiety. 

Brain scans showed those with COVID who also had anxiety and depression had shrinkage in the limbic area of the brain (which helps process emotion and memory), while those infected who didn’t have anxiety or depression did not. The researchers then scanned the brains of 148 healthy people without COVID and found no shrinkage.

The atrophy, Dr. Yasuda said, “is not something you can see with your eyes. It was only detected with computer analysis. Visualization on an MRI is normal.”

The number of people in this study with mental health issues was surprisingly high, Dr. Yasuda said. “It was intriguing for us that we noticed many individuals have both symptoms, anxiety and depression. We were not expecting it at that proportion.”

The researchers found a pattern of change not only in brain structure but in brain communication. They found those changes by using specialized software to analyze brain networks in some of the participants. Those with anxiety and depression had widespread functional changes in each of 12 networks tested. The participants without mental health symptoms showed changes in just five networks. These changes are enough to lead to problems with thinking skills and memory, Dr. Yasuda said.
 

Explaining the links

Several ideas have been proposed to explain the link between psychological distress and long COVID risk, Dr. Wang said. “The first and most mainstream mechanism for long COVID is chronic inflammation and immune dysregulation. Several mental health conditions, such as anxiety and depression, are associated with inflammation and dysfunction and that might be the link between depression, anxiety, and long COVID.”

Another less mainstream hypothesis, she said, is that “those with long COVID have more autoantibodies and they are more likely to have blood clotting issues. These have also been found in people with anxiety, depression, or other psychological distress.”

Other researchers are looking more broadly at how COVID infections affect the brain. When German researchers evaluated the brain and other body parts of 20 patients who died from non-COVID causes but had documented COVID infections, they found that 12 had accumulations of the SARS-CoV-2 spike protein in the brain tissue as well as the skull and meninges, the membranes that line the skull and spinal cord. Healthy controls did not. 

The findings suggest the persistence of the spike protein may contribute to the long-term neurologic symptoms of long COVID and may also lead to understanding of the molecular mechanisms as well as therapies for long COVID, the researchers said in their preprint report, which has not yet been peer reviewed. 

In another recent study, researchers from Germany performed neuroimaging and neuropsychological assessments of 223 people who were not vaccinated and recovered from mild to moderate COVID infections, comparing them with 223 matched healthy controls who had the same testing. In those infected, they found alterations in the cerebral white matter but no worse cognitive function in the first year after recovering. They conclude that the infection triggers a prolonged neuroinflammatory response. 

Can the brain changes reverse? “We don’t have an answer right now, but we are working on that,” Dr. Yasuda said. For now, she speculates about the return of brain volume: “I think for most it will. But I think we need to treat the symptoms. We can’t disregard the symptoms of long COVID. People are suffering a lot, and this suffering is causing some brain damage.”
 

Lifestyle habits and risk of long COVID

Meanwhile, healthy lifestyle habits in those infected can reduce the risk of long COVID, research by Dr. Wang and colleagues found. They followed nearly 2,000 women with a positive COVID test over 19 months. Of these, 44%, or 871, developed long COVID. Compared with women who followed none of the healthy lifestyle habits evaluated, those with five to six of the habits had a 49% lower risk of long COVID.

The habits included: a healthy body mass index (18.5-24.9 kg/m²), never smoking, at least 150 minutes weekly of moderate to vigorous physical activity, moderate alcohol intake (5-15 grams a day), high diet quality, and good sleep (7-9 hours nightly).
 

Long-term solutions 

Dr. Yasuda hopes that mental health care – of those infected and those not – will be taken more seriously. In a commentary on her own long COVID experience, she wrote, in part: “I fear for the numerous survivors of COVID-19 who do not have access to medical attention for their post-COVID symptoms. ... The mental health system needs to become prepared to receive survivors with different neuropsychiatric symptoms, including anxiety and depression.” 

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

Sowing the seeds of cancer prevention

Are you looking to add to your quality of life, even though pets are not your speed? Might we suggest something with lower maintenance? Something a little greener?

Indoor plants can purify the air that comes from outside. Researchers at the University of Technology Sydney, in partnership with the plantscaping company Ambius, showed that a “green wall” made up of mixed indoor plants was able to suck up 97% of “the most toxic compounds” from the air in just 8 hours. We’re talking about lung-irritating, headache-inducing, cancer risk–boosting compounds from gasoline fumes, including benzene.

Fraser Torpy/University of Technology Sydney

Public health initiatives often strive to reduce cardiovascular and obesity risks, but breathing seems pretty important too. According to the World Health Organization, household air pollution is responsible for about 2.5 million global premature deaths each year. And since 2020 we’ve become accustomed to spending more time inside and at home.

“This new research proves that plants should not just be seen as ‘nice to have,’ but rather a crucial part of every workplace wellness plan,” Ambius General Manager Johan Hodgson said in statement released by the university.

So don’t spend hundreds of dollars on a fancy air filtration system when a wall of plants can do that for next to nothing. Find what works for you and your space and become a plant parent today! Your lungs will thank you.
 

But officer, I had to swerve to miss the duodenal ampulla

Tiny video capsule endoscopes have been around for many years, but they have one big weakness: The ingestible cameras’ journey through the GI tract is passively driven by gravity and the natural movement of the body, so they often miss potential problem areas.

AnX Robotica

Not anymore. That flaw has been addressed by medical technology company AnX Robotica, which has taken endoscopy to the next level by adding that wondrous directional control device of the modern electronic age, a joystick.

The new system “uses an external magnet and hand-held video game style joysticks to move the capsule in three dimensions,” which allows physicians to “remotely drive a miniature video capsule to all regions of the stomach to visualize and photograph potential problem areas,” according to Andrew C. Meltzer, MD, of George Washington University and associates, who conducted a pilot study funded by AnX Robotica.

The video capsule provided a 95% rate of visualization in the stomachs of 40 patients who were examined at a medical office building by an emergency medicine physician who had no previous specialty training in endoscopy. “Capsules were driven by the ER physician and then the study reports were reviewed by an attending gastroenterologist who was physically off site,” the investigators said in a written statement.

The capsule operator did receive some additional training, and development of artificial intelligence to self-drive the capsule is in the works, but for now, we’re talking about a device controlled by a human using a joystick. And we all know that 50-year-olds are not especially known for their joystick skills. For that we need real experts. Yup, we need to put those joystick-controlled capsule endoscopes in the hands of teenage gamers. Who wants to go first?
 

Maybe AI isn’t ready for the big time after all

“How long before some intrepid stockholder says: ‘Hey, instead of paying doctors, why don’t we just use the free robot instead?’ ” Those words appeared on LOTME but a month ago. After all, the AI is supposed to be smarter and more empathetic than a doctor. And did we mention it’s free? Or at least extremely cheap. Cheaper than, say, a group of recently unionized health care workers.

maewjpho/Thinkstock

In early May, the paid employees manning the National Eating Disorders Association emergency hotline voted to unionize, as they felt overwhelmed and underpaid. Apparently, paying six people an extra few thousand a year was too much for NEDA’s leadership, as they decided a few weeks later to fire those workers, fully closing down the hotline. Instead of talking to a real person, people “calling in” for support would be met with Tessa, a wellness chatbot that would hopefully guide them through their crisis. Key word, hopefully.

In perhaps the least surprising twist of the year, NEDA was forced to walk back its decision about a week after its initial announcement. It all started with a viral Instagram post from a woman who called in and received the following advice from Tessa: Lose 1-2 pounds a week, count calories and work for a 500- to 1,000-calorie deficit, weigh herself weekly, and restrict her diet. Unfortunately, all of these suggestions were things that led to the development of the woman’s eating disorder.

Naturally, NEDA responded in good grace, accusing the woman of lying. A NEDA vice president even left some nasty comments on the post, but hastily deleted them a day later when NEDA announced it was shutting down Tessa “until further notice for a complete investigation.” NEDA’s CEO insisted they hadn’t seen that behavior from Tessa before, calling it a “bug” and insisting the bot would only be down temporarily until the triggers causing the bug were fixed.

In the aftermath, several doctors and psychologists chimed in, terming the rush to automate human roles dangerous and risky. After all, much of what makes these hotlines effective is the volunteers speaking from their own experience. An unsupervised bot doesn’t seem to have what it takes to deal with a mental health crisis, but we’re betting that Tessa will be back. As a wise cephalopod once said: Nobody gives a care about the fate of labor as long as they can get their instant gratification.
 

You can’t spell existential without s-t-e-n-t

This week, we’re including a special “bonus” item that, to be honest, has nothing to do with stents. That’s why our editor is making us call this a “bonus” (and making us use quote marks, too): It doesn’t really have anything to do with stents or health care or those who practice health care. Actually, his exact words were, “You can’t just give the readers someone else’s ****ing list and expect to get paid for it.” Did we mention that he looks like Jack Nicklaus but acts like BoJack Horseman?

Anywaaay, we’re pretty sure that the list in question – “America’s Top 10 Most Googled Existential Questions” – says something about the human condition, just not about stents:

1. Why is the sky blue?

2. What do dreams mean?

3. What is the meaning of life?

4. Why am I so tired?

5. Who am I?

6. What is love?

7. Is a hot dog a sandwich?

8. What came first, the chicken or the egg?

9. What should I do?

10. Do animals have souls?

Sowing the seeds of cancer prevention

Are you looking to add to your quality of life, even though pets are not your speed? Might we suggest something with lower maintenance? Something a little greener?

Indoor plants can purify the air that comes from outside. Researchers at the University of Technology Sydney, in partnership with the plantscaping company Ambius, showed that a “green wall” made up of mixed indoor plants was able to suck up 97% of “the most toxic compounds” from the air in just 8 hours. We’re talking about lung-irritating, headache-inducing, cancer risk–boosting compounds from gasoline fumes, including benzene.

Fraser Torpy/University of Technology Sydney

Public health initiatives often strive to reduce cardiovascular and obesity risks, but breathing seems pretty important too. According to the World Health Organization, household air pollution is responsible for about 2.5 million global premature deaths each year. And since 2020 we’ve become accustomed to spending more time inside and at home.

“This new research proves that plants should not just be seen as ‘nice to have,’ but rather a crucial part of every workplace wellness plan,” Ambius General Manager Johan Hodgson said in statement released by the university.

So don’t spend hundreds of dollars on a fancy air filtration system when a wall of plants can do that for next to nothing. Find what works for you and your space and become a plant parent today! Your lungs will thank you.
 

But officer, I had to swerve to miss the duodenal ampulla

Tiny video capsule endoscopes have been around for many years, but they have one big weakness: The ingestible cameras’ journey through the GI tract is passively driven by gravity and the natural movement of the body, so they often miss potential problem areas.

AnX Robotica

Not anymore. That flaw has been addressed by medical technology company AnX Robotica, which has taken endoscopy to the next level by adding that wondrous directional control device of the modern electronic age, a joystick.

The new system “uses an external magnet and hand-held video game style joysticks to move the capsule in three dimensions,” which allows physicians to “remotely drive a miniature video capsule to all regions of the stomach to visualize and photograph potential problem areas,” according to Andrew C. Meltzer, MD, of George Washington University and associates, who conducted a pilot study funded by AnX Robotica.

The video capsule provided a 95% rate of visualization in the stomachs of 40 patients who were examined at a medical office building by an emergency medicine physician who had no previous specialty training in endoscopy. “Capsules were driven by the ER physician and then the study reports were reviewed by an attending gastroenterologist who was physically off site,” the investigators said in a written statement.

The capsule operator did receive some additional training, and development of artificial intelligence to self-drive the capsule is in the works, but for now, we’re talking about a device controlled by a human using a joystick. And we all know that 50-year-olds are not especially known for their joystick skills. For that we need real experts. Yup, we need to put those joystick-controlled capsule endoscopes in the hands of teenage gamers. Who wants to go first?
 

Maybe AI isn’t ready for the big time after all

“How long before some intrepid stockholder says: ‘Hey, instead of paying doctors, why don’t we just use the free robot instead?’ ” Those words appeared on LOTME but a month ago. After all, the AI is supposed to be smarter and more empathetic than a doctor. And did we mention it’s free? Or at least extremely cheap. Cheaper than, say, a group of recently unionized health care workers.

maewjpho/Thinkstock

In early May, the paid employees manning the National Eating Disorders Association emergency hotline voted to unionize, as they felt overwhelmed and underpaid. Apparently, paying six people an extra few thousand a year was too much for NEDA’s leadership, as they decided a few weeks later to fire those workers, fully closing down the hotline. Instead of talking to a real person, people “calling in” for support would be met with Tessa, a wellness chatbot that would hopefully guide them through their crisis. Key word, hopefully.

In perhaps the least surprising twist of the year, NEDA was forced to walk back its decision about a week after its initial announcement. It all started with a viral Instagram post from a woman who called in and received the following advice from Tessa: Lose 1-2 pounds a week, count calories and work for a 500- to 1,000-calorie deficit, weigh herself weekly, and restrict her diet. Unfortunately, all of these suggestions were things that led to the development of the woman’s eating disorder.

Naturally, NEDA responded in good grace, accusing the woman of lying. A NEDA vice president even left some nasty comments on the post, but hastily deleted them a day later when NEDA announced it was shutting down Tessa “until further notice for a complete investigation.” NEDA’s CEO insisted they hadn’t seen that behavior from Tessa before, calling it a “bug” and insisting the bot would only be down temporarily until the triggers causing the bug were fixed.

In the aftermath, several doctors and psychologists chimed in, terming the rush to automate human roles dangerous and risky. After all, much of what makes these hotlines effective is the volunteers speaking from their own experience. An unsupervised bot doesn’t seem to have what it takes to deal with a mental health crisis, but we’re betting that Tessa will be back. As a wise cephalopod once said: Nobody gives a care about the fate of labor as long as they can get their instant gratification.
 

You can’t spell existential without s-t-e-n-t

This week, we’re including a special “bonus” item that, to be honest, has nothing to do with stents. That’s why our editor is making us call this a “bonus” (and making us use quote marks, too): It doesn’t really have anything to do with stents or health care or those who practice health care. Actually, his exact words were, “You can’t just give the readers someone else’s ****ing list and expect to get paid for it.” Did we mention that he looks like Jack Nicklaus but acts like BoJack Horseman?

Anywaaay, we’re pretty sure that the list in question – “America’s Top 10 Most Googled Existential Questions” – says something about the human condition, just not about stents:

1. Why is the sky blue?

2. What do dreams mean?

3. What is the meaning of life?

4. Why am I so tired?

5. Who am I?

6. What is love?

7. Is a hot dog a sandwich?

8. What came first, the chicken or the egg?

9. What should I do?

10. Do animals have souls?

Sowing the seeds of cancer prevention

Are you looking to add to your quality of life, even though pets are not your speed? Might we suggest something with lower maintenance? Something a little greener?

Indoor plants can purify the air that comes from outside. Researchers at the University of Technology Sydney, in partnership with the plantscaping company Ambius, showed that a “green wall” made up of mixed indoor plants was able to suck up 97% of “the most toxic compounds” from the air in just 8 hours. We’re talking about lung-irritating, headache-inducing, cancer risk–boosting compounds from gasoline fumes, including benzene.

Fraser Torpy/University of Technology Sydney

Public health initiatives often strive to reduce cardiovascular and obesity risks, but breathing seems pretty important too. According to the World Health Organization, household air pollution is responsible for about 2.5 million global premature deaths each year. And since 2020 we’ve become accustomed to spending more time inside and at home.

“This new research proves that plants should not just be seen as ‘nice to have,’ but rather a crucial part of every workplace wellness plan,” Ambius General Manager Johan Hodgson said in statement released by the university.

So don’t spend hundreds of dollars on a fancy air filtration system when a wall of plants can do that for next to nothing. Find what works for you and your space and become a plant parent today! Your lungs will thank you.
 

But officer, I had to swerve to miss the duodenal ampulla

Tiny video capsule endoscopes have been around for many years, but they have one big weakness: The ingestible cameras’ journey through the GI tract is passively driven by gravity and the natural movement of the body, so they often miss potential problem areas.

AnX Robotica

Not anymore. That flaw has been addressed by medical technology company AnX Robotica, which has taken endoscopy to the next level by adding that wondrous directional control device of the modern electronic age, a joystick.

The new system “uses an external magnet and hand-held video game style joysticks to move the capsule in three dimensions,” which allows physicians to “remotely drive a miniature video capsule to all regions of the stomach to visualize and photograph potential problem areas,” according to Andrew C. Meltzer, MD, of George Washington University and associates, who conducted a pilot study funded by AnX Robotica.

The video capsule provided a 95% rate of visualization in the stomachs of 40 patients who were examined at a medical office building by an emergency medicine physician who had no previous specialty training in endoscopy. “Capsules were driven by the ER physician and then the study reports were reviewed by an attending gastroenterologist who was physically off site,” the investigators said in a written statement.

The capsule operator did receive some additional training, and development of artificial intelligence to self-drive the capsule is in the works, but for now, we’re talking about a device controlled by a human using a joystick. And we all know that 50-year-olds are not especially known for their joystick skills. For that we need real experts. Yup, we need to put those joystick-controlled capsule endoscopes in the hands of teenage gamers. Who wants to go first?
 

Maybe AI isn’t ready for the big time after all

“How long before some intrepid stockholder says: ‘Hey, instead of paying doctors, why don’t we just use the free robot instead?’ ” Those words appeared on LOTME but a month ago. After all, the AI is supposed to be smarter and more empathetic than a doctor. And did we mention it’s free? Or at least extremely cheap. Cheaper than, say, a group of recently unionized health care workers.

maewjpho/Thinkstock

In early May, the paid employees manning the National Eating Disorders Association emergency hotline voted to unionize, as they felt overwhelmed and underpaid. Apparently, paying six people an extra few thousand a year was too much for NEDA’s leadership, as they decided a few weeks later to fire those workers, fully closing down the hotline. Instead of talking to a real person, people “calling in” for support would be met with Tessa, a wellness chatbot that would hopefully guide them through their crisis. Key word, hopefully.

In perhaps the least surprising twist of the year, NEDA was forced to walk back its decision about a week after its initial announcement. It all started with a viral Instagram post from a woman who called in and received the following advice from Tessa: Lose 1-2 pounds a week, count calories and work for a 500- to 1,000-calorie deficit, weigh herself weekly, and restrict her diet. Unfortunately, all of these suggestions were things that led to the development of the woman’s eating disorder.

Naturally, NEDA responded in good grace, accusing the woman of lying. A NEDA vice president even left some nasty comments on the post, but hastily deleted them a day later when NEDA announced it was shutting down Tessa “until further notice for a complete investigation.” NEDA’s CEO insisted they hadn’t seen that behavior from Tessa before, calling it a “bug” and insisting the bot would only be down temporarily until the triggers causing the bug were fixed.

In the aftermath, several doctors and psychologists chimed in, terming the rush to automate human roles dangerous and risky. After all, much of what makes these hotlines effective is the volunteers speaking from their own experience. An unsupervised bot doesn’t seem to have what it takes to deal with a mental health crisis, but we’re betting that Tessa will be back. As a wise cephalopod once said: Nobody gives a care about the fate of labor as long as they can get their instant gratification.
 

You can’t spell existential without s-t-e-n-t

This week, we’re including a special “bonus” item that, to be honest, has nothing to do with stents. That’s why our editor is making us call this a “bonus” (and making us use quote marks, too): It doesn’t really have anything to do with stents or health care or those who practice health care. Actually, his exact words were, “You can’t just give the readers someone else’s ****ing list and expect to get paid for it.” Did we mention that he looks like Jack Nicklaus but acts like BoJack Horseman?

Anywaaay, we’re pretty sure that the list in question – “America’s Top 10 Most Googled Existential Questions” – says something about the human condition, just not about stents:

1. Why is the sky blue?

2. What do dreams mean?

3. What is the meaning of life?

4. Why am I so tired?

5. Who am I?

6. What is love?

7. Is a hot dog a sandwich?

8. What came first, the chicken or the egg?

9. What should I do?

10. Do animals have souls?

Six distinct microribonucleic acids were down-regulated in adults with major depressive disorder (MDD), compared with healthy controls, based on data from 120 individuals.

National University Health System, Singapore

“Given the multifaceted nature of MDD, the multiple small but dynamic genetic alterations in biomolecular pathways, which are modulated by epigenetic modifications, could contribute to a better understanding of the underlying aetiology and pathophysiology of this disorder,” wrote Cyrus Su Hui Ho, MD, of National University Health System, Singapore, and colleagues. However, studies of biomarkers in psychiatry are limited, and the predictive potential of microribonucleic acids (miRNAs) has not been examined, they said.

In a study published in Comprehensive Psychiatry, the researchers identified 60 adults with depression and 60 healthy controls. Depression severity was assessed with the Hamilton Depression Rating Scale. Other demographic and clinical characteristics were similar between the patients and controls; 10 patients were unmedicated.

The researchers used QUIAGEN Ingenuity Pathway Analysis to identify the specific depression-related biological pathways affected by various miRNAs.

A total of six miRNAs (miR-542-3p, miR-181b-3p, miR-190a-5p, miR-33a-3p, miR-3690, and miR-6895-3p) were down-regulated in unmedicated depressed patients, compared with healthy controls.

In a receiver operating characteristic (ROC) analysis, a combination panel with three miRNAs (miR-542-3p, miR-181b-3p, and miR-3690) in whole blood yielded an area under the curve (AUC) of 0.67. This combination correctly classified 66.7% of MDD patients and 63.3% of healthy controls.

The ability of individual miRNAs to differentiate between MDD patients and controls in the current study was limited, the researchers wrote in their discussion. “However, when three miRNAs (miR-542b-3p, miR-181b-3p, and miR-3690) were combined as a panel, the AUC was enhanced to an almost acceptable degree (AUC of 0.67, approaching 0.7) and might have value in complementing clinical diagnoses,” they said.

The study findings were limited by several factors including the small sample size and the use of medications by most MDD patients, which resulted in an especially small number of unmedicated patients, the researchers noted. Other limitations included the use of study population from a single center, and the inability to explain the link between blood and brain miRNA expression, they said.

However, the study is the first clinical trial in Singapore to examine the role of miRNA in depression and to identify miRNAs as potential biomarkers for MDD, they said.

Additional studies are needed to explore miRNA biomarkers for diagnosis, disease prognosis, and treatment response in MDD, they concluded.

The study was supported by the National University Health System Seed Fund. The researchers had no financial conflicts to disclose.

Six distinct microribonucleic acids were down-regulated in adults with major depressive disorder (MDD), compared with healthy controls, based on data from 120 individuals.

National University Health System, Singapore

“Given the multifaceted nature of MDD, the multiple small but dynamic genetic alterations in biomolecular pathways, which are modulated by epigenetic modifications, could contribute to a better understanding of the underlying aetiology and pathophysiology of this disorder,” wrote Cyrus Su Hui Ho, MD, of National University Health System, Singapore, and colleagues. However, studies of biomarkers in psychiatry are limited, and the predictive potential of microribonucleic acids (miRNAs) has not been examined, they said.

In a study published in Comprehensive Psychiatry, the researchers identified 60 adults with depression and 60 healthy controls. Depression severity was assessed with the Hamilton Depression Rating Scale. Other demographic and clinical characteristics were similar between the patients and controls; 10 patients were unmedicated.

The researchers used QUIAGEN Ingenuity Pathway Analysis to identify the specific depression-related biological pathways affected by various miRNAs.

A total of six miRNAs (miR-542-3p, miR-181b-3p, miR-190a-5p, miR-33a-3p, miR-3690, and miR-6895-3p) were down-regulated in unmedicated depressed patients, compared with healthy controls.

In a receiver operating characteristic (ROC) analysis, a combination panel with three miRNAs (miR-542-3p, miR-181b-3p, and miR-3690) in whole blood yielded an area under the curve (AUC) of 0.67. This combination correctly classified 66.7% of MDD patients and 63.3% of healthy controls.

The ability of individual miRNAs to differentiate between MDD patients and controls in the current study was limited, the researchers wrote in their discussion. “However, when three miRNAs (miR-542b-3p, miR-181b-3p, and miR-3690) were combined as a panel, the AUC was enhanced to an almost acceptable degree (AUC of 0.67, approaching 0.7) and might have value in complementing clinical diagnoses,” they said.

The study findings were limited by several factors including the small sample size and the use of medications by most MDD patients, which resulted in an especially small number of unmedicated patients, the researchers noted. Other limitations included the use of study population from a single center, and the inability to explain the link between blood and brain miRNA expression, they said.

However, the study is the first clinical trial in Singapore to examine the role of miRNA in depression and to identify miRNAs as potential biomarkers for MDD, they said.

Additional studies are needed to explore miRNA biomarkers for diagnosis, disease prognosis, and treatment response in MDD, they concluded.

The study was supported by the National University Health System Seed Fund. The researchers had no financial conflicts to disclose.

Six distinct microribonucleic acids were down-regulated in adults with major depressive disorder (MDD), compared with healthy controls, based on data from 120 individuals.

National University Health System, Singapore

“Given the multifaceted nature of MDD, the multiple small but dynamic genetic alterations in biomolecular pathways, which are modulated by epigenetic modifications, could contribute to a better understanding of the underlying aetiology and pathophysiology of this disorder,” wrote Cyrus Su Hui Ho, MD, of National University Health System, Singapore, and colleagues. However, studies of biomarkers in psychiatry are limited, and the predictive potential of microribonucleic acids (miRNAs) has not been examined, they said.

In a study published in Comprehensive Psychiatry, the researchers identified 60 adults with depression and 60 healthy controls. Depression severity was assessed with the Hamilton Depression Rating Scale. Other demographic and clinical characteristics were similar between the patients and controls; 10 patients were unmedicated.

The researchers used QUIAGEN Ingenuity Pathway Analysis to identify the specific depression-related biological pathways affected by various miRNAs.

A total of six miRNAs (miR-542-3p, miR-181b-3p, miR-190a-5p, miR-33a-3p, miR-3690, and miR-6895-3p) were down-regulated in unmedicated depressed patients, compared with healthy controls.

In a receiver operating characteristic (ROC) analysis, a combination panel with three miRNAs (miR-542-3p, miR-181b-3p, and miR-3690) in whole blood yielded an area under the curve (AUC) of 0.67. This combination correctly classified 66.7% of MDD patients and 63.3% of healthy controls.

The ability of individual miRNAs to differentiate between MDD patients and controls in the current study was limited, the researchers wrote in their discussion. “However, when three miRNAs (miR-542b-3p, miR-181b-3p, and miR-3690) were combined as a panel, the AUC was enhanced to an almost acceptable degree (AUC of 0.67, approaching 0.7) and might have value in complementing clinical diagnoses,” they said.

The study findings were limited by several factors including the small sample size and the use of medications by most MDD patients, which resulted in an especially small number of unmedicated patients, the researchers noted. Other limitations included the use of study population from a single center, and the inability to explain the link between blood and brain miRNA expression, they said.

However, the study is the first clinical trial in Singapore to examine the role of miRNA in depression and to identify miRNAs as potential biomarkers for MDD, they said.

Additional studies are needed to explore miRNA biomarkers for diagnosis, disease prognosis, and treatment response in MDD, they concluded.

The study was supported by the National University Health System Seed Fund. The researchers had no financial conflicts to disclose.

After Canada legalized recreational cannabis in 2018, the rate of acute care for cannabis use during pregnancy in Ontario nearly doubled, data indicate.

A population-based study shows that the rate of cannabis-related acute care use during pregnancy increased from 11 per 100,000 pregnancies before legalization to 20 per 100,000 pregnancies afterward: an increase of 82%. Absolute increases were small, however.

“Our findings are consistent with studies highlighting that cannabis use during pregnancy has been increasing in North America, and this study suggests that cannabis legalization might contribute to and accelerate such trends,” study author Daniel Myran, MD, MPH, a public health and preventive medicine physician at the University of Ottawa in Ontario, said in an interview.

University of Ottawa

The study was published online in the Canadian Medical Association Journal.
 

Risks for newborns  

In a 2019 study, 7% of U.S. women reported using cannabis during pregnancy during 2016-2017, which was double the rate of 3.4% for 2002-2003.

Dr. Myran and colleagues hypothesized that legalizing nonmedical cannabis has affected the drug’s use during pregnancy in Ontario. “We also hypothesized that hospital care for cannabis use would be associated with adverse neonatal outcomes, even after adjusting for other important risk factors that may differ between people with and without cannabis use,” he said.

The researchers’ repeated cross-sectional analysis evaluated changes in the number of pregnant people who received acute care from January 2015 to July 2021 among all patients who were eligible for Ontario’s public health coverage. The final study cohort included 691,242 pregnant patients, of whom 533 had at least one pregnancy with cannabis-related acute care visits. These mothers had a mean age of 24 years vs. 30 for their counterparts with no such visits.

Using segmented regression, the researchers compared changes in the quarterly rate of pregnant people with acute care related to cannabis use (the primary outcome) with those of acute care for mental health conditions or for noncannabis substance use (the control conditions).

“Severe morning sickness was a major risk factor for care in the emergency department or hospital for cannabis use,” said Dr. Myran. “Prior work has found that people who use cannabis during pregnancy often state that it was used to manage challenging symptoms of pregnancy such as morning sickness.”

Most acute care events (72.2%) were emergency department visits. The most common reasons for acute care were harmful cannabis use (57.6%), followed by cannabis dependence or withdrawal (21.5%), and acute cannabis intoxication (12.8%).

Compared with pregnancies without acute care, those with acute care related to cannabis had higher rates of adverse neonatal outcomes such as birth before 37 weeks’ gestational age (16.9% vs. 7.2%), birth weight at or below the bottom fifth percentile after adjustment for gestational age (12.1% vs. 4.4%), and neonatal intensive care unit admission in the first 28 days of life (31.5% vs. 13%).

An adjusted analysis found that patients younger than 35 years and those living in rural settings or the lowest-income neighborhoods had higher odds of acute cannabis-related care during pregnancy. Patients who received acute care for any substance use or schizophrenia before pregnancy or who accessed outpatient mental health services before pregnancy had higher risk for cannabis-related acute care during pregnancy. Mothers receiving acute care for cannabis also had higher risk for acute care for hyperemesis gravidarum during pregnancy (30.9%). 

The rate of acute care for other types of substance use such as alcohol and opioids did not change after cannabis legalization, and acute care for mental health conditions such as anxiety and depression during pregnancy declined by 14%, Dr. Myran noted.

“Physicians who care for pregnant people should consider increasing screening for cannabis use during pregnancy,” said Dr. Myran. “In addition, repeated nonstigmatizing screening and counseling may be indicated for higher-risk groups identified in the study, including pregnancies with severe morning sickness.”
 

The U.S. perspective

Commenting on the study, M. Camille Hoffman, MD, MSc, a maternal-fetal medicine specialist at the University of Colorado in Aurora, said that the findings likely indicate that legalization has made cannabis users less reluctant to come forward for urgent care. “They cannot really claim that this is equivalent to more use, just that more people are willing to present,” she said. Dr. Hoffman was not involved in the study.

The Canadian results do not align perfectly with what is seen in the United States. “It does suggest that there may be more cannabinoid hyperemesis being coded as hyperemesis gravidarum, which is a pregnancy-specific condition vs. a cannabis-dependence-related one,” said Dr. Hoffman.

Literature in the United States often includes tobacco use as a covariate, she added. “This study does not appear to do that,” she said. “Rather, it uses any substance use. Because of this, it is difficult to really know the contribution of cannabis to the adverse pregnancy outcomes vs. the combination of tobacco and cannabis.”

Finally, she pointed out, the proportion of those presenting for acute care for substance use in the 2 years before conception was 22% for acute care visits for cannabis vs 1% for no acute care visits. “This suggests to me that this was a highly vulnerable group before the legalization of cannabis as well. The overall absolute difference is nine in total per 100,000 – hardly enough to draw any real conclusions. Again, maybe those nine were simply more willing to come forth with concerns with cannabis being legal.” 

There is no known safe level of cannabis consumption, and its use by pregnant women has been linked to later neurodevelopmental issues in their offspring. A 2022 U.S. study suggested that cannabis exposure in the womb may leave children later in life at risk for autism, psychiatric disorders, and problematic substance abuse, particularly as they enter peak periods of vulnerability in late adolescence.

As to the impact of legalization in certain U.S. states, a 2022 study found that women perceived legalization to mean greater access to cannabis, increased acceptance of use, and greater trust in cannabis retailers. In line with Dr. Hoffman’s view, this study suggested that legalization made pregnant women more willing to discuss cannabis use during pregnancy honestly with their care providers.

In the United States, prenatal cannabis use is still included in definitions of child abuse or neglect and can lead to termination of parental rights, even in states with full legalization.

“These findings highlight the need for ongoing monitoring of markers of cannabis use during pregnancy after legalization,” said Dr. Myran. He also called for effective policies in regions with legal cannabis, such as increased warning labels on cannabis products.

This study was supported by the Canadian Institutes of Health Research and the University of Ottawa site of ICES, which is funded by an annual grant from the Ontario Ministry of Health and Ministry of Long-Term Care. Dr. Myran reports a speaker fee from McMaster University. Dr. Hoffman reports no relevant financial relationships.
 

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

After Canada legalized recreational cannabis in 2018, the rate of acute care for cannabis use during pregnancy in Ontario nearly doubled, data indicate.

A population-based study shows that the rate of cannabis-related acute care use during pregnancy increased from 11 per 100,000 pregnancies before legalization to 20 per 100,000 pregnancies afterward: an increase of 82%. Absolute increases were small, however.

“Our findings are consistent with studies highlighting that cannabis use during pregnancy has been increasing in North America, and this study suggests that cannabis legalization might contribute to and accelerate such trends,” study author Daniel Myran, MD, MPH, a public health and preventive medicine physician at the University of Ottawa in Ontario, said in an interview.

University of Ottawa

The study was published online in the Canadian Medical Association Journal.
 

Risks for newborns  

In a 2019 study, 7% of U.S. women reported using cannabis during pregnancy during 2016-2017, which was double the rate of 3.4% for 2002-2003.

Dr. Myran and colleagues hypothesized that legalizing nonmedical cannabis has affected the drug’s use during pregnancy in Ontario. “We also hypothesized that hospital care for cannabis use would be associated with adverse neonatal outcomes, even after adjusting for other important risk factors that may differ between people with and without cannabis use,” he said.

The researchers’ repeated cross-sectional analysis evaluated changes in the number of pregnant people who received acute care from January 2015 to July 2021 among all patients who were eligible for Ontario’s public health coverage. The final study cohort included 691,242 pregnant patients, of whom 533 had at least one pregnancy with cannabis-related acute care visits. These mothers had a mean age of 24 years vs. 30 for their counterparts with no such visits.

Using segmented regression, the researchers compared changes in the quarterly rate of pregnant people with acute care related to cannabis use (the primary outcome) with those of acute care for mental health conditions or for noncannabis substance use (the control conditions).

“Severe morning sickness was a major risk factor for care in the emergency department or hospital for cannabis use,” said Dr. Myran. “Prior work has found that people who use cannabis during pregnancy often state that it was used to manage challenging symptoms of pregnancy such as morning sickness.”

Most acute care events (72.2%) were emergency department visits. The most common reasons for acute care were harmful cannabis use (57.6%), followed by cannabis dependence or withdrawal (21.5%), and acute cannabis intoxication (12.8%).

Compared with pregnancies without acute care, those with acute care related to cannabis had higher rates of adverse neonatal outcomes such as birth before 37 weeks’ gestational age (16.9% vs. 7.2%), birth weight at or below the bottom fifth percentile after adjustment for gestational age (12.1% vs. 4.4%), and neonatal intensive care unit admission in the first 28 days of life (31.5% vs. 13%).

An adjusted analysis found that patients younger than 35 years and those living in rural settings or the lowest-income neighborhoods had higher odds of acute cannabis-related care during pregnancy. Patients who received acute care for any substance use or schizophrenia before pregnancy or who accessed outpatient mental health services before pregnancy had higher risk for cannabis-related acute care during pregnancy. Mothers receiving acute care for cannabis also had higher risk for acute care for hyperemesis gravidarum during pregnancy (30.9%). 

The rate of acute care for other types of substance use such as alcohol and opioids did not change after cannabis legalization, and acute care for mental health conditions such as anxiety and depression during pregnancy declined by 14%, Dr. Myran noted.

“Physicians who care for pregnant people should consider increasing screening for cannabis use during pregnancy,” said Dr. Myran. “In addition, repeated nonstigmatizing screening and counseling may be indicated for higher-risk groups identified in the study, including pregnancies with severe morning sickness.”
 

The U.S. perspective

Commenting on the study, M. Camille Hoffman, MD, MSc, a maternal-fetal medicine specialist at the University of Colorado in Aurora, said that the findings likely indicate that legalization has made cannabis users less reluctant to come forward for urgent care. “They cannot really claim that this is equivalent to more use, just that more people are willing to present,” she said. Dr. Hoffman was not involved in the study.

The Canadian results do not align perfectly with what is seen in the United States. “It does suggest that there may be more cannabinoid hyperemesis being coded as hyperemesis gravidarum, which is a pregnancy-specific condition vs. a cannabis-dependence-related one,” said Dr. Hoffman.

Literature in the United States often includes tobacco use as a covariate, she added. “This study does not appear to do that,” she said. “Rather, it uses any substance use. Because of this, it is difficult to really know the contribution of cannabis to the adverse pregnancy outcomes vs. the combination of tobacco and cannabis.”

Finally, she pointed out, the proportion of those presenting for acute care for substance use in the 2 years before conception was 22% for acute care visits for cannabis vs 1% for no acute care visits. “This suggests to me that this was a highly vulnerable group before the legalization of cannabis as well. The overall absolute difference is nine in total per 100,000 – hardly enough to draw any real conclusions. Again, maybe those nine were simply more willing to come forth with concerns with cannabis being legal.” 

There is no known safe level of cannabis consumption, and its use by pregnant women has been linked to later neurodevelopmental issues in their offspring. A 2022 U.S. study suggested that cannabis exposure in the womb may leave children later in life at risk for autism, psychiatric disorders, and problematic substance abuse, particularly as they enter peak periods of vulnerability in late adolescence.

As to the impact of legalization in certain U.S. states, a 2022 study found that women perceived legalization to mean greater access to cannabis, increased acceptance of use, and greater trust in cannabis retailers. In line with Dr. Hoffman’s view, this study suggested that legalization made pregnant women more willing to discuss cannabis use during pregnancy honestly with their care providers.

In the United States, prenatal cannabis use is still included in definitions of child abuse or neglect and can lead to termination of parental rights, even in states with full legalization.

“These findings highlight the need for ongoing monitoring of markers of cannabis use during pregnancy after legalization,” said Dr. Myran. He also called for effective policies in regions with legal cannabis, such as increased warning labels on cannabis products.

This study was supported by the Canadian Institutes of Health Research and the University of Ottawa site of ICES, which is funded by an annual grant from the Ontario Ministry of Health and Ministry of Long-Term Care. Dr. Myran reports a speaker fee from McMaster University. Dr. Hoffman reports no relevant financial relationships.
 

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

After Canada legalized recreational cannabis in 2018, the rate of acute care for cannabis use during pregnancy in Ontario nearly doubled, data indicate.

A population-based study shows that the rate of cannabis-related acute care use during pregnancy increased from 11 per 100,000 pregnancies before legalization to 20 per 100,000 pregnancies afterward: an increase of 82%. Absolute increases were small, however.

“Our findings are consistent with studies highlighting that cannabis use during pregnancy has been increasing in North America, and this study suggests that cannabis legalization might contribute to and accelerate such trends,” study author Daniel Myran, MD, MPH, a public health and preventive medicine physician at the University of Ottawa in Ontario, said in an interview.

University of Ottawa

The study was published online in the Canadian Medical Association Journal.
 

Risks for newborns  

In a 2019 study, 7% of U.S. women reported using cannabis during pregnancy during 2016-2017, which was double the rate of 3.4% for 2002-2003.

Dr. Myran and colleagues hypothesized that legalizing nonmedical cannabis has affected the drug’s use during pregnancy in Ontario. “We also hypothesized that hospital care for cannabis use would be associated with adverse neonatal outcomes, even after adjusting for other important risk factors that may differ between people with and without cannabis use,” he said.

The researchers’ repeated cross-sectional analysis evaluated changes in the number of pregnant people who received acute care from January 2015 to July 2021 among all patients who were eligible for Ontario’s public health coverage. The final study cohort included 691,242 pregnant patients, of whom 533 had at least one pregnancy with cannabis-related acute care visits. These mothers had a mean age of 24 years vs. 30 for their counterparts with no such visits.

Using segmented regression, the researchers compared changes in the quarterly rate of pregnant people with acute care related to cannabis use (the primary outcome) with those of acute care for mental health conditions or for noncannabis substance use (the control conditions).

“Severe morning sickness was a major risk factor for care in the emergency department or hospital for cannabis use,” said Dr. Myran. “Prior work has found that people who use cannabis during pregnancy often state that it was used to manage challenging symptoms of pregnancy such as morning sickness.”

Most acute care events (72.2%) were emergency department visits. The most common reasons for acute care were harmful cannabis use (57.6%), followed by cannabis dependence or withdrawal (21.5%), and acute cannabis intoxication (12.8%).

Compared with pregnancies without acute care, those with acute care related to cannabis had higher rates of adverse neonatal outcomes such as birth before 37 weeks’ gestational age (16.9% vs. 7.2%), birth weight at or below the bottom fifth percentile after adjustment for gestational age (12.1% vs. 4.4%), and neonatal intensive care unit admission in the first 28 days of life (31.5% vs. 13%).

An adjusted analysis found that patients younger than 35 years and those living in rural settings or the lowest-income neighborhoods had higher odds of acute cannabis-related care during pregnancy. Patients who received acute care for any substance use or schizophrenia before pregnancy or who accessed outpatient mental health services before pregnancy had higher risk for cannabis-related acute care during pregnancy. Mothers receiving acute care for cannabis also had higher risk for acute care for hyperemesis gravidarum during pregnancy (30.9%). 

The rate of acute care for other types of substance use such as alcohol and opioids did not change after cannabis legalization, and acute care for mental health conditions such as anxiety and depression during pregnancy declined by 14%, Dr. Myran noted.

“Physicians who care for pregnant people should consider increasing screening for cannabis use during pregnancy,” said Dr. Myran. “In addition, repeated nonstigmatizing screening and counseling may be indicated for higher-risk groups identified in the study, including pregnancies with severe morning sickness.”
 

The U.S. perspective

Commenting on the study, M. Camille Hoffman, MD, MSc, a maternal-fetal medicine specialist at the University of Colorado in Aurora, said that the findings likely indicate that legalization has made cannabis users less reluctant to come forward for urgent care. “They cannot really claim that this is equivalent to more use, just that more people are willing to present,” she said. Dr. Hoffman was not involved in the study.

The Canadian results do not align perfectly with what is seen in the United States. “It does suggest that there may be more cannabinoid hyperemesis being coded as hyperemesis gravidarum, which is a pregnancy-specific condition vs. a cannabis-dependence-related one,” said Dr. Hoffman.

Literature in the United States often includes tobacco use as a covariate, she added. “This study does not appear to do that,” she said. “Rather, it uses any substance use. Because of this, it is difficult to really know the contribution of cannabis to the adverse pregnancy outcomes vs. the combination of tobacco and cannabis.”

Finally, she pointed out, the proportion of those presenting for acute care for substance use in the 2 years before conception was 22% for acute care visits for cannabis vs 1% for no acute care visits. “This suggests to me that this was a highly vulnerable group before the legalization of cannabis as well. The overall absolute difference is nine in total per 100,000 – hardly enough to draw any real conclusions. Again, maybe those nine were simply more willing to come forth with concerns with cannabis being legal.” 

There is no known safe level of cannabis consumption, and its use by pregnant women has been linked to later neurodevelopmental issues in their offspring. A 2022 U.S. study suggested that cannabis exposure in the womb may leave children later in life at risk for autism, psychiatric disorders, and problematic substance abuse, particularly as they enter peak periods of vulnerability in late adolescence.

As to the impact of legalization in certain U.S. states, a 2022 study found that women perceived legalization to mean greater access to cannabis, increased acceptance of use, and greater trust in cannabis retailers. In line with Dr. Hoffman’s view, this study suggested that legalization made pregnant women more willing to discuss cannabis use during pregnancy honestly with their care providers.

In the United States, prenatal cannabis use is still included in definitions of child abuse or neglect and can lead to termination of parental rights, even in states with full legalization.

“These findings highlight the need for ongoing monitoring of markers of cannabis use during pregnancy after legalization,” said Dr. Myran. He also called for effective policies in regions with legal cannabis, such as increased warning labels on cannabis products.

This study was supported by the Canadian Institutes of Health Research and the University of Ottawa site of ICES, which is funded by an annual grant from the Ontario Ministry of Health and Ministry of Long-Term Care. Dr. Myran reports a speaker fee from McMaster University. Dr. Hoffman reports no relevant financial relationships.
 

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

This transcript has been edited for clarity.

Robert D. Glatter, MD: Welcome. I’m Dr. Robert Glatter, medical adviser for Medscape Emergency Medicine. Joining me to discuss ways to address and reform the toxic culture associated with medical training is Dr. Amy Faith Ho, senior vice president of clinical informatics and analytics at Integrative Emergency Services in Dallas. Also joining us is Dr. Júlia Loyola Ferreira, a pediatric surgeon originally from Brazil, now practicing at Montreal Children’s and focused on advocacy for gender equity and patient-centered care.

Welcome to both of you. Thanks so much for joining me.

Amy Faith Ho, MD, MPH: Thanks so much for having us, Rob.

Dr. Glatter: Amy, I noticed a tweet recently where you talked about how your career choice was affected by the toxic environment in medical school, affecting your choice of residency. Can you elaborate on that?

Dr. Ho: This is a super-important topic, not in just one specialty but in all of medicine, because what you’re talking about is toxic workplace culture that is certainly directed toward certain groups. In this instance, what we’re talking about is gender, but it can be directed toward any number of other groups as well.

What you’re alluding to is a tweet by Stanford Surgery Group showing the next residency class, and what was really stunning about this residency class was that it was almost all females. And this was something that took off on social media.

When I saw this, I was really brought back to one of my personal experiences that I chose to share, which was basically that, as a medical student, I really wanted to be a surgeon. I’m an emergency medicine doctor now, so you know that didn’t happen.

The story that I was sharing was that when I was a third-year medical student rotating on surgery, we had a male attending who was very well known at that school at the time who basically would take the female medical students, and instead of clinic, he would round us up. He would have us sit around him in the workplace room while everyone else was seeing patients, and he would have you look at news clippings of himself. He would tell you stories about himself, like he was holding court for the ladies.

It was this very weird culture where my takeaway as a med student was like, “Wow, this is kind of abusive patriarchy that is supported,” because everyone knew about it and was complicit. Even though I really liked surgery, this was just one instance and one example of where you see this culture that really resonates into the rest of life that I didn’t really want to be a part of.

I went into emergency medicine and loved it. It’s also highly procedural, and I was very happy with where I was. What was really interesting about this tweet to me, though, is that it really took off and garnered hundreds of thousands of views on a very niche topic, because what was most revealing is that everyone has a story like this.

It is not just surgery. It is definitely not just one specialty and it is not just one school. It is an endemic problem in medicine. Not only does it change the lives of young women, but it also says so much about the complicity and the culture that we have in medicine that many people were upset about just the same way I was.
 

Medical training experience in other countries vs. the United States

Dr. Glatter: Júlia, I want to hear about your experience in medical school, surgery, and then fellowship training and up to the present, if possible.

Júlia Loyola Ferreira, MD: In Brazil, as in many countries now, women have made up the majority of the medical students since 2010. It’s a more female-friendly environment when you’re going through medical school, and I was lucky enough to do rotations in areas of surgery where people were friendly to women.

I lived in this tiny bubble that also gave me the privilege of not facing some things that I can imagine that people in Brazil in different areas and smaller towns face. In Brazil, people try to not talk about this gender agenda. This is something that’s being talked about outside Brazil. But in Brazil, we are years back. People are not really engaging on this conversation. I thought it was going to be hard for me as a woman, because Brazil has around 20% female surgeons.

I knew it was going to be challenging, but I had no idea how bad it was. When I started and things started happening, the list was big. I have an example of everything that is written about – microaggression, implicit bias, discrimination, harassment.

Every time I would try to speak about it and talk to someone, I would be strongly gaslighted. It was the whole training, the whole 5 years. People would say, “Oh, I don’t think it was like that. I think you were overreacting.” People would come with all these different answers for what I was experiencing, and that was frustrating. That was even harder because I had to cope with everything that was happening and I had no one to turn to. I had no mentors.

When I looked up to women who were in surgery, they would be tougher on us young surgeons than the men and they would tell us that we should not complain because in their time it was even harder. Now, it’s getting better and we are supposed to accept whatever comes.

That was at least a little bit of what I experienced in my training. It was only after I finished and started to do research about it that I really encountered a field of people who would echo what I was trying to say to many people in different hospitals that I attended to.

That was the key for me to get out of that situation of being gaslighted and of not being able to really talk about it. Suddenly, I started to publish things about Brazil that nobody was even writing or studying. That gave me a large amount of responsibility, but also motivation to keep going and to see the change.
 

Valuing women in medicine

Dr. Glatter: This is a very important point that you’re raising about the environment of women being hard on other women. We know that men can be very difficult on and also judgmental toward their trainees.

Amy, how would you respond to that? Was your experience similar in emergency medicine training?

Dr. Ho: I actually don’t feel like it was. I think what Júlia is alluding to is this “mean girls” idea, of “I went through it and thus you have to go through it.” I think you do see this in many specialties. One of the classic ones we hear about, and I don’t want to speak to it too much because it’s not my specialty, is ob.gyn., where it is a very female-dominant surgery group. There’s almost a hazing level that you hear about in some of the more malignant workplaces.

I think that you speak to two really important things. Number one is the numbers game. As you were saying, Brazil actually has many women. That’s awesome. That’s actually different from the United States, especially for the historic, existing workplace and less so for the medical students and for residents. I think step one is having minorities like women just present and there.

Step two is actually including and valuing them. While I think it’s really easy to move away from the women discussion, because there are women when you look around in medicine, it doesn’t mean that women are actually being heard, that they’re actually being accepted, or that their viewpoints are being listened to. A big part of it is normalizing not only seeing women in medicine but also normalizing the narrative of women in medicine.

It’s not just about motherhood; it’s about things like normalizing talking about advancement, academic promotions, pay, culture, being called things like “too reactive,” “anxious,” or “too assertive.” These are all classic things that we hear about when we talk about women.

That’s why we’re looking to not only conversations like this, but also structured ways for women to discuss being women in medicine. There are many women in medicine groups in emergency medicine, including: Females Working in Emergency Medicine (FemInEM); the American College of Emergency Physicians (ACEP) and Society for Academic Emergency Medicine (SAEM) women’s groups, which are American Association of Women Emergency Physicians (AAWEP) and Academy for Women in Academic Emergency Medicine (AWAEM), respectively; and the American Medical Women’s Association (AMWA), which is the American Medical Association’s offshoot.

All of these groups are geared toward normalizing women in medicine, normalizing the narrative of women in medicine, and then working on mentoring and educating so that we can advance our initiatives.
 

Gender balance is not gender equity

Dr. Glatter: Amy, you bring up a very critical point that mentoring is sort of the antidote to gender-based discrimination. Júlia had written a paper back in November of 2022 that was published in the Journal of Surgical Research talking exactly about this and how important it is to develop mentoring. Part of her research showed that about 20% of medical students who took the survey, about 1,000 people, had mentors, which was very disturbing.

Dr. Loyola Ferreira: Mentorship is one of the ways of changing the reality about gender-based discrimination. Amy’s comment was very strong and we need to really keep saying it, which is that gender balance is not gender equity.

The idea of having more women is not the same as women being recognized as equals, as able as men, and as valued as men. To change this very long culture of male domination, we need support, and this support comes from mentorship.

Although I didn’t have one, I feel that since I started being a mentor for some students, it changed not only them but myself. It gave me strength to keep going, studying, publishing, and going further with this discussion. I feel like the relationship was as good for them as it is for me. That’s how things change.
 

Diversity, equity, and inclusion training

Dr. Glatter: We’re talking about the reality of gender equity in terms of the ability to have equal respect, recognition, opportunities, and access. That’s really an important point to realize, and for our audience, to understand that gender equity is not gender balance.

Amy, I want to talk about medical school curriculums. Are there advances that you’re aware of being made at certain schools, programs, even in residencies, to enforce these things and make it a priority?

Dr. Ho: We’re really lucky that, as a culture in the United States, medical training is certainly very geared toward diversity. Some of that is certainly unofficial. Some of that just means when they’re looking at a medical school class or looking at rank lists for residency, that they’re cognizant of the different backgrounds that people have. That’s still a step. That is a step, that we’re at least acknowledging it.

There are multiple medical schools and residencies that have more formal unconscious-bias training or diversity, equity, and inclusion (DEI) training, both of which are excellent not only for us in the workplace but also for our patients. Almost all of us will see patients of highly diverse backgrounds. I think the biggest push is looking toward the criteria that we use for selecting trainees and students into our programs. Historically, it’s been MCAT, GPA, and so on.

We’ve really started to ask the question of, are these sorts of “objective criteria” actually biased in institutional ways? They talk about this all the time where GPAs will bias against students from underrepresented minorities (URM). I think all medical students and residencies have really acknowledged that. Although there are still test cutoffs, we are putting an inquisitive eye to what those mean, why they exist, and what are the other things that we should consider. This is all very heartening from what I’m seeing in medical training.

Dr. Glatter: There’s no formal rating system for DEI curriculums right now, like ranking of this school, or this program has more advanced recognition in terms of DEI?

Dr. Ho: No, but on the flip side, the U.S. News & World Report was classically one of the major rankings for medical schools. What we saw fairly recently was that very high-tier schools like Harvard and University of Chicago pulled out of that ranking because that ranking did not acknowledge the value of diversity. That was an incredible stance for medical schools to take, to say, “Hey, you are not evaluating an important criterion of ours.”

Dr. Glatter: That’s a great point. Júlia, where are we now in Brazil in terms of awareness of DEI and curriculum in schools and training programs?

Dr. Loyola Ferreira: Our reality is not as good as in the U.S., unfortunately. I don’t see much discussion on residency programs or medical schools at the moment. I see many students bringing it out and trying to make their schools engage in that discussion. This is something that is coming from the bottom up and not from the top down. I think it can lead to change as well. It is a step and it’s a beginning. Institutions should take the responsibility of doing this from the beginning. This is something where Brazil is still years behind you guys.

Dr. Glatter: It’s unfortunate, but certainly it’s important to hear that. What about in Canada and certainly your institution, McGill, where you just completed a master’s degree?

Dr. Loyola Ferreira: Canada is very much like the U.S. This is something that is really happening and it’s happening fast. I see, at least at McGill, a large amount of DEI inclusion and everything on this discussion. They have institutional courses for us to do as students, and we are all obliged to do many courses, which I think is really educating, especially for people with different cultures and backgrounds.

Dr. Glatter: Amy, where do you think we are in emergency medicine to look at the other side of it? Comparing surgery with emergency medicine, do you think we’re well advanced in terms of DEI, inclusion criteria, respect, and dignity, or are we really far off?

Dr. Ho: I may be biased, but I think emergency medicine is one of the best in terms of this, and I think there are a couple of reasons for it. One is that we are an inherently team-based organization. The attending, the residents, and the students all work in line with one another. There’s less of a hierarchy.

The same is true for our nurses, pharmacists, techs, and EMS. We all work together as a team. Because of that fairly flat structure, it’s really easy for us to value one another as individuals with our diverse backgrounds. In a way, that’s harder for specialties that are more hierarchical, and I think surgery is certainly one of the most hierarchical.

The second reason why emergency medicine is fairly well off in this is that we’re, by nature, a safety-net specialty. We see patients of all-comers, all walks, all backgrounds. I think we both recognize the value of physician-patient concordance. When we share characteristics with our patients, we recognize that value immediately at the bedside.

It exposes us to so much diversity. I see a refugee one day and the next patient is someone who is incarcerated. The next patient after that is an important businessman in society. That diversity and whiplash in the type of patients that we see back-to-back helps us see the playing field in a really flat, diverse way. Because of that, I think our culture is much better, as is our understanding of the value and importance of diversity not only for our programs, but also for our patients.
 

Do female doctors have better patient outcomes?

Dr. Glatter: Specialties working together in the emergency department is so important. Building that team and that togetherness is so critical. Júlia, would you agree?

Dr. Loyola Ferreira: Definitely. Something Amy said that is beautiful is that you recognize yourself in these patients. In surgery, we are taught to try to be away from the patients and not to put ourselves in the same position. We are taught to be less engaging, and this is not good. The good thing is when we really have patient-centered care, when we listen to them, and when we are involved with them.

I saw a publication showing that female and male surgeons treating similar patients had the same surgical outcomes. Women are as good as men technically to do surgery and have the same surgical outcomes. However, there is research showing that surgical teams with greater representation of women have improved surgical outcomes because of patient-centered care and the way women conduct bedside attention to patients. And they have better patient experience measures afterward. That is not only from the women who are treating the patients, but the whole environment. Women end up bringing men [into the conversation] and this better improves patient-centered care, and that makes the whole team a better team attending patients. Definitely, we are in the moment of patient experience and satisfaction, and increasing women is a way of achieving better patient satisfaction and experience.

Dr. Ho: There’s much to be said about having female clinicians available for patients. It doesn’t have to be just for female patients, although again, concordance between physicians and patients is certainly beneficial. Besides outcomes benefit, there’s even just a communication benefit. The way that women and men communicate is inherently different. The way women and men experience certain things is also inherently different.

A classic example of this is women who are experiencing a heart attack may not actually have chest pain but present with nausea. As a female who’s sensitive to this, when I see a woman throwing up, I am very attuned to something actually being wrong, knowing that they may not present with classic pain for a syndrome, but actually may be presenting with nausea instead. It doesn’t have to be a woman who takes that knowledge and turns it into something at the bedside. It certainly doesn’t have to, but it is just a natural, easy thing to step into as a female.

While I’m really careful to not step into this “women are better than men” or “men are better than women” argument, there’s something to be said about how the availability of female clinicians for all patients, not just female patients, can have benefit. Again, it’s shown in studies with cardiovascular outcomes and cardiologists, it’s certainly shown in ob.gyn., particularly for underrepresented minorities as well for maternal outcomes of Black mothers. It’s certainly shown again in patient satisfaction, which is concordance.

There is a profound level of research already on this that goes beyond just the idea of stacking the bench and putting more women in there. That’s not the value. We’re not just here to check off the box. We’re here to actually lend some value to our patients and, again, to one another as well.

Dr. Glatter: Absolutely. These are excellent points. The point you make about patient presentation is so vital. The fact that women have nausea sometimes in ACS presentations, the research never was really attentive to this. It was biased. The symptoms that women may have that are not “typical” for ACS weren’t included in patient presentations. Educating everyone about, overall, the types of presentations that we can recognize is vital and important.

Dr. Ho: Yes. It’s worth saying that, when you look at how medicine and research developed, classically, who were the research participants? They were often White men. They were college students who, historically, because women were not allowed to go to college, were men.

I say that not to fault the institution, because that was the culture of our history, but to just say it is okay to question things. It is okay to realize that someone’s presenting outside of the box and that maybe we actually need to reframe what even created the walls of the box in the first place.

Dr. Glatter: Thank you again for joining us. I truly appreciate your insight and expertise.

Dr. Glatter is assistant professor of emergency medicine, department of emergency medicine, Hofstra/Northwell, New York. Dr. Ho is senior vice president of clinical informatics & analytics, department of emergency medicine, Integrative Emergency Services, Dallas. Dr. Loyola Ferreira is a master of science candidate, department of experimental surgery, McGill University, Montreal. They reported that they had no conflicts of interest.

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

This transcript has been edited for clarity.

Robert D. Glatter, MD: Welcome. I’m Dr. Robert Glatter, medical adviser for Medscape Emergency Medicine. Joining me to discuss ways to address and reform the toxic culture associated with medical training is Dr. Amy Faith Ho, senior vice president of clinical informatics and analytics at Integrative Emergency Services in Dallas. Also joining us is Dr. Júlia Loyola Ferreira, a pediatric surgeon originally from Brazil, now practicing at Montreal Children’s and focused on advocacy for gender equity and patient-centered care.

Welcome to both of you. Thanks so much for joining me.

Amy Faith Ho, MD, MPH: Thanks so much for having us, Rob.

Dr. Glatter: Amy, I noticed a tweet recently where you talked about how your career choice was affected by the toxic environment in medical school, affecting your choice of residency. Can you elaborate on that?

Dr. Ho: This is a super-important topic, not in just one specialty but in all of medicine, because what you’re talking about is toxic workplace culture that is certainly directed toward certain groups. In this instance, what we’re talking about is gender, but it can be directed toward any number of other groups as well.

What you’re alluding to is a tweet by Stanford Surgery Group showing the next residency class, and what was really stunning about this residency class was that it was almost all females. And this was something that took off on social media.

When I saw this, I was really brought back to one of my personal experiences that I chose to share, which was basically that, as a medical student, I really wanted to be a surgeon. I’m an emergency medicine doctor now, so you know that didn’t happen.

The story that I was sharing was that when I was a third-year medical student rotating on surgery, we had a male attending who was very well known at that school at the time who basically would take the female medical students, and instead of clinic, he would round us up. He would have us sit around him in the workplace room while everyone else was seeing patients, and he would have you look at news clippings of himself. He would tell you stories about himself, like he was holding court for the ladies.

It was this very weird culture where my takeaway as a med student was like, “Wow, this is kind of abusive patriarchy that is supported,” because everyone knew about it and was complicit. Even though I really liked surgery, this was just one instance and one example of where you see this culture that really resonates into the rest of life that I didn’t really want to be a part of.

I went into emergency medicine and loved it. It’s also highly procedural, and I was very happy with where I was. What was really interesting about this tweet to me, though, is that it really took off and garnered hundreds of thousands of views on a very niche topic, because what was most revealing is that everyone has a story like this.

It is not just surgery. It is definitely not just one specialty and it is not just one school. It is an endemic problem in medicine. Not only does it change the lives of young women, but it also says so much about the complicity and the culture that we have in medicine that many people were upset about just the same way I was.
 

Medical training experience in other countries vs. the United States

Dr. Glatter: Júlia, I want to hear about your experience in medical school, surgery, and then fellowship training and up to the present, if possible.

Júlia Loyola Ferreira, MD: In Brazil, as in many countries now, women have made up the majority of the medical students since 2010. It’s a more female-friendly environment when you’re going through medical school, and I was lucky enough to do rotations in areas of surgery where people were friendly to women.

I lived in this tiny bubble that also gave me the privilege of not facing some things that I can imagine that people in Brazil in different areas and smaller towns face. In Brazil, people try to not talk about this gender agenda. This is something that’s being talked about outside Brazil. But in Brazil, we are years back. People are not really engaging on this conversation. I thought it was going to be hard for me as a woman, because Brazil has around 20% female surgeons.

I knew it was going to be challenging, but I had no idea how bad it was. When I started and things started happening, the list was big. I have an example of everything that is written about – microaggression, implicit bias, discrimination, harassment.

Every time I would try to speak about it and talk to someone, I would be strongly gaslighted. It was the whole training, the whole 5 years. People would say, “Oh, I don’t think it was like that. I think you were overreacting.” People would come with all these different answers for what I was experiencing, and that was frustrating. That was even harder because I had to cope with everything that was happening and I had no one to turn to. I had no mentors.

When I looked up to women who were in surgery, they would be tougher on us young surgeons than the men and they would tell us that we should not complain because in their time it was even harder. Now, it’s getting better and we are supposed to accept whatever comes.

That was at least a little bit of what I experienced in my training. It was only after I finished and started to do research about it that I really encountered a field of people who would echo what I was trying to say to many people in different hospitals that I attended to.

That was the key for me to get out of that situation of being gaslighted and of not being able to really talk about it. Suddenly, I started to publish things about Brazil that nobody was even writing or studying. That gave me a large amount of responsibility, but also motivation to keep going and to see the change.
 

Valuing women in medicine

Dr. Glatter: This is a very important point that you’re raising about the environment of women being hard on other women. We know that men can be very difficult on and also judgmental toward their trainees.

Amy, how would you respond to that? Was your experience similar in emergency medicine training?

Dr. Ho: I actually don’t feel like it was. I think what Júlia is alluding to is this “mean girls” idea, of “I went through it and thus you have to go through it.” I think you do see this in many specialties. One of the classic ones we hear about, and I don’t want to speak to it too much because it’s not my specialty, is ob.gyn., where it is a very female-dominant surgery group. There’s almost a hazing level that you hear about in some of the more malignant workplaces.

I think that you speak to two really important things. Number one is the numbers game. As you were saying, Brazil actually has many women. That’s awesome. That’s actually different from the United States, especially for the historic, existing workplace and less so for the medical students and for residents. I think step one is having minorities like women just present and there.

Step two is actually including and valuing them. While I think it’s really easy to move away from the women discussion, because there are women when you look around in medicine, it doesn’t mean that women are actually being heard, that they’re actually being accepted, or that their viewpoints are being listened to. A big part of it is normalizing not only seeing women in medicine but also normalizing the narrative of women in medicine.

It’s not just about motherhood; it’s about things like normalizing talking about advancement, academic promotions, pay, culture, being called things like “too reactive,” “anxious,” or “too assertive.” These are all classic things that we hear about when we talk about women.

That’s why we’re looking to not only conversations like this, but also structured ways for women to discuss being women in medicine. There are many women in medicine groups in emergency medicine, including: Females Working in Emergency Medicine (FemInEM); the American College of Emergency Physicians (ACEP) and Society for Academic Emergency Medicine (SAEM) women’s groups, which are American Association of Women Emergency Physicians (AAWEP) and Academy for Women in Academic Emergency Medicine (AWAEM), respectively; and the American Medical Women’s Association (AMWA), which is the American Medical Association’s offshoot.

All of these groups are geared toward normalizing women in medicine, normalizing the narrative of women in medicine, and then working on mentoring and educating so that we can advance our initiatives.
 

Gender balance is not gender equity

Dr. Glatter: Amy, you bring up a very critical point that mentoring is sort of the antidote to gender-based discrimination. Júlia had written a paper back in November of 2022 that was published in the Journal of Surgical Research talking exactly about this and how important it is to develop mentoring. Part of her research showed that about 20% of medical students who took the survey, about 1,000 people, had mentors, which was very disturbing.

Dr. Loyola Ferreira: Mentorship is one of the ways of changing the reality about gender-based discrimination. Amy’s comment was very strong and we need to really keep saying it, which is that gender balance is not gender equity.

The idea of having more women is not the same as women being recognized as equals, as able as men, and as valued as men. To change this very long culture of male domination, we need support, and this support comes from mentorship.

Although I didn’t have one, I feel that since I started being a mentor for some students, it changed not only them but myself. It gave me strength to keep going, studying, publishing, and going further with this discussion. I feel like the relationship was as good for them as it is for me. That’s how things change.
 

Diversity, equity, and inclusion training

Dr. Glatter: We’re talking about the reality of gender equity in terms of the ability to have equal respect, recognition, opportunities, and access. That’s really an important point to realize, and for our audience, to understand that gender equity is not gender balance.

Amy, I want to talk about medical school curriculums. Are there advances that you’re aware of being made at certain schools, programs, even in residencies, to enforce these things and make it a priority?

Dr. Ho: We’re really lucky that, as a culture in the United States, medical training is certainly very geared toward diversity. Some of that is certainly unofficial. Some of that just means when they’re looking at a medical school class or looking at rank lists for residency, that they’re cognizant of the different backgrounds that people have. That’s still a step. That is a step, that we’re at least acknowledging it.

There are multiple medical schools and residencies that have more formal unconscious-bias training or diversity, equity, and inclusion (DEI) training, both of which are excellent not only for us in the workplace but also for our patients. Almost all of us will see patients of highly diverse backgrounds. I think the biggest push is looking toward the criteria that we use for selecting trainees and students into our programs. Historically, it’s been MCAT, GPA, and so on.

We’ve really started to ask the question of, are these sorts of “objective criteria” actually biased in institutional ways? They talk about this all the time where GPAs will bias against students from underrepresented minorities (URM). I think all medical students and residencies have really acknowledged that. Although there are still test cutoffs, we are putting an inquisitive eye to what those mean, why they exist, and what are the other things that we should consider. This is all very heartening from what I’m seeing in medical training.

Dr. Glatter: There’s no formal rating system for DEI curriculums right now, like ranking of this school, or this program has more advanced recognition in terms of DEI?

Dr. Ho: No, but on the flip side, the U.S. News & World Report was classically one of the major rankings for medical schools. What we saw fairly recently was that very high-tier schools like Harvard and University of Chicago pulled out of that ranking because that ranking did not acknowledge the value of diversity. That was an incredible stance for medical schools to take, to say, “Hey, you are not evaluating an important criterion of ours.”

Dr. Glatter: That’s a great point. Júlia, where are we now in Brazil in terms of awareness of DEI and curriculum in schools and training programs?

Dr. Loyola Ferreira: Our reality is not as good as in the U.S., unfortunately. I don’t see much discussion on residency programs or medical schools at the moment. I see many students bringing it out and trying to make their schools engage in that discussion. This is something that is coming from the bottom up and not from the top down. I think it can lead to change as well. It is a step and it’s a beginning. Institutions should take the responsibility of doing this from the beginning. This is something where Brazil is still years behind you guys.

Dr. Glatter: It’s unfortunate, but certainly it’s important to hear that. What about in Canada and certainly your institution, McGill, where you just completed a master’s degree?

Dr. Loyola Ferreira: Canada is very much like the U.S. This is something that is really happening and it’s happening fast. I see, at least at McGill, a large amount of DEI inclusion and everything on this discussion. They have institutional courses for us to do as students, and we are all obliged to do many courses, which I think is really educating, especially for people with different cultures and backgrounds.

Dr. Glatter: Amy, where do you think we are in emergency medicine to look at the other side of it? Comparing surgery with emergency medicine, do you think we’re well advanced in terms of DEI, inclusion criteria, respect, and dignity, or are we really far off?

Dr. Ho: I may be biased, but I think emergency medicine is one of the best in terms of this, and I think there are a couple of reasons for it. One is that we are an inherently team-based organization. The attending, the residents, and the students all work in line with one another. There’s less of a hierarchy.

The same is true for our nurses, pharmacists, techs, and EMS. We all work together as a team. Because of that fairly flat structure, it’s really easy for us to value one another as individuals with our diverse backgrounds. In a way, that’s harder for specialties that are more hierarchical, and I think surgery is certainly one of the most hierarchical.

The second reason why emergency medicine is fairly well off in this is that we’re, by nature, a safety-net specialty. We see patients of all-comers, all walks, all backgrounds. I think we both recognize the value of physician-patient concordance. When we share characteristics with our patients, we recognize that value immediately at the bedside.

It exposes us to so much diversity. I see a refugee one day and the next patient is someone who is incarcerated. The next patient after that is an important businessman in society. That diversity and whiplash in the type of patients that we see back-to-back helps us see the playing field in a really flat, diverse way. Because of that, I think our culture is much better, as is our understanding of the value and importance of diversity not only for our programs, but also for our patients.
 

Do female doctors have better patient outcomes?

Dr. Glatter: Specialties working together in the emergency department is so important. Building that team and that togetherness is so critical. Júlia, would you agree?

Dr. Loyola Ferreira: Definitely. Something Amy said that is beautiful is that you recognize yourself in these patients. In surgery, we are taught to try to be away from the patients and not to put ourselves in the same position. We are taught to be less engaging, and this is not good. The good thing is when we really have patient-centered care, when we listen to them, and when we are involved with them.

I saw a publication showing that female and male surgeons treating similar patients had the same surgical outcomes. Women are as good as men technically to do surgery and have the same surgical outcomes. However, there is research showing that surgical teams with greater representation of women have improved surgical outcomes because of patient-centered care and the way women conduct bedside attention to patients. And they have better patient experience measures afterward. That is not only from the women who are treating the patients, but the whole environment. Women end up bringing men [into the conversation] and this better improves patient-centered care, and that makes the whole team a better team attending patients. Definitely, we are in the moment of patient experience and satisfaction, and increasing women is a way of achieving better patient satisfaction and experience.

Dr. Ho: There’s much to be said about having female clinicians available for patients. It doesn’t have to be just for female patients, although again, concordance between physicians and patients is certainly beneficial. Besides outcomes benefit, there’s even just a communication benefit. The way that women and men communicate is inherently different. The way women and men experience certain things is also inherently different.

A classic example of this is women who are experiencing a heart attack may not actually have chest pain but present with nausea. As a female who’s sensitive to this, when I see a woman throwing up, I am very attuned to something actually being wrong, knowing that they may not present with classic pain for a syndrome, but actually may be presenting with nausea instead. It doesn’t have to be a woman who takes that knowledge and turns it into something at the bedside. It certainly doesn’t have to, but it is just a natural, easy thing to step into as a female.

While I’m really careful to not step into this “women are better than men” or “men are better than women” argument, there’s something to be said about how the availability of female clinicians for all patients, not just female patients, can have benefit. Again, it’s shown in studies with cardiovascular outcomes and cardiologists, it’s certainly shown in ob.gyn., particularly for underrepresented minorities as well for maternal outcomes of Black mothers. It’s certainly shown again in patient satisfaction, which is concordance.

There is a profound level of research already on this that goes beyond just the idea of stacking the bench and putting more women in there. That’s not the value. We’re not just here to check off the box. We’re here to actually lend some value to our patients and, again, to one another as well.

Dr. Glatter: Absolutely. These are excellent points. The point you make about patient presentation is so vital. The fact that women have nausea sometimes in ACS presentations, the research never was really attentive to this. It was biased. The symptoms that women may have that are not “typical” for ACS weren’t included in patient presentations. Educating everyone about, overall, the types of presentations that we can recognize is vital and important.

Dr. Ho: Yes. It’s worth saying that, when you look at how medicine and research developed, classically, who were the research participants? They were often White men. They were college students who, historically, because women were not allowed to go to college, were men.

I say that not to fault the institution, because that was the culture of our history, but to just say it is okay to question things. It is okay to realize that someone’s presenting outside of the box and that maybe we actually need to reframe what even created the walls of the box in the first place.

Dr. Glatter: Thank you again for joining us. I truly appreciate your insight and expertise.

Dr. Glatter is assistant professor of emergency medicine, department of emergency medicine, Hofstra/Northwell, New York. Dr. Ho is senior vice president of clinical informatics & analytics, department of emergency medicine, Integrative Emergency Services, Dallas. Dr. Loyola Ferreira is a master of science candidate, department of experimental surgery, McGill University, Montreal. They reported that they had no conflicts of interest.

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

This transcript has been edited for clarity.

Robert D. Glatter, MD: Welcome. I’m Dr. Robert Glatter, medical adviser for Medscape Emergency Medicine. Joining me to discuss ways to address and reform the toxic culture associated with medical training is Dr. Amy Faith Ho, senior vice president of clinical informatics and analytics at Integrative Emergency Services in Dallas. Also joining us is Dr. Júlia Loyola Ferreira, a pediatric surgeon originally from Brazil, now practicing at Montreal Children’s and focused on advocacy for gender equity and patient-centered care.

Welcome to both of you. Thanks so much for joining me.

Amy Faith Ho, MD, MPH: Thanks so much for having us, Rob.

Dr. Glatter: Amy, I noticed a tweet recently where you talked about how your career choice was affected by the toxic environment in medical school, affecting your choice of residency. Can you elaborate on that?

Dr. Ho: This is a super-important topic, not in just one specialty but in all of medicine, because what you’re talking about is toxic workplace culture that is certainly directed toward certain groups. In this instance, what we’re talking about is gender, but it can be directed toward any number of other groups as well.

What you’re alluding to is a tweet by Stanford Surgery Group showing the next residency class, and what was really stunning about this residency class was that it was almost all females. And this was something that took off on social media.

When I saw this, I was really brought back to one of my personal experiences that I chose to share, which was basically that, as a medical student, I really wanted to be a surgeon. I’m an emergency medicine doctor now, so you know that didn’t happen.

The story that I was sharing was that when I was a third-year medical student rotating on surgery, we had a male attending who was very well known at that school at the time who basically would take the female medical students, and instead of clinic, he would round us up. He would have us sit around him in the workplace room while everyone else was seeing patients, and he would have you look at news clippings of himself. He would tell you stories about himself, like he was holding court for the ladies.

It was this very weird culture where my takeaway as a med student was like, “Wow, this is kind of abusive patriarchy that is supported,” because everyone knew about it and was complicit. Even though I really liked surgery, this was just one instance and one example of where you see this culture that really resonates into the rest of life that I didn’t really want to be a part of.

I went into emergency medicine and loved it. It’s also highly procedural, and I was very happy with where I was. What was really interesting about this tweet to me, though, is that it really took off and garnered hundreds of thousands of views on a very niche topic, because what was most revealing is that everyone has a story like this.

It is not just surgery. It is definitely not just one specialty and it is not just one school. It is an endemic problem in medicine. Not only does it change the lives of young women, but it also says so much about the complicity and the culture that we have in medicine that many people were upset about just the same way I was.
 

Medical training experience in other countries vs. the United States

Dr. Glatter: Júlia, I want to hear about your experience in medical school, surgery, and then fellowship training and up to the present, if possible.

Júlia Loyola Ferreira, MD: In Brazil, as in many countries now, women have made up the majority of the medical students since 2010. It’s a more female-friendly environment when you’re going through medical school, and I was lucky enough to do rotations in areas of surgery where people were friendly to women.

I lived in this tiny bubble that also gave me the privilege of not facing some things that I can imagine that people in Brazil in different areas and smaller towns face. In Brazil, people try to not talk about this gender agenda. This is something that’s being talked about outside Brazil. But in Brazil, we are years back. People are not really engaging on this conversation. I thought it was going to be hard for me as a woman, because Brazil has around 20% female surgeons.

I knew it was going to be challenging, but I had no idea how bad it was. When I started and things started happening, the list was big. I have an example of everything that is written about – microaggression, implicit bias, discrimination, harassment.

Every time I would try to speak about it and talk to someone, I would be strongly gaslighted. It was the whole training, the whole 5 years. People would say, “Oh, I don’t think it was like that. I think you were overreacting.” People would come with all these different answers for what I was experiencing, and that was frustrating. That was even harder because I had to cope with everything that was happening and I had no one to turn to. I had no mentors.

When I looked up to women who were in surgery, they would be tougher on us young surgeons than the men and they would tell us that we should not complain because in their time it was even harder. Now, it’s getting better and we are supposed to accept whatever comes.

That was at least a little bit of what I experienced in my training. It was only after I finished and started to do research about it that I really encountered a field of people who would echo what I was trying to say to many people in different hospitals that I attended to.

That was the key for me to get out of that situation of being gaslighted and of not being able to really talk about it. Suddenly, I started to publish things about Brazil that nobody was even writing or studying. That gave me a large amount of responsibility, but also motivation to keep going and to see the change.
 

Valuing women in medicine

Dr. Glatter: This is a very important point that you’re raising about the environment of women being hard on other women. We know that men can be very difficult on and also judgmental toward their trainees.

Amy, how would you respond to that? Was your experience similar in emergency medicine training?

Dr. Ho: I actually don’t feel like it was. I think what Júlia is alluding to is this “mean girls” idea, of “I went through it and thus you have to go through it.” I think you do see this in many specialties. One of the classic ones we hear about, and I don’t want to speak to it too much because it’s not my specialty, is ob.gyn., where it is a very female-dominant surgery group. There’s almost a hazing level that you hear about in some of the more malignant workplaces.

I think that you speak to two really important things. Number one is the numbers game. As you were saying, Brazil actually has many women. That’s awesome. That’s actually different from the United States, especially for the historic, existing workplace and less so for the medical students and for residents. I think step one is having minorities like women just present and there.

Step two is actually including and valuing them. While I think it’s really easy to move away from the women discussion, because there are women when you look around in medicine, it doesn’t mean that women are actually being heard, that they’re actually being accepted, or that their viewpoints are being listened to. A big part of it is normalizing not only seeing women in medicine but also normalizing the narrative of women in medicine.

It’s not just about motherhood; it’s about things like normalizing talking about advancement, academic promotions, pay, culture, being called things like “too reactive,” “anxious,” or “too assertive.” These are all classic things that we hear about when we talk about women.

That’s why we’re looking to not only conversations like this, but also structured ways for women to discuss being women in medicine. There are many women in medicine groups in emergency medicine, including: Females Working in Emergency Medicine (FemInEM); the American College of Emergency Physicians (ACEP) and Society for Academic Emergency Medicine (SAEM) women’s groups, which are American Association of Women Emergency Physicians (AAWEP) and Academy for Women in Academic Emergency Medicine (AWAEM), respectively; and the American Medical Women’s Association (AMWA), which is the American Medical Association’s offshoot.

All of these groups are geared toward normalizing women in medicine, normalizing the narrative of women in medicine, and then working on mentoring and educating so that we can advance our initiatives.
 

Gender balance is not gender equity

Dr. Glatter: Amy, you bring up a very critical point that mentoring is sort of the antidote to gender-based discrimination. Júlia had written a paper back in November of 2022 that was published in the Journal of Surgical Research talking exactly about this and how important it is to develop mentoring. Part of her research showed that about 20% of medical students who took the survey, about 1,000 people, had mentors, which was very disturbing.

Dr. Loyola Ferreira: Mentorship is one of the ways of changing the reality about gender-based discrimination. Amy’s comment was very strong and we need to really keep saying it, which is that gender balance is not gender equity.

The idea of having more women is not the same as women being recognized as equals, as able as men, and as valued as men. To change this very long culture of male domination, we need support, and this support comes from mentorship.

Although I didn’t have one, I feel that since I started being a mentor for some students, it changed not only them but myself. It gave me strength to keep going, studying, publishing, and going further with this discussion. I feel like the relationship was as good for them as it is for me. That’s how things change.
 

Diversity, equity, and inclusion training

Dr. Glatter: We’re talking about the reality of gender equity in terms of the ability to have equal respect, recognition, opportunities, and access. That’s really an important point to realize, and for our audience, to understand that gender equity is not gender balance.

Amy, I want to talk about medical school curriculums. Are there advances that you’re aware of being made at certain schools, programs, even in residencies, to enforce these things and make it a priority?

Dr. Ho: We’re really lucky that, as a culture in the United States, medical training is certainly very geared toward diversity. Some of that is certainly unofficial. Some of that just means when they’re looking at a medical school class or looking at rank lists for residency, that they’re cognizant of the different backgrounds that people have. That’s still a step. That is a step, that we’re at least acknowledging it.

There are multiple medical schools and residencies that have more formal unconscious-bias training or diversity, equity, and inclusion (DEI) training, both of which are excellent not only for us in the workplace but also for our patients. Almost all of us will see patients of highly diverse backgrounds. I think the biggest push is looking toward the criteria that we use for selecting trainees and students into our programs. Historically, it’s been MCAT, GPA, and so on.

We’ve really started to ask the question of, are these sorts of “objective criteria” actually biased in institutional ways? They talk about this all the time where GPAs will bias against students from underrepresented minorities (URM). I think all medical students and residencies have really acknowledged that. Although there are still test cutoffs, we are putting an inquisitive eye to what those mean, why they exist, and what are the other things that we should consider. This is all very heartening from what I’m seeing in medical training.

Dr. Glatter: There’s no formal rating system for DEI curriculums right now, like ranking of this school, or this program has more advanced recognition in terms of DEI?

Dr. Ho: No, but on the flip side, the U.S. News & World Report was classically one of the major rankings for medical schools. What we saw fairly recently was that very high-tier schools like Harvard and University of Chicago pulled out of that ranking because that ranking did not acknowledge the value of diversity. That was an incredible stance for medical schools to take, to say, “Hey, you are not evaluating an important criterion of ours.”

Dr. Glatter: That’s a great point. Júlia, where are we now in Brazil in terms of awareness of DEI and curriculum in schools and training programs?

Dr. Loyola Ferreira: Our reality is not as good as in the U.S., unfortunately. I don’t see much discussion on residency programs or medical schools at the moment. I see many students bringing it out and trying to make their schools engage in that discussion. This is something that is coming from the bottom up and not from the top down. I think it can lead to change as well. It is a step and it’s a beginning. Institutions should take the responsibility of doing this from the beginning. This is something where Brazil is still years behind you guys.

Dr. Glatter: It’s unfortunate, but certainly it’s important to hear that. What about in Canada and certainly your institution, McGill, where you just completed a master’s degree?

Dr. Loyola Ferreira: Canada is very much like the U.S. This is something that is really happening and it’s happening fast. I see, at least at McGill, a large amount of DEI inclusion and everything on this discussion. They have institutional courses for us to do as students, and we are all obliged to do many courses, which I think is really educating, especially for people with different cultures and backgrounds.

Dr. Glatter: Amy, where do you think we are in emergency medicine to look at the other side of it? Comparing surgery with emergency medicine, do you think we’re well advanced in terms of DEI, inclusion criteria, respect, and dignity, or are we really far off?

Dr. Ho: I may be biased, but I think emergency medicine is one of the best in terms of this, and I think there are a couple of reasons for it. One is that we are an inherently team-based organization. The attending, the residents, and the students all work in line with one another. There’s less of a hierarchy.

The same is true for our nurses, pharmacists, techs, and EMS. We all work together as a team. Because of that fairly flat structure, it’s really easy for us to value one another as individuals with our diverse backgrounds. In a way, that’s harder for specialties that are more hierarchical, and I think surgery is certainly one of the most hierarchical.

The second reason why emergency medicine is fairly well off in this is that we’re, by nature, a safety-net specialty. We see patients of all-comers, all walks, all backgrounds. I think we both recognize the value of physician-patient concordance. When we share characteristics with our patients, we recognize that value immediately at the bedside.

It exposes us to so much diversity. I see a refugee one day and the next patient is someone who is incarcerated. The next patient after that is an important businessman in society. That diversity and whiplash in the type of patients that we see back-to-back helps us see the playing field in a really flat, diverse way. Because of that, I think our culture is much better, as is our understanding of the value and importance of diversity not only for our programs, but also for our patients.
 

Do female doctors have better patient outcomes?

Dr. Glatter: Specialties working together in the emergency department is so important. Building that team and that togetherness is so critical. Júlia, would you agree?

Dr. Loyola Ferreira: Definitely. Something Amy said that is beautiful is that you recognize yourself in these patients. In surgery, we are taught to try to be away from the patients and not to put ourselves in the same position. We are taught to be less engaging, and this is not good. The good thing is when we really have patient-centered care, when we listen to them, and when we are involved with them.

I saw a publication showing that female and male surgeons treating similar patients had the same surgical outcomes. Women are as good as men technically to do surgery and have the same surgical outcomes. However, there is research showing that surgical teams with greater representation of women have improved surgical outcomes because of patient-centered care and the way women conduct bedside attention to patients. And they have better patient experience measures afterward. That is not only from the women who are treating the patients, but the whole environment. Women end up bringing men [into the conversation] and this better improves patient-centered care, and that makes the whole team a better team attending patients. Definitely, we are in the moment of patient experience and satisfaction, and increasing women is a way of achieving better patient satisfaction and experience.

Dr. Ho: There’s much to be said about having female clinicians available for patients. It doesn’t have to be just for female patients, although again, concordance between physicians and patients is certainly beneficial. Besides outcomes benefit, there’s even just a communication benefit. The way that women and men communicate is inherently different. The way women and men experience certain things is also inherently different.

A classic example of this is women who are experiencing a heart attack may not actually have chest pain but present with nausea. As a female who’s sensitive to this, when I see a woman throwing up, I am very attuned to something actually being wrong, knowing that they may not present with classic pain for a syndrome, but actually may be presenting with nausea instead. It doesn’t have to be a woman who takes that knowledge and turns it into something at the bedside. It certainly doesn’t have to, but it is just a natural, easy thing to step into as a female.

While I’m really careful to not step into this “women are better than men” or “men are better than women” argument, there’s something to be said about how the availability of female clinicians for all patients, not just female patients, can have benefit. Again, it’s shown in studies with cardiovascular outcomes and cardiologists, it’s certainly shown in ob.gyn., particularly for underrepresented minorities as well for maternal outcomes of Black mothers. It’s certainly shown again in patient satisfaction, which is concordance.

There is a profound level of research already on this that goes beyond just the idea of stacking the bench and putting more women in there. That’s not the value. We’re not just here to check off the box. We’re here to actually lend some value to our patients and, again, to one another as well.

Dr. Glatter: Absolutely. These are excellent points. The point you make about patient presentation is so vital. The fact that women have nausea sometimes in ACS presentations, the research never was really attentive to this. It was biased. The symptoms that women may have that are not “typical” for ACS weren’t included in patient presentations. Educating everyone about, overall, the types of presentations that we can recognize is vital and important.

Dr. Ho: Yes. It’s worth saying that, when you look at how medicine and research developed, classically, who were the research participants? They were often White men. They were college students who, historically, because women were not allowed to go to college, were men.

I say that not to fault the institution, because that was the culture of our history, but to just say it is okay to question things. It is okay to realize that someone’s presenting outside of the box and that maybe we actually need to reframe what even created the walls of the box in the first place.

Dr. Glatter: Thank you again for joining us. I truly appreciate your insight and expertise.

Dr. Glatter is assistant professor of emergency medicine, department of emergency medicine, Hofstra/Northwell, New York. Dr. Ho is senior vice president of clinical informatics & analytics, department of emergency medicine, Integrative Emergency Services, Dallas. Dr. Loyola Ferreira is a master of science candidate, department of experimental surgery, McGill University, Montreal. They reported that they had no conflicts of interest.

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

Suicide risk in young people appears to follow a diurnal pattern, increasing at night, new research shows.

Investigators found that suicidal ideation and attempts were lowest in the mornings and highest in the evenings, particularly among youth with higher levels of self-critical rumination.

“These are preliminary findings, and there is a need for more data, but they signal potentially that there’s a need for support, particularly at nighttime, and that there might be a potential of targeting self-critical rumination in daily lives of youth,” said lead researcher Anastacia Kudinova, PhD, with the department of psychiatry and human behavior, Alpert Medical School of Brown University, Providence, R.I.

The findings were presented at the late-breaker session at the annual meeting of the Associated Professional Sleep Societies.
 

Urgent need

Suicidal ideation (SI) is a “robust” predictor of suicidal behavior and, “alarmingly,” both suicidal ideation and suicidal behavior have been increasing, Dr. Kudinova said.

“There is an urgent need to describe proximal time-period risk factors for suicide so that we can identify who is at a greater suicide risk on the time scale of weeks, days, or even hours,” she told attendees.

The researchers asked 165 psychiatrically hospitalized youth aged 11-18 (72% female) about the time of day of their most recent suicide attempt.

More than half (58%) said it occurred in the evenings and nights, followed by daytime (35%) and mornings (7%).

They also assessed the timing of suicidal ideation at home in 61 youth aged 12-15 (61% female) who were discharged after a partial hospitalization program.

They did this using ecological momentary assessments (EMAs) three times a day over 2 weeks. EMAs study people’s thoughts and behavior in their daily lives by repeatedly collecting data in an individual’s normal environment at or close to the time they carry out that behavior.

As in the other sample, youth in this sample also experienced significantly more frequent suicidal ideation later in the day (P < .01).

There was also a significant moderating effect of self-criticism (P < .01), such that more self-critical youth evidenced the highest levels of suicidal ideation later in the day.
 

True variation or mechanics?

Reached for comment, Paul Nestadt, MD, with Johns Hopkins Bloomberg School of Public Health, Baltimore, noted that EMA is becoming “an interesting way to track high-resolution temporal variation in suicidal ideation and other psych symptoms.”

Dr. Nestadt, who was not involved in the study, said that “it’s not surprising” that the majority of youth attempted suicide in evenings and nights, “as adolescents are generally being supervised in a school setting during daytime hours. It may not be the fluctuation in suicidality that impacts attempt timing so much as the mechanics – it is very hard to attempt suicide in math class.”

The same may be true for the youth in the second sample who were in the partial hospital program. “During the day, they were in therapy groups where feelings of suicidal ideation would have been solicited and addressed in real time,” Dr. Nestadt noted.

“Again, suicidal ideation later in the day may be a practical effect of how they are occupied in the partial hospital program, as opposed to some inherent suicidal ideation increase linked to something endogenous, such as circadian rhythm or cortisol level rises. That said, we do often see more attempts in the evenings in adults as well,” he added.
 

A vulnerable time

Also weighing in, Casey O’Brien, PsyD, a psychologist in the department of psychiatry at Columbia University Irving Medical Center, New York, said the findings in this study “track” with what she sees in the clinic.

Teens often report in session that the “unstructured time of night – especially the time when they usually should be getting to bed but are kind of staying up – tends to be a very vulnerable time for them,” Dr. O’Brien said in an interview.

“It’s really nice to have research confirm a lot of what we see reported anecdotally from the teens we work with,” said Dr. O’Brien.

Dr. O’Brien heads the intensive adolescent dialectical behavior therapy (DBT) program at Columbia for young people struggling with mental health issues.

“Within the DBT framework, we try to really focus on accepting that this is a vulnerable time and then planning ahead for what the strategies are that they can use to help them transition to bed quickly and smoothly,” Dr. O’Brien said.

These strategies may include spending time with their parents before bed, reading, or building into their bedtime routines things that they find soothing and comforting, like taking a longer shower or having comfortable pajamas to change into, she explained.

“We also work a lot on sleep hygiene strategies to help develop a regular bedtime and have a consistent sleep-wake cycle. We also will plan ahead for using distress tolerance skills during times of emotional vulnerability,” Dr. O’Brien said.

The Columbia DBT program also offers phone coaching “so teens can reach out to a therapist for help using skills outside of a therapeutic hour, and we do find that we get more coaching calls closer to around bedtime,” Dr. O’Brien said.

Support for the study was provided by the National Institute of Mental Health and Bradley Hospital COBRE Center. Dr. Kudinova, Dr. Nestadt, and Dr. O’Brien have disclosed no relevant financial relationships.

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

Suicide risk in young people appears to follow a diurnal pattern, increasing at night, new research shows.

Investigators found that suicidal ideation and attempts were lowest in the mornings and highest in the evenings, particularly among youth with higher levels of self-critical rumination.

“These are preliminary findings, and there is a need for more data, but they signal potentially that there’s a need for support, particularly at nighttime, and that there might be a potential of targeting self-critical rumination in daily lives of youth,” said lead researcher Anastacia Kudinova, PhD, with the department of psychiatry and human behavior, Alpert Medical School of Brown University, Providence, R.I.

The findings were presented at the late-breaker session at the annual meeting of the Associated Professional Sleep Societies.
 

Urgent need

Suicidal ideation (SI) is a “robust” predictor of suicidal behavior and, “alarmingly,” both suicidal ideation and suicidal behavior have been increasing, Dr. Kudinova said.

“There is an urgent need to describe proximal time-period risk factors for suicide so that we can identify who is at a greater suicide risk on the time scale of weeks, days, or even hours,” she told attendees.

The researchers asked 165 psychiatrically hospitalized youth aged 11-18 (72% female) about the time of day of their most recent suicide attempt.

More than half (58%) said it occurred in the evenings and nights, followed by daytime (35%) and mornings (7%).

They also assessed the timing of suicidal ideation at home in 61 youth aged 12-15 (61% female) who were discharged after a partial hospitalization program.

They did this using ecological momentary assessments (EMAs) three times a day over 2 weeks. EMAs study people’s thoughts and behavior in their daily lives by repeatedly collecting data in an individual’s normal environment at or close to the time they carry out that behavior.

As in the other sample, youth in this sample also experienced significantly more frequent suicidal ideation later in the day (P < .01).

There was also a significant moderating effect of self-criticism (P < .01), such that more self-critical youth evidenced the highest levels of suicidal ideation later in the day.
 

True variation or mechanics?

Reached for comment, Paul Nestadt, MD, with Johns Hopkins Bloomberg School of Public Health, Baltimore, noted that EMA is becoming “an interesting way to track high-resolution temporal variation in suicidal ideation and other psych symptoms.”

Dr. Nestadt, who was not involved in the study, said that “it’s not surprising” that the majority of youth attempted suicide in evenings and nights, “as adolescents are generally being supervised in a school setting during daytime hours. It may not be the fluctuation in suicidality that impacts attempt timing so much as the mechanics – it is very hard to attempt suicide in math class.”

The same may be true for the youth in the second sample who were in the partial hospital program. “During the day, they were in therapy groups where feelings of suicidal ideation would have been solicited and addressed in real time,” Dr. Nestadt noted.

“Again, suicidal ideation later in the day may be a practical effect of how they are occupied in the partial hospital program, as opposed to some inherent suicidal ideation increase linked to something endogenous, such as circadian rhythm or cortisol level rises. That said, we do often see more attempts in the evenings in adults as well,” he added.
 

A vulnerable time

Also weighing in, Casey O’Brien, PsyD, a psychologist in the department of psychiatry at Columbia University Irving Medical Center, New York, said the findings in this study “track” with what she sees in the clinic.

Teens often report in session that the “unstructured time of night – especially the time when they usually should be getting to bed but are kind of staying up – tends to be a very vulnerable time for them,” Dr. O’Brien said in an interview.

“It’s really nice to have research confirm a lot of what we see reported anecdotally from the teens we work with,” said Dr. O’Brien.

Dr. O’Brien heads the intensive adolescent dialectical behavior therapy (DBT) program at Columbia for young people struggling with mental health issues.

“Within the DBT framework, we try to really focus on accepting that this is a vulnerable time and then planning ahead for what the strategies are that they can use to help them transition to bed quickly and smoothly,” Dr. O’Brien said.

These strategies may include spending time with their parents before bed, reading, or building into their bedtime routines things that they find soothing and comforting, like taking a longer shower or having comfortable pajamas to change into, she explained.

“We also work a lot on sleep hygiene strategies to help develop a regular bedtime and have a consistent sleep-wake cycle. We also will plan ahead for using distress tolerance skills during times of emotional vulnerability,” Dr. O’Brien said.

The Columbia DBT program also offers phone coaching “so teens can reach out to a therapist for help using skills outside of a therapeutic hour, and we do find that we get more coaching calls closer to around bedtime,” Dr. O’Brien said.

Support for the study was provided by the National Institute of Mental Health and Bradley Hospital COBRE Center. Dr. Kudinova, Dr. Nestadt, and Dr. O’Brien have disclosed no relevant financial relationships.

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

Suicide risk in young people appears to follow a diurnal pattern, increasing at night, new research shows.

Investigators found that suicidal ideation and attempts were lowest in the mornings and highest in the evenings, particularly among youth with higher levels of self-critical rumination.

“These are preliminary findings, and there is a need for more data, but they signal potentially that there’s a need for support, particularly at nighttime, and that there might be a potential of targeting self-critical rumination in daily lives of youth,” said lead researcher Anastacia Kudinova, PhD, with the department of psychiatry and human behavior, Alpert Medical School of Brown University, Providence, R.I.

The findings were presented at the late-breaker session at the annual meeting of the Associated Professional Sleep Societies.
 

Urgent need

Suicidal ideation (SI) is a “robust” predictor of suicidal behavior and, “alarmingly,” both suicidal ideation and suicidal behavior have been increasing, Dr. Kudinova said.

“There is an urgent need to describe proximal time-period risk factors for suicide so that we can identify who is at a greater suicide risk on the time scale of weeks, days, or even hours,” she told attendees.

The researchers asked 165 psychiatrically hospitalized youth aged 11-18 (72% female) about the time of day of their most recent suicide attempt.

More than half (58%) said it occurred in the evenings and nights, followed by daytime (35%) and mornings (7%).

They also assessed the timing of suicidal ideation at home in 61 youth aged 12-15 (61% female) who were discharged after a partial hospitalization program.

They did this using ecological momentary assessments (EMAs) three times a day over 2 weeks. EMAs study people’s thoughts and behavior in their daily lives by repeatedly collecting data in an individual’s normal environment at or close to the time they carry out that behavior.

As in the other sample, youth in this sample also experienced significantly more frequent suicidal ideation later in the day (P < .01).

There was also a significant moderating effect of self-criticism (P < .01), such that more self-critical youth evidenced the highest levels of suicidal ideation later in the day.
 

True variation or mechanics?

Reached for comment, Paul Nestadt, MD, with Johns Hopkins Bloomberg School of Public Health, Baltimore, noted that EMA is becoming “an interesting way to track high-resolution temporal variation in suicidal ideation and other psych symptoms.”

Dr. Nestadt, who was not involved in the study, said that “it’s not surprising” that the majority of youth attempted suicide in evenings and nights, “as adolescents are generally being supervised in a school setting during daytime hours. It may not be the fluctuation in suicidality that impacts attempt timing so much as the mechanics – it is very hard to attempt suicide in math class.”

The same may be true for the youth in the second sample who were in the partial hospital program. “During the day, they were in therapy groups where feelings of suicidal ideation would have been solicited and addressed in real time,” Dr. Nestadt noted.

“Again, suicidal ideation later in the day may be a practical effect of how they are occupied in the partial hospital program, as opposed to some inherent suicidal ideation increase linked to something endogenous, such as circadian rhythm or cortisol level rises. That said, we do often see more attempts in the evenings in adults as well,” he added.
 

A vulnerable time

Also weighing in, Casey O’Brien, PsyD, a psychologist in the department of psychiatry at Columbia University Irving Medical Center, New York, said the findings in this study “track” with what she sees in the clinic.

Teens often report in session that the “unstructured time of night – especially the time when they usually should be getting to bed but are kind of staying up – tends to be a very vulnerable time for them,” Dr. O’Brien said in an interview.

“It’s really nice to have research confirm a lot of what we see reported anecdotally from the teens we work with,” said Dr. O’Brien.

Dr. O’Brien heads the intensive adolescent dialectical behavior therapy (DBT) program at Columbia for young people struggling with mental health issues.

“Within the DBT framework, we try to really focus on accepting that this is a vulnerable time and then planning ahead for what the strategies are that they can use to help them transition to bed quickly and smoothly,” Dr. O’Brien said.

These strategies may include spending time with their parents before bed, reading, or building into their bedtime routines things that they find soothing and comforting, like taking a longer shower or having comfortable pajamas to change into, she explained.

“We also work a lot on sleep hygiene strategies to help develop a regular bedtime and have a consistent sleep-wake cycle. We also will plan ahead for using distress tolerance skills during times of emotional vulnerability,” Dr. O’Brien said.

The Columbia DBT program also offers phone coaching “so teens can reach out to a therapist for help using skills outside of a therapeutic hour, and we do find that we get more coaching calls closer to around bedtime,” Dr. O’Brien said.

Support for the study was provided by the National Institute of Mental Health and Bradley Hospital COBRE Center. Dr. Kudinova, Dr. Nestadt, and Dr. O’Brien have disclosed no relevant financial relationships.

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

Electroconvulsive therapy (ECT) is the standard treatment for resistant depression, but results of a new randomized, head-to-head trial suggest intravenous ketamine is at least as effective and has fewer side effects.

“The take-home message right now is that if somebody is being referred for ECT, the treating clinician should think of offering ketamine first,” study investigator Amit Anand, MD, professor of psychiatry, Harvard Medical School, Boston, said in an interview.

The study was published online in the New England Journal of Medicine.
 

‘Preferred treatment’

More than one-third of cases of depression are treatment resistant, said Dr. Anand, who is also director of Psychiatry Translational Clinical Trials at Mass General Brigham. He noted that ECT has been the “gold standard for treating severe depression for over 80 years.”

Julia Hiebaum/Alamy

He added that although ECT is very effective and is fast acting, “it requires anesthesia, can be socially stigmatizing, and is associated with memory problems following the treatment.”

An anesthetic agent, ketamine has been shown to have rapid antidepressant effects and does not cause memory loss or carry the stigma associated with ECT, he added. For these reasons, the investigators examined whether it may be a viable alternative to ECT.

To date, no large, head-to-head trials have compared ECT to intravenous ketamine. A recent meta-analysis showed that ECT was superior to ketamine for major depression, but the total number of patients included in the analysis was small, Dr. Anand said.

In addition, most of the participants in that trial were drawn from a single center. Approximately 95 patients were enrolled in each arm of the trial, which included some participants with features of psychosis. “ECT is very effective for depression associated with psychotic features, which may be one reason ECT had a better response in that trial,” said Dr. Anand.

The investigators compared ECT to ketamine in a larger sample that excluded patients with psychosis. They randomly assigned 403 patients at five clinical sites in a 1:1 ratio to receive either ketamine or ECT (n = 200 and 203, respectively; 53% and 49.3% women, respectively; aged 45.6 ± 14.8 and 47.1 ± 14.1 years, respectively).

Patients were required to have had an unsatisfactory response to two or more adequate trials of antidepressant treatment.

Prior to initiation of the assigned treatment, 38 patients withdrew, leaving 195 in the ketamine group and 170 in the ECT group.

Treatment was administered over a 3-week period, during which patients received either ECT three times per week or ketamine (0.5 mg/kg of body weight) twice per week.

The primary outcome was treatment response, defined as a decrease of 50% or more from baseline in the16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16). Secondary outcomes included scores on memory tests and patient-reported quality of life.

Patients who had a response were followed for 6 months after the initial treatment phase.
 

More research needed

Following the 3-week treatment period, a total of 55.4% patients who received ketamine and 41.2% of patients who underwent ECT responded to treatment, which translates into a difference of 14.2 percentage points (95% confidence interval, 3.9-24.2; P < .001) – a finding that fell within the noninferiority threshold set by the investigators.

ECT was associated with decreased memory recall after the 3 weeks of treatment, with a mean (standard deviation) decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test–Revised of –0.9 (1.1) in the ketamine group vs. –9.7 (1.2) in the ECT group (difference, –1.8 points [–2.8 to –0.8]).

Remission, determined on the basis of QIDS-SR-16 score, occurred in 32% of the ketamine group and in 20% in the ECT group. Similar findings were seen on the Montgomery-Åsberg Depression Rating Scale.

Both groups showed significant improvements in quality of life, with changes of 12.3 and 12.9 points, respectively, on the 16-item Quality of Life Scale.

“ECT was associated with musculoskeletal adverse events, whereas ketamine was associated with dissociation,” the investigators note.

During the 6-month follow-up period, there were differences in relapse rates between the groups (defined as QIDS-SRS-16 score > 11). At 1 month, the rates were 19.0% for those receiving ketamine and 35.4% for those receiving ECT. At 3 months, the rates were 25.0% and 50.9%, respectively; at 6 months, the rates were 34.5% and 56.3%, respectively.

ECT has been shown to be effective for older adults, patients with MDD and psychosis, and in inpatient and research settings. Future studies are needed to determine the comparative effectiveness of ketamine in these populations, the authors note.
 

Not life-changing

In a comment, Dan Iosifescu, MD, professor of psychiatry, NYU Langone Health, New York, called it an “extraordinarily important and clinically relevant study, large, well-designed, and well-conducted.”

Dr. Iosifescu, director of the clinical research division, Nathan Kline Institute, Orangeburg, N.Y., who was not involved with the study, noted that the study wasn’t powered to determine whether one treatment was superior to the other, but rather it assessed noninferiority.

“The main point of this study is that the two treatments are largely equivalent, although numerically, ketamine was slightly associated with more beneficial outcomes and fewer cognitive side effects,” he said.

The findings suggest “that people who have no contraindications and are candidates for both ketamine and ECT – which is the vast majority of people with treatment-resistant depression – should consider getting ketamine first because it is somewhat easier in terms of side effects and logistics and consider ECT afterwards if the ketamine doesn’t work.”

In an accompanying editorial, Robert Freedman, MD, clinical professor, University of Colorado at Denver, Aurora, noted that although “3 weeks of lightened mood is undoubtedly a gift ... the results of this current trial suggests that the 3-week treatment was not life-changing,” since effects had largely worn off by 6 months in both groups.

Longer-term treatment with ketamine “increases the likelihood of both drug dependence and cognitive adverse effects, including dissociation, paranoia, and other psychotic symptoms,” Dr. Freedman said.

He recommends that informed consent documents be used to caution patients and clinicians considering ketamine “that temporary relief may come with longer-term costs.”

The study was supported by a grant from PCORI to Dr. Anand. Dr. Freedman has disclosed no relevant financial relationships. In the past 2 years, Dr. Iosifescu has been a consultant for Axsome, Allergan, Biogen, Clexio, Jazz, Neumora, Relmada, and Sage. He has also received a research grant from Otsuka.

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

Electroconvulsive therapy (ECT) is the standard treatment for resistant depression, but results of a new randomized, head-to-head trial suggest intravenous ketamine is at least as effective and has fewer side effects.

“The take-home message right now is that if somebody is being referred for ECT, the treating clinician should think of offering ketamine first,” study investigator Amit Anand, MD, professor of psychiatry, Harvard Medical School, Boston, said in an interview.

The study was published online in the New England Journal of Medicine.
 

‘Preferred treatment’

More than one-third of cases of depression are treatment resistant, said Dr. Anand, who is also director of Psychiatry Translational Clinical Trials at Mass General Brigham. He noted that ECT has been the “gold standard for treating severe depression for over 80 years.”

Julia Hiebaum/Alamy

He added that although ECT is very effective and is fast acting, “it requires anesthesia, can be socially stigmatizing, and is associated with memory problems following the treatment.”

An anesthetic agent, ketamine has been shown to have rapid antidepressant effects and does not cause memory loss or carry the stigma associated with ECT, he added. For these reasons, the investigators examined whether it may be a viable alternative to ECT.

To date, no large, head-to-head trials have compared ECT to intravenous ketamine. A recent meta-analysis showed that ECT was superior to ketamine for major depression, but the total number of patients included in the analysis was small, Dr. Anand said.

In addition, most of the participants in that trial were drawn from a single center. Approximately 95 patients were enrolled in each arm of the trial, which included some participants with features of psychosis. “ECT is very effective for depression associated with psychotic features, which may be one reason ECT had a better response in that trial,” said Dr. Anand.

The investigators compared ECT to ketamine in a larger sample that excluded patients with psychosis. They randomly assigned 403 patients at five clinical sites in a 1:1 ratio to receive either ketamine or ECT (n = 200 and 203, respectively; 53% and 49.3% women, respectively; aged 45.6 ± 14.8 and 47.1 ± 14.1 years, respectively).

Patients were required to have had an unsatisfactory response to two or more adequate trials of antidepressant treatment.

Prior to initiation of the assigned treatment, 38 patients withdrew, leaving 195 in the ketamine group and 170 in the ECT group.

Treatment was administered over a 3-week period, during which patients received either ECT three times per week or ketamine (0.5 mg/kg of body weight) twice per week.

The primary outcome was treatment response, defined as a decrease of 50% or more from baseline in the16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16). Secondary outcomes included scores on memory tests and patient-reported quality of life.

Patients who had a response were followed for 6 months after the initial treatment phase.
 

More research needed

Following the 3-week treatment period, a total of 55.4% patients who received ketamine and 41.2% of patients who underwent ECT responded to treatment, which translates into a difference of 14.2 percentage points (95% confidence interval, 3.9-24.2; P < .001) – a finding that fell within the noninferiority threshold set by the investigators.

ECT was associated with decreased memory recall after the 3 weeks of treatment, with a mean (standard deviation) decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test–Revised of –0.9 (1.1) in the ketamine group vs. –9.7 (1.2) in the ECT group (difference, –1.8 points [–2.8 to –0.8]).

Remission, determined on the basis of QIDS-SR-16 score, occurred in 32% of the ketamine group and in 20% in the ECT group. Similar findings were seen on the Montgomery-Åsberg Depression Rating Scale.

Both groups showed significant improvements in quality of life, with changes of 12.3 and 12.9 points, respectively, on the 16-item Quality of Life Scale.

“ECT was associated with musculoskeletal adverse events, whereas ketamine was associated with dissociation,” the investigators note.

During the 6-month follow-up period, there were differences in relapse rates between the groups (defined as QIDS-SRS-16 score > 11). At 1 month, the rates were 19.0% for those receiving ketamine and 35.4% for those receiving ECT. At 3 months, the rates were 25.0% and 50.9%, respectively; at 6 months, the rates were 34.5% and 56.3%, respectively.

ECT has been shown to be effective for older adults, patients with MDD and psychosis, and in inpatient and research settings. Future studies are needed to determine the comparative effectiveness of ketamine in these populations, the authors note.
 

Not life-changing

In a comment, Dan Iosifescu, MD, professor of psychiatry, NYU Langone Health, New York, called it an “extraordinarily important and clinically relevant study, large, well-designed, and well-conducted.”

Dr. Iosifescu, director of the clinical research division, Nathan Kline Institute, Orangeburg, N.Y., who was not involved with the study, noted that the study wasn’t powered to determine whether one treatment was superior to the other, but rather it assessed noninferiority.

“The main point of this study is that the two treatments are largely equivalent, although numerically, ketamine was slightly associated with more beneficial outcomes and fewer cognitive side effects,” he said.

The findings suggest “that people who have no contraindications and are candidates for both ketamine and ECT – which is the vast majority of people with treatment-resistant depression – should consider getting ketamine first because it is somewhat easier in terms of side effects and logistics and consider ECT afterwards if the ketamine doesn’t work.”

In an accompanying editorial, Robert Freedman, MD, clinical professor, University of Colorado at Denver, Aurora, noted that although “3 weeks of lightened mood is undoubtedly a gift ... the results of this current trial suggests that the 3-week treatment was not life-changing,” since effects had largely worn off by 6 months in both groups.

Longer-term treatment with ketamine “increases the likelihood of both drug dependence and cognitive adverse effects, including dissociation, paranoia, and other psychotic symptoms,” Dr. Freedman said.

He recommends that informed consent documents be used to caution patients and clinicians considering ketamine “that temporary relief may come with longer-term costs.”

The study was supported by a grant from PCORI to Dr. Anand. Dr. Freedman has disclosed no relevant financial relationships. In the past 2 years, Dr. Iosifescu has been a consultant for Axsome, Allergan, Biogen, Clexio, Jazz, Neumora, Relmada, and Sage. He has also received a research grant from Otsuka.

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

Electroconvulsive therapy (ECT) is the standard treatment for resistant depression, but results of a new randomized, head-to-head trial suggest intravenous ketamine is at least as effective and has fewer side effects.

“The take-home message right now is that if somebody is being referred for ECT, the treating clinician should think of offering ketamine first,” study investigator Amit Anand, MD, professor of psychiatry, Harvard Medical School, Boston, said in an interview.

The study was published online in the New England Journal of Medicine.
 

‘Preferred treatment’

More than one-third of cases of depression are treatment resistant, said Dr. Anand, who is also director of Psychiatry Translational Clinical Trials at Mass General Brigham. He noted that ECT has been the “gold standard for treating severe depression for over 80 years.”

Julia Hiebaum/Alamy

He added that although ECT is very effective and is fast acting, “it requires anesthesia, can be socially stigmatizing, and is associated with memory problems following the treatment.”

An anesthetic agent, ketamine has been shown to have rapid antidepressant effects and does not cause memory loss or carry the stigma associated with ECT, he added. For these reasons, the investigators examined whether it may be a viable alternative to ECT.

To date, no large, head-to-head trials have compared ECT to intravenous ketamine. A recent meta-analysis showed that ECT was superior to ketamine for major depression, but the total number of patients included in the analysis was small, Dr. Anand said.

In addition, most of the participants in that trial were drawn from a single center. Approximately 95 patients were enrolled in each arm of the trial, which included some participants with features of psychosis. “ECT is very effective for depression associated with psychotic features, which may be one reason ECT had a better response in that trial,” said Dr. Anand.

The investigators compared ECT to ketamine in a larger sample that excluded patients with psychosis. They randomly assigned 403 patients at five clinical sites in a 1:1 ratio to receive either ketamine or ECT (n = 200 and 203, respectively; 53% and 49.3% women, respectively; aged 45.6 ± 14.8 and 47.1 ± 14.1 years, respectively).

Patients were required to have had an unsatisfactory response to two or more adequate trials of antidepressant treatment.

Prior to initiation of the assigned treatment, 38 patients withdrew, leaving 195 in the ketamine group and 170 in the ECT group.

Treatment was administered over a 3-week period, during which patients received either ECT three times per week or ketamine (0.5 mg/kg of body weight) twice per week.

The primary outcome was treatment response, defined as a decrease of 50% or more from baseline in the16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16). Secondary outcomes included scores on memory tests and patient-reported quality of life.

Patients who had a response were followed for 6 months after the initial treatment phase.
 

More research needed

Following the 3-week treatment period, a total of 55.4% patients who received ketamine and 41.2% of patients who underwent ECT responded to treatment, which translates into a difference of 14.2 percentage points (95% confidence interval, 3.9-24.2; P < .001) – a finding that fell within the noninferiority threshold set by the investigators.

ECT was associated with decreased memory recall after the 3 weeks of treatment, with a mean (standard deviation) decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test–Revised of –0.9 (1.1) in the ketamine group vs. –9.7 (1.2) in the ECT group (difference, –1.8 points [–2.8 to –0.8]).

Remission, determined on the basis of QIDS-SR-16 score, occurred in 32% of the ketamine group and in 20% in the ECT group. Similar findings were seen on the Montgomery-Åsberg Depression Rating Scale.

Both groups showed significant improvements in quality of life, with changes of 12.3 and 12.9 points, respectively, on the 16-item Quality of Life Scale.

“ECT was associated with musculoskeletal adverse events, whereas ketamine was associated with dissociation,” the investigators note.

During the 6-month follow-up period, there were differences in relapse rates between the groups (defined as QIDS-SRS-16 score > 11). At 1 month, the rates were 19.0% for those receiving ketamine and 35.4% for those receiving ECT. At 3 months, the rates were 25.0% and 50.9%, respectively; at 6 months, the rates were 34.5% and 56.3%, respectively.

ECT has been shown to be effective for older adults, patients with MDD and psychosis, and in inpatient and research settings. Future studies are needed to determine the comparative effectiveness of ketamine in these populations, the authors note.
 

Not life-changing

In a comment, Dan Iosifescu, MD, professor of psychiatry, NYU Langone Health, New York, called it an “extraordinarily important and clinically relevant study, large, well-designed, and well-conducted.”

Dr. Iosifescu, director of the clinical research division, Nathan Kline Institute, Orangeburg, N.Y., who was not involved with the study, noted that the study wasn’t powered to determine whether one treatment was superior to the other, but rather it assessed noninferiority.

“The main point of this study is that the two treatments are largely equivalent, although numerically, ketamine was slightly associated with more beneficial outcomes and fewer cognitive side effects,” he said.

The findings suggest “that people who have no contraindications and are candidates for both ketamine and ECT – which is the vast majority of people with treatment-resistant depression – should consider getting ketamine first because it is somewhat easier in terms of side effects and logistics and consider ECT afterwards if the ketamine doesn’t work.”

In an accompanying editorial, Robert Freedman, MD, clinical professor, University of Colorado at Denver, Aurora, noted that although “3 weeks of lightened mood is undoubtedly a gift ... the results of this current trial suggests that the 3-week treatment was not life-changing,” since effects had largely worn off by 6 months in both groups.

Longer-term treatment with ketamine “increases the likelihood of both drug dependence and cognitive adverse effects, including dissociation, paranoia, and other psychotic symptoms,” Dr. Freedman said.

He recommends that informed consent documents be used to caution patients and clinicians considering ketamine “that temporary relief may come with longer-term costs.”

The study was supported by a grant from PCORI to Dr. Anand. Dr. Freedman has disclosed no relevant financial relationships. In the past 2 years, Dr. Iosifescu has been a consultant for Axsome, Allergan, Biogen, Clexio, Jazz, Neumora, Relmada, and Sage. He has also received a research grant from Otsuka.

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

SAN FRANCISCO – University of California, San Diego, psychiatrist Stephen M. Stahl, MD, PhD, has heard the scary stories about monoamine oxidase inhibitors (MAOIs): Patients supposedly need to be on restrictive diets free of culinary joys like cheese, beer, and wine; they can’t take cold medicines; and they can just forget about anesthesia for dental work or surgery.

Waketonay via Creative Commons (https://creativecommons.org/licenses/by-sa/4.0/legalcode)

Wrong, wrong, and wrong, Dr. Stahl told an audience at the annual meeting of the American Psychiatric Association. While the venerable antidepressants can transform the lives of patients with treatment-resistant depression, he said, MAOIs are plagued by myths that exaggerate their risks.

“These are good options,” he said. “Everybody who prescribes these today, without exception, has seen patients respond after nothing else has – including ECT (electroconvulsive therapy).”

Still, MAOIs, which were first developed in the 1950s, remain little-used in the United States. While an average of six selective serotonin reuptake inhibitors (SSRIs) are prescribed every second in the United States each day, Dr. Stahl said, “there are only a few hundred MAOI prescribers for a few thousand patients.”

The main barrier to the use of the drugs is unfamiliarity, he said. Despite their low profile, they’re appropriate to use after failures of monotherapy with SSRIs/serotonin and norepinephrine reuptake inhibitors (SNRIs) and augmentation with atypical antipsychotics. And they can be used in conjunction with ketamine/esketamine and ECT, which are other options for treatment-resistant depression, he said.

As for the myths about MAOIs, Dr. Stahl said the drugs can indeed interact with tyramine, which is found in foods like cheese, beer, and wine. The interaction can lead to potentially fatal hypertensive crises, Dr. Stahl said, noting that patients should avoid aged cheeses, tap and unpasteurized beer, soy products, and certain other foods. (Patients taking 6 mg transdermal or low-dose oral selegiline can ignore these restrictions.)

But canned beer, certain wines, yogurt, fresh American cheese, mozzarella/pizza chain cheese, cream cheese, and fresh or processed meat/poultry/fish are fine, he said. “Selectively, you can have a pretty high tyramine diet,” he added, although it’s a good idea for patients to have a blood pressure monitor at home.

As for cold medicines, sympathomimetic decongestants and stimulants should be used cautiously with blood pressure monitoring or not at all, he said, but those with codeine or expectorants are OK. Dextromethorphan, a weak serotonin reuptake inhibitor in some cough medicine, should be avoided. However, antihistamines other than chlorpheniramine/brompheniramine are OK to use, he added, and they may be the ideal choice for cold relief.

As for anesthesia, he cautioned that local anesthetics with epinephrine and general anesthesia can disrupt blood pressure. Choose a local anesthetic that does not contain vasoconstrictors, he said, and if surgery with general anesthesia is needed, “you can wash [the MAOI] out if you want” ahead of time.

Benzodiazepines, mivacurium, rapacuronium, morphine, or codeine can be used cautiously, he said, in urgent or elective surgery in a patient on an MAOI.

As for other myths, he said tricyclic antidepressants and related drugs aren’t as troublesome as psychiatrists may assume. Clomipramine and imipramine should be avoided. But other tricyclic antidepressants can be used with caution.

As for painkillers, he said it’s not true that they must be avoided, although MAIOs shouldn’t be taken with meperidine, fentanyl, methadone, tramadol, or tapentadol. Other painkillers, including over-the-counter products like aspirin, NSAIDs, and acetaminophen, should be used with caution, he said. And expert guidance is advised for use of hydromorphone, morphine, oxycodone, or oxymorphone.

In the big picture, he noted, myths are so prevalent “that you have more calls from patients – and other doctors, dentists, and anesthesiologists – about MAO inhibitors then you will ever have about any other drug there.”

Columbia University, New York, psychiatrist Jonathan W. Stewart, MD, also spoke at the presentation on MAIOs at the APA conference. He recommended that colleagues consider the drugs if two or more antidepressants that work in different ways fail to provide relief after 4 weeks at a sufficient dose. Start low with one pill a day, he recommended, and seek full remission – no depressed mood – instead of simply “better.”

Ultimately, he said, “we do patients a disservice” if MAOIs aren’t considered in the appropriate patients.

Dr. Stahl discloses grant/research support (Acadia, Allergan/AbbVie, Avanir, Boehringer Ingelheim Braeburn, Daiichi Sankyo-Brazil Eisai, Eli Lilly, Harmony, Indivior, Intra-Cellular Therapies, Ironshore, Neurocrine, Otsuka, Pear Therapeutics, Sage, Shire Sunovion, Supernus, and Torrent), consultant/advisor support (Acadia, Alkermes, Allergan, AbbVie, Axsome, Clearview, Done, Eisai Pharmaceuticals, Gedeon Richter, Intra-Cellular Therapies, Karuna, Levo, Lundbeck, Neurocrine, Neurawell, Otsuka, Relmada, Sage, Sunovion, Supernus, Taliaz, Teva, Tris Pharma, and VistaGen), speakers bureau payments (Acadia, Lundbeck, Neurocrine, Otsuka, Servier, Sunovion, and Teva), and options in Genomind, Lipidio, Neurawell and Delix. Dr. Stewart discloses unspecified relationships with Eli Lilly, Pfizer, Merck, Boeringer- Ingleheim, Bristol-Myers, Sinolfi-Aventis, Amilyn, Novartis, Organon, GlaxoSmithKlein, Shire, and Somerset.

SAN FRANCISCO – University of California, San Diego, psychiatrist Stephen M. Stahl, MD, PhD, has heard the scary stories about monoamine oxidase inhibitors (MAOIs): Patients supposedly need to be on restrictive diets free of culinary joys like cheese, beer, and wine; they can’t take cold medicines; and they can just forget about anesthesia for dental work or surgery.

Waketonay via Creative Commons (https://creativecommons.org/licenses/by-sa/4.0/legalcode)

Wrong, wrong, and wrong, Dr. Stahl told an audience at the annual meeting of the American Psychiatric Association. While the venerable antidepressants can transform the lives of patients with treatment-resistant depression, he said, MAOIs are plagued by myths that exaggerate their risks.

“These are good options,” he said. “Everybody who prescribes these today, without exception, has seen patients respond after nothing else has – including ECT (electroconvulsive therapy).”

Still, MAOIs, which were first developed in the 1950s, remain little-used in the United States. While an average of six selective serotonin reuptake inhibitors (SSRIs) are prescribed every second in the United States each day, Dr. Stahl said, “there are only a few hundred MAOI prescribers for a few thousand patients.”

The main barrier to the use of the drugs is unfamiliarity, he said. Despite their low profile, they’re appropriate to use after failures of monotherapy with SSRIs/serotonin and norepinephrine reuptake inhibitors (SNRIs) and augmentation with atypical antipsychotics. And they can be used in conjunction with ketamine/esketamine and ECT, which are other options for treatment-resistant depression, he said.

As for the myths about MAOIs, Dr. Stahl said the drugs can indeed interact with tyramine, which is found in foods like cheese, beer, and wine. The interaction can lead to potentially fatal hypertensive crises, Dr. Stahl said, noting that patients should avoid aged cheeses, tap and unpasteurized beer, soy products, and certain other foods. (Patients taking 6 mg transdermal or low-dose oral selegiline can ignore these restrictions.)

But canned beer, certain wines, yogurt, fresh American cheese, mozzarella/pizza chain cheese, cream cheese, and fresh or processed meat/poultry/fish are fine, he said. “Selectively, you can have a pretty high tyramine diet,” he added, although it’s a good idea for patients to have a blood pressure monitor at home.

As for cold medicines, sympathomimetic decongestants and stimulants should be used cautiously with blood pressure monitoring or not at all, he said, but those with codeine or expectorants are OK. Dextromethorphan, a weak serotonin reuptake inhibitor in some cough medicine, should be avoided. However, antihistamines other than chlorpheniramine/brompheniramine are OK to use, he added, and they may be the ideal choice for cold relief.

As for anesthesia, he cautioned that local anesthetics with epinephrine and general anesthesia can disrupt blood pressure. Choose a local anesthetic that does not contain vasoconstrictors, he said, and if surgery with general anesthesia is needed, “you can wash [the MAOI] out if you want” ahead of time.

Benzodiazepines, mivacurium, rapacuronium, morphine, or codeine can be used cautiously, he said, in urgent or elective surgery in a patient on an MAOI.

As for other myths, he said tricyclic antidepressants and related drugs aren’t as troublesome as psychiatrists may assume. Clomipramine and imipramine should be avoided. But other tricyclic antidepressants can be used with caution.

As for painkillers, he said it’s not true that they must be avoided, although MAIOs shouldn’t be taken with meperidine, fentanyl, methadone, tramadol, or tapentadol. Other painkillers, including over-the-counter products like aspirin, NSAIDs, and acetaminophen, should be used with caution, he said. And expert guidance is advised for use of hydromorphone, morphine, oxycodone, or oxymorphone.

In the big picture, he noted, myths are so prevalent “that you have more calls from patients – and other doctors, dentists, and anesthesiologists – about MAO inhibitors then you will ever have about any other drug there.”

Columbia University, New York, psychiatrist Jonathan W. Stewart, MD, also spoke at the presentation on MAIOs at the APA conference. He recommended that colleagues consider the drugs if two or more antidepressants that work in different ways fail to provide relief after 4 weeks at a sufficient dose. Start low with one pill a day, he recommended, and seek full remission – no depressed mood – instead of simply “better.”

Ultimately, he said, “we do patients a disservice” if MAOIs aren’t considered in the appropriate patients.

Dr. Stahl discloses grant/research support (Acadia, Allergan/AbbVie, Avanir, Boehringer Ingelheim Braeburn, Daiichi Sankyo-Brazil Eisai, Eli Lilly, Harmony, Indivior, Intra-Cellular Therapies, Ironshore, Neurocrine, Otsuka, Pear Therapeutics, Sage, Shire Sunovion, Supernus, and Torrent), consultant/advisor support (Acadia, Alkermes, Allergan, AbbVie, Axsome, Clearview, Done, Eisai Pharmaceuticals, Gedeon Richter, Intra-Cellular Therapies, Karuna, Levo, Lundbeck, Neurocrine, Neurawell, Otsuka, Relmada, Sage, Sunovion, Supernus, Taliaz, Teva, Tris Pharma, and VistaGen), speakers bureau payments (Acadia, Lundbeck, Neurocrine, Otsuka, Servier, Sunovion, and Teva), and options in Genomind, Lipidio, Neurawell and Delix. Dr. Stewart discloses unspecified relationships with Eli Lilly, Pfizer, Merck, Boeringer- Ingleheim, Bristol-Myers, Sinolfi-Aventis, Amilyn, Novartis, Organon, GlaxoSmithKlein, Shire, and Somerset.

SAN FRANCISCO – University of California, San Diego, psychiatrist Stephen M. Stahl, MD, PhD, has heard the scary stories about monoamine oxidase inhibitors (MAOIs): Patients supposedly need to be on restrictive diets free of culinary joys like cheese, beer, and wine; they can’t take cold medicines; and they can just forget about anesthesia for dental work or surgery.

Waketonay via Creative Commons (https://creativecommons.org/licenses/by-sa/4.0/legalcode)

Wrong, wrong, and wrong, Dr. Stahl told an audience at the annual meeting of the American Psychiatric Association. While the venerable antidepressants can transform the lives of patients with treatment-resistant depression, he said, MAOIs are plagued by myths that exaggerate their risks.

“These are good options,” he said. “Everybody who prescribes these today, without exception, has seen patients respond after nothing else has – including ECT (electroconvulsive therapy).”

Still, MAOIs, which were first developed in the 1950s, remain little-used in the United States. While an average of six selective serotonin reuptake inhibitors (SSRIs) are prescribed every second in the United States each day, Dr. Stahl said, “there are only a few hundred MAOI prescribers for a few thousand patients.”

The main barrier to the use of the drugs is unfamiliarity, he said. Despite their low profile, they’re appropriate to use after failures of monotherapy with SSRIs/serotonin and norepinephrine reuptake inhibitors (SNRIs) and augmentation with atypical antipsychotics. And they can be used in conjunction with ketamine/esketamine and ECT, which are other options for treatment-resistant depression, he said.

As for the myths about MAOIs, Dr. Stahl said the drugs can indeed interact with tyramine, which is found in foods like cheese, beer, and wine. The interaction can lead to potentially fatal hypertensive crises, Dr. Stahl said, noting that patients should avoid aged cheeses, tap and unpasteurized beer, soy products, and certain other foods. (Patients taking 6 mg transdermal or low-dose oral selegiline can ignore these restrictions.)

But canned beer, certain wines, yogurt, fresh American cheese, mozzarella/pizza chain cheese, cream cheese, and fresh or processed meat/poultry/fish are fine, he said. “Selectively, you can have a pretty high tyramine diet,” he added, although it’s a good idea for patients to have a blood pressure monitor at home.

As for cold medicines, sympathomimetic decongestants and stimulants should be used cautiously with blood pressure monitoring or not at all, he said, but those with codeine or expectorants are OK. Dextromethorphan, a weak serotonin reuptake inhibitor in some cough medicine, should be avoided. However, antihistamines other than chlorpheniramine/brompheniramine are OK to use, he added, and they may be the ideal choice for cold relief.

As for anesthesia, he cautioned that local anesthetics with epinephrine and general anesthesia can disrupt blood pressure. Choose a local anesthetic that does not contain vasoconstrictors, he said, and if surgery with general anesthesia is needed, “you can wash [the MAOI] out if you want” ahead of time.

Benzodiazepines, mivacurium, rapacuronium, morphine, or codeine can be used cautiously, he said, in urgent or elective surgery in a patient on an MAOI.

As for other myths, he said tricyclic antidepressants and related drugs aren’t as troublesome as psychiatrists may assume. Clomipramine and imipramine should be avoided. But other tricyclic antidepressants can be used with caution.

As for painkillers, he said it’s not true that they must be avoided, although MAIOs shouldn’t be taken with meperidine, fentanyl, methadone, tramadol, or tapentadol. Other painkillers, including over-the-counter products like aspirin, NSAIDs, and acetaminophen, should be used with caution, he said. And expert guidance is advised for use of hydromorphone, morphine, oxycodone, or oxymorphone.

In the big picture, he noted, myths are so prevalent “that you have more calls from patients – and other doctors, dentists, and anesthesiologists – about MAO inhibitors then you will ever have about any other drug there.”

Columbia University, New York, psychiatrist Jonathan W. Stewart, MD, also spoke at the presentation on MAIOs at the APA conference. He recommended that colleagues consider the drugs if two or more antidepressants that work in different ways fail to provide relief after 4 weeks at a sufficient dose. Start low with one pill a day, he recommended, and seek full remission – no depressed mood – instead of simply “better.”

Ultimately, he said, “we do patients a disservice” if MAOIs aren’t considered in the appropriate patients.

Dr. Stahl discloses grant/research support (Acadia, Allergan/AbbVie, Avanir, Boehringer Ingelheim Braeburn, Daiichi Sankyo-Brazil Eisai, Eli Lilly, Harmony, Indivior, Intra-Cellular Therapies, Ironshore, Neurocrine, Otsuka, Pear Therapeutics, Sage, Shire Sunovion, Supernus, and Torrent), consultant/advisor support (Acadia, Alkermes, Allergan, AbbVie, Axsome, Clearview, Done, Eisai Pharmaceuticals, Gedeon Richter, Intra-Cellular Therapies, Karuna, Levo, Lundbeck, Neurocrine, Neurawell, Otsuka, Relmada, Sage, Sunovion, Supernus, Taliaz, Teva, Tris Pharma, and VistaGen), speakers bureau payments (Acadia, Lundbeck, Neurocrine, Otsuka, Servier, Sunovion, and Teva), and options in Genomind, Lipidio, Neurawell and Delix. Dr. Stewart discloses unspecified relationships with Eli Lilly, Pfizer, Merck, Boeringer- Ingleheim, Bristol-Myers, Sinolfi-Aventis, Amilyn, Novartis, Organon, GlaxoSmithKlein, Shire, and Somerset.