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Peak seasons, times for suicidal thoughts, attempts identified
In addition, the results from Harvard University’s Project Implicit Health also show that people are most likely to make an attempt at suicide between 4 and 6 a.m.
“No research has demonstrated a peak in suicidal ideation in winter until our paper,” study investigator Brian O’Shea, PhD, assistant professor of social psychology at the University of Nottingham, England, told this news organization.
“Most people incorrectly assume that suicide behaviours peak in winter and are surprised, as I was, when learning about this phenomenon, that suicide actually peaks in spring/early summer,” he added.
However, at least one expert cautioned that the database, which comprises mostly responses from younger women, doesn’t capture responses from those who are most likely to attempt suicide: older men with substance abuse.
The findings were published online in Translational Psychiatry.
New insight into suicide risk
Previous studies examining the seasonality of suicides and suicide attempts have reported a peak in spring and early summer, but there has been very little information about why this may be, the investigators noted.
Dr. O’Shea and his colleague from the University of Amsterdam, René Freichel, mined one of the databases from Project Implicit Health, which contains self-report measures on suicidal ideation, self-harm, and past suicide attempts, as well as respondents’ implicit biases on these topics.
The analysis included data from 10,000 respondents living in the United States, United Kingdom, and Canada provided between April 2012 and November 2018.
The sample was predominantly young and female, with 38% (3,247) of the sample reporting that they had made at least one suicide attempt.
The researchers found a peak in negative mood and desire to die occurring in December, especially among those who reported attempting suicide (P ≤ .001)
Suicidal ideation peaked approximately 3-4 months before the annual seasonal crest of suicide attempts in early spring and summer.
“Affected individuals may become severely depressed and experience a lack of energy throughout the winter months. Essentially, this period may put them below a threshold of severe suicide risk as the high level of suicidal ideation coincides with a low level of energy,” said Dr. O’Shea.
When the days get longer, brighter, and warmer, these changes likely improve an individuals’ mood, he explained. “Hence, the most at-risk individuals become slightly less depressed and may gain more energy to contemplate and plan their method to attempt suicide,” Dr. O’Shea noted.
A major limitation of the study is that all responses included in analysis were based on self-report.
To confirm the findings, future research should include ecological momentary assessment, which involves using a large community sample to question participants about suicidal intent at various time points, along with real-time monitoring of vital signs, said Dr. O’Shea.
Ideally, the investigators noted, the study’s findings will inform clinician assessments of patients who are at risk for suicide.
A research gap?
Commenting on the findings, Justin Shuster, MD, MPH, assistant professor of psychiatry at the University of Pittsburgh and medical director of two psychiatric units at Western Psychiatric Hospital, noted that the database used in the study did not include responses from those who were most likely to attempt or commit suicide: older men with a history of substance abuse, who require social supports, and who have a family history of suicide.
Though Dr. Shuster agreed with Dr. O’Shea about the possibility that spring brought energy to a desire to take one’s life, he had another theory.
“When people are depressed in the winter, they expect to feel better with the advent of the warmer weather in spring. When they don’t feel better, they may think to themselves, ‘If I’m going to feel like this forever, I may as well follow through with these plans,’ ” he said.
As for the early morning attempts, he noted that 4-6 a.m. is often when people are alone, and there are fewer distractions.
“The other thing I see a great deal of clinically is intoxication,” said Dr. Shuster. “Either intoxication with substances or alcohol, or the fact that intoxication is waning at those early morning hours, and people are becoming desperate as they face a new day,” he said.
The study was funded by a German Academic Exchange Service Scholarship and an EU Horizon 2020 Fellowship. Dr. O’Shea reports being an unpaid member of Project Implicit’s scientific advisory board and is on the executive committee of Project Implicit Health.
A version of this article first appeared on Medscape.com.
In addition, the results from Harvard University’s Project Implicit Health also show that people are most likely to make an attempt at suicide between 4 and 6 a.m.
“No research has demonstrated a peak in suicidal ideation in winter until our paper,” study investigator Brian O’Shea, PhD, assistant professor of social psychology at the University of Nottingham, England, told this news organization.
“Most people incorrectly assume that suicide behaviours peak in winter and are surprised, as I was, when learning about this phenomenon, that suicide actually peaks in spring/early summer,” he added.
However, at least one expert cautioned that the database, which comprises mostly responses from younger women, doesn’t capture responses from those who are most likely to attempt suicide: older men with substance abuse.
The findings were published online in Translational Psychiatry.
New insight into suicide risk
Previous studies examining the seasonality of suicides and suicide attempts have reported a peak in spring and early summer, but there has been very little information about why this may be, the investigators noted.
Dr. O’Shea and his colleague from the University of Amsterdam, René Freichel, mined one of the databases from Project Implicit Health, which contains self-report measures on suicidal ideation, self-harm, and past suicide attempts, as well as respondents’ implicit biases on these topics.
The analysis included data from 10,000 respondents living in the United States, United Kingdom, and Canada provided between April 2012 and November 2018.
The sample was predominantly young and female, with 38% (3,247) of the sample reporting that they had made at least one suicide attempt.
The researchers found a peak in negative mood and desire to die occurring in December, especially among those who reported attempting suicide (P ≤ .001)
Suicidal ideation peaked approximately 3-4 months before the annual seasonal crest of suicide attempts in early spring and summer.
“Affected individuals may become severely depressed and experience a lack of energy throughout the winter months. Essentially, this period may put them below a threshold of severe suicide risk as the high level of suicidal ideation coincides with a low level of energy,” said Dr. O’Shea.
When the days get longer, brighter, and warmer, these changes likely improve an individuals’ mood, he explained. “Hence, the most at-risk individuals become slightly less depressed and may gain more energy to contemplate and plan their method to attempt suicide,” Dr. O’Shea noted.
A major limitation of the study is that all responses included in analysis were based on self-report.
To confirm the findings, future research should include ecological momentary assessment, which involves using a large community sample to question participants about suicidal intent at various time points, along with real-time monitoring of vital signs, said Dr. O’Shea.
Ideally, the investigators noted, the study’s findings will inform clinician assessments of patients who are at risk for suicide.
A research gap?
Commenting on the findings, Justin Shuster, MD, MPH, assistant professor of psychiatry at the University of Pittsburgh and medical director of two psychiatric units at Western Psychiatric Hospital, noted that the database used in the study did not include responses from those who were most likely to attempt or commit suicide: older men with a history of substance abuse, who require social supports, and who have a family history of suicide.
Though Dr. Shuster agreed with Dr. O’Shea about the possibility that spring brought energy to a desire to take one’s life, he had another theory.
“When people are depressed in the winter, they expect to feel better with the advent of the warmer weather in spring. When they don’t feel better, they may think to themselves, ‘If I’m going to feel like this forever, I may as well follow through with these plans,’ ” he said.
As for the early morning attempts, he noted that 4-6 a.m. is often when people are alone, and there are fewer distractions.
“The other thing I see a great deal of clinically is intoxication,” said Dr. Shuster. “Either intoxication with substances or alcohol, or the fact that intoxication is waning at those early morning hours, and people are becoming desperate as they face a new day,” he said.
The study was funded by a German Academic Exchange Service Scholarship and an EU Horizon 2020 Fellowship. Dr. O’Shea reports being an unpaid member of Project Implicit’s scientific advisory board and is on the executive committee of Project Implicit Health.
A version of this article first appeared on Medscape.com.
In addition, the results from Harvard University’s Project Implicit Health also show that people are most likely to make an attempt at suicide between 4 and 6 a.m.
“No research has demonstrated a peak in suicidal ideation in winter until our paper,” study investigator Brian O’Shea, PhD, assistant professor of social psychology at the University of Nottingham, England, told this news organization.
“Most people incorrectly assume that suicide behaviours peak in winter and are surprised, as I was, when learning about this phenomenon, that suicide actually peaks in spring/early summer,” he added.
However, at least one expert cautioned that the database, which comprises mostly responses from younger women, doesn’t capture responses from those who are most likely to attempt suicide: older men with substance abuse.
The findings were published online in Translational Psychiatry.
New insight into suicide risk
Previous studies examining the seasonality of suicides and suicide attempts have reported a peak in spring and early summer, but there has been very little information about why this may be, the investigators noted.
Dr. O’Shea and his colleague from the University of Amsterdam, René Freichel, mined one of the databases from Project Implicit Health, which contains self-report measures on suicidal ideation, self-harm, and past suicide attempts, as well as respondents’ implicit biases on these topics.
The analysis included data from 10,000 respondents living in the United States, United Kingdom, and Canada provided between April 2012 and November 2018.
The sample was predominantly young and female, with 38% (3,247) of the sample reporting that they had made at least one suicide attempt.
The researchers found a peak in negative mood and desire to die occurring in December, especially among those who reported attempting suicide (P ≤ .001)
Suicidal ideation peaked approximately 3-4 months before the annual seasonal crest of suicide attempts in early spring and summer.
“Affected individuals may become severely depressed and experience a lack of energy throughout the winter months. Essentially, this period may put them below a threshold of severe suicide risk as the high level of suicidal ideation coincides with a low level of energy,” said Dr. O’Shea.
When the days get longer, brighter, and warmer, these changes likely improve an individuals’ mood, he explained. “Hence, the most at-risk individuals become slightly less depressed and may gain more energy to contemplate and plan their method to attempt suicide,” Dr. O’Shea noted.
A major limitation of the study is that all responses included in analysis were based on self-report.
To confirm the findings, future research should include ecological momentary assessment, which involves using a large community sample to question participants about suicidal intent at various time points, along with real-time monitoring of vital signs, said Dr. O’Shea.
Ideally, the investigators noted, the study’s findings will inform clinician assessments of patients who are at risk for suicide.
A research gap?
Commenting on the findings, Justin Shuster, MD, MPH, assistant professor of psychiatry at the University of Pittsburgh and medical director of two psychiatric units at Western Psychiatric Hospital, noted that the database used in the study did not include responses from those who were most likely to attempt or commit suicide: older men with a history of substance abuse, who require social supports, and who have a family history of suicide.
Though Dr. Shuster agreed with Dr. O’Shea about the possibility that spring brought energy to a desire to take one’s life, he had another theory.
“When people are depressed in the winter, they expect to feel better with the advent of the warmer weather in spring. When they don’t feel better, they may think to themselves, ‘If I’m going to feel like this forever, I may as well follow through with these plans,’ ” he said.
As for the early morning attempts, he noted that 4-6 a.m. is often when people are alone, and there are fewer distractions.
“The other thing I see a great deal of clinically is intoxication,” said Dr. Shuster. “Either intoxication with substances or alcohol, or the fact that intoxication is waning at those early morning hours, and people are becoming desperate as they face a new day,” he said.
The study was funded by a German Academic Exchange Service Scholarship and an EU Horizon 2020 Fellowship. Dr. O’Shea reports being an unpaid member of Project Implicit’s scientific advisory board and is on the executive committee of Project Implicit Health.
A version of this article first appeared on Medscape.com.
FROM TRANSLATIONAL PSYCHIATRY
Significant increase in vitamin D deficiency in kids with major depressive disorder
SAN FRANCISCO – , according to new findings that suggest spending more time indoors may have fueled this uptick.
“We suspect that this may be due to the COVID lockdowns and kids schooling from home and having less time outside,” study investigator Oluwatomiwa Babade, MD, MPH, with Virginia Tech Carilion School of Medicine, Roanoke, Va., said in an interview.
The study was presented at the annual meeting of the American Psychiatric Association.
Anecdotal observation confirmed
During the pandemic, investigators noticed an uptick in the number of children and adolescents attending their clinic for psychiatric hospitalization who had low vitamin D levels.
To investigate, they analyzed the records of all patients aged 6-17 years with psychiatric diagnoses and vitamin D level assessment who were admitted into the inpatient psychiatry unit from March 18, 2020, to June 30, 2021.
Among 599 unique patients, 275 (83% female) had a diagnosis of MDD and 226 of these patients were vitamin D deficient (< 30 ng/mL) – a prevalence rate of roughly 82%. Among 246 patients with psychiatric disorders other than MDD, the prevalence of vitamin D deficiency was 76%.
“This was very surprising and much higher than prior to the pandemic. Prior to COVID, the prevalence of vitamin D deficiency was around 14% in similar patients,” Dr. Babade said.
“Now that we are post-lockdown, it would be good to repeat the study. I think the prevalence should drop. That’s my guess,” he added.
Important research, no surprises
In a comment, Cemre Robinson, MD, director of the Mount Sinai Pediatric Bone Health and Calcium Metabolism Clinic, New York, said that although the study’s findings aren’t surprising, “it’s important to present such data in adolescents with major depression.”
“These findings reiterate the importance of screening for vitamin D deficiency in children and adolescents, with or without depression, particularly during winter, which is associated with less sun exposure,” Dr. Robinson, assistant professor of pediatrics, endocrinology, and diabetes at Icahn School of Medicine at Mount Sinai, said.
She noted that vitamin D deficiency is prevalent in the general population, and it can be easily corrected with supplementation.
“Vitamin D is important for bone growth, mineralization, and accretion as well as calcium absorption. Adolescence, in particular, is a period of rapid physical, cognitive, and psychosocial growth,” Dr. Robinson said.
“The requirement of all minerals and vitamins changes in this phase of life. Therefore, it is important to have sufficient vitamin D levels during adolescence for several health benefits,” she noted.
Dr. Robinson said that “more research is needed to validate the present findings in adolescents with major depression, and larger studies, including randomized control trials, are required to establish a causal association between MDD and vitamin D deficiency.”
The study had no specific funding. Dr. Babade and Dr. Robinson report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – , according to new findings that suggest spending more time indoors may have fueled this uptick.
“We suspect that this may be due to the COVID lockdowns and kids schooling from home and having less time outside,” study investigator Oluwatomiwa Babade, MD, MPH, with Virginia Tech Carilion School of Medicine, Roanoke, Va., said in an interview.
The study was presented at the annual meeting of the American Psychiatric Association.
Anecdotal observation confirmed
During the pandemic, investigators noticed an uptick in the number of children and adolescents attending their clinic for psychiatric hospitalization who had low vitamin D levels.
To investigate, they analyzed the records of all patients aged 6-17 years with psychiatric diagnoses and vitamin D level assessment who were admitted into the inpatient psychiatry unit from March 18, 2020, to June 30, 2021.
Among 599 unique patients, 275 (83% female) had a diagnosis of MDD and 226 of these patients were vitamin D deficient (< 30 ng/mL) – a prevalence rate of roughly 82%. Among 246 patients with psychiatric disorders other than MDD, the prevalence of vitamin D deficiency was 76%.
“This was very surprising and much higher than prior to the pandemic. Prior to COVID, the prevalence of vitamin D deficiency was around 14% in similar patients,” Dr. Babade said.
“Now that we are post-lockdown, it would be good to repeat the study. I think the prevalence should drop. That’s my guess,” he added.
Important research, no surprises
In a comment, Cemre Robinson, MD, director of the Mount Sinai Pediatric Bone Health and Calcium Metabolism Clinic, New York, said that although the study’s findings aren’t surprising, “it’s important to present such data in adolescents with major depression.”
“These findings reiterate the importance of screening for vitamin D deficiency in children and adolescents, with or without depression, particularly during winter, which is associated with less sun exposure,” Dr. Robinson, assistant professor of pediatrics, endocrinology, and diabetes at Icahn School of Medicine at Mount Sinai, said.
She noted that vitamin D deficiency is prevalent in the general population, and it can be easily corrected with supplementation.
“Vitamin D is important for bone growth, mineralization, and accretion as well as calcium absorption. Adolescence, in particular, is a period of rapid physical, cognitive, and psychosocial growth,” Dr. Robinson said.
“The requirement of all minerals and vitamins changes in this phase of life. Therefore, it is important to have sufficient vitamin D levels during adolescence for several health benefits,” she noted.
Dr. Robinson said that “more research is needed to validate the present findings in adolescents with major depression, and larger studies, including randomized control trials, are required to establish a causal association between MDD and vitamin D deficiency.”
The study had no specific funding. Dr. Babade and Dr. Robinson report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – , according to new findings that suggest spending more time indoors may have fueled this uptick.
“We suspect that this may be due to the COVID lockdowns and kids schooling from home and having less time outside,” study investigator Oluwatomiwa Babade, MD, MPH, with Virginia Tech Carilion School of Medicine, Roanoke, Va., said in an interview.
The study was presented at the annual meeting of the American Psychiatric Association.
Anecdotal observation confirmed
During the pandemic, investigators noticed an uptick in the number of children and adolescents attending their clinic for psychiatric hospitalization who had low vitamin D levels.
To investigate, they analyzed the records of all patients aged 6-17 years with psychiatric diagnoses and vitamin D level assessment who were admitted into the inpatient psychiatry unit from March 18, 2020, to June 30, 2021.
Among 599 unique patients, 275 (83% female) had a diagnosis of MDD and 226 of these patients were vitamin D deficient (< 30 ng/mL) – a prevalence rate of roughly 82%. Among 246 patients with psychiatric disorders other than MDD, the prevalence of vitamin D deficiency was 76%.
“This was very surprising and much higher than prior to the pandemic. Prior to COVID, the prevalence of vitamin D deficiency was around 14% in similar patients,” Dr. Babade said.
“Now that we are post-lockdown, it would be good to repeat the study. I think the prevalence should drop. That’s my guess,” he added.
Important research, no surprises
In a comment, Cemre Robinson, MD, director of the Mount Sinai Pediatric Bone Health and Calcium Metabolism Clinic, New York, said that although the study’s findings aren’t surprising, “it’s important to present such data in adolescents with major depression.”
“These findings reiterate the importance of screening for vitamin D deficiency in children and adolescents, with or without depression, particularly during winter, which is associated with less sun exposure,” Dr. Robinson, assistant professor of pediatrics, endocrinology, and diabetes at Icahn School of Medicine at Mount Sinai, said.
She noted that vitamin D deficiency is prevalent in the general population, and it can be easily corrected with supplementation.
“Vitamin D is important for bone growth, mineralization, and accretion as well as calcium absorption. Adolescence, in particular, is a period of rapid physical, cognitive, and psychosocial growth,” Dr. Robinson said.
“The requirement of all minerals and vitamins changes in this phase of life. Therefore, it is important to have sufficient vitamin D levels during adolescence for several health benefits,” she noted.
Dr. Robinson said that “more research is needed to validate the present findings in adolescents with major depression, and larger studies, including randomized control trials, are required to establish a causal association between MDD and vitamin D deficiency.”
The study had no specific funding. Dr. Babade and Dr. Robinson report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT APA 2023
Harmful emotional hit of antidepressants underappreciated
SAN FRANCISCO – , new research shows.
Emotional blunting can be described as feeling emotionally flat and incapable of finding pleasure. The patient may feel less sadness, guilt, or hopelessness, but that may come at the cost of feeling less joy, surprise, and happiness. Some people with SSRI-induced blunting even report caring less about important relationships.
It’s an issue that needs greater attention, study investigator Mujeeb U. Shad, MD, with Valley Health Services and University of Nevada, Las Vegas, said in an interview.
“Patients may come to the clinic and report feeling emotionally and cognitively flat and not be taken seriously by their provider, but they are genuinely reporting something that is happening to them and decreasing their quality of life,” Dr. Shad explained.
The study was presented at the annual meeting of the American Psychiatric Association.
Something ‘missing’
Dr. Shad said that the genesis for the study came from a resident who noticed that many patients receiving SSRIs reported feeling better and not as bothered by the depression, yet, at the same time, they felt something was “missing. Their families would say, ‘You’re better but you’re not the same person.’ ”
To investigate further, the researchers did a “scoping review” of 25 original studies that assessed antidepressant-related emotional blunting. Until now, there hasn’t been a systematic review of this issue, Dr. Shad said.
Ten of the studies looked at the role of SSRIs in emotional blunting, whereas the other 15 looked at serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and second-generation antipsychotic medications.
The results of the review show that emotional blunting is a significant patient-reported concern. It often presents as a subjective complaint of changed personality, feeling a lesser intensity of overall emotions, and the manifestation of not being oneself often attributed to antidepressant use, the researchers found. Emotional blunting was more commonly associated with SSRIs than with the other medications in the studies.
Common clinical strategies to manage antidepressant-induced emotional blunting reported in the literature include dose reduction or switching to a different antidepressant class; however, the literature did not make the distinction between emotional blunting as a primary symptom of depression or an adverse effect of antidepressants.
Dr. Shad said that there is a need to develop valid and reliable measures to assess emotional blunting related to antidepressants.
He noted that optimal patient care should include pre- and posttreatment assessment of emotional blunting. One useful tool is the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants.
Can’t get to the top
Jacob Cross, MD, who wasn’t involved in the study, said that he has seen the impact of antidepressant-related emotional blunting first-hand.
“I’ve had multiple patients report emotional blunting on antidepressant therapy,” Dr. Cross, with the department of psychiatry, Rush Medical College, Chicago, said.
“These patients feel like their emotions are not as high and not as low; so they experience directional improvement, but they’re still not feeling like they can get that top peak emotion. It’s kind of similar to anhedonia. They’re just feeling like a little cut off, like they’re climbing a cliff and just can’t get to that top,” Dr. Cross said.
For a patient with emotional blunting, Dr. Cross said he might “switch to an antidepressant that’s more stimulating like an SNRI from an SSRI. You could also lower the dose and see if that helps, but I usually change the drug class.”
The study had no specific funding. Dr. Shad and Dr. Cross have no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – , new research shows.
Emotional blunting can be described as feeling emotionally flat and incapable of finding pleasure. The patient may feel less sadness, guilt, or hopelessness, but that may come at the cost of feeling less joy, surprise, and happiness. Some people with SSRI-induced blunting even report caring less about important relationships.
It’s an issue that needs greater attention, study investigator Mujeeb U. Shad, MD, with Valley Health Services and University of Nevada, Las Vegas, said in an interview.
“Patients may come to the clinic and report feeling emotionally and cognitively flat and not be taken seriously by their provider, but they are genuinely reporting something that is happening to them and decreasing their quality of life,” Dr. Shad explained.
The study was presented at the annual meeting of the American Psychiatric Association.
Something ‘missing’
Dr. Shad said that the genesis for the study came from a resident who noticed that many patients receiving SSRIs reported feeling better and not as bothered by the depression, yet, at the same time, they felt something was “missing. Their families would say, ‘You’re better but you’re not the same person.’ ”
To investigate further, the researchers did a “scoping review” of 25 original studies that assessed antidepressant-related emotional blunting. Until now, there hasn’t been a systematic review of this issue, Dr. Shad said.
Ten of the studies looked at the role of SSRIs in emotional blunting, whereas the other 15 looked at serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and second-generation antipsychotic medications.
The results of the review show that emotional blunting is a significant patient-reported concern. It often presents as a subjective complaint of changed personality, feeling a lesser intensity of overall emotions, and the manifestation of not being oneself often attributed to antidepressant use, the researchers found. Emotional blunting was more commonly associated with SSRIs than with the other medications in the studies.
Common clinical strategies to manage antidepressant-induced emotional blunting reported in the literature include dose reduction or switching to a different antidepressant class; however, the literature did not make the distinction between emotional blunting as a primary symptom of depression or an adverse effect of antidepressants.
Dr. Shad said that there is a need to develop valid and reliable measures to assess emotional blunting related to antidepressants.
He noted that optimal patient care should include pre- and posttreatment assessment of emotional blunting. One useful tool is the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants.
Can’t get to the top
Jacob Cross, MD, who wasn’t involved in the study, said that he has seen the impact of antidepressant-related emotional blunting first-hand.
“I’ve had multiple patients report emotional blunting on antidepressant therapy,” Dr. Cross, with the department of psychiatry, Rush Medical College, Chicago, said.
“These patients feel like their emotions are not as high and not as low; so they experience directional improvement, but they’re still not feeling like they can get that top peak emotion. It’s kind of similar to anhedonia. They’re just feeling like a little cut off, like they’re climbing a cliff and just can’t get to that top,” Dr. Cross said.
For a patient with emotional blunting, Dr. Cross said he might “switch to an antidepressant that’s more stimulating like an SNRI from an SSRI. You could also lower the dose and see if that helps, but I usually change the drug class.”
The study had no specific funding. Dr. Shad and Dr. Cross have no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – , new research shows.
Emotional blunting can be described as feeling emotionally flat and incapable of finding pleasure. The patient may feel less sadness, guilt, or hopelessness, but that may come at the cost of feeling less joy, surprise, and happiness. Some people with SSRI-induced blunting even report caring less about important relationships.
It’s an issue that needs greater attention, study investigator Mujeeb U. Shad, MD, with Valley Health Services and University of Nevada, Las Vegas, said in an interview.
“Patients may come to the clinic and report feeling emotionally and cognitively flat and not be taken seriously by their provider, but they are genuinely reporting something that is happening to them and decreasing their quality of life,” Dr. Shad explained.
The study was presented at the annual meeting of the American Psychiatric Association.
Something ‘missing’
Dr. Shad said that the genesis for the study came from a resident who noticed that many patients receiving SSRIs reported feeling better and not as bothered by the depression, yet, at the same time, they felt something was “missing. Their families would say, ‘You’re better but you’re not the same person.’ ”
To investigate further, the researchers did a “scoping review” of 25 original studies that assessed antidepressant-related emotional blunting. Until now, there hasn’t been a systematic review of this issue, Dr. Shad said.
Ten of the studies looked at the role of SSRIs in emotional blunting, whereas the other 15 looked at serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and second-generation antipsychotic medications.
The results of the review show that emotional blunting is a significant patient-reported concern. It often presents as a subjective complaint of changed personality, feeling a lesser intensity of overall emotions, and the manifestation of not being oneself often attributed to antidepressant use, the researchers found. Emotional blunting was more commonly associated with SSRIs than with the other medications in the studies.
Common clinical strategies to manage antidepressant-induced emotional blunting reported in the literature include dose reduction or switching to a different antidepressant class; however, the literature did not make the distinction between emotional blunting as a primary symptom of depression or an adverse effect of antidepressants.
Dr. Shad said that there is a need to develop valid and reliable measures to assess emotional blunting related to antidepressants.
He noted that optimal patient care should include pre- and posttreatment assessment of emotional blunting. One useful tool is the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants.
Can’t get to the top
Jacob Cross, MD, who wasn’t involved in the study, said that he has seen the impact of antidepressant-related emotional blunting first-hand.
“I’ve had multiple patients report emotional blunting on antidepressant therapy,” Dr. Cross, with the department of psychiatry, Rush Medical College, Chicago, said.
“These patients feel like their emotions are not as high and not as low; so they experience directional improvement, but they’re still not feeling like they can get that top peak emotion. It’s kind of similar to anhedonia. They’re just feeling like a little cut off, like they’re climbing a cliff and just can’t get to that top,” Dr. Cross said.
For a patient with emotional blunting, Dr. Cross said he might “switch to an antidepressant that’s more stimulating like an SNRI from an SSRI. You could also lower the dose and see if that helps, but I usually change the drug class.”
The study had no specific funding. Dr. Shad and Dr. Cross have no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
AT APA 2023
The family firearm often used in youth suicide
SAN FRANCISCO – , according to results of a novel “psychological autopsy study” of loved ones of youth who died by gun-related suicide.
Yet, families don’t always recognize the danger firearms pose to a young person with suicide risk factors, even when there is a young person in the house with a mental health condition, the data show.
Perhaps most importantly, many parents indicated that they would have removed firearms from the home if it had been suggested by their health care professionals.
The study was presented at the American Psychiatric Association annual meeting.
The message is very clear: Clinicians need to ask about guns and gun safety with patients and families, said study investigator Paul Nestadt, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore.
“It’s never illegal to ask about gun access and it’s medically relevant. Just do it,” he said during a briefing with reporters.
Grim statistics
Suicide rates have been climbing in the United States for the majority of the past 20 years. Suicide is the second most common cause of death among youth.
Dr. Nestadt noted that overall about 8% of suicide attempts result in death, but when an attempt involves a firearm the percentage jumps astronomically to 90%.
Research has shown that for every 10% increase in household firearms in a given community there is a 27% increase in youth suicide deaths.
“In the world of public health and mental health, we think about having access to firearms as an important risk factor for completed suicide. But in the United States, guns have become an important part of how many Americans see themselves,” Dr. Nestadt told reporters.
Research has shown that half of gun owners say owning a gun is central to their identity and three quarters say it’s essential to their freedom, he noted.
To explore these attitudes further, Dr. Nestadt and colleagues did 11 “psychological autopsy interviews” with the loved ones of nine young people aged 17-21 who died by gun-related suicide. They interviewed six mothers, three fathers, one sibling, and one close friend.
Most of the families had some level of “familial engagement” with firearms, Dr. Nestadt reported.
In more than two-thirds of the families, the youth used a family-owned firearm to commit suicide.
Notably, more than three-quarters of the youth had received mental health care before taking their lives, with many receiving care in the weeks prior to their suicide; 44% had made a prior suicide attempt.
In many cases, parents shared that they had not considered their family-owned firearms to be sources of danger and indicated that had their clinicians expressed concern about the gun in the home, they may have acted to reduce the risk by removing it.
Several also shared that they would have considered using Maryland’s Extreme Risk Protective Order Law if it had existed at the time and they had been made aware of it.
Extreme risk protection order (ERPO) laws, or “red flag laws,” prohibit individuals at risk for harming themselves or others from purchasing or owning a firearm.
Dr. Nestadt said youth suicide interventions “must acknowledge culturally embedded roots of identity formation while rescripting firearms from expressions of family cohesion to instruments that may undermine that cohesion.”
‘Courageous study’
Dr. Nestadt noted that while this study was challenging on many fronts, it took no convincing to get these grieving families to participate.
“They wanted to talk to us, especially because they were hopeful that our work could help prevent future suicides, but also they wanted to talk about their loved ones,” he said.
“When you lose someone to cancer, people give you hugs and flowers. When you lose someone to suicide, people don’t discuss it. Suicide has a stigma to it.”
Briefing moderator Howard Liu, MD, MBA, chair of the department of psychiatry, University of Nebraska Medical Center, Omaha, praised the study team for a “courageous study that really required a tremendous amount of vulnerability from the research team and clearly from the survivors as well.”
This is an “important and timely public health discussion,” said Dr. Liu, chair of the APA Council on Communications.
“We’re all facing this challenge of how do we reduce suicide across all ages, from youth to adults as well. This is a really vital discussion and such an important clue about access and trying to reduce access in a moment of impulsivity,” he added.
The study had no commercial funding. Dr. Nestadt and Dr. Liu report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – , according to results of a novel “psychological autopsy study” of loved ones of youth who died by gun-related suicide.
Yet, families don’t always recognize the danger firearms pose to a young person with suicide risk factors, even when there is a young person in the house with a mental health condition, the data show.
Perhaps most importantly, many parents indicated that they would have removed firearms from the home if it had been suggested by their health care professionals.
The study was presented at the American Psychiatric Association annual meeting.
The message is very clear: Clinicians need to ask about guns and gun safety with patients and families, said study investigator Paul Nestadt, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore.
“It’s never illegal to ask about gun access and it’s medically relevant. Just do it,” he said during a briefing with reporters.
Grim statistics
Suicide rates have been climbing in the United States for the majority of the past 20 years. Suicide is the second most common cause of death among youth.
Dr. Nestadt noted that overall about 8% of suicide attempts result in death, but when an attempt involves a firearm the percentage jumps astronomically to 90%.
Research has shown that for every 10% increase in household firearms in a given community there is a 27% increase in youth suicide deaths.
“In the world of public health and mental health, we think about having access to firearms as an important risk factor for completed suicide. But in the United States, guns have become an important part of how many Americans see themselves,” Dr. Nestadt told reporters.
Research has shown that half of gun owners say owning a gun is central to their identity and three quarters say it’s essential to their freedom, he noted.
To explore these attitudes further, Dr. Nestadt and colleagues did 11 “psychological autopsy interviews” with the loved ones of nine young people aged 17-21 who died by gun-related suicide. They interviewed six mothers, three fathers, one sibling, and one close friend.
Most of the families had some level of “familial engagement” with firearms, Dr. Nestadt reported.
In more than two-thirds of the families, the youth used a family-owned firearm to commit suicide.
Notably, more than three-quarters of the youth had received mental health care before taking their lives, with many receiving care in the weeks prior to their suicide; 44% had made a prior suicide attempt.
In many cases, parents shared that they had not considered their family-owned firearms to be sources of danger and indicated that had their clinicians expressed concern about the gun in the home, they may have acted to reduce the risk by removing it.
Several also shared that they would have considered using Maryland’s Extreme Risk Protective Order Law if it had existed at the time and they had been made aware of it.
Extreme risk protection order (ERPO) laws, or “red flag laws,” prohibit individuals at risk for harming themselves or others from purchasing or owning a firearm.
Dr. Nestadt said youth suicide interventions “must acknowledge culturally embedded roots of identity formation while rescripting firearms from expressions of family cohesion to instruments that may undermine that cohesion.”
‘Courageous study’
Dr. Nestadt noted that while this study was challenging on many fronts, it took no convincing to get these grieving families to participate.
“They wanted to talk to us, especially because they were hopeful that our work could help prevent future suicides, but also they wanted to talk about their loved ones,” he said.
“When you lose someone to cancer, people give you hugs and flowers. When you lose someone to suicide, people don’t discuss it. Suicide has a stigma to it.”
Briefing moderator Howard Liu, MD, MBA, chair of the department of psychiatry, University of Nebraska Medical Center, Omaha, praised the study team for a “courageous study that really required a tremendous amount of vulnerability from the research team and clearly from the survivors as well.”
This is an “important and timely public health discussion,” said Dr. Liu, chair of the APA Council on Communications.
“We’re all facing this challenge of how do we reduce suicide across all ages, from youth to adults as well. This is a really vital discussion and such an important clue about access and trying to reduce access in a moment of impulsivity,” he added.
The study had no commercial funding. Dr. Nestadt and Dr. Liu report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – , according to results of a novel “psychological autopsy study” of loved ones of youth who died by gun-related suicide.
Yet, families don’t always recognize the danger firearms pose to a young person with suicide risk factors, even when there is a young person in the house with a mental health condition, the data show.
Perhaps most importantly, many parents indicated that they would have removed firearms from the home if it had been suggested by their health care professionals.
The study was presented at the American Psychiatric Association annual meeting.
The message is very clear: Clinicians need to ask about guns and gun safety with patients and families, said study investigator Paul Nestadt, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore.
“It’s never illegal to ask about gun access and it’s medically relevant. Just do it,” he said during a briefing with reporters.
Grim statistics
Suicide rates have been climbing in the United States for the majority of the past 20 years. Suicide is the second most common cause of death among youth.
Dr. Nestadt noted that overall about 8% of suicide attempts result in death, but when an attempt involves a firearm the percentage jumps astronomically to 90%.
Research has shown that for every 10% increase in household firearms in a given community there is a 27% increase in youth suicide deaths.
“In the world of public health and mental health, we think about having access to firearms as an important risk factor for completed suicide. But in the United States, guns have become an important part of how many Americans see themselves,” Dr. Nestadt told reporters.
Research has shown that half of gun owners say owning a gun is central to their identity and three quarters say it’s essential to their freedom, he noted.
To explore these attitudes further, Dr. Nestadt and colleagues did 11 “psychological autopsy interviews” with the loved ones of nine young people aged 17-21 who died by gun-related suicide. They interviewed six mothers, three fathers, one sibling, and one close friend.
Most of the families had some level of “familial engagement” with firearms, Dr. Nestadt reported.
In more than two-thirds of the families, the youth used a family-owned firearm to commit suicide.
Notably, more than three-quarters of the youth had received mental health care before taking their lives, with many receiving care in the weeks prior to their suicide; 44% had made a prior suicide attempt.
In many cases, parents shared that they had not considered their family-owned firearms to be sources of danger and indicated that had their clinicians expressed concern about the gun in the home, they may have acted to reduce the risk by removing it.
Several also shared that they would have considered using Maryland’s Extreme Risk Protective Order Law if it had existed at the time and they had been made aware of it.
Extreme risk protection order (ERPO) laws, or “red flag laws,” prohibit individuals at risk for harming themselves or others from purchasing or owning a firearm.
Dr. Nestadt said youth suicide interventions “must acknowledge culturally embedded roots of identity formation while rescripting firearms from expressions of family cohesion to instruments that may undermine that cohesion.”
‘Courageous study’
Dr. Nestadt noted that while this study was challenging on many fronts, it took no convincing to get these grieving families to participate.
“They wanted to talk to us, especially because they were hopeful that our work could help prevent future suicides, but also they wanted to talk about their loved ones,” he said.
“When you lose someone to cancer, people give you hugs and flowers. When you lose someone to suicide, people don’t discuss it. Suicide has a stigma to it.”
Briefing moderator Howard Liu, MD, MBA, chair of the department of psychiatry, University of Nebraska Medical Center, Omaha, praised the study team for a “courageous study that really required a tremendous amount of vulnerability from the research team and clearly from the survivors as well.”
This is an “important and timely public health discussion,” said Dr. Liu, chair of the APA Council on Communications.
“We’re all facing this challenge of how do we reduce suicide across all ages, from youth to adults as well. This is a really vital discussion and such an important clue about access and trying to reduce access in a moment of impulsivity,” he added.
The study had no commercial funding. Dr. Nestadt and Dr. Liu report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT APA 2023
We can reduce suicide with enforced treatment and eyesight supervision
The old man was restrained at the last moment from jumping off the hospital’s fifth floor atrium parapet. He was suffering from terminal cancer and had been racked with chronic, severe pain for months.
The consult recognized symptoms of depression arising from his continuous physical suffering, advising that a male aide be dispatched to sit with the man and that he be put on a regimen of 10 mg of methadone twice a day to alleviate the pain. The following day the man was calm; he no longer wanted to kill himself. He expressed a strong desire to go home, return to gardening, and to play with his grandchildren.
Most of the 47,000 suicides that occur in the United States every year are preventable.1 Our national policy on this front has been nothing short of an abject failure. The government implemented a system with limited effect on completed suicides – a telephone hotline. This hotline is not called by the most common suicide victims: male, old, and quiet.2
The consequences of this national policy disaster have been profound, resulting in the biggest loss of productive years of life for any fatal condition.3 The grief experienced by the families of those who commit suicide is far greater than normal bereavement: The cause of death of their loved ones was not an unfortunate accident or a disease, it was an intentional act, and families take it personally.
One of the greatest achievements of psychiatry during the 20th century was the lowering of suicide rates in prisons by 70% with no treatment, no additional staffing, and no additional expenditures of funds. Today if inmates threaten suicide, they are immediately placed under eyesight supervision by guards. The federal pamphlet that describes this protocol was published in 1995 and is freely available online.4
Half of all suicide attempts are made by individuals who are legally drunk.5 Watch them for 6 hours and then ask them if they want to kill themselves and the response will almost invariably be “Of course not,” with the risk of further attempts dissipating in step with their blood alcohol level. The best resources to provide this kind of intervention are responsible adult family members, at no cost to the government. Indeed, in many cases family supervision is superior to that provided by a locked psychiatric ward with three staff members chasing after 20 agitated people all night long. The one-on-one attention that a family member can provide is free as well as far more personal and insightful, and more sincerely caring.
Guarantees in the field of medicine are rare. But, one such guarantee is that after their mood has improved, 100% of people will be thankful that they did not hurt themselves.6 This means that successful treatment will prevent 100% of all suicides.7 Not all treatments are successful, but 95% can be.8 At autopsy, few successful suicide victims have psychiatric medications in their system.9 The urge to kill oneself might best be characterized as a temporary chemical alteration of the brain causing delusional thoughts, including the ultimate delusion that life is not worth living.10 This alteration suppresses the strongest, most fundamental urge of all, namely, the survival instinct.
We must overturn the catastrophic decision of the U.S. Supreme Court that requires the showing of a dangerous act and the holding of a trial employing at least three lawyers for involuntary commitment to be authorized. Rather, involuntary treatment is justified by medical necessity as determined by two licensed professionals with no conflicts of interest. It can be outpatient.
The Supreme Court’s decision in O’Connor v. Donaldson in 1975 remedied an illusory wrong, addressing an act of blatant malpractice, not policy inequity.11 The superintendent of the state facility in that case was not even a doctor. He kept O’Connor prisoner for more than a decade, perhaps to keep a bed filled. Over the past half-century, this one decision has resulted in 1 million preventable suicides12 and half a million senseless murders by paranoid individuals, including many rampage shootings.13
More than two-thirds of homeless individuals suffer from an untreated mental condition.14 The vast majority of them will refuse all offers of treatment because they also have anosognosia, a brain-based disorder causing denial of illness.15 By referring to these individuals as “homeless,” we are also lowering real estate values for a square block around where they happen to be camped out. That cost has never been calculated, but it is another real consequence of this devastating Supreme Court decision.16
Detractors and mental health rights activists may argue that individual rights cannot be infringed. In that case, those same detractors and mental health rights activists must take responsibility for the thousands of lives and billions of dollars in economic damage caused by their refusal to allow an effective solution to the suicide epidemic to be implemented. Enforced outpatient treatment by the U.S. Air Force dropped its suicide rate by 60%. As an unintended benefit, the murder rate dropped by 50%.17
It is high time we did so.
Dr. Behar is a psychiatrist in Lower Merion, Pa. He graduated from Hahnemann Medical College, Philadelphia, in 1975, and has had postgraduate training at SUNY Stony Brook, University of Iowa, the National Institute of Mental Health, and Columbia University. His practice focuses on difficult, treatment-resistant cases.
References
1. U.S. Centers for Disease Control and Prevention. Suicide Prevention. 2020.
2. Luoma JB et al. Contact with mental health and primary care providers before suicide: A review of the evidence. Am J Psychiatry. 2002 Jun 1. doi: 10.1176/appi.ajp.159.6.909.
3. World Health Organization. Suicide. 2021 Jun 17.
4. National Institute of Corrections. Correctional suicide prevention: Policies and procedures. 1995.
5. Hufford MR. Alcohol and suicidal behavior. Clin Psychol Rev. 2001 Jul;21(5):797-811.
6. Stanley B and Brown GK. Safety planning intervention: A brief intervention to mitigate suicide risk. Cogn Behav Pract. 2012 May;19(2):256-64.
7. Ibid.
8. Brown GK and Jager-Hyman S. Evidence-based psychotherapies for suicide prevention: Future directions. Am J Prev Med. 2014 Sep;47(3 Suppl 2):S186-94.
9. Isometsä ET. Psychological autopsy studies – A review. Eur Psychiatry. 2001 Nov;16(7):379-85.
10. Van Orden KA et al. The interpersonal theory of suicide. Psychol Rev. 2010 Apr; 117(2):575-600.
11. O’Connor v. Donaldson, 422 U.S. 563 (1975).
12. Calculated based on annual suicide statistics from the CDC and the time elapsed since the Supreme Court decision in O’Connor v. Donaldson.
13. Metzl JM and MacLeish KT. Mental illness, mass shootings, and the politics of American firearms. Am J Public Health. 2015 Feb;105(2):240-9.
14. Fazel S et al. The prevalence of mental disorders among the homeless in western countries: Systematic review and meta-regression analysis. PLoS Med. 2008 Dec 2;5(12):e225.
15. Amador XF and David AS. (eds.) Insight and psychosis: Awareness of illness in schizophrenia and related disorders (2nd ed.). Oxford Univ Press. 2004.
16. Calculated based on the potential impact of homelessness on property values and the relationship between untreated mental illness and homelessness.
17. Armed Forces Health Surveillance Branch. Surveillance snapshot: Manner and cause of death, active component, U.S. Armed Forces, 1998-2015. Medical Surveillance Monthly Report. 2016 Apr;23(4):19.
The old man was restrained at the last moment from jumping off the hospital’s fifth floor atrium parapet. He was suffering from terminal cancer and had been racked with chronic, severe pain for months.
The consult recognized symptoms of depression arising from his continuous physical suffering, advising that a male aide be dispatched to sit with the man and that he be put on a regimen of 10 mg of methadone twice a day to alleviate the pain. The following day the man was calm; he no longer wanted to kill himself. He expressed a strong desire to go home, return to gardening, and to play with his grandchildren.
Most of the 47,000 suicides that occur in the United States every year are preventable.1 Our national policy on this front has been nothing short of an abject failure. The government implemented a system with limited effect on completed suicides – a telephone hotline. This hotline is not called by the most common suicide victims: male, old, and quiet.2
The consequences of this national policy disaster have been profound, resulting in the biggest loss of productive years of life for any fatal condition.3 The grief experienced by the families of those who commit suicide is far greater than normal bereavement: The cause of death of their loved ones was not an unfortunate accident or a disease, it was an intentional act, and families take it personally.
One of the greatest achievements of psychiatry during the 20th century was the lowering of suicide rates in prisons by 70% with no treatment, no additional staffing, and no additional expenditures of funds. Today if inmates threaten suicide, they are immediately placed under eyesight supervision by guards. The federal pamphlet that describes this protocol was published in 1995 and is freely available online.4
Half of all suicide attempts are made by individuals who are legally drunk.5 Watch them for 6 hours and then ask them if they want to kill themselves and the response will almost invariably be “Of course not,” with the risk of further attempts dissipating in step with their blood alcohol level. The best resources to provide this kind of intervention are responsible adult family members, at no cost to the government. Indeed, in many cases family supervision is superior to that provided by a locked psychiatric ward with three staff members chasing after 20 agitated people all night long. The one-on-one attention that a family member can provide is free as well as far more personal and insightful, and more sincerely caring.
Guarantees in the field of medicine are rare. But, one such guarantee is that after their mood has improved, 100% of people will be thankful that they did not hurt themselves.6 This means that successful treatment will prevent 100% of all suicides.7 Not all treatments are successful, but 95% can be.8 At autopsy, few successful suicide victims have psychiatric medications in their system.9 The urge to kill oneself might best be characterized as a temporary chemical alteration of the brain causing delusional thoughts, including the ultimate delusion that life is not worth living.10 This alteration suppresses the strongest, most fundamental urge of all, namely, the survival instinct.
We must overturn the catastrophic decision of the U.S. Supreme Court that requires the showing of a dangerous act and the holding of a trial employing at least three lawyers for involuntary commitment to be authorized. Rather, involuntary treatment is justified by medical necessity as determined by two licensed professionals with no conflicts of interest. It can be outpatient.
The Supreme Court’s decision in O’Connor v. Donaldson in 1975 remedied an illusory wrong, addressing an act of blatant malpractice, not policy inequity.11 The superintendent of the state facility in that case was not even a doctor. He kept O’Connor prisoner for more than a decade, perhaps to keep a bed filled. Over the past half-century, this one decision has resulted in 1 million preventable suicides12 and half a million senseless murders by paranoid individuals, including many rampage shootings.13
More than two-thirds of homeless individuals suffer from an untreated mental condition.14 The vast majority of them will refuse all offers of treatment because they also have anosognosia, a brain-based disorder causing denial of illness.15 By referring to these individuals as “homeless,” we are also lowering real estate values for a square block around where they happen to be camped out. That cost has never been calculated, but it is another real consequence of this devastating Supreme Court decision.16
Detractors and mental health rights activists may argue that individual rights cannot be infringed. In that case, those same detractors and mental health rights activists must take responsibility for the thousands of lives and billions of dollars in economic damage caused by their refusal to allow an effective solution to the suicide epidemic to be implemented. Enforced outpatient treatment by the U.S. Air Force dropped its suicide rate by 60%. As an unintended benefit, the murder rate dropped by 50%.17
It is high time we did so.
Dr. Behar is a psychiatrist in Lower Merion, Pa. He graduated from Hahnemann Medical College, Philadelphia, in 1975, and has had postgraduate training at SUNY Stony Brook, University of Iowa, the National Institute of Mental Health, and Columbia University. His practice focuses on difficult, treatment-resistant cases.
References
1. U.S. Centers for Disease Control and Prevention. Suicide Prevention. 2020.
2. Luoma JB et al. Contact with mental health and primary care providers before suicide: A review of the evidence. Am J Psychiatry. 2002 Jun 1. doi: 10.1176/appi.ajp.159.6.909.
3. World Health Organization. Suicide. 2021 Jun 17.
4. National Institute of Corrections. Correctional suicide prevention: Policies and procedures. 1995.
5. Hufford MR. Alcohol and suicidal behavior. Clin Psychol Rev. 2001 Jul;21(5):797-811.
6. Stanley B and Brown GK. Safety planning intervention: A brief intervention to mitigate suicide risk. Cogn Behav Pract. 2012 May;19(2):256-64.
7. Ibid.
8. Brown GK and Jager-Hyman S. Evidence-based psychotherapies for suicide prevention: Future directions. Am J Prev Med. 2014 Sep;47(3 Suppl 2):S186-94.
9. Isometsä ET. Psychological autopsy studies – A review. Eur Psychiatry. 2001 Nov;16(7):379-85.
10. Van Orden KA et al. The interpersonal theory of suicide. Psychol Rev. 2010 Apr; 117(2):575-600.
11. O’Connor v. Donaldson, 422 U.S. 563 (1975).
12. Calculated based on annual suicide statistics from the CDC and the time elapsed since the Supreme Court decision in O’Connor v. Donaldson.
13. Metzl JM and MacLeish KT. Mental illness, mass shootings, and the politics of American firearms. Am J Public Health. 2015 Feb;105(2):240-9.
14. Fazel S et al. The prevalence of mental disorders among the homeless in western countries: Systematic review and meta-regression analysis. PLoS Med. 2008 Dec 2;5(12):e225.
15. Amador XF and David AS. (eds.) Insight and psychosis: Awareness of illness in schizophrenia and related disorders (2nd ed.). Oxford Univ Press. 2004.
16. Calculated based on the potential impact of homelessness on property values and the relationship between untreated mental illness and homelessness.
17. Armed Forces Health Surveillance Branch. Surveillance snapshot: Manner and cause of death, active component, U.S. Armed Forces, 1998-2015. Medical Surveillance Monthly Report. 2016 Apr;23(4):19.
The old man was restrained at the last moment from jumping off the hospital’s fifth floor atrium parapet. He was suffering from terminal cancer and had been racked with chronic, severe pain for months.
The consult recognized symptoms of depression arising from his continuous physical suffering, advising that a male aide be dispatched to sit with the man and that he be put on a regimen of 10 mg of methadone twice a day to alleviate the pain. The following day the man was calm; he no longer wanted to kill himself. He expressed a strong desire to go home, return to gardening, and to play with his grandchildren.
Most of the 47,000 suicides that occur in the United States every year are preventable.1 Our national policy on this front has been nothing short of an abject failure. The government implemented a system with limited effect on completed suicides – a telephone hotline. This hotline is not called by the most common suicide victims: male, old, and quiet.2
The consequences of this national policy disaster have been profound, resulting in the biggest loss of productive years of life for any fatal condition.3 The grief experienced by the families of those who commit suicide is far greater than normal bereavement: The cause of death of their loved ones was not an unfortunate accident or a disease, it was an intentional act, and families take it personally.
One of the greatest achievements of psychiatry during the 20th century was the lowering of suicide rates in prisons by 70% with no treatment, no additional staffing, and no additional expenditures of funds. Today if inmates threaten suicide, they are immediately placed under eyesight supervision by guards. The federal pamphlet that describes this protocol was published in 1995 and is freely available online.4
Half of all suicide attempts are made by individuals who are legally drunk.5 Watch them for 6 hours and then ask them if they want to kill themselves and the response will almost invariably be “Of course not,” with the risk of further attempts dissipating in step with their blood alcohol level. The best resources to provide this kind of intervention are responsible adult family members, at no cost to the government. Indeed, in many cases family supervision is superior to that provided by a locked psychiatric ward with three staff members chasing after 20 agitated people all night long. The one-on-one attention that a family member can provide is free as well as far more personal and insightful, and more sincerely caring.
Guarantees in the field of medicine are rare. But, one such guarantee is that after their mood has improved, 100% of people will be thankful that they did not hurt themselves.6 This means that successful treatment will prevent 100% of all suicides.7 Not all treatments are successful, but 95% can be.8 At autopsy, few successful suicide victims have psychiatric medications in their system.9 The urge to kill oneself might best be characterized as a temporary chemical alteration of the brain causing delusional thoughts, including the ultimate delusion that life is not worth living.10 This alteration suppresses the strongest, most fundamental urge of all, namely, the survival instinct.
We must overturn the catastrophic decision of the U.S. Supreme Court that requires the showing of a dangerous act and the holding of a trial employing at least three lawyers for involuntary commitment to be authorized. Rather, involuntary treatment is justified by medical necessity as determined by two licensed professionals with no conflicts of interest. It can be outpatient.
The Supreme Court’s decision in O’Connor v. Donaldson in 1975 remedied an illusory wrong, addressing an act of blatant malpractice, not policy inequity.11 The superintendent of the state facility in that case was not even a doctor. He kept O’Connor prisoner for more than a decade, perhaps to keep a bed filled. Over the past half-century, this one decision has resulted in 1 million preventable suicides12 and half a million senseless murders by paranoid individuals, including many rampage shootings.13
More than two-thirds of homeless individuals suffer from an untreated mental condition.14 The vast majority of them will refuse all offers of treatment because they also have anosognosia, a brain-based disorder causing denial of illness.15 By referring to these individuals as “homeless,” we are also lowering real estate values for a square block around where they happen to be camped out. That cost has never been calculated, but it is another real consequence of this devastating Supreme Court decision.16
Detractors and mental health rights activists may argue that individual rights cannot be infringed. In that case, those same detractors and mental health rights activists must take responsibility for the thousands of lives and billions of dollars in economic damage caused by their refusal to allow an effective solution to the suicide epidemic to be implemented. Enforced outpatient treatment by the U.S. Air Force dropped its suicide rate by 60%. As an unintended benefit, the murder rate dropped by 50%.17
It is high time we did so.
Dr. Behar is a psychiatrist in Lower Merion, Pa. He graduated from Hahnemann Medical College, Philadelphia, in 1975, and has had postgraduate training at SUNY Stony Brook, University of Iowa, the National Institute of Mental Health, and Columbia University. His practice focuses on difficult, treatment-resistant cases.
References
1. U.S. Centers for Disease Control and Prevention. Suicide Prevention. 2020.
2. Luoma JB et al. Contact with mental health and primary care providers before suicide: A review of the evidence. Am J Psychiatry. 2002 Jun 1. doi: 10.1176/appi.ajp.159.6.909.
3. World Health Organization. Suicide. 2021 Jun 17.
4. National Institute of Corrections. Correctional suicide prevention: Policies and procedures. 1995.
5. Hufford MR. Alcohol and suicidal behavior. Clin Psychol Rev. 2001 Jul;21(5):797-811.
6. Stanley B and Brown GK. Safety planning intervention: A brief intervention to mitigate suicide risk. Cogn Behav Pract. 2012 May;19(2):256-64.
7. Ibid.
8. Brown GK and Jager-Hyman S. Evidence-based psychotherapies for suicide prevention: Future directions. Am J Prev Med. 2014 Sep;47(3 Suppl 2):S186-94.
9. Isometsä ET. Psychological autopsy studies – A review. Eur Psychiatry. 2001 Nov;16(7):379-85.
10. Van Orden KA et al. The interpersonal theory of suicide. Psychol Rev. 2010 Apr; 117(2):575-600.
11. O’Connor v. Donaldson, 422 U.S. 563 (1975).
12. Calculated based on annual suicide statistics from the CDC and the time elapsed since the Supreme Court decision in O’Connor v. Donaldson.
13. Metzl JM and MacLeish KT. Mental illness, mass shootings, and the politics of American firearms. Am J Public Health. 2015 Feb;105(2):240-9.
14. Fazel S et al. The prevalence of mental disorders among the homeless in western countries: Systematic review and meta-regression analysis. PLoS Med. 2008 Dec 2;5(12):e225.
15. Amador XF and David AS. (eds.) Insight and psychosis: Awareness of illness in schizophrenia and related disorders (2nd ed.). Oxford Univ Press. 2004.
16. Calculated based on the potential impact of homelessness on property values and the relationship between untreated mental illness and homelessness.
17. Armed Forces Health Surveillance Branch. Surveillance snapshot: Manner and cause of death, active component, U.S. Armed Forces, 1998-2015. Medical Surveillance Monthly Report. 2016 Apr;23(4):19.
Long-term impact of childhood trauma explained
WASHINGTON –
“We already knew childhood trauma is associated with the later development of depressive and anxiety disorders, but it’s been unclear what makes sufferers of early trauma more likely to develop these psychiatric conditions,” study investigator Erika Kuzminskaite, PhD candidate, department of psychiatry, Amsterdam University Medical Center (UMC), the Netherlands, told this news organization.
“The evidence now points to unbalanced stress systems as a possible cause of this vulnerability, and now the most important question is, how we can develop preventive interventions,” she added.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Elevated cortisol, inflammation
The study included 2,779 adults from the Netherlands Study of Depression and Anxiety (NESDA). Two thirds of participants were female.
Participants retrospectively reported childhood trauma, defined as emotional, physical, or sexual abuse or emotional or physical neglect, before the age of 18 years. Severe trauma was defined as multiple types or increased frequency of abuse.
Of the total cohort, 48% reported experiencing some childhood trauma – 21% reported severe trauma, 27% reported mild trauma, and 42% reported no childhood trauma.
Among those with trauma, 89% had a current or remitted anxiety or depressive disorder, and 11% had no psychiatric sequelae. Among participants who reported no trauma, 68% had a current or remitted disorder, and 32% had no psychiatric disorders.
At baseline, researchers assessed markers of major bodily stress systems, including the hypothalamic-pituitary-adrenal (HPA) axis, the immune-inflammatory system, and the autonomic nervous system (ANS). They examined these markers separately and cumulatively.
In one model, investigators found that levels of cortisol and inflammation were significantly elevated in those with severe childhood trauma compared to those with no childhood trauma. The effects were largest for the cumulative markers for HPA-axis, inflammation, and all stress system markers (Cohen’s d = 0.23, 0.12, and 0.25, respectively). There was no association with ANS markers.
The results were partially explained by lifestyle, said Ms. Kuzminskaite, who noted that people with severe childhood trauma tend to have a higher body mass index, smoke more, and have other unhealthy habits that may represent a “coping” mechanism for trauma.
Those who experienced childhood trauma also have higher rates of other disorders, including asthma, diabetes, and cardiovascular disease. Ms. Kuzminskaite noted that people with childhood trauma have at least double the risk of cancer in later life.
When researchers adjusted for lifestyle factors and chronic conditions, the association for cortisol was reduced and that for inflammation disappeared. However, the cumulative inflammatory markers remained significant.
Another model examined lipopolysaccharide-stimulated (LPS) immune-inflammatory markers by childhood trauma severity. This provides a more “dynamic” measure of stress systems than looking only at static circulating levels in the blood, as was done in the first model, said Ms. Kuzminskaite.
“These levels should theoretically be more affected by experiences such as childhood trauma and they are also less sensitive to lifestyle.”
Here, researchers found significant positive associations with childhood trauma, especially severe trauma, after adjusting for lifestyle and health-related covariates (cumulative index d = 0.19).
“Almost all people with childhood trauma, especially severe trauma, had LPS-stimulated cytokines upregulated,” said Ms. Kuzminskaite. “So again, there is this dysregulation of immune system functioning in these subjects.”
And again, the strongest effect was for the cumulative index of all cytokines, she said.
Personalized interventions
Ms. Kuzminskaite noted the importance of learning the impact of early trauma on stress responses. “The goal is to eventually have personalized interventions for people with depression or anxiety related to childhood trauma, or even preventative interventions. If we know, for example, something is going wrong with a patient’s stress systems, we can suggest some therapeutic targets.”
Investigators in Amsterdam are examining the efficacy of mifepristone, which blocks progesterone and is used along with misoprostol for medication abortions and to treat high blood sugar. “The drug is supposed to reset the stress system functioning,” said Ms. Kuzminskaite.
It’s still important to target unhealthy lifestyle habits “that are really impacting the functioning of the stress systems,” she said. Lifestyle interventions could improve the efficacy of treatments for depression, for example, she added.
Luana Marques, PhD, associate professor, department of psychiatry, Harvard Medical School, Boston, said such research is important.
“It reveals the potentially extensive and long-lasting impact of childhood trauma on functioning. The findings underscore the importance of equipping at-risk and trauma-exposed youth with evidence-based skills for managing stress,” she said.
No conflicts of interest were reported.
A version of this article first appeared on Medscape.com.
WASHINGTON –
“We already knew childhood trauma is associated with the later development of depressive and anxiety disorders, but it’s been unclear what makes sufferers of early trauma more likely to develop these psychiatric conditions,” study investigator Erika Kuzminskaite, PhD candidate, department of psychiatry, Amsterdam University Medical Center (UMC), the Netherlands, told this news organization.
“The evidence now points to unbalanced stress systems as a possible cause of this vulnerability, and now the most important question is, how we can develop preventive interventions,” she added.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Elevated cortisol, inflammation
The study included 2,779 adults from the Netherlands Study of Depression and Anxiety (NESDA). Two thirds of participants were female.
Participants retrospectively reported childhood trauma, defined as emotional, physical, or sexual abuse or emotional or physical neglect, before the age of 18 years. Severe trauma was defined as multiple types or increased frequency of abuse.
Of the total cohort, 48% reported experiencing some childhood trauma – 21% reported severe trauma, 27% reported mild trauma, and 42% reported no childhood trauma.
Among those with trauma, 89% had a current or remitted anxiety or depressive disorder, and 11% had no psychiatric sequelae. Among participants who reported no trauma, 68% had a current or remitted disorder, and 32% had no psychiatric disorders.
At baseline, researchers assessed markers of major bodily stress systems, including the hypothalamic-pituitary-adrenal (HPA) axis, the immune-inflammatory system, and the autonomic nervous system (ANS). They examined these markers separately and cumulatively.
In one model, investigators found that levels of cortisol and inflammation were significantly elevated in those with severe childhood trauma compared to those with no childhood trauma. The effects were largest for the cumulative markers for HPA-axis, inflammation, and all stress system markers (Cohen’s d = 0.23, 0.12, and 0.25, respectively). There was no association with ANS markers.
The results were partially explained by lifestyle, said Ms. Kuzminskaite, who noted that people with severe childhood trauma tend to have a higher body mass index, smoke more, and have other unhealthy habits that may represent a “coping” mechanism for trauma.
Those who experienced childhood trauma also have higher rates of other disorders, including asthma, diabetes, and cardiovascular disease. Ms. Kuzminskaite noted that people with childhood trauma have at least double the risk of cancer in later life.
When researchers adjusted for lifestyle factors and chronic conditions, the association for cortisol was reduced and that for inflammation disappeared. However, the cumulative inflammatory markers remained significant.
Another model examined lipopolysaccharide-stimulated (LPS) immune-inflammatory markers by childhood trauma severity. This provides a more “dynamic” measure of stress systems than looking only at static circulating levels in the blood, as was done in the first model, said Ms. Kuzminskaite.
“These levels should theoretically be more affected by experiences such as childhood trauma and they are also less sensitive to lifestyle.”
Here, researchers found significant positive associations with childhood trauma, especially severe trauma, after adjusting for lifestyle and health-related covariates (cumulative index d = 0.19).
“Almost all people with childhood trauma, especially severe trauma, had LPS-stimulated cytokines upregulated,” said Ms. Kuzminskaite. “So again, there is this dysregulation of immune system functioning in these subjects.”
And again, the strongest effect was for the cumulative index of all cytokines, she said.
Personalized interventions
Ms. Kuzminskaite noted the importance of learning the impact of early trauma on stress responses. “The goal is to eventually have personalized interventions for people with depression or anxiety related to childhood trauma, or even preventative interventions. If we know, for example, something is going wrong with a patient’s stress systems, we can suggest some therapeutic targets.”
Investigators in Amsterdam are examining the efficacy of mifepristone, which blocks progesterone and is used along with misoprostol for medication abortions and to treat high blood sugar. “The drug is supposed to reset the stress system functioning,” said Ms. Kuzminskaite.
It’s still important to target unhealthy lifestyle habits “that are really impacting the functioning of the stress systems,” she said. Lifestyle interventions could improve the efficacy of treatments for depression, for example, she added.
Luana Marques, PhD, associate professor, department of psychiatry, Harvard Medical School, Boston, said such research is important.
“It reveals the potentially extensive and long-lasting impact of childhood trauma on functioning. The findings underscore the importance of equipping at-risk and trauma-exposed youth with evidence-based skills for managing stress,” she said.
No conflicts of interest were reported.
A version of this article first appeared on Medscape.com.
WASHINGTON –
“We already knew childhood trauma is associated with the later development of depressive and anxiety disorders, but it’s been unclear what makes sufferers of early trauma more likely to develop these psychiatric conditions,” study investigator Erika Kuzminskaite, PhD candidate, department of psychiatry, Amsterdam University Medical Center (UMC), the Netherlands, told this news organization.
“The evidence now points to unbalanced stress systems as a possible cause of this vulnerability, and now the most important question is, how we can develop preventive interventions,” she added.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Elevated cortisol, inflammation
The study included 2,779 adults from the Netherlands Study of Depression and Anxiety (NESDA). Two thirds of participants were female.
Participants retrospectively reported childhood trauma, defined as emotional, physical, or sexual abuse or emotional or physical neglect, before the age of 18 years. Severe trauma was defined as multiple types or increased frequency of abuse.
Of the total cohort, 48% reported experiencing some childhood trauma – 21% reported severe trauma, 27% reported mild trauma, and 42% reported no childhood trauma.
Among those with trauma, 89% had a current or remitted anxiety or depressive disorder, and 11% had no psychiatric sequelae. Among participants who reported no trauma, 68% had a current or remitted disorder, and 32% had no psychiatric disorders.
At baseline, researchers assessed markers of major bodily stress systems, including the hypothalamic-pituitary-adrenal (HPA) axis, the immune-inflammatory system, and the autonomic nervous system (ANS). They examined these markers separately and cumulatively.
In one model, investigators found that levels of cortisol and inflammation were significantly elevated in those with severe childhood trauma compared to those with no childhood trauma. The effects were largest for the cumulative markers for HPA-axis, inflammation, and all stress system markers (Cohen’s d = 0.23, 0.12, and 0.25, respectively). There was no association with ANS markers.
The results were partially explained by lifestyle, said Ms. Kuzminskaite, who noted that people with severe childhood trauma tend to have a higher body mass index, smoke more, and have other unhealthy habits that may represent a “coping” mechanism for trauma.
Those who experienced childhood trauma also have higher rates of other disorders, including asthma, diabetes, and cardiovascular disease. Ms. Kuzminskaite noted that people with childhood trauma have at least double the risk of cancer in later life.
When researchers adjusted for lifestyle factors and chronic conditions, the association for cortisol was reduced and that for inflammation disappeared. However, the cumulative inflammatory markers remained significant.
Another model examined lipopolysaccharide-stimulated (LPS) immune-inflammatory markers by childhood trauma severity. This provides a more “dynamic” measure of stress systems than looking only at static circulating levels in the blood, as was done in the first model, said Ms. Kuzminskaite.
“These levels should theoretically be more affected by experiences such as childhood trauma and they are also less sensitive to lifestyle.”
Here, researchers found significant positive associations with childhood trauma, especially severe trauma, after adjusting for lifestyle and health-related covariates (cumulative index d = 0.19).
“Almost all people with childhood trauma, especially severe trauma, had LPS-stimulated cytokines upregulated,” said Ms. Kuzminskaite. “So again, there is this dysregulation of immune system functioning in these subjects.”
And again, the strongest effect was for the cumulative index of all cytokines, she said.
Personalized interventions
Ms. Kuzminskaite noted the importance of learning the impact of early trauma on stress responses. “The goal is to eventually have personalized interventions for people with depression or anxiety related to childhood trauma, or even preventative interventions. If we know, for example, something is going wrong with a patient’s stress systems, we can suggest some therapeutic targets.”
Investigators in Amsterdam are examining the efficacy of mifepristone, which blocks progesterone and is used along with misoprostol for medication abortions and to treat high blood sugar. “The drug is supposed to reset the stress system functioning,” said Ms. Kuzminskaite.
It’s still important to target unhealthy lifestyle habits “that are really impacting the functioning of the stress systems,” she said. Lifestyle interventions could improve the efficacy of treatments for depression, for example, she added.
Luana Marques, PhD, associate professor, department of psychiatry, Harvard Medical School, Boston, said such research is important.
“It reveals the potentially extensive and long-lasting impact of childhood trauma on functioning. The findings underscore the importance of equipping at-risk and trauma-exposed youth with evidence-based skills for managing stress,” she said.
No conflicts of interest were reported.
A version of this article first appeared on Medscape.com.
AT ADAA 2023
Transcranial magnetic stimulation during pregnancy: An alternative to antidepressant treatment?
A growing number of women ask about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy.
The last several decades have brought an increasing level of comfort with respect to antidepressant use during pregnancy, which derives from several factors.
First, it’s been well described that there’s an increased risk of relapse and morbidity associated with discontinuation of antidepressants proximate to pregnancy, particularly in women with histories of recurrent disease (JAMA Psychiatry. 2023;80[5]:441-50 and JAMA. 2006;295[5]:499-507).
Second, there’s an obvious increased confidence about using antidepressants during pregnancy given the robust reproductive safety data about antidepressants with respect to both teratogenesis and risk for organ malformation. Other studies also fail to demonstrate a relationship between fetal exposure to antidepressants and risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD) and autism. These latter studies have been reviewed extensively in systematic reviews of meta-analyses addressing this question.
However, there are women who, as they approach the question of antidepressant use during pregnancy, would prefer a nonpharmacologic approach to managing depression in the setting of either a planned pregnancy, or sometimes in the setting of acute onset of depressive symptoms during pregnancy. Other women are more comfortable with the data in hand regarding the reproductive safety of antidepressants and continue antidepressants that have afforded emotional well-being, particularly if the road to well-being or euthymia has been a long one.
Still, we at Massachusetts General Hospital (MGH) Center for Women’s Mental Health along with multidisciplinary colleagues with whom we engage during our weekly Virtual Rounds community have observed a growing number of women asking about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy. They ask about these options for personal reasons, regardless of what we may know (and what we may not know) about existing pharmacologic interventions. In these scenarios, it is important to keep in mind that it is not about what we as clinicians necessarily know about these medicines per se that drives treatment, but rather about the private calculus that women and their partners apply about risk and benefit of pharmacologic treatment during pregnancy.
Nonpharmacologic treatment options
Mindfulness-based cognitive therapy (MBCT), cognitive behavioral therapy (CBT), and behavioral activation are therapies all of which have an evidence base with respect to their effectiveness for either the acute treatment of both depression (and perinatal depression specifically) or for mitigating risk for depressive relapse (MBCT). Several investigations are underway evaluating digital apps that utilize MBCT and CBT in these patient populations as well.
New treatments for which we have none or exceedingly sparse data to support use during pregnancy are neurosteroids. We are asked all the time about the use of neurosteroids such as brexanolone or zuranolone during pregnancy. Given the data on effectiveness of these agents for treatment of postpartum depression, the question about use during pregnancy is intuitive. But at this point in time, absent data, their use during pregnancy cannot be recommended.
With respect to newer nonpharmacologic approaches that have been looked at for treatment of major depressive disorder, the Food and Drug Administration has approved transcranial magnetic stimulation (TMS), a noninvasive form of neuromodulating therapy that use magnetic pulses to stimulate specific regions of the brain that have been implicated in psychiatric illness.
While there are no safety concerns that have been noted about use of TMS, the data regarding its use during pregnancy are still relatively limited, but it has been used to treat certain neurologic conditions during pregnancy. We now have a small randomized controlled study using TMS during pregnancy and multiple small case series suggesting a signal of efficacy in women with perinatal major depressive disorder. Side effects of TMS use during pregnancy have included hypotension, which has sometimes required repositioning of subjects, particularly later in pregnancy. Unlike electroconvulsive therapy, (ECT), often used when clinicians have exhausted other treatment options, TMS has no risk of seizure associated with its use.
TMS is now entering into the clinical arena in a more robust way. In certain settings, insurance companies are reimbursing for TMS treatment more often than was the case previously, making it a more viable option for a larger number of patients. There are also several exciting newer protocols, including theta burst stimulation, a new form of TMS treatment with less of a time commitment, and which may be more cost effective. However, data on this modality of treatment remain limited.
Where TMS fits in treating depression during pregnancy
The real question we are getting asked in clinic, both in person and during virtual rounds with multidisciplinary colleagues from across the world, is where TMS might fit into the algorithm for treating of depression during pregnancy. Where is it appropriate to be thinking about TMS in pregnancy, and where should it perhaps be deferred at this moment (and where is it not appropriate)?
It is probably of limited value (and possibly of potential harm) to switch to TMS in patients who have severe recurrent major depression and who are on maintenance antidepressant, and who believe that a switch to TMS will be effective for relapse prevention; there are simply no data currently suggesting that TMS can be used as a relapse prevention tool, unlike certain other nonpharmacologic interventions.
What about managing relapse of major depressive disorder during pregnancy in a patient who had responded to an antidepressant? We have seen patients with histories of severe recurrent disease who are managed well on antidepressants during pregnancy who then have breakthrough symptoms and inquire about using TMS as an augmentation strategy. Although we don’t have clear data supporting the use of TMS as an adjunct in that setting, in those patients, one could argue that a trial of TMS may be appropriate – as opposed to introducing multiple medicines to recapture euthymia during pregnancy where the benefit is unclear and where more exposure is implied by having to do potentially multiple trials.
Other patients with new onset of depression during pregnancy who, for personal reasons, will not take an antidepressant or pursue other nonpharmacologic interventions will frequently ask about TMS. and the increased availability of TMS in the community in various centers – as opposed to previously where it was more restricted to large academic medical centers.
I think it is a time of excitement in reproductive psychiatry where we have a growing number of tools to treat perinatal depression – from medications to digital tools. These tools – either alone or in combination with medicines that we’ve been using for years – are able to afford women a greater number of choices with respect to the treatment of perinatal depression than was available even 5 years ago. That takes us closer to an ability to use interventions that truly combine patient wishes and “precision perinatal psychiatry,” where we can match effective therapies with the individual clinical presentations and wishes with which patients come to us.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
A growing number of women ask about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy.
The last several decades have brought an increasing level of comfort with respect to antidepressant use during pregnancy, which derives from several factors.
First, it’s been well described that there’s an increased risk of relapse and morbidity associated with discontinuation of antidepressants proximate to pregnancy, particularly in women with histories of recurrent disease (JAMA Psychiatry. 2023;80[5]:441-50 and JAMA. 2006;295[5]:499-507).
Second, there’s an obvious increased confidence about using antidepressants during pregnancy given the robust reproductive safety data about antidepressants with respect to both teratogenesis and risk for organ malformation. Other studies also fail to demonstrate a relationship between fetal exposure to antidepressants and risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD) and autism. These latter studies have been reviewed extensively in systematic reviews of meta-analyses addressing this question.
However, there are women who, as they approach the question of antidepressant use during pregnancy, would prefer a nonpharmacologic approach to managing depression in the setting of either a planned pregnancy, or sometimes in the setting of acute onset of depressive symptoms during pregnancy. Other women are more comfortable with the data in hand regarding the reproductive safety of antidepressants and continue antidepressants that have afforded emotional well-being, particularly if the road to well-being or euthymia has been a long one.
Still, we at Massachusetts General Hospital (MGH) Center for Women’s Mental Health along with multidisciplinary colleagues with whom we engage during our weekly Virtual Rounds community have observed a growing number of women asking about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy. They ask about these options for personal reasons, regardless of what we may know (and what we may not know) about existing pharmacologic interventions. In these scenarios, it is important to keep in mind that it is not about what we as clinicians necessarily know about these medicines per se that drives treatment, but rather about the private calculus that women and their partners apply about risk and benefit of pharmacologic treatment during pregnancy.
Nonpharmacologic treatment options
Mindfulness-based cognitive therapy (MBCT), cognitive behavioral therapy (CBT), and behavioral activation are therapies all of which have an evidence base with respect to their effectiveness for either the acute treatment of both depression (and perinatal depression specifically) or for mitigating risk for depressive relapse (MBCT). Several investigations are underway evaluating digital apps that utilize MBCT and CBT in these patient populations as well.
New treatments for which we have none or exceedingly sparse data to support use during pregnancy are neurosteroids. We are asked all the time about the use of neurosteroids such as brexanolone or zuranolone during pregnancy. Given the data on effectiveness of these agents for treatment of postpartum depression, the question about use during pregnancy is intuitive. But at this point in time, absent data, their use during pregnancy cannot be recommended.
With respect to newer nonpharmacologic approaches that have been looked at for treatment of major depressive disorder, the Food and Drug Administration has approved transcranial magnetic stimulation (TMS), a noninvasive form of neuromodulating therapy that use magnetic pulses to stimulate specific regions of the brain that have been implicated in psychiatric illness.
While there are no safety concerns that have been noted about use of TMS, the data regarding its use during pregnancy are still relatively limited, but it has been used to treat certain neurologic conditions during pregnancy. We now have a small randomized controlled study using TMS during pregnancy and multiple small case series suggesting a signal of efficacy in women with perinatal major depressive disorder. Side effects of TMS use during pregnancy have included hypotension, which has sometimes required repositioning of subjects, particularly later in pregnancy. Unlike electroconvulsive therapy, (ECT), often used when clinicians have exhausted other treatment options, TMS has no risk of seizure associated with its use.
TMS is now entering into the clinical arena in a more robust way. In certain settings, insurance companies are reimbursing for TMS treatment more often than was the case previously, making it a more viable option for a larger number of patients. There are also several exciting newer protocols, including theta burst stimulation, a new form of TMS treatment with less of a time commitment, and which may be more cost effective. However, data on this modality of treatment remain limited.
Where TMS fits in treating depression during pregnancy
The real question we are getting asked in clinic, both in person and during virtual rounds with multidisciplinary colleagues from across the world, is where TMS might fit into the algorithm for treating of depression during pregnancy. Where is it appropriate to be thinking about TMS in pregnancy, and where should it perhaps be deferred at this moment (and where is it not appropriate)?
It is probably of limited value (and possibly of potential harm) to switch to TMS in patients who have severe recurrent major depression and who are on maintenance antidepressant, and who believe that a switch to TMS will be effective for relapse prevention; there are simply no data currently suggesting that TMS can be used as a relapse prevention tool, unlike certain other nonpharmacologic interventions.
What about managing relapse of major depressive disorder during pregnancy in a patient who had responded to an antidepressant? We have seen patients with histories of severe recurrent disease who are managed well on antidepressants during pregnancy who then have breakthrough symptoms and inquire about using TMS as an augmentation strategy. Although we don’t have clear data supporting the use of TMS as an adjunct in that setting, in those patients, one could argue that a trial of TMS may be appropriate – as opposed to introducing multiple medicines to recapture euthymia during pregnancy where the benefit is unclear and where more exposure is implied by having to do potentially multiple trials.
Other patients with new onset of depression during pregnancy who, for personal reasons, will not take an antidepressant or pursue other nonpharmacologic interventions will frequently ask about TMS. and the increased availability of TMS in the community in various centers – as opposed to previously where it was more restricted to large academic medical centers.
I think it is a time of excitement in reproductive psychiatry where we have a growing number of tools to treat perinatal depression – from medications to digital tools. These tools – either alone or in combination with medicines that we’ve been using for years – are able to afford women a greater number of choices with respect to the treatment of perinatal depression than was available even 5 years ago. That takes us closer to an ability to use interventions that truly combine patient wishes and “precision perinatal psychiatry,” where we can match effective therapies with the individual clinical presentations and wishes with which patients come to us.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
A growing number of women ask about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy.
The last several decades have brought an increasing level of comfort with respect to antidepressant use during pregnancy, which derives from several factors.
First, it’s been well described that there’s an increased risk of relapse and morbidity associated with discontinuation of antidepressants proximate to pregnancy, particularly in women with histories of recurrent disease (JAMA Psychiatry. 2023;80[5]:441-50 and JAMA. 2006;295[5]:499-507).
Second, there’s an obvious increased confidence about using antidepressants during pregnancy given the robust reproductive safety data about antidepressants with respect to both teratogenesis and risk for organ malformation. Other studies also fail to demonstrate a relationship between fetal exposure to antidepressants and risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD) and autism. These latter studies have been reviewed extensively in systematic reviews of meta-analyses addressing this question.
However, there are women who, as they approach the question of antidepressant use during pregnancy, would prefer a nonpharmacologic approach to managing depression in the setting of either a planned pregnancy, or sometimes in the setting of acute onset of depressive symptoms during pregnancy. Other women are more comfortable with the data in hand regarding the reproductive safety of antidepressants and continue antidepressants that have afforded emotional well-being, particularly if the road to well-being or euthymia has been a long one.
Still, we at Massachusetts General Hospital (MGH) Center for Women’s Mental Health along with multidisciplinary colleagues with whom we engage during our weekly Virtual Rounds community have observed a growing number of women asking about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy. They ask about these options for personal reasons, regardless of what we may know (and what we may not know) about existing pharmacologic interventions. In these scenarios, it is important to keep in mind that it is not about what we as clinicians necessarily know about these medicines per se that drives treatment, but rather about the private calculus that women and their partners apply about risk and benefit of pharmacologic treatment during pregnancy.
Nonpharmacologic treatment options
Mindfulness-based cognitive therapy (MBCT), cognitive behavioral therapy (CBT), and behavioral activation are therapies all of which have an evidence base with respect to their effectiveness for either the acute treatment of both depression (and perinatal depression specifically) or for mitigating risk for depressive relapse (MBCT). Several investigations are underway evaluating digital apps that utilize MBCT and CBT in these patient populations as well.
New treatments for which we have none or exceedingly sparse data to support use during pregnancy are neurosteroids. We are asked all the time about the use of neurosteroids such as brexanolone or zuranolone during pregnancy. Given the data on effectiveness of these agents for treatment of postpartum depression, the question about use during pregnancy is intuitive. But at this point in time, absent data, their use during pregnancy cannot be recommended.
With respect to newer nonpharmacologic approaches that have been looked at for treatment of major depressive disorder, the Food and Drug Administration has approved transcranial magnetic stimulation (TMS), a noninvasive form of neuromodulating therapy that use magnetic pulses to stimulate specific regions of the brain that have been implicated in psychiatric illness.
While there are no safety concerns that have been noted about use of TMS, the data regarding its use during pregnancy are still relatively limited, but it has been used to treat certain neurologic conditions during pregnancy. We now have a small randomized controlled study using TMS during pregnancy and multiple small case series suggesting a signal of efficacy in women with perinatal major depressive disorder. Side effects of TMS use during pregnancy have included hypotension, which has sometimes required repositioning of subjects, particularly later in pregnancy. Unlike electroconvulsive therapy, (ECT), often used when clinicians have exhausted other treatment options, TMS has no risk of seizure associated with its use.
TMS is now entering into the clinical arena in a more robust way. In certain settings, insurance companies are reimbursing for TMS treatment more often than was the case previously, making it a more viable option for a larger number of patients. There are also several exciting newer protocols, including theta burst stimulation, a new form of TMS treatment with less of a time commitment, and which may be more cost effective. However, data on this modality of treatment remain limited.
Where TMS fits in treating depression during pregnancy
The real question we are getting asked in clinic, both in person and during virtual rounds with multidisciplinary colleagues from across the world, is where TMS might fit into the algorithm for treating of depression during pregnancy. Where is it appropriate to be thinking about TMS in pregnancy, and where should it perhaps be deferred at this moment (and where is it not appropriate)?
It is probably of limited value (and possibly of potential harm) to switch to TMS in patients who have severe recurrent major depression and who are on maintenance antidepressant, and who believe that a switch to TMS will be effective for relapse prevention; there are simply no data currently suggesting that TMS can be used as a relapse prevention tool, unlike certain other nonpharmacologic interventions.
What about managing relapse of major depressive disorder during pregnancy in a patient who had responded to an antidepressant? We have seen patients with histories of severe recurrent disease who are managed well on antidepressants during pregnancy who then have breakthrough symptoms and inquire about using TMS as an augmentation strategy. Although we don’t have clear data supporting the use of TMS as an adjunct in that setting, in those patients, one could argue that a trial of TMS may be appropriate – as opposed to introducing multiple medicines to recapture euthymia during pregnancy where the benefit is unclear and where more exposure is implied by having to do potentially multiple trials.
Other patients with new onset of depression during pregnancy who, for personal reasons, will not take an antidepressant or pursue other nonpharmacologic interventions will frequently ask about TMS. and the increased availability of TMS in the community in various centers – as opposed to previously where it was more restricted to large academic medical centers.
I think it is a time of excitement in reproductive psychiatry where we have a growing number of tools to treat perinatal depression – from medications to digital tools. These tools – either alone or in combination with medicines that we’ve been using for years – are able to afford women a greater number of choices with respect to the treatment of perinatal depression than was available even 5 years ago. That takes us closer to an ability to use interventions that truly combine patient wishes and “precision perinatal psychiatry,” where we can match effective therapies with the individual clinical presentations and wishes with which patients come to us.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].
Disrupted gut microbiome a key driver of major depression?
Investigators found that MDD had specific metabolic “signatures” consisting of 124 metabolites that spanned energy and lipid pathways, with some involving the tricarboxylic acid cycle in particular. These changes in metabolites were consistent with differences in composition of several gut microbiota.
The researchers found that fatty acids and intermediate and very large lipoproteins changed in association with the depressive disease process. However, high-density lipoproteins and metabolites in the tricarboxylic acid cycle did not.
“As we wait to establish causal influences through clinical trials, clinicians should advise patients suffering from mood disorders to modify their diet by increasing the intake of fresh fruits, vegetables, and whole grains, as these provide the required fuel/fiber to the gut microbiota for their enrichment, and more short-chain fatty acids are produced for the optimal functioning of the body,” study investigator Najaf Amin, PhD, DSc, senior researcher, Nuffield Department of Population Health, Oxford University, England, told this news organization.
“At the same time, patients should be advised to minimize the intake of sugars and processed foods, which are known to have an inverse impact on the gut microbiome and are associated with higher inflammation,” she said.
The study was published online in JAMA Psychiatry.
MDD poorly understood
Although most antidepressants target the monoamine pathway, “evidence is increasing for a more complex interplay of multiple pathways involving a wide range of metabolic alterations spanning energy and lipid metabolism,” the authors wrote.
Previous research using the Nightingale proton nuclear magnetic resonance (NMR) metabolomics platform showed a “shift” toward decreased levels of high-density lipoproteins (HDLs) and increased levels of very low-density lipoproteins (VLDLs) and triglycerides among patients with depression.
The gut microbiome, which is primarily modulated by diet, “has been shown to be a major determinant of circulating lipids, specifically triglycerides and HDLs, and to regulate mitochondrial function,” the investigators noted. Patients with MDD are known to have disruptions in the gut microbiome.
The gut microbiome may “explain part of the shift in VLDL and HDL levels observed in patients with depression and if the metabolic signatures of the disease based on Nightingale metabolites can be used as a tool to infer the association between gut microbiome and depression.”
Dr. Amin called depression “one of the most poorly understood diseases, as underlying mechanisms remain elusive.”
Large-scale genetic studies “have shown that the contribution of genetics to depression is modest,” she continued. On the other hand, initial animal studies suggest the gut microbiome “may potentially have a causal influence on depression.”
Several studies have evaluated the influence of gut microbiome on depression, “but, due to small sample sizes and inadequate control for confounding factors, most of their findings were not reproducible.”
Harnessing the power of the UK Biobank, the investigators studied 58,257 individuals who were between the ages of 37 and 73 years at recruitment. They used data on NMR spectroscopy–based plasma metabolites in depression. Individuals who didn’t report depression at baseline served as controls.
Logistic regression analysis was used to test the association of metabolite levels with depression in four models, each with an increasing number of covariates.
To identify patterns of correlation in the “metabolic signatures of MDD and the human gut biome,” they regressed the metabolic signatures of MDD on the metabolic signatures of the gut microbiota and then regressed the metabolic signature of gut microbiota on the metabolic signatures of MDD.
Bidirectional 2-sample Mendelian randomization was used to ascertain the direction of the association observed between metabolites and MDD.
Individuals with lifetime and recurrent MDD were compared with controls (6,811 vs. 51,446 and 4,370 vs. 62,508, respectively).
Participants with lifetime MDD were significantly younger (median [IQR] age, 56 [49-62] years vs. 58 [51-64] years) and were more likely to be female in comparison with controls (54% vs. 35%).
‘Novel findings’
In the fully adjusted analysis, metabolic signatures of MDD were found to consist of 124 metabolites that spanned energy and lipid metabolism pathways.
The investigators noted that these “novel findings” included 49 metabolites encompassing those involved in the tricarboxylic acid cycle – citrate and pyruvate.
The findings revealed that fatty acids and intermediate and VLDL changed in association with the disease process. On the other hand, HDL and the metabolites in the tricarboxylic acid cycle did not.
“We observed that the genera Sellimonas, Eggerthella, Hungatella, and Lachnoclostridium were more abundant, while genera Ruminococcaceae ... Coprococcus, Lachnospiraceae ... Eubacterium ventriosum, Subdoligranulum, and family Ruminococcaceae were depleted in the guts of individuals with more symptoms of depression,” said Dr. Amin. “Of these, genus Eggerthella showed statistical evidence of being involved in the causal pathway.”
These microbes are involved in the synthesis of important neurotransmitters, such as gamma aminobutyric acid, butyrate, glutamate, and serotonin, she noted.
Butyrate produced by the gut can cross the blood-brain barrier, enter the brain, and affect transcriptional and translational activity or be used by the cells for generating energy, she added. “So basically, butyrate can influence depression through several routes – i.e., via immune regulation, genomic transcript/translation, and/or affecting energy metabolism.”
No causality
Commenting on the study, Emeran Mayer, MD, distinguished research professor of medicine, G. Oppenheimer Center for Neurobiology of Stress and Resilience and UCLA Brain Gut Microbiome Center, called it the “largest, most comprehensive and best validated association study to date providing further evidence for an association between gut microbial taxa, previously identified in patients with MDD, blood metabolites (generated by host and by microbes) and questionnaire data.”
However, “despite its strengths, the study does not allow [us] to identify a causal role of the microbiome alterations in the observed microbial and metabolic changes (fatty acids, Krebs cycle components),” cautioned Dr. Mayer, who was not involved with the study.
Moreover, “causality of gut microbial changes on the behavioral phenotype of depression cannot been inferred,” he concluded.
Metabolomics data were provided by the Alzheimer’s Disease Metabolomics Consortium. The study was funded wholly or in part by grants from the National Institute on Aging and Foundation for the National Institutes of Health. It was further supported by a grant from ZonMW Memorabel. Dr. Amin reports no relevant financial relationships. The other authors’ disclosures are listed oin the original article. Dr. Mayer is a scientific advisory board member of Danone, Axial Therapeutics, Viome, Amare, Mahana Therapeutics, Pendulum, Bloom Biosciences, and APC Microbiome Ireland.
A version of this article originally appeared on Medscape.com.
Investigators found that MDD had specific metabolic “signatures” consisting of 124 metabolites that spanned energy and lipid pathways, with some involving the tricarboxylic acid cycle in particular. These changes in metabolites were consistent with differences in composition of several gut microbiota.
The researchers found that fatty acids and intermediate and very large lipoproteins changed in association with the depressive disease process. However, high-density lipoproteins and metabolites in the tricarboxylic acid cycle did not.
“As we wait to establish causal influences through clinical trials, clinicians should advise patients suffering from mood disorders to modify their diet by increasing the intake of fresh fruits, vegetables, and whole grains, as these provide the required fuel/fiber to the gut microbiota for their enrichment, and more short-chain fatty acids are produced for the optimal functioning of the body,” study investigator Najaf Amin, PhD, DSc, senior researcher, Nuffield Department of Population Health, Oxford University, England, told this news organization.
“At the same time, patients should be advised to minimize the intake of sugars and processed foods, which are known to have an inverse impact on the gut microbiome and are associated with higher inflammation,” she said.
The study was published online in JAMA Psychiatry.
MDD poorly understood
Although most antidepressants target the monoamine pathway, “evidence is increasing for a more complex interplay of multiple pathways involving a wide range of metabolic alterations spanning energy and lipid metabolism,” the authors wrote.
Previous research using the Nightingale proton nuclear magnetic resonance (NMR) metabolomics platform showed a “shift” toward decreased levels of high-density lipoproteins (HDLs) and increased levels of very low-density lipoproteins (VLDLs) and triglycerides among patients with depression.
The gut microbiome, which is primarily modulated by diet, “has been shown to be a major determinant of circulating lipids, specifically triglycerides and HDLs, and to regulate mitochondrial function,” the investigators noted. Patients with MDD are known to have disruptions in the gut microbiome.
The gut microbiome may “explain part of the shift in VLDL and HDL levels observed in patients with depression and if the metabolic signatures of the disease based on Nightingale metabolites can be used as a tool to infer the association between gut microbiome and depression.”
Dr. Amin called depression “one of the most poorly understood diseases, as underlying mechanisms remain elusive.”
Large-scale genetic studies “have shown that the contribution of genetics to depression is modest,” she continued. On the other hand, initial animal studies suggest the gut microbiome “may potentially have a causal influence on depression.”
Several studies have evaluated the influence of gut microbiome on depression, “but, due to small sample sizes and inadequate control for confounding factors, most of their findings were not reproducible.”
Harnessing the power of the UK Biobank, the investigators studied 58,257 individuals who were between the ages of 37 and 73 years at recruitment. They used data on NMR spectroscopy–based plasma metabolites in depression. Individuals who didn’t report depression at baseline served as controls.
Logistic regression analysis was used to test the association of metabolite levels with depression in four models, each with an increasing number of covariates.
To identify patterns of correlation in the “metabolic signatures of MDD and the human gut biome,” they regressed the metabolic signatures of MDD on the metabolic signatures of the gut microbiota and then regressed the metabolic signature of gut microbiota on the metabolic signatures of MDD.
Bidirectional 2-sample Mendelian randomization was used to ascertain the direction of the association observed between metabolites and MDD.
Individuals with lifetime and recurrent MDD were compared with controls (6,811 vs. 51,446 and 4,370 vs. 62,508, respectively).
Participants with lifetime MDD were significantly younger (median [IQR] age, 56 [49-62] years vs. 58 [51-64] years) and were more likely to be female in comparison with controls (54% vs. 35%).
‘Novel findings’
In the fully adjusted analysis, metabolic signatures of MDD were found to consist of 124 metabolites that spanned energy and lipid metabolism pathways.
The investigators noted that these “novel findings” included 49 metabolites encompassing those involved in the tricarboxylic acid cycle – citrate and pyruvate.
The findings revealed that fatty acids and intermediate and VLDL changed in association with the disease process. On the other hand, HDL and the metabolites in the tricarboxylic acid cycle did not.
“We observed that the genera Sellimonas, Eggerthella, Hungatella, and Lachnoclostridium were more abundant, while genera Ruminococcaceae ... Coprococcus, Lachnospiraceae ... Eubacterium ventriosum, Subdoligranulum, and family Ruminococcaceae were depleted in the guts of individuals with more symptoms of depression,” said Dr. Amin. “Of these, genus Eggerthella showed statistical evidence of being involved in the causal pathway.”
These microbes are involved in the synthesis of important neurotransmitters, such as gamma aminobutyric acid, butyrate, glutamate, and serotonin, she noted.
Butyrate produced by the gut can cross the blood-brain barrier, enter the brain, and affect transcriptional and translational activity or be used by the cells for generating energy, she added. “So basically, butyrate can influence depression through several routes – i.e., via immune regulation, genomic transcript/translation, and/or affecting energy metabolism.”
No causality
Commenting on the study, Emeran Mayer, MD, distinguished research professor of medicine, G. Oppenheimer Center for Neurobiology of Stress and Resilience and UCLA Brain Gut Microbiome Center, called it the “largest, most comprehensive and best validated association study to date providing further evidence for an association between gut microbial taxa, previously identified in patients with MDD, blood metabolites (generated by host and by microbes) and questionnaire data.”
However, “despite its strengths, the study does not allow [us] to identify a causal role of the microbiome alterations in the observed microbial and metabolic changes (fatty acids, Krebs cycle components),” cautioned Dr. Mayer, who was not involved with the study.
Moreover, “causality of gut microbial changes on the behavioral phenotype of depression cannot been inferred,” he concluded.
Metabolomics data were provided by the Alzheimer’s Disease Metabolomics Consortium. The study was funded wholly or in part by grants from the National Institute on Aging and Foundation for the National Institutes of Health. It was further supported by a grant from ZonMW Memorabel. Dr. Amin reports no relevant financial relationships. The other authors’ disclosures are listed oin the original article. Dr. Mayer is a scientific advisory board member of Danone, Axial Therapeutics, Viome, Amare, Mahana Therapeutics, Pendulum, Bloom Biosciences, and APC Microbiome Ireland.
A version of this article originally appeared on Medscape.com.
Investigators found that MDD had specific metabolic “signatures” consisting of 124 metabolites that spanned energy and lipid pathways, with some involving the tricarboxylic acid cycle in particular. These changes in metabolites were consistent with differences in composition of several gut microbiota.
The researchers found that fatty acids and intermediate and very large lipoproteins changed in association with the depressive disease process. However, high-density lipoproteins and metabolites in the tricarboxylic acid cycle did not.
“As we wait to establish causal influences through clinical trials, clinicians should advise patients suffering from mood disorders to modify their diet by increasing the intake of fresh fruits, vegetables, and whole grains, as these provide the required fuel/fiber to the gut microbiota for their enrichment, and more short-chain fatty acids are produced for the optimal functioning of the body,” study investigator Najaf Amin, PhD, DSc, senior researcher, Nuffield Department of Population Health, Oxford University, England, told this news organization.
“At the same time, patients should be advised to minimize the intake of sugars and processed foods, which are known to have an inverse impact on the gut microbiome and are associated with higher inflammation,” she said.
The study was published online in JAMA Psychiatry.
MDD poorly understood
Although most antidepressants target the monoamine pathway, “evidence is increasing for a more complex interplay of multiple pathways involving a wide range of metabolic alterations spanning energy and lipid metabolism,” the authors wrote.
Previous research using the Nightingale proton nuclear magnetic resonance (NMR) metabolomics platform showed a “shift” toward decreased levels of high-density lipoproteins (HDLs) and increased levels of very low-density lipoproteins (VLDLs) and triglycerides among patients with depression.
The gut microbiome, which is primarily modulated by diet, “has been shown to be a major determinant of circulating lipids, specifically triglycerides and HDLs, and to regulate mitochondrial function,” the investigators noted. Patients with MDD are known to have disruptions in the gut microbiome.
The gut microbiome may “explain part of the shift in VLDL and HDL levels observed in patients with depression and if the metabolic signatures of the disease based on Nightingale metabolites can be used as a tool to infer the association between gut microbiome and depression.”
Dr. Amin called depression “one of the most poorly understood diseases, as underlying mechanisms remain elusive.”
Large-scale genetic studies “have shown that the contribution of genetics to depression is modest,” she continued. On the other hand, initial animal studies suggest the gut microbiome “may potentially have a causal influence on depression.”
Several studies have evaluated the influence of gut microbiome on depression, “but, due to small sample sizes and inadequate control for confounding factors, most of their findings were not reproducible.”
Harnessing the power of the UK Biobank, the investigators studied 58,257 individuals who were between the ages of 37 and 73 years at recruitment. They used data on NMR spectroscopy–based plasma metabolites in depression. Individuals who didn’t report depression at baseline served as controls.
Logistic regression analysis was used to test the association of metabolite levels with depression in four models, each with an increasing number of covariates.
To identify patterns of correlation in the “metabolic signatures of MDD and the human gut biome,” they regressed the metabolic signatures of MDD on the metabolic signatures of the gut microbiota and then regressed the metabolic signature of gut microbiota on the metabolic signatures of MDD.
Bidirectional 2-sample Mendelian randomization was used to ascertain the direction of the association observed between metabolites and MDD.
Individuals with lifetime and recurrent MDD were compared with controls (6,811 vs. 51,446 and 4,370 vs. 62,508, respectively).
Participants with lifetime MDD were significantly younger (median [IQR] age, 56 [49-62] years vs. 58 [51-64] years) and were more likely to be female in comparison with controls (54% vs. 35%).
‘Novel findings’
In the fully adjusted analysis, metabolic signatures of MDD were found to consist of 124 metabolites that spanned energy and lipid metabolism pathways.
The investigators noted that these “novel findings” included 49 metabolites encompassing those involved in the tricarboxylic acid cycle – citrate and pyruvate.
The findings revealed that fatty acids and intermediate and VLDL changed in association with the disease process. On the other hand, HDL and the metabolites in the tricarboxylic acid cycle did not.
“We observed that the genera Sellimonas, Eggerthella, Hungatella, and Lachnoclostridium were more abundant, while genera Ruminococcaceae ... Coprococcus, Lachnospiraceae ... Eubacterium ventriosum, Subdoligranulum, and family Ruminococcaceae were depleted in the guts of individuals with more symptoms of depression,” said Dr. Amin. “Of these, genus Eggerthella showed statistical evidence of being involved in the causal pathway.”
These microbes are involved in the synthesis of important neurotransmitters, such as gamma aminobutyric acid, butyrate, glutamate, and serotonin, she noted.
Butyrate produced by the gut can cross the blood-brain barrier, enter the brain, and affect transcriptional and translational activity or be used by the cells for generating energy, she added. “So basically, butyrate can influence depression through several routes – i.e., via immune regulation, genomic transcript/translation, and/or affecting energy metabolism.”
No causality
Commenting on the study, Emeran Mayer, MD, distinguished research professor of medicine, G. Oppenheimer Center for Neurobiology of Stress and Resilience and UCLA Brain Gut Microbiome Center, called it the “largest, most comprehensive and best validated association study to date providing further evidence for an association between gut microbial taxa, previously identified in patients with MDD, blood metabolites (generated by host and by microbes) and questionnaire data.”
However, “despite its strengths, the study does not allow [us] to identify a causal role of the microbiome alterations in the observed microbial and metabolic changes (fatty acids, Krebs cycle components),” cautioned Dr. Mayer, who was not involved with the study.
Moreover, “causality of gut microbial changes on the behavioral phenotype of depression cannot been inferred,” he concluded.
Metabolomics data were provided by the Alzheimer’s Disease Metabolomics Consortium. The study was funded wholly or in part by grants from the National Institute on Aging and Foundation for the National Institutes of Health. It was further supported by a grant from ZonMW Memorabel. Dr. Amin reports no relevant financial relationships. The other authors’ disclosures are listed oin the original article. Dr. Mayer is a scientific advisory board member of Danone, Axial Therapeutics, Viome, Amare, Mahana Therapeutics, Pendulum, Bloom Biosciences, and APC Microbiome Ireland.
A version of this article originally appeared on Medscape.com.
FROM JAMA PSYCHIATRY
Telehealth suicide prevention program safe, acceptable
WASHINGTON –
Skeptics had worried that participating in the program through telehealth would exacerbate safety and other issues veterans had about discussing suicide in a group setting, study investigator Sarah Sullivan, PhD student, Health Psychology & Clinical Science, City University of New York, told this news organization.
“But that for us was not really true. People opened up about their suicidal thoughts and triggers even on this telehealth format, and that’s really important for providers to know,” she said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Trial run
Suicide is a major public health issue, particularly for veterans. Recent data from the Veterans Administration show 17 veterans die by suicide every day.
The current study included 15 male and 2 female veterans (29.4% White, 70.6% Hispanic) from New York City and Philadelphia. Participants had an average age of 50 and all were either deemed by a clinician to be at extremely high risk for suicide or were hospitalized for this reason.
The individuals completed an online version of the Project Life Force (PLF) program, which uses dialectical behavioral therapy and psychoeducational approaches. The program includes the brief Safety Planning intervention (SPI), aimed at reducing short-term suicide risk.
Considered a best practice, the SPI includes a written list of personal suicide warning signs or triggers, internal coping strategies, social contacts who offer support and distraction from suicidal thoughts, contact information for professionals, a suicide crisis hotline, and nearby emergency services.
In addition to these steps, the PLF program focuses on sleep, exercise, and making the safety plan accessible.
The telehealth platform for the program was WebEx software. Participants were offered a “trial run” to orient them to the technology, said Ms. Sullivan.
Group sessions were held once weekly for 10 weeks, with optional “booster” sessions if needed. Each session included about five participants.
To ensure privacy, participants were provided with headphones and laptops. This was especially important for those sharing a living space, including spouses and children, said Ms. Sullivan.
High ratings
Participants completed the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Each of these yields scores from four items rated on a Likert scale of 1-5, for a total score ranging from 5 to 20, with higher scores indicating higher ratings.
Veterans rated PLF-T as highly acceptable (mean AIM, 17.50), appropriate (mean IAM, 17.25), and feasible (mean FIM, 18).
Study participants reported the program was convenient and noted that it decreased the burden of traveling to sessions, especially during the COVID-19 pandemic.
They also reported the program was less likely to compete with other demands such as childcare and other appointments, said Ms. Sullivan.
In addition, it helped those with comorbidities such as posttraumatic stress disorder, she added. She noted veterans with PTSD may be triggered on subways or buses when traveling to in-person treatment sessions.
“That can take away from addressing the suicidal triggers,” said Ms. Sullivan. “So, this program allows them to fully concentrate on the safety plan.”
Results showed that study participants “enjoyed the group and would recommend it to others,” said Ms. Sullivan. “I think that signifies the group was effective in its goal of mitigating loneliness, which was exacerbated during the COVID-19 pandemic, and creating a socially supportive environment, especially for the vets living alone.”
Veterans also reported that the program helped them understand the connection between depression or PTSD and suicidal thoughts, urges, and plans. In addition, they appreciated the group dynamics, where they felt connected to other veterans experiencing similar challenges.
Hopeful results
Commenting on the study, Paul E. Holtzheimer, MD, deputy director for research at the National Center for PTSD, praised the study for focusing on a very high-risk group.
“This gets you closer to the population you’re probably going to have an impact on in terms of preventing suicide,” said Dr. Holtzheimer, a professor of psychiatry and surgery at Dartmouth College’s Geisel School of Medicine, Hanover, N.H.
The fact that many of the participants had attempted suicide in the last year underlines that this was a very high-risk population, said Dr. Holtzheimer. “Not only are they thinking about suicide, but almost two-thirds had actually attempted or tried something.”
This kind of program “would be great for rural environments where people may be living like four hours away from the VA or a clinic,” said Dr. Holtzheimer, noting that many veterans are often quite isolated.
“One of the very positive outcomes of the COVID-19 pandemic was helping us strengthen our ability to do telehealth,” he said.
However, Dr. Holtzheimer noted the study was small and qualitative. “The next step ideally would be a controlled trial looking at not just ideation but at risky behavior or clear suicide attempts or preparation, like buying a gun or hoarding medication, to help determine efficacy.”
The researchers and Dr. Holtzheimer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON –
Skeptics had worried that participating in the program through telehealth would exacerbate safety and other issues veterans had about discussing suicide in a group setting, study investigator Sarah Sullivan, PhD student, Health Psychology & Clinical Science, City University of New York, told this news organization.
“But that for us was not really true. People opened up about their suicidal thoughts and triggers even on this telehealth format, and that’s really important for providers to know,” she said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Trial run
Suicide is a major public health issue, particularly for veterans. Recent data from the Veterans Administration show 17 veterans die by suicide every day.
The current study included 15 male and 2 female veterans (29.4% White, 70.6% Hispanic) from New York City and Philadelphia. Participants had an average age of 50 and all were either deemed by a clinician to be at extremely high risk for suicide or were hospitalized for this reason.
The individuals completed an online version of the Project Life Force (PLF) program, which uses dialectical behavioral therapy and psychoeducational approaches. The program includes the brief Safety Planning intervention (SPI), aimed at reducing short-term suicide risk.
Considered a best practice, the SPI includes a written list of personal suicide warning signs or triggers, internal coping strategies, social contacts who offer support and distraction from suicidal thoughts, contact information for professionals, a suicide crisis hotline, and nearby emergency services.
In addition to these steps, the PLF program focuses on sleep, exercise, and making the safety plan accessible.
The telehealth platform for the program was WebEx software. Participants were offered a “trial run” to orient them to the technology, said Ms. Sullivan.
Group sessions were held once weekly for 10 weeks, with optional “booster” sessions if needed. Each session included about five participants.
To ensure privacy, participants were provided with headphones and laptops. This was especially important for those sharing a living space, including spouses and children, said Ms. Sullivan.
High ratings
Participants completed the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Each of these yields scores from four items rated on a Likert scale of 1-5, for a total score ranging from 5 to 20, with higher scores indicating higher ratings.
Veterans rated PLF-T as highly acceptable (mean AIM, 17.50), appropriate (mean IAM, 17.25), and feasible (mean FIM, 18).
Study participants reported the program was convenient and noted that it decreased the burden of traveling to sessions, especially during the COVID-19 pandemic.
They also reported the program was less likely to compete with other demands such as childcare and other appointments, said Ms. Sullivan.
In addition, it helped those with comorbidities such as posttraumatic stress disorder, she added. She noted veterans with PTSD may be triggered on subways or buses when traveling to in-person treatment sessions.
“That can take away from addressing the suicidal triggers,” said Ms. Sullivan. “So, this program allows them to fully concentrate on the safety plan.”
Results showed that study participants “enjoyed the group and would recommend it to others,” said Ms. Sullivan. “I think that signifies the group was effective in its goal of mitigating loneliness, which was exacerbated during the COVID-19 pandemic, and creating a socially supportive environment, especially for the vets living alone.”
Veterans also reported that the program helped them understand the connection between depression or PTSD and suicidal thoughts, urges, and plans. In addition, they appreciated the group dynamics, where they felt connected to other veterans experiencing similar challenges.
Hopeful results
Commenting on the study, Paul E. Holtzheimer, MD, deputy director for research at the National Center for PTSD, praised the study for focusing on a very high-risk group.
“This gets you closer to the population you’re probably going to have an impact on in terms of preventing suicide,” said Dr. Holtzheimer, a professor of psychiatry and surgery at Dartmouth College’s Geisel School of Medicine, Hanover, N.H.
The fact that many of the participants had attempted suicide in the last year underlines that this was a very high-risk population, said Dr. Holtzheimer. “Not only are they thinking about suicide, but almost two-thirds had actually attempted or tried something.”
This kind of program “would be great for rural environments where people may be living like four hours away from the VA or a clinic,” said Dr. Holtzheimer, noting that many veterans are often quite isolated.
“One of the very positive outcomes of the COVID-19 pandemic was helping us strengthen our ability to do telehealth,” he said.
However, Dr. Holtzheimer noted the study was small and qualitative. “The next step ideally would be a controlled trial looking at not just ideation but at risky behavior or clear suicide attempts or preparation, like buying a gun or hoarding medication, to help determine efficacy.”
The researchers and Dr. Holtzheimer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON –
Skeptics had worried that participating in the program through telehealth would exacerbate safety and other issues veterans had about discussing suicide in a group setting, study investigator Sarah Sullivan, PhD student, Health Psychology & Clinical Science, City University of New York, told this news organization.
“But that for us was not really true. People opened up about their suicidal thoughts and triggers even on this telehealth format, and that’s really important for providers to know,” she said.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Trial run
Suicide is a major public health issue, particularly for veterans. Recent data from the Veterans Administration show 17 veterans die by suicide every day.
The current study included 15 male and 2 female veterans (29.4% White, 70.6% Hispanic) from New York City and Philadelphia. Participants had an average age of 50 and all were either deemed by a clinician to be at extremely high risk for suicide or were hospitalized for this reason.
The individuals completed an online version of the Project Life Force (PLF) program, which uses dialectical behavioral therapy and psychoeducational approaches. The program includes the brief Safety Planning intervention (SPI), aimed at reducing short-term suicide risk.
Considered a best practice, the SPI includes a written list of personal suicide warning signs or triggers, internal coping strategies, social contacts who offer support and distraction from suicidal thoughts, contact information for professionals, a suicide crisis hotline, and nearby emergency services.
In addition to these steps, the PLF program focuses on sleep, exercise, and making the safety plan accessible.
The telehealth platform for the program was WebEx software. Participants were offered a “trial run” to orient them to the technology, said Ms. Sullivan.
Group sessions were held once weekly for 10 weeks, with optional “booster” sessions if needed. Each session included about five participants.
To ensure privacy, participants were provided with headphones and laptops. This was especially important for those sharing a living space, including spouses and children, said Ms. Sullivan.
High ratings
Participants completed the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Each of these yields scores from four items rated on a Likert scale of 1-5, for a total score ranging from 5 to 20, with higher scores indicating higher ratings.
Veterans rated PLF-T as highly acceptable (mean AIM, 17.50), appropriate (mean IAM, 17.25), and feasible (mean FIM, 18).
Study participants reported the program was convenient and noted that it decreased the burden of traveling to sessions, especially during the COVID-19 pandemic.
They also reported the program was less likely to compete with other demands such as childcare and other appointments, said Ms. Sullivan.
In addition, it helped those with comorbidities such as posttraumatic stress disorder, she added. She noted veterans with PTSD may be triggered on subways or buses when traveling to in-person treatment sessions.
“That can take away from addressing the suicidal triggers,” said Ms. Sullivan. “So, this program allows them to fully concentrate on the safety plan.”
Results showed that study participants “enjoyed the group and would recommend it to others,” said Ms. Sullivan. “I think that signifies the group was effective in its goal of mitigating loneliness, which was exacerbated during the COVID-19 pandemic, and creating a socially supportive environment, especially for the vets living alone.”
Veterans also reported that the program helped them understand the connection between depression or PTSD and suicidal thoughts, urges, and plans. In addition, they appreciated the group dynamics, where they felt connected to other veterans experiencing similar challenges.
Hopeful results
Commenting on the study, Paul E. Holtzheimer, MD, deputy director for research at the National Center for PTSD, praised the study for focusing on a very high-risk group.
“This gets you closer to the population you’re probably going to have an impact on in terms of preventing suicide,” said Dr. Holtzheimer, a professor of psychiatry and surgery at Dartmouth College’s Geisel School of Medicine, Hanover, N.H.
The fact that many of the participants had attempted suicide in the last year underlines that this was a very high-risk population, said Dr. Holtzheimer. “Not only are they thinking about suicide, but almost two-thirds had actually attempted or tried something.”
This kind of program “would be great for rural environments where people may be living like four hours away from the VA or a clinic,” said Dr. Holtzheimer, noting that many veterans are often quite isolated.
“One of the very positive outcomes of the COVID-19 pandemic was helping us strengthen our ability to do telehealth,” he said.
However, Dr. Holtzheimer noted the study was small and qualitative. “The next step ideally would be a controlled trial looking at not just ideation but at risky behavior or clear suicide attempts or preparation, like buying a gun or hoarding medication, to help determine efficacy.”
The researchers and Dr. Holtzheimer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ADAA 2023
ECT vs. ketamine for major depressive disorder: New data
“Although ECT is superior to ketamine for patients with a major depressive episode, our findings suggest that the therapeutic advantage may be smaller than what was demonstrated in prior analyses,” first author Vikas Menon, MD, department of psychiatry, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India, told this news organization.
“This supports a recommendation for a trial of ketamine before a trial of ECT for patients with MDE, though this recommendation is limited by the small size and number of existing trials,” Dr. Menon said.
The study was published online in JAMA Psychiatry.
Questions remain
The meta-analysis included five trials of 278 adults with MDE (141 treated with ketamine and 137 with ECT).
In the main analysis, posttreatment depression ratings showed a trend for lower scores with ECT, compared with ketamine (standardized mean difference, −0.39; 95% confidence interval, −0.81 to 0.02).
In a sensitivity analysis of the two methodologically stronger trials, ECT was superior to ketamine (pooled SMD, −0.45; 95% CI, −0.75 to −0.14).
ECT was also superior to ketamine in terms of response rates (risk ratio, 1.27; 95% CI, 1.06-1.53) and remission rates (RR, 1.43; 95% CI, 1.12-1.82).
There were no significant between-group differences for number of sessions to response and remission and for cognitive outcomes.
Key limitations of the analysis were the small number of studies with limited sample sizes and a high risk of bias in all trials.
“There is a need for more comparative studies with adequate sample size in non-inferiority designs, examining a wider range of benefits and side effects and followed up for longer durations to answer clinically relevant questions about the nature and durability of observed benefits with ketamine,” said Dr. Menon.
“In patients with MDE for whom the administration of ECT is limited by restricted availability of the treatment, concerns about its cognitive adverse effects, negative patient attitudes, and other issues, clinicians may consider a trial of ketamine,” he added.
‘Important research’
Several experts offered perspective on the analysis in a statement from the U.K.-based nonprofit Science Media Centre, which was not involved with the conduct of this study.
Rupert McShane, MD, psychiatrist at the University of Oxford (England), noted that ECT and ketamine are both “potent” treatments for depression, and this meta-analysis shows that they are, “broadly speaking, equally as good as each other with perhaps a slight advantage for ECT.”
“Whether or not there is a difference depends on exactly how you define it and how you cut the data. Despite the slight advantage for ECT in this analysis, the authors support using ketamine before ECT, especially in patients who are worried about the cognitive risks of ECT. This seems sensible,” Dr. McShane said.
Allan Young, MBChB, clinical psychiatrist at King’s College London, noted that both ketamine and ECT have been shown to help some patients with treatment-resistant depression.
“Clearly the relative benefits of these two treatments need to be understood better, but this review of the existing literature suggests that ECT may benefit some more than ketamine,” said Mr. Young.
“There is evidence that ketamine with ECT may add little extra benefit, but much more work needs to be done to fully understand how these treatments fit best into the treatment pathway for major depressive episodes. However, based on this evidence, ECT clearly still merits a place in the treatment pathway,” Mr. Young added.
George Kirov, PhD, clinical professor, division of psychological medicine and clinical neurosciences, Cardiff University (England), said while the study is conducted well, most of the evidence is coming from one large trial conducted in Sweden.
“The other studies add small numbers of patients and the authors even present a sensitivity analysis after removing studies of poor quality, thus leaving only two studies and exposing even further the dependence of the results on one single study,” Dr. Kirov noted.
“The small studies should not be blamed for their size, as this is very difficult research to perform. On the other hand, the trends were in the same direction,” he added.
With those caveats in mind, Dr. Kirov said he still thinks this is “important research. It establishes the superiority of ECT against an active comparator (ketamine) which is very popular now and accepted to be quite effective.”
The study had no specific funding. Dr. Menon reports no relevant financial relationships. Dr. McShane is former chair of the ECT and Related Treatments Committee, Royal College of Psychiatrists and runs a ketamine clinic and an ECT service. Mr. Young has received compensation for lectures and advisory boards for AstraZeneca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allergan, Bionomics, Sumitomo Dainippon Pharma, COMPASS, and Sage, and has served as principal investigator on a trial of intranasal esketamine in treatment-resistant depression. Dr. Kirov has no interest to declare other than running the ECT service in Cardiff.
A version of this article first appeared on Medscape.com.
“Although ECT is superior to ketamine for patients with a major depressive episode, our findings suggest that the therapeutic advantage may be smaller than what was demonstrated in prior analyses,” first author Vikas Menon, MD, department of psychiatry, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India, told this news organization.
“This supports a recommendation for a trial of ketamine before a trial of ECT for patients with MDE, though this recommendation is limited by the small size and number of existing trials,” Dr. Menon said.
The study was published online in JAMA Psychiatry.
Questions remain
The meta-analysis included five trials of 278 adults with MDE (141 treated with ketamine and 137 with ECT).
In the main analysis, posttreatment depression ratings showed a trend for lower scores with ECT, compared with ketamine (standardized mean difference, −0.39; 95% confidence interval, −0.81 to 0.02).
In a sensitivity analysis of the two methodologically stronger trials, ECT was superior to ketamine (pooled SMD, −0.45; 95% CI, −0.75 to −0.14).
ECT was also superior to ketamine in terms of response rates (risk ratio, 1.27; 95% CI, 1.06-1.53) and remission rates (RR, 1.43; 95% CI, 1.12-1.82).
There were no significant between-group differences for number of sessions to response and remission and for cognitive outcomes.
Key limitations of the analysis were the small number of studies with limited sample sizes and a high risk of bias in all trials.
“There is a need for more comparative studies with adequate sample size in non-inferiority designs, examining a wider range of benefits and side effects and followed up for longer durations to answer clinically relevant questions about the nature and durability of observed benefits with ketamine,” said Dr. Menon.
“In patients with MDE for whom the administration of ECT is limited by restricted availability of the treatment, concerns about its cognitive adverse effects, negative patient attitudes, and other issues, clinicians may consider a trial of ketamine,” he added.
‘Important research’
Several experts offered perspective on the analysis in a statement from the U.K.-based nonprofit Science Media Centre, which was not involved with the conduct of this study.
Rupert McShane, MD, psychiatrist at the University of Oxford (England), noted that ECT and ketamine are both “potent” treatments for depression, and this meta-analysis shows that they are, “broadly speaking, equally as good as each other with perhaps a slight advantage for ECT.”
“Whether or not there is a difference depends on exactly how you define it and how you cut the data. Despite the slight advantage for ECT in this analysis, the authors support using ketamine before ECT, especially in patients who are worried about the cognitive risks of ECT. This seems sensible,” Dr. McShane said.
Allan Young, MBChB, clinical psychiatrist at King’s College London, noted that both ketamine and ECT have been shown to help some patients with treatment-resistant depression.
“Clearly the relative benefits of these two treatments need to be understood better, but this review of the existing literature suggests that ECT may benefit some more than ketamine,” said Mr. Young.
“There is evidence that ketamine with ECT may add little extra benefit, but much more work needs to be done to fully understand how these treatments fit best into the treatment pathway for major depressive episodes. However, based on this evidence, ECT clearly still merits a place in the treatment pathway,” Mr. Young added.
George Kirov, PhD, clinical professor, division of psychological medicine and clinical neurosciences, Cardiff University (England), said while the study is conducted well, most of the evidence is coming from one large trial conducted in Sweden.
“The other studies add small numbers of patients and the authors even present a sensitivity analysis after removing studies of poor quality, thus leaving only two studies and exposing even further the dependence of the results on one single study,” Dr. Kirov noted.
“The small studies should not be blamed for their size, as this is very difficult research to perform. On the other hand, the trends were in the same direction,” he added.
With those caveats in mind, Dr. Kirov said he still thinks this is “important research. It establishes the superiority of ECT against an active comparator (ketamine) which is very popular now and accepted to be quite effective.”
The study had no specific funding. Dr. Menon reports no relevant financial relationships. Dr. McShane is former chair of the ECT and Related Treatments Committee, Royal College of Psychiatrists and runs a ketamine clinic and an ECT service. Mr. Young has received compensation for lectures and advisory boards for AstraZeneca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allergan, Bionomics, Sumitomo Dainippon Pharma, COMPASS, and Sage, and has served as principal investigator on a trial of intranasal esketamine in treatment-resistant depression. Dr. Kirov has no interest to declare other than running the ECT service in Cardiff.
A version of this article first appeared on Medscape.com.
“Although ECT is superior to ketamine for patients with a major depressive episode, our findings suggest that the therapeutic advantage may be smaller than what was demonstrated in prior analyses,” first author Vikas Menon, MD, department of psychiatry, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India, told this news organization.
“This supports a recommendation for a trial of ketamine before a trial of ECT for patients with MDE, though this recommendation is limited by the small size and number of existing trials,” Dr. Menon said.
The study was published online in JAMA Psychiatry.
Questions remain
The meta-analysis included five trials of 278 adults with MDE (141 treated with ketamine and 137 with ECT).
In the main analysis, posttreatment depression ratings showed a trend for lower scores with ECT, compared with ketamine (standardized mean difference, −0.39; 95% confidence interval, −0.81 to 0.02).
In a sensitivity analysis of the two methodologically stronger trials, ECT was superior to ketamine (pooled SMD, −0.45; 95% CI, −0.75 to −0.14).
ECT was also superior to ketamine in terms of response rates (risk ratio, 1.27; 95% CI, 1.06-1.53) and remission rates (RR, 1.43; 95% CI, 1.12-1.82).
There were no significant between-group differences for number of sessions to response and remission and for cognitive outcomes.
Key limitations of the analysis were the small number of studies with limited sample sizes and a high risk of bias in all trials.
“There is a need for more comparative studies with adequate sample size in non-inferiority designs, examining a wider range of benefits and side effects and followed up for longer durations to answer clinically relevant questions about the nature and durability of observed benefits with ketamine,” said Dr. Menon.
“In patients with MDE for whom the administration of ECT is limited by restricted availability of the treatment, concerns about its cognitive adverse effects, negative patient attitudes, and other issues, clinicians may consider a trial of ketamine,” he added.
‘Important research’
Several experts offered perspective on the analysis in a statement from the U.K.-based nonprofit Science Media Centre, which was not involved with the conduct of this study.
Rupert McShane, MD, psychiatrist at the University of Oxford (England), noted that ECT and ketamine are both “potent” treatments for depression, and this meta-analysis shows that they are, “broadly speaking, equally as good as each other with perhaps a slight advantage for ECT.”
“Whether or not there is a difference depends on exactly how you define it and how you cut the data. Despite the slight advantage for ECT in this analysis, the authors support using ketamine before ECT, especially in patients who are worried about the cognitive risks of ECT. This seems sensible,” Dr. McShane said.
Allan Young, MBChB, clinical psychiatrist at King’s College London, noted that both ketamine and ECT have been shown to help some patients with treatment-resistant depression.
“Clearly the relative benefits of these two treatments need to be understood better, but this review of the existing literature suggests that ECT may benefit some more than ketamine,” said Mr. Young.
“There is evidence that ketamine with ECT may add little extra benefit, but much more work needs to be done to fully understand how these treatments fit best into the treatment pathway for major depressive episodes. However, based on this evidence, ECT clearly still merits a place in the treatment pathway,” Mr. Young added.
George Kirov, PhD, clinical professor, division of psychological medicine and clinical neurosciences, Cardiff University (England), said while the study is conducted well, most of the evidence is coming from one large trial conducted in Sweden.
“The other studies add small numbers of patients and the authors even present a sensitivity analysis after removing studies of poor quality, thus leaving only two studies and exposing even further the dependence of the results on one single study,” Dr. Kirov noted.
“The small studies should not be blamed for their size, as this is very difficult research to perform. On the other hand, the trends were in the same direction,” he added.
With those caveats in mind, Dr. Kirov said he still thinks this is “important research. It establishes the superiority of ECT against an active comparator (ketamine) which is very popular now and accepted to be quite effective.”
The study had no specific funding. Dr. Menon reports no relevant financial relationships. Dr. McShane is former chair of the ECT and Related Treatments Committee, Royal College of Psychiatrists and runs a ketamine clinic and an ECT service. Mr. Young has received compensation for lectures and advisory boards for AstraZeneca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allergan, Bionomics, Sumitomo Dainippon Pharma, COMPASS, and Sage, and has served as principal investigator on a trial of intranasal esketamine in treatment-resistant depression. Dr. Kirov has no interest to declare other than running the ECT service in Cardiff.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY