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PUFAs a promising add-on for borderline personality disorder
Marine omega-3 fatty acids may be a promising add-on therapy for improving symptoms of borderline personality disorder (BPD), new research suggests.
A meta-analysis of four randomized controlled trials showed that adjunctive omega-3 fatty polyunsaturated fatty acids (PUFAs) significantly reduced overall BPD symptom severity, particularly affect dysregulation and impulsive behavior.
“Given the mechanisms of action and beneficial side effect profile, this [analysis] suggests that omega-3 fatty acids could be considered as add-on treatment” for patients with BPD, senior author Roel J. T. Mocking MD, PhD, resident in psychiatry and postdoctoral researcher at Academisch Medisch Centrum, Amsterdam, said in an interview.
The findings were published online in the Journal of Clinical Psychiatry.
Urgent need
“There are several effective treatments, but not all patients respond sufficiently,” which points to an urgent need for additional treatment options, Dr. Mocking said.
He noted that, although “several prior studies showed promising effects of omega-3 fatty acids” for patients with BPD, those studies were relatively small, which precluded more definitive overall conclusions.
The investigators wanted to combine results of the earlier studies to provide a combined estimate of overall effectiveness of the use of omega-3 fatty acids for patients with BP, with the intention of “guiding clinicians and individuals suffering from borderline personality disorder to decide on whether they should add omega-3 fatty acids to their treatment.”
The analyzed four studies that had a total of 137 patients. Three of the studies included patients diagnosed with BPD; one included individuals with recurrent self-harm, most of whom were also diagnosed with BPD.
Omega-3 fatty acids were used as monotherapy in one study. In the other studies, they were used as add-on therapy to other agents, such as antidepressants, benzodiazepines, and/or valproic acid. None of the studies included patients who were taking antipsychotics.
The type of omega-3 PUFAs were derived from marine rather than plant sources.
Three studies compared omega-3 fatty acids with placebo. One study compared valproic acid monotherapy with valproic acid plus omega-3 fatty acids and did not include a placebo group.
Significant symptom reduction
Random-effects meta-analyses showed an “overall significant decreasing effect” of omega-3 fatty acids on overall BPD symptom severity (standardized difference in means, 0.54; 95% CI, 0.91-0.17; P = .004) in the omega-3 group compared with the control group, with a medium effect size.
The investigators added that there was “no relevant heterogeneity” (P = .45).
Although heterogeneity was “more pronounced” in the affective dysregulation symptom domain, it did not reach statistical significance, the researchers noted.
The impulsive behavioral dyscontrol and cognitive perceptual symptom domains had “no relevant heterogeneity.” On the other hand, there was “substantial heterogeneity” in the global functioning symptom group.
Omega-3 fatty acids “have multiple bioactive roles in the brain. For example, they form essential components of the membrane of brain cells and thereby influence the structure and functioning of the brain. They also have an effect on inflammation levels in the brain,” Dr. Mocking said.
“Because we cannot synthesize these omega-3 fatty acids ourselves, we are dependent on our diet. The main dietary source of omega-3 fatty acids is fatty fish. However, since the industrial revolution, we eat less and less fatty fish, risking deficiency of omega-3 fatty acids causing brain dysfunction,” he added.
Dr. Mocking noted that
This “suggests that they could be combined to increase overall effectiveness,” he said.
Important benefit
Commenting on the study, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said that the benefit of omega-3 “on impulsivity and mood symptoms is especially important, as these are some of the most debilitating aspects of BPD and lead to service utilization, such as ER, primary care, and specialty care.”
In addition, “impulsivity often presages suicidality,” he noted.
Dr. McIntyre, who is also chair and executive director of the Brain and Cognition Discovery Foundation in Toronto and was not involved with the study, called the effect size “quite reasonable.”
“The mechanistic story is very strong around anti-inflammatory effect, which particularly implied mood and cognition. In other words, inflammation is highly associated with mood and cognitive difficulties,” he said.
However, Dr. McIntyre also pointed to several significant challenges, including “quality assurance on the purchase of the product of fish oil, as it is not sufficiently regulated.” It is also unclear which individuals are more likely to benefit from it.
For example, major depressive disorder data have shown that “fish oils are not as effective as we hoped but are especially effective in people with baseline elevation of inflammatory markers,” Dr. McIntyre said.
“In other words, is there a way to identify a biomarkers/biosignature or phenomenology that’s more likely to identify a subgroup of people with BPD who might benefit benefiting from omega-3?” he asked.
Dr. Mocking and the other investigators reported no relevant financial relationships. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.
A version of this article first appeared on Medscape.com.
Marine omega-3 fatty acids may be a promising add-on therapy for improving symptoms of borderline personality disorder (BPD), new research suggests.
A meta-analysis of four randomized controlled trials showed that adjunctive omega-3 fatty polyunsaturated fatty acids (PUFAs) significantly reduced overall BPD symptom severity, particularly affect dysregulation and impulsive behavior.
“Given the mechanisms of action and beneficial side effect profile, this [analysis] suggests that omega-3 fatty acids could be considered as add-on treatment” for patients with BPD, senior author Roel J. T. Mocking MD, PhD, resident in psychiatry and postdoctoral researcher at Academisch Medisch Centrum, Amsterdam, said in an interview.
The findings were published online in the Journal of Clinical Psychiatry.
Urgent need
“There are several effective treatments, but not all patients respond sufficiently,” which points to an urgent need for additional treatment options, Dr. Mocking said.
He noted that, although “several prior studies showed promising effects of omega-3 fatty acids” for patients with BPD, those studies were relatively small, which precluded more definitive overall conclusions.
The investigators wanted to combine results of the earlier studies to provide a combined estimate of overall effectiveness of the use of omega-3 fatty acids for patients with BP, with the intention of “guiding clinicians and individuals suffering from borderline personality disorder to decide on whether they should add omega-3 fatty acids to their treatment.”
The analyzed four studies that had a total of 137 patients. Three of the studies included patients diagnosed with BPD; one included individuals with recurrent self-harm, most of whom were also diagnosed with BPD.
Omega-3 fatty acids were used as monotherapy in one study. In the other studies, they were used as add-on therapy to other agents, such as antidepressants, benzodiazepines, and/or valproic acid. None of the studies included patients who were taking antipsychotics.
The type of omega-3 PUFAs were derived from marine rather than plant sources.
Three studies compared omega-3 fatty acids with placebo. One study compared valproic acid monotherapy with valproic acid plus omega-3 fatty acids and did not include a placebo group.
Significant symptom reduction
Random-effects meta-analyses showed an “overall significant decreasing effect” of omega-3 fatty acids on overall BPD symptom severity (standardized difference in means, 0.54; 95% CI, 0.91-0.17; P = .004) in the omega-3 group compared with the control group, with a medium effect size.
The investigators added that there was “no relevant heterogeneity” (P = .45).
Although heterogeneity was “more pronounced” in the affective dysregulation symptom domain, it did not reach statistical significance, the researchers noted.
The impulsive behavioral dyscontrol and cognitive perceptual symptom domains had “no relevant heterogeneity.” On the other hand, there was “substantial heterogeneity” in the global functioning symptom group.
Omega-3 fatty acids “have multiple bioactive roles in the brain. For example, they form essential components of the membrane of brain cells and thereby influence the structure and functioning of the brain. They also have an effect on inflammation levels in the brain,” Dr. Mocking said.
“Because we cannot synthesize these omega-3 fatty acids ourselves, we are dependent on our diet. The main dietary source of omega-3 fatty acids is fatty fish. However, since the industrial revolution, we eat less and less fatty fish, risking deficiency of omega-3 fatty acids causing brain dysfunction,” he added.
Dr. Mocking noted that
This “suggests that they could be combined to increase overall effectiveness,” he said.
Important benefit
Commenting on the study, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said that the benefit of omega-3 “on impulsivity and mood symptoms is especially important, as these are some of the most debilitating aspects of BPD and lead to service utilization, such as ER, primary care, and specialty care.”
In addition, “impulsivity often presages suicidality,” he noted.
Dr. McIntyre, who is also chair and executive director of the Brain and Cognition Discovery Foundation in Toronto and was not involved with the study, called the effect size “quite reasonable.”
“The mechanistic story is very strong around anti-inflammatory effect, which particularly implied mood and cognition. In other words, inflammation is highly associated with mood and cognitive difficulties,” he said.
However, Dr. McIntyre also pointed to several significant challenges, including “quality assurance on the purchase of the product of fish oil, as it is not sufficiently regulated.” It is also unclear which individuals are more likely to benefit from it.
For example, major depressive disorder data have shown that “fish oils are not as effective as we hoped but are especially effective in people with baseline elevation of inflammatory markers,” Dr. McIntyre said.
“In other words, is there a way to identify a biomarkers/biosignature or phenomenology that’s more likely to identify a subgroup of people with BPD who might benefit benefiting from omega-3?” he asked.
Dr. Mocking and the other investigators reported no relevant financial relationships. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.
A version of this article first appeared on Medscape.com.
Marine omega-3 fatty acids may be a promising add-on therapy for improving symptoms of borderline personality disorder (BPD), new research suggests.
A meta-analysis of four randomized controlled trials showed that adjunctive omega-3 fatty polyunsaturated fatty acids (PUFAs) significantly reduced overall BPD symptom severity, particularly affect dysregulation and impulsive behavior.
“Given the mechanisms of action and beneficial side effect profile, this [analysis] suggests that omega-3 fatty acids could be considered as add-on treatment” for patients with BPD, senior author Roel J. T. Mocking MD, PhD, resident in psychiatry and postdoctoral researcher at Academisch Medisch Centrum, Amsterdam, said in an interview.
The findings were published online in the Journal of Clinical Psychiatry.
Urgent need
“There are several effective treatments, but not all patients respond sufficiently,” which points to an urgent need for additional treatment options, Dr. Mocking said.
He noted that, although “several prior studies showed promising effects of omega-3 fatty acids” for patients with BPD, those studies were relatively small, which precluded more definitive overall conclusions.
The investigators wanted to combine results of the earlier studies to provide a combined estimate of overall effectiveness of the use of omega-3 fatty acids for patients with BP, with the intention of “guiding clinicians and individuals suffering from borderline personality disorder to decide on whether they should add omega-3 fatty acids to their treatment.”
The analyzed four studies that had a total of 137 patients. Three of the studies included patients diagnosed with BPD; one included individuals with recurrent self-harm, most of whom were also diagnosed with BPD.
Omega-3 fatty acids were used as monotherapy in one study. In the other studies, they were used as add-on therapy to other agents, such as antidepressants, benzodiazepines, and/or valproic acid. None of the studies included patients who were taking antipsychotics.
The type of omega-3 PUFAs were derived from marine rather than plant sources.
Three studies compared omega-3 fatty acids with placebo. One study compared valproic acid monotherapy with valproic acid plus omega-3 fatty acids and did not include a placebo group.
Significant symptom reduction
Random-effects meta-analyses showed an “overall significant decreasing effect” of omega-3 fatty acids on overall BPD symptom severity (standardized difference in means, 0.54; 95% CI, 0.91-0.17; P = .004) in the omega-3 group compared with the control group, with a medium effect size.
The investigators added that there was “no relevant heterogeneity” (P = .45).
Although heterogeneity was “more pronounced” in the affective dysregulation symptom domain, it did not reach statistical significance, the researchers noted.
The impulsive behavioral dyscontrol and cognitive perceptual symptom domains had “no relevant heterogeneity.” On the other hand, there was “substantial heterogeneity” in the global functioning symptom group.
Omega-3 fatty acids “have multiple bioactive roles in the brain. For example, they form essential components of the membrane of brain cells and thereby influence the structure and functioning of the brain. They also have an effect on inflammation levels in the brain,” Dr. Mocking said.
“Because we cannot synthesize these omega-3 fatty acids ourselves, we are dependent on our diet. The main dietary source of omega-3 fatty acids is fatty fish. However, since the industrial revolution, we eat less and less fatty fish, risking deficiency of omega-3 fatty acids causing brain dysfunction,” he added.
Dr. Mocking noted that
This “suggests that they could be combined to increase overall effectiveness,” he said.
Important benefit
Commenting on the study, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said that the benefit of omega-3 “on impulsivity and mood symptoms is especially important, as these are some of the most debilitating aspects of BPD and lead to service utilization, such as ER, primary care, and specialty care.”
In addition, “impulsivity often presages suicidality,” he noted.
Dr. McIntyre, who is also chair and executive director of the Brain and Cognition Discovery Foundation in Toronto and was not involved with the study, called the effect size “quite reasonable.”
“The mechanistic story is very strong around anti-inflammatory effect, which particularly implied mood and cognition. In other words, inflammation is highly associated with mood and cognitive difficulties,” he said.
However, Dr. McIntyre also pointed to several significant challenges, including “quality assurance on the purchase of the product of fish oil, as it is not sufficiently regulated.” It is also unclear which individuals are more likely to benefit from it.
For example, major depressive disorder data have shown that “fish oils are not as effective as we hoped but are especially effective in people with baseline elevation of inflammatory markers,” Dr. McIntyre said.
“In other words, is there a way to identify a biomarkers/biosignature or phenomenology that’s more likely to identify a subgroup of people with BPD who might benefit benefiting from omega-3?” he asked.
Dr. Mocking and the other investigators reported no relevant financial relationships. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.
A version of this article first appeared on Medscape.com.
Ketamine and psychosis risk: New data
Ketamine used to treat severe depression in patients with a history of psychosis does not exacerbate psychosis risk, new research suggests.
A meta-analysis of nine studies, encompassing 41 patients with TRD and a history of psychosis, suggests ketamine is safe and effective and did not exacerbate psychotic symptoms in this patient population.
“We believe our findings could encourage clinicians and researchers to examine a broadened indication for ketamine treatment in individual patients with high levels of treatment resistance, carefully monitoring both clinical response and side effects, specifically looking at possible increases in psychotic symptoms,” study investigator Jolien K. E. Veraart, MD, University of Groningen, University Medical Center Groningen, the Netherlands, told this news organization.
The study was published online July 13 in the Journal of Clinical Psychiatry.
Rapid, robust effects
Ketamine has shown “rapid and robust antidepressant effects” in clinical studies. However, this research has not included patients with past or current psychosis, based on the assumption that psychosis will increase with ketamine administration, since side effects of ketamine can include transient “schizophrenia-like” psychotomimetic phenomena, including perceptual disorders and hallucinations in healthy individuals, the investigators note.
Dr. Veraart said psychotic symptoms are “common in people with severe depression,” and these patients have poorer outcomes with pharmacotherapy, psychotherapy, and electroconvulsive therapy.
Additionally, up to 60% of patients with schizophrenia experience negative symptomatology, including loss of motivation, affective blunting, and anhedonia, which “has a clear phenomenological overlap with depression,” the authors write. They also note anti-anhedonic effects of subanesthetic ketamine doses have been reported, without adversely impacting long-term psychotic symptoms in patients with schizophrenia.
“Positive results from carefully monitored trials with ketamine treatment in these patients have motivated us to summarize the currently available knowledge to inform our colleagues,” she said.
To investigate, the researchers conducted a literature search and selected 9 articles (N = 41 patients) that reported on ketamine treatment in patients with a history of psychosis or current psychotic symptoms.
All studies were either case reports or pilot studies, the authors report. Types of patients included those with bipolar or unipolar depression, or depression in schizoaffective disorder , or patients with schizophrenia and concurrent depression. Depressive symptomatology was the treatment target in eight studies, and one study targeted negative symptoms in patients with schizophrenia.
Dosing, frequency, and types of administration (ketamine IV, esketamine IV, or esketamine subcutaneous) varied from study to study.
In seven studies, ketamine was found to improve depressive symptoms, and in two studies, improvement in psychotic symptoms was also shown. Two studies revealed improvement in symptoms of suicidality. Results of the study that measured negative symptoms showed “significant improvement” in five of six patients, with a -37.3% decrease in mean Brief Negative Symptoms Scale (BNSS) from the baseline to the end of four infusions.
“Ketamine showed good antidepressant effects, and, in some cases, the comorbid symptoms even improved or disappeared after ketamine treatment,” Dr. Veraart summarized. However, the effect size of ketamine might be lower in those with a history of psychosis, she added.
She also noted that
She pointed to one study limitation, which is that only small, uncontrolled trials were included and that there is a risk for publication bias.
Larger trials needed
Commenting on the study, Dan Iosifescu, MD, MSc, associate professor of psychiatry, New York University School of Medicine, said that if the finding “were based on a larger study it would be very important, as a theoretical risk of psychosis is preventing such patients from access to an otherwise beneficial treatment.”
However, “since the review is based on a small sample, a low risk of psychosis exacerbation after IV ketamine is still possible,” said Dr. Iosifescu, who is also the director of clinical research at the Kline Institute for Psychiatric Research in Orangeburg, New York, and was not involved with the study.
Dr. Veraart agreed, adding that the “efficacy, safety, and tolerability of ketamine in depressed patients with a vulnerability to psychosis should be investigated in well-designed randomized controlled trials before application on a large scale is promoted.”
The study had no specific funding. Dr. Veraart has received speaker honoraria from Janssen outside of the submitted work. The other authors’ disclosures are listed in the original article. Dr. Iosifescu has been a consultant to the Centers of Psychiatric Excellence, advising clinics on the best methods of providing treatment with IV ketamine.
A version of this article first appeared on Medscape.com.
Ketamine used to treat severe depression in patients with a history of psychosis does not exacerbate psychosis risk, new research suggests.
A meta-analysis of nine studies, encompassing 41 patients with TRD and a history of psychosis, suggests ketamine is safe and effective and did not exacerbate psychotic symptoms in this patient population.
“We believe our findings could encourage clinicians and researchers to examine a broadened indication for ketamine treatment in individual patients with high levels of treatment resistance, carefully monitoring both clinical response and side effects, specifically looking at possible increases in psychotic symptoms,” study investigator Jolien K. E. Veraart, MD, University of Groningen, University Medical Center Groningen, the Netherlands, told this news organization.
The study was published online July 13 in the Journal of Clinical Psychiatry.
Rapid, robust effects
Ketamine has shown “rapid and robust antidepressant effects” in clinical studies. However, this research has not included patients with past or current psychosis, based on the assumption that psychosis will increase with ketamine administration, since side effects of ketamine can include transient “schizophrenia-like” psychotomimetic phenomena, including perceptual disorders and hallucinations in healthy individuals, the investigators note.
Dr. Veraart said psychotic symptoms are “common in people with severe depression,” and these patients have poorer outcomes with pharmacotherapy, psychotherapy, and electroconvulsive therapy.
Additionally, up to 60% of patients with schizophrenia experience negative symptomatology, including loss of motivation, affective blunting, and anhedonia, which “has a clear phenomenological overlap with depression,” the authors write. They also note anti-anhedonic effects of subanesthetic ketamine doses have been reported, without adversely impacting long-term psychotic symptoms in patients with schizophrenia.
“Positive results from carefully monitored trials with ketamine treatment in these patients have motivated us to summarize the currently available knowledge to inform our colleagues,” she said.
To investigate, the researchers conducted a literature search and selected 9 articles (N = 41 patients) that reported on ketamine treatment in patients with a history of psychosis or current psychotic symptoms.
All studies were either case reports or pilot studies, the authors report. Types of patients included those with bipolar or unipolar depression, or depression in schizoaffective disorder , or patients with schizophrenia and concurrent depression. Depressive symptomatology was the treatment target in eight studies, and one study targeted negative symptoms in patients with schizophrenia.
Dosing, frequency, and types of administration (ketamine IV, esketamine IV, or esketamine subcutaneous) varied from study to study.
In seven studies, ketamine was found to improve depressive symptoms, and in two studies, improvement in psychotic symptoms was also shown. Two studies revealed improvement in symptoms of suicidality. Results of the study that measured negative symptoms showed “significant improvement” in five of six patients, with a -37.3% decrease in mean Brief Negative Symptoms Scale (BNSS) from the baseline to the end of four infusions.
“Ketamine showed good antidepressant effects, and, in some cases, the comorbid symptoms even improved or disappeared after ketamine treatment,” Dr. Veraart summarized. However, the effect size of ketamine might be lower in those with a history of psychosis, she added.
She also noted that
She pointed to one study limitation, which is that only small, uncontrolled trials were included and that there is a risk for publication bias.
Larger trials needed
Commenting on the study, Dan Iosifescu, MD, MSc, associate professor of psychiatry, New York University School of Medicine, said that if the finding “were based on a larger study it would be very important, as a theoretical risk of psychosis is preventing such patients from access to an otherwise beneficial treatment.”
However, “since the review is based on a small sample, a low risk of psychosis exacerbation after IV ketamine is still possible,” said Dr. Iosifescu, who is also the director of clinical research at the Kline Institute for Psychiatric Research in Orangeburg, New York, and was not involved with the study.
Dr. Veraart agreed, adding that the “efficacy, safety, and tolerability of ketamine in depressed patients with a vulnerability to psychosis should be investigated in well-designed randomized controlled trials before application on a large scale is promoted.”
The study had no specific funding. Dr. Veraart has received speaker honoraria from Janssen outside of the submitted work. The other authors’ disclosures are listed in the original article. Dr. Iosifescu has been a consultant to the Centers of Psychiatric Excellence, advising clinics on the best methods of providing treatment with IV ketamine.
A version of this article first appeared on Medscape.com.
Ketamine used to treat severe depression in patients with a history of psychosis does not exacerbate psychosis risk, new research suggests.
A meta-analysis of nine studies, encompassing 41 patients with TRD and a history of psychosis, suggests ketamine is safe and effective and did not exacerbate psychotic symptoms in this patient population.
“We believe our findings could encourage clinicians and researchers to examine a broadened indication for ketamine treatment in individual patients with high levels of treatment resistance, carefully monitoring both clinical response and side effects, specifically looking at possible increases in psychotic symptoms,” study investigator Jolien K. E. Veraart, MD, University of Groningen, University Medical Center Groningen, the Netherlands, told this news organization.
The study was published online July 13 in the Journal of Clinical Psychiatry.
Rapid, robust effects
Ketamine has shown “rapid and robust antidepressant effects” in clinical studies. However, this research has not included patients with past or current psychosis, based on the assumption that psychosis will increase with ketamine administration, since side effects of ketamine can include transient “schizophrenia-like” psychotomimetic phenomena, including perceptual disorders and hallucinations in healthy individuals, the investigators note.
Dr. Veraart said psychotic symptoms are “common in people with severe depression,” and these patients have poorer outcomes with pharmacotherapy, psychotherapy, and electroconvulsive therapy.
Additionally, up to 60% of patients with schizophrenia experience negative symptomatology, including loss of motivation, affective blunting, and anhedonia, which “has a clear phenomenological overlap with depression,” the authors write. They also note anti-anhedonic effects of subanesthetic ketamine doses have been reported, without adversely impacting long-term psychotic symptoms in patients with schizophrenia.
“Positive results from carefully monitored trials with ketamine treatment in these patients have motivated us to summarize the currently available knowledge to inform our colleagues,” she said.
To investigate, the researchers conducted a literature search and selected 9 articles (N = 41 patients) that reported on ketamine treatment in patients with a history of psychosis or current psychotic symptoms.
All studies were either case reports or pilot studies, the authors report. Types of patients included those with bipolar or unipolar depression, or depression in schizoaffective disorder , or patients with schizophrenia and concurrent depression. Depressive symptomatology was the treatment target in eight studies, and one study targeted negative symptoms in patients with schizophrenia.
Dosing, frequency, and types of administration (ketamine IV, esketamine IV, or esketamine subcutaneous) varied from study to study.
In seven studies, ketamine was found to improve depressive symptoms, and in two studies, improvement in psychotic symptoms was also shown. Two studies revealed improvement in symptoms of suicidality. Results of the study that measured negative symptoms showed “significant improvement” in five of six patients, with a -37.3% decrease in mean Brief Negative Symptoms Scale (BNSS) from the baseline to the end of four infusions.
“Ketamine showed good antidepressant effects, and, in some cases, the comorbid symptoms even improved or disappeared after ketamine treatment,” Dr. Veraart summarized. However, the effect size of ketamine might be lower in those with a history of psychosis, she added.
She also noted that
She pointed to one study limitation, which is that only small, uncontrolled trials were included and that there is a risk for publication bias.
Larger trials needed
Commenting on the study, Dan Iosifescu, MD, MSc, associate professor of psychiatry, New York University School of Medicine, said that if the finding “were based on a larger study it would be very important, as a theoretical risk of psychosis is preventing such patients from access to an otherwise beneficial treatment.”
However, “since the review is based on a small sample, a low risk of psychosis exacerbation after IV ketamine is still possible,” said Dr. Iosifescu, who is also the director of clinical research at the Kline Institute for Psychiatric Research in Orangeburg, New York, and was not involved with the study.
Dr. Veraart agreed, adding that the “efficacy, safety, and tolerability of ketamine in depressed patients with a vulnerability to psychosis should be investigated in well-designed randomized controlled trials before application on a large scale is promoted.”
The study had no specific funding. Dr. Veraart has received speaker honoraria from Janssen outside of the submitted work. The other authors’ disclosures are listed in the original article. Dr. Iosifescu has been a consultant to the Centers of Psychiatric Excellence, advising clinics on the best methods of providing treatment with IV ketamine.
A version of this article first appeared on Medscape.com.
Common parasite now tied to impaired cognitive function
Investigators reviewed and conducted a meta-analysis of 13 studies that encompassed more than 13,000 healthy adults and found a modest but significant association between T. gondii seropositivity and impaired performance on cognitive tests of processing speed, working memory, short-term verbal memory, and executive function. The average age of the persons in the studies was close to 50 years.
“Our findings show that T. gondii could have a negative but small effect on cognition,” study investigator Arjen Sutterland, MD, of the Amsterdam Neuroscience Research Institute and the Amsterdam Institute for Infection and Immunity, University of Amsterdam, said in an interview.
The study was published online July 14, 2021, in JAMA Psychiatry.
Mental illness link
T. gondii is “an intracellular parasite that produces quiescent infection in approximately 30% of humans worldwide,” the authors wrote. The parasite that causes the infection not only settles in muscle and liver tissue but also can cross the blood-brain barrier and settle quiescently in brain tissue. It can be spread through contact with cat feces or by consuming contaminated meat.
Previous research has shown that neurocognitive changes associated with toxoplasmosis can occur in humans, and meta-analyses suggest an association with neuropsychiatric disorders. Some research has also tied T. gondii infection to increased motor vehicle crashes and suicide attempts.
Dr. Sutterland said he had been inspired by the work of E. Fuller Torrey and Bob Yolken, who proposed the connection between T. gondii and schizophrenia.
Some years ago, Dr. Sutterland and his group analyzed the mental health consequences of T. gondii infection and found “several interesting associations,” but they were unable to “rule out reverse causation – i.e., people with mental health disorders more often get these infections – as well as determine the impact on the population of this common infection.”
For the current study, the investigators analyzed studies that examined specifically cognitive functioning in otherwise healthy individuals in relation to T. gondii infection, “because reverse causation would be less likely in this population and a grasp of global impact would become more clear.”
The researchers conducted a literature search of studies conducted through June 7, 2019, that analyzed cognitive function among healthy participants for whom data on T. gondii seropositivity were available.
A total of 13 studies (n = 13,289 participants; mean age, 46.7 years; 49.6% male) were used in the review and meta-analysis. Some of the studies enrolled a healthy population sample; other studies compared participants with and those without psychiatric disorders. From these, the researchers extracted only the data concerning healthy participants.
The studies analyzed four cognitive domains: processing speed, working memory, short-term verbal memory, and executive functioning.
All cognitive domains affected
Of all the participants, 22.6% had antibodies against T. gondii.
Participants who were seropositive for T. gondii had less favorable functioning in all cognitive domains, with “small but significant” differences. 
The researchers conducted a meta-regression analysis of mean age in the analysis of executive functioning and found greater effect sizes as age increased (Q = 6.17; R2 = 81%; P = .01).
The studies were of “high quality,” and there was “little suggestion of publication bias was detected,” the authors noted.
“Although the extent of the associations was modest, the ubiquitous prevalence of the quiescent infection worldwide ... suggests that the consequences for cognitive function of the population as a whole may be substantial, although it is difficult to quantify the global impact,” they wrote.
They note that because the studies were cross-sectional in nature, causality cannot be established.
Nevertheless, Dr. Sutterland suggested several possible mechanisms through which T. gondii might affect neurocognition.
“We know the parasite forms cysts in the brain and can influence dopaminergic neurotransmission, which, in turn, affects neurocognition. Alternatively, it is also possible that the immune response to the infection in the brain causes cognitive impairment. This remains an important question to explore further,” he said.
He noted that clinicians can reassure patients who test positive for T. gondii that although the infection can have a negative impact on cognition, the effect is “small.”
Prevention programs warranted
Commenting on the study in an interview, Shawn D. Gale, PhD, associate professor, department of psychology and neuroscience center, Brigham Young University, Provo, Utah, called it a “great meta-analysis.” He noted that his group is researching the subject and has obtained similar findings. A big plus is that the researchers assessed several cognitive domains, not just one.
Although the data showed “mild effects,” the findings could be important on a population level. Because 30% of the world’s population are seropositive for T. gondii, a potentially large number of people are at risk for cognitive impairment, noted Dr. Gale, who was not involved with the study.
“If you look at the United States, perhaps 10%-15% of people might test positive [for T. gondii], but in Germany and France, the number comes closer to 50%, and in other places in the world – especially countries that have a harder time economically – the rates are even higher. So if it can affect cognition, even a small effect is a big deal,” Dr. Gale said.
“I think prevention will be the most important thing, and perhaps down the road, I hope that a vaccine will be considered,” Dr. Gale added.
“These findings indicate that primary prevention of the infection could have substantial global impact on mental health” and that public health programs to prevent T. gondii “are warranted.”
These programs might consist of hygienic measures, especially after human contact with contaminated sources, as well as research into vaccine development.
No source of funding for the study was listed. The authors and Dr. Gale reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators reviewed and conducted a meta-analysis of 13 studies that encompassed more than 13,000 healthy adults and found a modest but significant association between T. gondii seropositivity and impaired performance on cognitive tests of processing speed, working memory, short-term verbal memory, and executive function. The average age of the persons in the studies was close to 50 years.
“Our findings show that T. gondii could have a negative but small effect on cognition,” study investigator Arjen Sutterland, MD, of the Amsterdam Neuroscience Research Institute and the Amsterdam Institute for Infection and Immunity, University of Amsterdam, said in an interview.
The study was published online July 14, 2021, in JAMA Psychiatry.
Mental illness link
T. gondii is “an intracellular parasite that produces quiescent infection in approximately 30% of humans worldwide,” the authors wrote. The parasite that causes the infection not only settles in muscle and liver tissue but also can cross the blood-brain barrier and settle quiescently in brain tissue. It can be spread through contact with cat feces or by consuming contaminated meat.
Previous research has shown that neurocognitive changes associated with toxoplasmosis can occur in humans, and meta-analyses suggest an association with neuropsychiatric disorders. Some research has also tied T. gondii infection to increased motor vehicle crashes and suicide attempts.
Dr. Sutterland said he had been inspired by the work of E. Fuller Torrey and Bob Yolken, who proposed the connection between T. gondii and schizophrenia.
Some years ago, Dr. Sutterland and his group analyzed the mental health consequences of T. gondii infection and found “several interesting associations,” but they were unable to “rule out reverse causation – i.e., people with mental health disorders more often get these infections – as well as determine the impact on the population of this common infection.”
For the current study, the investigators analyzed studies that examined specifically cognitive functioning in otherwise healthy individuals in relation to T. gondii infection, “because reverse causation would be less likely in this population and a grasp of global impact would become more clear.”
The researchers conducted a literature search of studies conducted through June 7, 2019, that analyzed cognitive function among healthy participants for whom data on T. gondii seropositivity were available.
A total of 13 studies (n = 13,289 participants; mean age, 46.7 years; 49.6% male) were used in the review and meta-analysis. Some of the studies enrolled a healthy population sample; other studies compared participants with and those without psychiatric disorders. From these, the researchers extracted only the data concerning healthy participants.
The studies analyzed four cognitive domains: processing speed, working memory, short-term verbal memory, and executive functioning.
All cognitive domains affected
Of all the participants, 22.6% had antibodies against T. gondii.
Participants who were seropositive for T. gondii had less favorable functioning in all cognitive domains, with “small but significant” differences.
The researchers conducted a meta-regression analysis of mean age in the analysis of executive functioning and found greater effect sizes as age increased (Q = 6.17; R2 = 81%; P = .01).
The studies were of “high quality,” and there was “little suggestion of publication bias was detected,” the authors noted.
“Although the extent of the associations was modest, the ubiquitous prevalence of the quiescent infection worldwide ... suggests that the consequences for cognitive function of the population as a whole may be substantial, although it is difficult to quantify the global impact,” they wrote.
They note that because the studies were cross-sectional in nature, causality cannot be established.
Nevertheless, Dr. Sutterland suggested several possible mechanisms through which T. gondii might affect neurocognition.
“We know the parasite forms cysts in the brain and can influence dopaminergic neurotransmission, which, in turn, affects neurocognition. Alternatively, it is also possible that the immune response to the infection in the brain causes cognitive impairment. This remains an important question to explore further,” he said.
He noted that clinicians can reassure patients who test positive for T. gondii that although the infection can have a negative impact on cognition, the effect is “small.”
Prevention programs warranted
Commenting on the study in an interview, Shawn D. Gale, PhD, associate professor, department of psychology and neuroscience center, Brigham Young University, Provo, Utah, called it a “great meta-analysis.” He noted that his group is researching the subject and has obtained similar findings. A big plus is that the researchers assessed several cognitive domains, not just one.
Although the data showed “mild effects,” the findings could be important on a population level. Because 30% of the world’s population are seropositive for T. gondii, a potentially large number of people are at risk for cognitive impairment, noted Dr. Gale, who was not involved with the study.
“If you look at the United States, perhaps 10%-15% of people might test positive [for T. gondii], but in Germany and France, the number comes closer to 50%, and in other places in the world – especially countries that have a harder time economically – the rates are even higher. So if it can affect cognition, even a small effect is a big deal,” Dr. Gale said.
“I think prevention will be the most important thing, and perhaps down the road, I hope that a vaccine will be considered,” Dr. Gale added.
“These findings indicate that primary prevention of the infection could have substantial global impact on mental health” and that public health programs to prevent T. gondii “are warranted.”
These programs might consist of hygienic measures, especially after human contact with contaminated sources, as well as research into vaccine development.
No source of funding for the study was listed. The authors and Dr. Gale reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators reviewed and conducted a meta-analysis of 13 studies that encompassed more than 13,000 healthy adults and found a modest but significant association between T. gondii seropositivity and impaired performance on cognitive tests of processing speed, working memory, short-term verbal memory, and executive function. The average age of the persons in the studies was close to 50 years.
“Our findings show that T. gondii could have a negative but small effect on cognition,” study investigator Arjen Sutterland, MD, of the Amsterdam Neuroscience Research Institute and the Amsterdam Institute for Infection and Immunity, University of Amsterdam, said in an interview.
The study was published online July 14, 2021, in JAMA Psychiatry.
Mental illness link
T. gondii is “an intracellular parasite that produces quiescent infection in approximately 30% of humans worldwide,” the authors wrote. The parasite that causes the infection not only settles in muscle and liver tissue but also can cross the blood-brain barrier and settle quiescently in brain tissue. It can be spread through contact with cat feces or by consuming contaminated meat.
Previous research has shown that neurocognitive changes associated with toxoplasmosis can occur in humans, and meta-analyses suggest an association with neuropsychiatric disorders. Some research has also tied T. gondii infection to increased motor vehicle crashes and suicide attempts.
Dr. Sutterland said he had been inspired by the work of E. Fuller Torrey and Bob Yolken, who proposed the connection between T. gondii and schizophrenia.
Some years ago, Dr. Sutterland and his group analyzed the mental health consequences of T. gondii infection and found “several interesting associations,” but they were unable to “rule out reverse causation – i.e., people with mental health disorders more often get these infections – as well as determine the impact on the population of this common infection.”
For the current study, the investigators analyzed studies that examined specifically cognitive functioning in otherwise healthy individuals in relation to T. gondii infection, “because reverse causation would be less likely in this population and a grasp of global impact would become more clear.”
The researchers conducted a literature search of studies conducted through June 7, 2019, that analyzed cognitive function among healthy participants for whom data on T. gondii seropositivity were available.
A total of 13 studies (n = 13,289 participants; mean age, 46.7 years; 49.6% male) were used in the review and meta-analysis. Some of the studies enrolled a healthy population sample; other studies compared participants with and those without psychiatric disorders. From these, the researchers extracted only the data concerning healthy participants.
The studies analyzed four cognitive domains: processing speed, working memory, short-term verbal memory, and executive functioning.
All cognitive domains affected
Of all the participants, 22.6% had antibodies against T. gondii.
Participants who were seropositive for T. gondii had less favorable functioning in all cognitive domains, with “small but significant” differences.
The researchers conducted a meta-regression analysis of mean age in the analysis of executive functioning and found greater effect sizes as age increased (Q = 6.17; R2 = 81%; P = .01).
The studies were of “high quality,” and there was “little suggestion of publication bias was detected,” the authors noted.
“Although the extent of the associations was modest, the ubiquitous prevalence of the quiescent infection worldwide ... suggests that the consequences for cognitive function of the population as a whole may be substantial, although it is difficult to quantify the global impact,” they wrote.
They note that because the studies were cross-sectional in nature, causality cannot be established.
Nevertheless, Dr. Sutterland suggested several possible mechanisms through which T. gondii might affect neurocognition.
“We know the parasite forms cysts in the brain and can influence dopaminergic neurotransmission, which, in turn, affects neurocognition. Alternatively, it is also possible that the immune response to the infection in the brain causes cognitive impairment. This remains an important question to explore further,” he said.
He noted that clinicians can reassure patients who test positive for T. gondii that although the infection can have a negative impact on cognition, the effect is “small.”
Prevention programs warranted
Commenting on the study in an interview, Shawn D. Gale, PhD, associate professor, department of psychology and neuroscience center, Brigham Young University, Provo, Utah, called it a “great meta-analysis.” He noted that his group is researching the subject and has obtained similar findings. A big plus is that the researchers assessed several cognitive domains, not just one.
Although the data showed “mild effects,” the findings could be important on a population level. Because 30% of the world’s population are seropositive for T. gondii, a potentially large number of people are at risk for cognitive impairment, noted Dr. Gale, who was not involved with the study.
“If you look at the United States, perhaps 10%-15% of people might test positive [for T. gondii], but in Germany and France, the number comes closer to 50%, and in other places in the world – especially countries that have a harder time economically – the rates are even higher. So if it can affect cognition, even a small effect is a big deal,” Dr. Gale said.
“I think prevention will be the most important thing, and perhaps down the road, I hope that a vaccine will be considered,” Dr. Gale added.
“These findings indicate that primary prevention of the infection could have substantial global impact on mental health” and that public health programs to prevent T. gondii “are warranted.”
These programs might consist of hygienic measures, especially after human contact with contaminated sources, as well as research into vaccine development.
No source of funding for the study was listed. The authors and Dr. Gale reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Could the Surgisphere Lancet and NEJM retractions debacle happen again?
In May 2020, two major scientific journals published and subsequently retracted studies that relied on data provided by the now-disgraced data analytics company Surgisphere.
One of the studies, published in The Lancet, reported an association between the antimalarial drugs hydroxychloroquine and chloroquine and increased in-hospital mortality and cardiac arrhythmias in patients with COVID-19. The second study, which appeared in the New England Journal of Medicine, described an association between underlying cardiovascular disease, but not related drug therapy, with increased mortality in COVID-19 patients.
The retractions in June 2020 followed an open letter to each publication penned by scientists, ethicists, and clinicians who flagged serious methodological and ethical anomalies in the data used in the studies.
On the 1-year anniversary, researchers and journal editors spoke about what was learned to reduce the risk of something like this happening again.
“The Surgisphere incident served as a wake-up call for everyone involved with scientific research to make sure that data have integrity and are robust,” Sunil Rao, MD, professor of medicine, Duke University Health System, Durham, N.C., and editor-in-chief of Circulation: Cardiovascular Interventions, said in an interview.
“I’m sure this isn’t going to be the last incident of this nature, and we have to be vigilant about new datasets or datasets that we haven’t heard of as having a track record of publication,” Dr. Rao said.
Spotlight on authors
The editors of the Lancet Group responded to the “wake-up call” with a statement, Learning From a Retraction, which announced changes to reduce the risks of research and publication misconduct.
The changes affect multiple phases of the publication process. For example, the declaration form that authors must sign “will require that more than one author has directly accessed and verified the data reported in the manuscript.” Additionally, when a research article is the result of an academic and commercial partnership – as was the case in the two retracted studies – “one of the authors named as having accessed and verified data must be from the academic team.”
This was particularly important because it appears that the academic coauthors of the retracted studies did not have access to the data provided by Surgisphere, a private commercial entity.
Mandeep R. Mehra, MD, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, who was the lead author of both studies, declined to be interviewed for this article. In a letter to the New England Journal of Medicine editors requesting that the article be retracted, he wrote: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article.”
In a similar communication with The Lancet, Dr. Mehra wrote even more pointedly that, in light of the refusal of Surgisphere to make the data available to the third-party auditor, “we can no longer vouch for the veracity of the primary data sources.”
“It is very disturbing that the authors were willing to put their names on a paper without ever seeing and verifying the data,” Mario Malički, MD, PhD, a postdoctoral researcher at METRICS at Stanford (Calif.) University, said in an interview. “Saying that they could ‘no longer vouch’ suggests that at one point they could vouch for it. Most likely they took its existence and veracity entirely on trust.”
Dr. Malički pointed out that one of the four criteria of the International Committee of Medical Journal Editors for being an author on a study is the “agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.”
The new policies put forth by The Lancet are “encouraging,” but perhaps do not go far enough. “Every author, not only one or two authors, should personally take responsibility for the integrity of data,” he stated.
Many journals “adhere to ICMJE rules in principle and have checkboxes for authors to confirm that they guarantee the veracity of the data.” However, they “do not have the resources to verify the authors’ statements.”
Ideally, “it is the institutions where the researchers work that should guarantee the veracity of the raw data – but I do not know any university or institute that does this,” he said.
No ‘good-housekeeping’ seal
For articles based on large, real-world datasets, the Lancet Group will now require that editors ensure that at least one peer reviewer is “knowledgeable about the details of the dataset being reported and can understand its strengths and limitations in relation to the question being addressed.”
For studies that use “very large datasets,” the editors are now required to ensure that, in addition to a statistical peer review, a review from an “expert in data science” is obtained. Reviewers will also be explicitly asked if they have “concerns about research integrity or publication ethics regarding the manuscript they are reviewing.”
Although these changes are encouraging, Harlan Krumholz, MD, professor of medicine (cardiology), Yale University, New Haven, Conn., is not convinced that they are realistic.
Dr. Krumholz, who is also the founder and director of the Yale New Haven Hospital Center for Outcome Research and Evaluation, said in an interview that “large, real-world datasets” are of two varieties. Datasets drawn from publicly available sources, such as Medicare or Medicaid health records, are utterly transparent.
By contrast, Surgisphere was a privately owned database, and “it is not unusual for privately owned databases to have proprietary data from multiple sources that the company may choose to keep confidential,” Dr. Krumholz said.
He noted that several large datasets are widely used for research purposes, such as IBM, Optum, and Komodo – a data analytics company that recently entered into partnership with a fourth company, PicnicHealth.
These companies receive deidentified electronic health records from health systems and insurers nationwide. Komodo boasts “real-time and longitudinal data on more than 325 million patients, representing more than 65 billion clinical encounters with 15 million new encounters added daily.”
“One has to raise an eyebrow – how were these data acquired? And, given that the U.S. has a population of around 328 million people, is it really plausible that a single company has health records of almost the entire U.S. population?” Dr. Krumholz commented. (A spokesperson for Komodo said in an interview that the company has records on 325 million U.S. patients.)
This is “an issue across the board with ‘real-world evidence,’ which is that it’s like the ‘Wild West’ – the transparencies of private databases are less than optimal and there are no common standards to help us move forward,” Dr. Krumholz said, noting that there is “no external authority overseeing, validating, or auditing these databases. In the end, we are trusting the companies.”
Although the Food and Drug Administration has laid out a framework for how real-world data and real-world evidence can be used to advance scientific research, the FDA does not oversee the databases.
“Thus, there is no ‘good housekeeping seal’ that a peer reviewer or author would be in a position to evaluate,” Dr. Krumholz said. “No journal can do an audit of these types of private databases, so ultimately, it boils down to trust.”
Nevertheless, there were red flags with Surgisphere, Dr. Rao pointed out. Unlike more established and widely used databases, the Surgisphere database had been catapulted from relative obscurity onto center stage, which should have given researchers pause.
AI-assisted peer review
A series of investigative reports by The Guardian raised questions about Sapan Desai, the CEO of Surgisphere, including the fact that hospitals purporting to have contributed data to Surgisphere had never heard of the company.
However, peer reviewers are not expected to be investigative reporters, explained Dr. Malički.
“In an ideal world, editors and peer reviewers would have a chance to look at raw data or would have a certificate from the academic institution the authors are affiliated with that the data have been inspected by the institution, but in the real world, of course, this does not happen,” he said.
Artificial intelligence software is being developed and deployed to assist in the peer review process, Dr. Malički noted. In July 2020, Frontiers Science News debuted its Artificial Intelligence Review Assistant to help editors, reviewers, and authors evaluate the quality of a manuscript. The program can make up to 20 recommendations, including “the assessment of language quality, the detection of plagiarism, and identification of potential conflicts of interest.” The program is now in use in all 103 journals published by Frontiers. Preliminary software is also available to detect statistical errors.
Another system under development is FAIRware, an initiative of the Research on Research Institute in partnership with the Stanford Center for Biomedical Informatics Research. The partnership’s goal is to “develop an automated online tool (or suite of tools) to help researchers ensure that the datasets they produce are ‘FAIR’ at the point of creation,” said Dr. Malički, referring to the findability, accessibility, interoperability, and reusability (FAIR) guiding principles for data management. The principles aim to increase the ability of machines to automatically find and use the data, as well as to support its reuse by individuals.
He added that these advanced tools cannot replace human reviewers, who will “likely always be a necessary quality check in the process.”
Greater transparency needed
Another limitation of peer review is the reviewers themselves, according to Dr. Malički. “It’s a step in the right direction that The Lancet is now requesting a peer reviewer with expertise in big datasets, but it does not go far enough to increase accountability of peer reviewers,” he said.
Dr. Malički is the co–editor-in-chief of the journal Research Integrity and Peer Review , which has “an open and transparent review process – meaning that we reveal the names of the reviewers to the public and we publish the full review report alongside the paper.” The publication also allows the authors to make public the original version they sent.
Dr. Malički cited several advantages to transparent peer review, particularly the increased accountability that results from placing potential conflicts of interest under the microscope.
As for the concern that identifying the reviewers might soften the review process, “there is little evidence to substantiate that concern,” he added.
Dr. Malički emphasized that making reviews public “is not a problem – people voice strong opinions at conferences and elsewhere. The question remains, who gets to decide if the criticism has been adequately addressed, so that the findings of the study still stand?”
He acknowledged that, “as in politics and on many social platforms, rage, hatred, and personal attacks divert the discussion from the topic at hand, which is why a good moderator is needed.”
A journal editor or a moderator at a scientific conference may be tasked with “stopping all talk not directly related to the topic.”
Widening the circle of scrutiny
Dr. Malički added: “A published paper should not be considered the ‘final word,’ even if it has gone through peer review and is published in a reputable journal. The peer-review process means that a limited number of people have seen the study.”
Once the study is published, “the whole world gets to see it and criticize it, and that widens the circle of scrutiny.”
One classic way to raise concerns about a study post publication is to write a letter to the journal editor. But there is no guarantee that the letter will be published or the authors notified of the feedback.
Dr. Malički encourages readers to use PubPeer, an online forum in which members of the public can post comments on scientific studies and articles.
Once a comment is posted, the authors are alerted. “There is no ‘police department’ that forces authors to acknowledge comments or forces journal editors to take action, but at least PubPeer guarantees that readers’ messages will reach the authors and – depending on how many people raise similar issues – the comments can lead to errata or even full retractions,” he said.
PubPeer was key in pointing out errors in a suspect study from France (which did not involve Surgisphere) that supported the use of hydroxychloroquine in COVID-19.
A message to policy makers
High stakes are involved in ensuring the integrity of scientific publications: The French government revoked a decree that allowed hospitals to prescribe hydroxychloroquine for certain COVID-19 patients.
After the Surgisphere Lancet article, the World Health Organization temporarily halted enrollment in the hydroxychloroquine component of the Solidarity international randomized trial of medications to treat COVID-19.
Similarly, the U.K. Medicines and Healthcare Products Regulatory Agency instructed the organizers of COPCOV, an international trial of the use of hydroxychloroquine as prophylaxis against COVID-19, to suspend recruitment of patients. The SOLIDARITY trial briefly resumed, but that arm of the trial was ultimately suspended after a preliminary analysis suggested that hydroxychloroquine provided no benefit for patients with COVID-19.
Dr. Malički emphasized that governments and organizations should not “blindly trust journal articles” and make policy decisions based exclusively on study findings in published journals – even with the current improvements in the peer review process – without having their own experts conduct a thorough review of the data.
“If you are not willing to do your own due diligence, then at least be brave enough and say transparently why you are making this policy, or any other changes, and clearly state if your decision is based primarily or solely on the fact that ‘X’ study was published in ‘Y’ journal,” he stated.
Dr. Rao believes that the most important take-home message of the Surgisphere scandal is “that we should be skeptical and do our own due diligence about the kinds of data published – a responsibility that applies to all of us, whether we are investigators, editors at journals, the press, scientists, and readers.”
Dr. Rao reported being on the steering committee of the National Heart, Lung, and Blood Institute–sponsored MINT trial and the Bayer-sponsored PACIFIC AMI trial. Dr. Malički reports being a postdoc at METRICS Stanford in the past 3 years. Dr. Krumholz received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Facebook, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases in Beijing. He is an owner of Refactor Health and HugoHealth and had grants and/or contracts from the Centers for Medicare & Medicaid Services, the FDA, Johnson & Johnson, and the Shenzhen Center for Health Information.
A version of this article first appeared on Medscape.com.
In May 2020, two major scientific journals published and subsequently retracted studies that relied on data provided by the now-disgraced data analytics company Surgisphere.
One of the studies, published in The Lancet, reported an association between the antimalarial drugs hydroxychloroquine and chloroquine and increased in-hospital mortality and cardiac arrhythmias in patients with COVID-19. The second study, which appeared in the New England Journal of Medicine, described an association between underlying cardiovascular disease, but not related drug therapy, with increased mortality in COVID-19 patients.
The retractions in June 2020 followed an open letter to each publication penned by scientists, ethicists, and clinicians who flagged serious methodological and ethical anomalies in the data used in the studies.
On the 1-year anniversary, researchers and journal editors spoke about what was learned to reduce the risk of something like this happening again.
“The Surgisphere incident served as a wake-up call for everyone involved with scientific research to make sure that data have integrity and are robust,” Sunil Rao, MD, professor of medicine, Duke University Health System, Durham, N.C., and editor-in-chief of Circulation: Cardiovascular Interventions, said in an interview.
“I’m sure this isn’t going to be the last incident of this nature, and we have to be vigilant about new datasets or datasets that we haven’t heard of as having a track record of publication,” Dr. Rao said.
Spotlight on authors
The editors of the Lancet Group responded to the “wake-up call” with a statement, Learning From a Retraction, which announced changes to reduce the risks of research and publication misconduct.
The changes affect multiple phases of the publication process. For example, the declaration form that authors must sign “will require that more than one author has directly accessed and verified the data reported in the manuscript.” Additionally, when a research article is the result of an academic and commercial partnership – as was the case in the two retracted studies – “one of the authors named as having accessed and verified data must be from the academic team.”
This was particularly important because it appears that the academic coauthors of the retracted studies did not have access to the data provided by Surgisphere, a private commercial entity.
Mandeep R. Mehra, MD, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, who was the lead author of both studies, declined to be interviewed for this article. In a letter to the New England Journal of Medicine editors requesting that the article be retracted, he wrote: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article.”
In a similar communication with The Lancet, Dr. Mehra wrote even more pointedly that, in light of the refusal of Surgisphere to make the data available to the third-party auditor, “we can no longer vouch for the veracity of the primary data sources.”
“It is very disturbing that the authors were willing to put their names on a paper without ever seeing and verifying the data,” Mario Malički, MD, PhD, a postdoctoral researcher at METRICS at Stanford (Calif.) University, said in an interview. “Saying that they could ‘no longer vouch’ suggests that at one point they could vouch for it. Most likely they took its existence and veracity entirely on trust.”
Dr. Malički pointed out that one of the four criteria of the International Committee of Medical Journal Editors for being an author on a study is the “agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.”
The new policies put forth by The Lancet are “encouraging,” but perhaps do not go far enough. “Every author, not only one or two authors, should personally take responsibility for the integrity of data,” he stated.
Many journals “adhere to ICMJE rules in principle and have checkboxes for authors to confirm that they guarantee the veracity of the data.” However, they “do not have the resources to verify the authors’ statements.”
Ideally, “it is the institutions where the researchers work that should guarantee the veracity of the raw data – but I do not know any university or institute that does this,” he said.
No ‘good-housekeeping’ seal
For articles based on large, real-world datasets, the Lancet Group will now require that editors ensure that at least one peer reviewer is “knowledgeable about the details of the dataset being reported and can understand its strengths and limitations in relation to the question being addressed.”
For studies that use “very large datasets,” the editors are now required to ensure that, in addition to a statistical peer review, a review from an “expert in data science” is obtained. Reviewers will also be explicitly asked if they have “concerns about research integrity or publication ethics regarding the manuscript they are reviewing.”
Although these changes are encouraging, Harlan Krumholz, MD, professor of medicine (cardiology), Yale University, New Haven, Conn., is not convinced that they are realistic.
Dr. Krumholz, who is also the founder and director of the Yale New Haven Hospital Center for Outcome Research and Evaluation, said in an interview that “large, real-world datasets” are of two varieties. Datasets drawn from publicly available sources, such as Medicare or Medicaid health records, are utterly transparent.
By contrast, Surgisphere was a privately owned database, and “it is not unusual for privately owned databases to have proprietary data from multiple sources that the company may choose to keep confidential,” Dr. Krumholz said.
He noted that several large datasets are widely used for research purposes, such as IBM, Optum, and Komodo – a data analytics company that recently entered into partnership with a fourth company, PicnicHealth.
These companies receive deidentified electronic health records from health systems and insurers nationwide. Komodo boasts “real-time and longitudinal data on more than 325 million patients, representing more than 65 billion clinical encounters with 15 million new encounters added daily.”
“One has to raise an eyebrow – how were these data acquired? And, given that the U.S. has a population of around 328 million people, is it really plausible that a single company has health records of almost the entire U.S. population?” Dr. Krumholz commented. (A spokesperson for Komodo said in an interview that the company has records on 325 million U.S. patients.)
This is “an issue across the board with ‘real-world evidence,’ which is that it’s like the ‘Wild West’ – the transparencies of private databases are less than optimal and there are no common standards to help us move forward,” Dr. Krumholz said, noting that there is “no external authority overseeing, validating, or auditing these databases. In the end, we are trusting the companies.”
Although the Food and Drug Administration has laid out a framework for how real-world data and real-world evidence can be used to advance scientific research, the FDA does not oversee the databases.
“Thus, there is no ‘good housekeeping seal’ that a peer reviewer or author would be in a position to evaluate,” Dr. Krumholz said. “No journal can do an audit of these types of private databases, so ultimately, it boils down to trust.”
Nevertheless, there were red flags with Surgisphere, Dr. Rao pointed out. Unlike more established and widely used databases, the Surgisphere database had been catapulted from relative obscurity onto center stage, which should have given researchers pause.
AI-assisted peer review
A series of investigative reports by The Guardian raised questions about Sapan Desai, the CEO of Surgisphere, including the fact that hospitals purporting to have contributed data to Surgisphere had never heard of the company.
However, peer reviewers are not expected to be investigative reporters, explained Dr. Malički.
“In an ideal world, editors and peer reviewers would have a chance to look at raw data or would have a certificate from the academic institution the authors are affiliated with that the data have been inspected by the institution, but in the real world, of course, this does not happen,” he said.
Artificial intelligence software is being developed and deployed to assist in the peer review process, Dr. Malički noted. In July 2020, Frontiers Science News debuted its Artificial Intelligence Review Assistant to help editors, reviewers, and authors evaluate the quality of a manuscript. The program can make up to 20 recommendations, including “the assessment of language quality, the detection of plagiarism, and identification of potential conflicts of interest.” The program is now in use in all 103 journals published by Frontiers. Preliminary software is also available to detect statistical errors.
Another system under development is FAIRware, an initiative of the Research on Research Institute in partnership with the Stanford Center for Biomedical Informatics Research. The partnership’s goal is to “develop an automated online tool (or suite of tools) to help researchers ensure that the datasets they produce are ‘FAIR’ at the point of creation,” said Dr. Malički, referring to the findability, accessibility, interoperability, and reusability (FAIR) guiding principles for data management. The principles aim to increase the ability of machines to automatically find and use the data, as well as to support its reuse by individuals.
He added that these advanced tools cannot replace human reviewers, who will “likely always be a necessary quality check in the process.”
Greater transparency needed
Another limitation of peer review is the reviewers themselves, according to Dr. Malički. “It’s a step in the right direction that The Lancet is now requesting a peer reviewer with expertise in big datasets, but it does not go far enough to increase accountability of peer reviewers,” he said.
Dr. Malički is the co–editor-in-chief of the journal Research Integrity and Peer Review , which has “an open and transparent review process – meaning that we reveal the names of the reviewers to the public and we publish the full review report alongside the paper.” The publication also allows the authors to make public the original version they sent.
Dr. Malički cited several advantages to transparent peer review, particularly the increased accountability that results from placing potential conflicts of interest under the microscope.
As for the concern that identifying the reviewers might soften the review process, “there is little evidence to substantiate that concern,” he added.
Dr. Malički emphasized that making reviews public “is not a problem – people voice strong opinions at conferences and elsewhere. The question remains, who gets to decide if the criticism has been adequately addressed, so that the findings of the study still stand?”
He acknowledged that, “as in politics and on many social platforms, rage, hatred, and personal attacks divert the discussion from the topic at hand, which is why a good moderator is needed.”
A journal editor or a moderator at a scientific conference may be tasked with “stopping all talk not directly related to the topic.”
Widening the circle of scrutiny
Dr. Malički added: “A published paper should not be considered the ‘final word,’ even if it has gone through peer review and is published in a reputable journal. The peer-review process means that a limited number of people have seen the study.”
Once the study is published, “the whole world gets to see it and criticize it, and that widens the circle of scrutiny.”
One classic way to raise concerns about a study post publication is to write a letter to the journal editor. But there is no guarantee that the letter will be published or the authors notified of the feedback.
Dr. Malički encourages readers to use PubPeer, an online forum in which members of the public can post comments on scientific studies and articles.
Once a comment is posted, the authors are alerted. “There is no ‘police department’ that forces authors to acknowledge comments or forces journal editors to take action, but at least PubPeer guarantees that readers’ messages will reach the authors and – depending on how many people raise similar issues – the comments can lead to errata or even full retractions,” he said.
PubPeer was key in pointing out errors in a suspect study from France (which did not involve Surgisphere) that supported the use of hydroxychloroquine in COVID-19.
A message to policy makers
High stakes are involved in ensuring the integrity of scientific publications: The French government revoked a decree that allowed hospitals to prescribe hydroxychloroquine for certain COVID-19 patients.
After the Surgisphere Lancet article, the World Health Organization temporarily halted enrollment in the hydroxychloroquine component of the Solidarity international randomized trial of medications to treat COVID-19.
Similarly, the U.K. Medicines and Healthcare Products Regulatory Agency instructed the organizers of COPCOV, an international trial of the use of hydroxychloroquine as prophylaxis against COVID-19, to suspend recruitment of patients. The SOLIDARITY trial briefly resumed, but that arm of the trial was ultimately suspended after a preliminary analysis suggested that hydroxychloroquine provided no benefit for patients with COVID-19.
Dr. Malički emphasized that governments and organizations should not “blindly trust journal articles” and make policy decisions based exclusively on study findings in published journals – even with the current improvements in the peer review process – without having their own experts conduct a thorough review of the data.
“If you are not willing to do your own due diligence, then at least be brave enough and say transparently why you are making this policy, or any other changes, and clearly state if your decision is based primarily or solely on the fact that ‘X’ study was published in ‘Y’ journal,” he stated.
Dr. Rao believes that the most important take-home message of the Surgisphere scandal is “that we should be skeptical and do our own due diligence about the kinds of data published – a responsibility that applies to all of us, whether we are investigators, editors at journals, the press, scientists, and readers.”
Dr. Rao reported being on the steering committee of the National Heart, Lung, and Blood Institute–sponsored MINT trial and the Bayer-sponsored PACIFIC AMI trial. Dr. Malički reports being a postdoc at METRICS Stanford in the past 3 years. Dr. Krumholz received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Facebook, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases in Beijing. He is an owner of Refactor Health and HugoHealth and had grants and/or contracts from the Centers for Medicare & Medicaid Services, the FDA, Johnson & Johnson, and the Shenzhen Center for Health Information.
A version of this article first appeared on Medscape.com.
In May 2020, two major scientific journals published and subsequently retracted studies that relied on data provided by the now-disgraced data analytics company Surgisphere.
One of the studies, published in The Lancet, reported an association between the antimalarial drugs hydroxychloroquine and chloroquine and increased in-hospital mortality and cardiac arrhythmias in patients with COVID-19. The second study, which appeared in the New England Journal of Medicine, described an association between underlying cardiovascular disease, but not related drug therapy, with increased mortality in COVID-19 patients.
The retractions in June 2020 followed an open letter to each publication penned by scientists, ethicists, and clinicians who flagged serious methodological and ethical anomalies in the data used in the studies.
On the 1-year anniversary, researchers and journal editors spoke about what was learned to reduce the risk of something like this happening again.
“The Surgisphere incident served as a wake-up call for everyone involved with scientific research to make sure that data have integrity and are robust,” Sunil Rao, MD, professor of medicine, Duke University Health System, Durham, N.C., and editor-in-chief of Circulation: Cardiovascular Interventions, said in an interview.
“I’m sure this isn’t going to be the last incident of this nature, and we have to be vigilant about new datasets or datasets that we haven’t heard of as having a track record of publication,” Dr. Rao said.
Spotlight on authors
The editors of the Lancet Group responded to the “wake-up call” with a statement, Learning From a Retraction, which announced changes to reduce the risks of research and publication misconduct.
The changes affect multiple phases of the publication process. For example, the declaration form that authors must sign “will require that more than one author has directly accessed and verified the data reported in the manuscript.” Additionally, when a research article is the result of an academic and commercial partnership – as was the case in the two retracted studies – “one of the authors named as having accessed and verified data must be from the academic team.”
This was particularly important because it appears that the academic coauthors of the retracted studies did not have access to the data provided by Surgisphere, a private commercial entity.
Mandeep R. Mehra, MD, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, who was the lead author of both studies, declined to be interviewed for this article. In a letter to the New England Journal of Medicine editors requesting that the article be retracted, he wrote: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article.”
In a similar communication with The Lancet, Dr. Mehra wrote even more pointedly that, in light of the refusal of Surgisphere to make the data available to the third-party auditor, “we can no longer vouch for the veracity of the primary data sources.”
“It is very disturbing that the authors were willing to put their names on a paper without ever seeing and verifying the data,” Mario Malički, MD, PhD, a postdoctoral researcher at METRICS at Stanford (Calif.) University, said in an interview. “Saying that they could ‘no longer vouch’ suggests that at one point they could vouch for it. Most likely they took its existence and veracity entirely on trust.”
Dr. Malički pointed out that one of the four criteria of the International Committee of Medical Journal Editors for being an author on a study is the “agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.”
The new policies put forth by The Lancet are “encouraging,” but perhaps do not go far enough. “Every author, not only one or two authors, should personally take responsibility for the integrity of data,” he stated.
Many journals “adhere to ICMJE rules in principle and have checkboxes for authors to confirm that they guarantee the veracity of the data.” However, they “do not have the resources to verify the authors’ statements.”
Ideally, “it is the institutions where the researchers work that should guarantee the veracity of the raw data – but I do not know any university or institute that does this,” he said.
No ‘good-housekeeping’ seal
For articles based on large, real-world datasets, the Lancet Group will now require that editors ensure that at least one peer reviewer is “knowledgeable about the details of the dataset being reported and can understand its strengths and limitations in relation to the question being addressed.”
For studies that use “very large datasets,” the editors are now required to ensure that, in addition to a statistical peer review, a review from an “expert in data science” is obtained. Reviewers will also be explicitly asked if they have “concerns about research integrity or publication ethics regarding the manuscript they are reviewing.”
Although these changes are encouraging, Harlan Krumholz, MD, professor of medicine (cardiology), Yale University, New Haven, Conn., is not convinced that they are realistic.
Dr. Krumholz, who is also the founder and director of the Yale New Haven Hospital Center for Outcome Research and Evaluation, said in an interview that “large, real-world datasets” are of two varieties. Datasets drawn from publicly available sources, such as Medicare or Medicaid health records, are utterly transparent.
By contrast, Surgisphere was a privately owned database, and “it is not unusual for privately owned databases to have proprietary data from multiple sources that the company may choose to keep confidential,” Dr. Krumholz said.
He noted that several large datasets are widely used for research purposes, such as IBM, Optum, and Komodo – a data analytics company that recently entered into partnership with a fourth company, PicnicHealth.
These companies receive deidentified electronic health records from health systems and insurers nationwide. Komodo boasts “real-time and longitudinal data on more than 325 million patients, representing more than 65 billion clinical encounters with 15 million new encounters added daily.”
“One has to raise an eyebrow – how were these data acquired? And, given that the U.S. has a population of around 328 million people, is it really plausible that a single company has health records of almost the entire U.S. population?” Dr. Krumholz commented. (A spokesperson for Komodo said in an interview that the company has records on 325 million U.S. patients.)
This is “an issue across the board with ‘real-world evidence,’ which is that it’s like the ‘Wild West’ – the transparencies of private databases are less than optimal and there are no common standards to help us move forward,” Dr. Krumholz said, noting that there is “no external authority overseeing, validating, or auditing these databases. In the end, we are trusting the companies.”
Although the Food and Drug Administration has laid out a framework for how real-world data and real-world evidence can be used to advance scientific research, the FDA does not oversee the databases.
“Thus, there is no ‘good housekeeping seal’ that a peer reviewer or author would be in a position to evaluate,” Dr. Krumholz said. “No journal can do an audit of these types of private databases, so ultimately, it boils down to trust.”
Nevertheless, there were red flags with Surgisphere, Dr. Rao pointed out. Unlike more established and widely used databases, the Surgisphere database had been catapulted from relative obscurity onto center stage, which should have given researchers pause.
AI-assisted peer review
A series of investigative reports by The Guardian raised questions about Sapan Desai, the CEO of Surgisphere, including the fact that hospitals purporting to have contributed data to Surgisphere had never heard of the company.
However, peer reviewers are not expected to be investigative reporters, explained Dr. Malički.
“In an ideal world, editors and peer reviewers would have a chance to look at raw data or would have a certificate from the academic institution the authors are affiliated with that the data have been inspected by the institution, but in the real world, of course, this does not happen,” he said.
Artificial intelligence software is being developed and deployed to assist in the peer review process, Dr. Malički noted. In July 2020, Frontiers Science News debuted its Artificial Intelligence Review Assistant to help editors, reviewers, and authors evaluate the quality of a manuscript. The program can make up to 20 recommendations, including “the assessment of language quality, the detection of plagiarism, and identification of potential conflicts of interest.” The program is now in use in all 103 journals published by Frontiers. Preliminary software is also available to detect statistical errors.
Another system under development is FAIRware, an initiative of the Research on Research Institute in partnership with the Stanford Center for Biomedical Informatics Research. The partnership’s goal is to “develop an automated online tool (or suite of tools) to help researchers ensure that the datasets they produce are ‘FAIR’ at the point of creation,” said Dr. Malički, referring to the findability, accessibility, interoperability, and reusability (FAIR) guiding principles for data management. The principles aim to increase the ability of machines to automatically find and use the data, as well as to support its reuse by individuals.
He added that these advanced tools cannot replace human reviewers, who will “likely always be a necessary quality check in the process.”
Greater transparency needed
Another limitation of peer review is the reviewers themselves, according to Dr. Malički. “It’s a step in the right direction that The Lancet is now requesting a peer reviewer with expertise in big datasets, but it does not go far enough to increase accountability of peer reviewers,” he said.
Dr. Malički is the co–editor-in-chief of the journal Research Integrity and Peer Review , which has “an open and transparent review process – meaning that we reveal the names of the reviewers to the public and we publish the full review report alongside the paper.” The publication also allows the authors to make public the original version they sent.
Dr. Malički cited several advantages to transparent peer review, particularly the increased accountability that results from placing potential conflicts of interest under the microscope.
As for the concern that identifying the reviewers might soften the review process, “there is little evidence to substantiate that concern,” he added.
Dr. Malički emphasized that making reviews public “is not a problem – people voice strong opinions at conferences and elsewhere. The question remains, who gets to decide if the criticism has been adequately addressed, so that the findings of the study still stand?”
He acknowledged that, “as in politics and on many social platforms, rage, hatred, and personal attacks divert the discussion from the topic at hand, which is why a good moderator is needed.”
A journal editor or a moderator at a scientific conference may be tasked with “stopping all talk not directly related to the topic.”
Widening the circle of scrutiny
Dr. Malički added: “A published paper should not be considered the ‘final word,’ even if it has gone through peer review and is published in a reputable journal. The peer-review process means that a limited number of people have seen the study.”
Once the study is published, “the whole world gets to see it and criticize it, and that widens the circle of scrutiny.”
One classic way to raise concerns about a study post publication is to write a letter to the journal editor. But there is no guarantee that the letter will be published or the authors notified of the feedback.
Dr. Malički encourages readers to use PubPeer, an online forum in which members of the public can post comments on scientific studies and articles.
Once a comment is posted, the authors are alerted. “There is no ‘police department’ that forces authors to acknowledge comments or forces journal editors to take action, but at least PubPeer guarantees that readers’ messages will reach the authors and – depending on how many people raise similar issues – the comments can lead to errata or even full retractions,” he said.
PubPeer was key in pointing out errors in a suspect study from France (which did not involve Surgisphere) that supported the use of hydroxychloroquine in COVID-19.
A message to policy makers
High stakes are involved in ensuring the integrity of scientific publications: The French government revoked a decree that allowed hospitals to prescribe hydroxychloroquine for certain COVID-19 patients.
After the Surgisphere Lancet article, the World Health Organization temporarily halted enrollment in the hydroxychloroquine component of the Solidarity international randomized trial of medications to treat COVID-19.
Similarly, the U.K. Medicines and Healthcare Products Regulatory Agency instructed the organizers of COPCOV, an international trial of the use of hydroxychloroquine as prophylaxis against COVID-19, to suspend recruitment of patients. The SOLIDARITY trial briefly resumed, but that arm of the trial was ultimately suspended after a preliminary analysis suggested that hydroxychloroquine provided no benefit for patients with COVID-19.
Dr. Malički emphasized that governments and organizations should not “blindly trust journal articles” and make policy decisions based exclusively on study findings in published journals – even with the current improvements in the peer review process – without having their own experts conduct a thorough review of the data.
“If you are not willing to do your own due diligence, then at least be brave enough and say transparently why you are making this policy, or any other changes, and clearly state if your decision is based primarily or solely on the fact that ‘X’ study was published in ‘Y’ journal,” he stated.
Dr. Rao believes that the most important take-home message of the Surgisphere scandal is “that we should be skeptical and do our own due diligence about the kinds of data published – a responsibility that applies to all of us, whether we are investigators, editors at journals, the press, scientists, and readers.”
Dr. Rao reported being on the steering committee of the National Heart, Lung, and Blood Institute–sponsored MINT trial and the Bayer-sponsored PACIFIC AMI trial. Dr. Malički reports being a postdoc at METRICS Stanford in the past 3 years. Dr. Krumholz received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Facebook, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases in Beijing. He is an owner of Refactor Health and HugoHealth and had grants and/or contracts from the Centers for Medicare & Medicaid Services, the FDA, Johnson & Johnson, and the Shenzhen Center for Health Information.
A version of this article first appeared on Medscape.com.
High rates of work-related trauma, PTSD in intern physicians
Work-related posttraumatic stress disorder is three times higher in interns than the general population, new research shows.
Investigators assessed PTSD in more than 1,100 physicians at the end of their internship year and found that a little over half reported work-related trauma exposure, and of these, 20% screened positive for PTSD.
Overall, 10% of participants screened positive for PTSD by the end of the internship year, compared with a 12-month PTSD prevalence of 3.6% in the general population.
“Work-related trauma exposure and PTSD are common and underdiscussed phenomena among intern physicians,” lead author Mary Vance, MD, assistant professor of psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Md., said in an interview.
“I urge medical educators and policy makers to include this topic in their discussions about physician well-being and to implement effective interventions to mitigate the impact of work-related trauma and PTSD among physician trainees,” she said.
The study was published online June 8 in JAMA Network Open.
Burnout, depression, suicide
“Burnout, depression, and suicide are increasingly recognized as occupational mental health hazards among health care professionals, including physicians,” Dr. Vance said.
“However, in my professional experience as a physician and educator, despite observing anecdotal evidence among my peers and trainees that this is also an issue,” she added.
This gap prompted her “to investigate rates of work-related trauma exposure and PTSD among physicians.”
The researchers sent emails to 4,350 individuals during academic year 2018-2019, 2 months prior to starting internships. Of these, 2,129 agreed to participate and 1,134 (58.6% female, 61.6% non-Hispanic White; mean age, 27.52) completed the study.
Prior to beginning internship, participants completed a baseline survey that assessed demographic characteristics as well as medical education and psychological and psychosocial factors.
Participants completed follow-up surveys sent by email at 3, 6, 9, and 12 months of the internship year. The surveys assessed stressful life events, concern over perceived medical errors in the past 3 months, and number of hours worked over the past week.
At month 12, current PTSD and symptoms of depression and anxiety were also assessed using the Primary Care PTSD Screen for DSM-5, the 9-item Patient Health Questionnaire, and the Generalized Anxiety Disorder 7-item scale, respectively.
Participants were asked to self-report whether they ever had an episode of depression and to complete the Risky Families Questionnaire to assess if they had experienced childhood abuse, neglect, and family conflict. Additionally, they completed an 11-item scale developed specifically for the study regarding recent stressful events.
‘Crucible’ year
A total of 56.4% of respondents reported work-related trauma exposure, and among these, 19.0% screened positive for PTSD. One-tenth (10.8%) of the entire sample screened positive for PTSD by the end of internship year, which is three times higher than the 12-month prevalence of PTSD in the general population (3.6%), the authors noted.
Trauma exposure differed by specialty, ranging from 43.1% in anesthesiology to 72.4% in emergency medicine. Of the respondents in internal medicine, surgery, and medicine/pediatrics, 56.6%, 63.3%, and 71%, respectively, reported work-related trauma exposure.
Work-related PTSD also differed by specialty, ranging from 7.5% in ob.gyn. to 30.0% in pediatrics. Of respondents in internal medicine and family practice, 23.9% and 25.9%, respectively, reported work-related PTSD.
Dr. Vance called the intern year “a crucible, during which newly minted doctors receive intensive on-the-job training at the front lines of patient care [and] work long hours in rapidly shifting environments, often caring for critically ill patients.”
Work-related trauma exposure “is more likely to occur during this high-stress internship year than during the same year in the general population,” she said.
She noted that the “issue of workplace trauma and PTSD among health care workers became even more salient during the height of COVID,” adding that she expects it “to remain a pressure issue for healthcare workers in the post-COVID era.”
Call to action
Commenting on the study David A. Marcus, MD, chair, GME Physician Well-Being Committee, Northwell Health, New Hyde Park, N.Y., noted the study’s “relatively low response rate” is a “significant limitation” of the study.
An additional limitation is the lack of a baseline PTSD assessment, said Dr. Marcus, an assistant professor at Hofstra University, Hempstead, N.Y., who was not involved in the research.
Nevertheless, the “overall prevalence [of work-related PTSD] should serve as a call to action for physician leaders and for leaders in academic medicine,” he said.
Additionally, the study “reminds us that trauma-informed care should be an essential part of mental health support services provided to trainees and to physicians in general,” Dr. Marcus stated.
Also commenting on the study, Lotte N. Dyrbye, MD, professor of medicine and medical education, Mayo Clinic, Rochester, Minn., agreed.
“Organizational strategies should include system-level interventions to reduce the risk of frightening, horrible, or traumatic events from occurring in the workplace in the first place, as well as faculty development efforts to upskill teaching faculty in their ability to support trainees when such events do occur,” she said.
These approaches “should coincide with organizational efforts to support individual trainees by providing adequate time off after traumatic events, ensuring trainees can access affordable mental healthcare, and reducing other barriers to appropriate help-seeking, such as stigma, and efforts to build a culture of well-being,” suggested Dr. Dyrbye, who is codirector of the Mayo Clinic Program on Physician Wellbeing and was not involved in the study.
The study was supported by grants from the Blue Cross Blue Shield Foundation of Michigan and National Institutes of Health. Dr. Vance and coauthors, Dr. Marcus, and Dr. Dyrbye reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Work-related posttraumatic stress disorder is three times higher in interns than the general population, new research shows.
Investigators assessed PTSD in more than 1,100 physicians at the end of their internship year and found that a little over half reported work-related trauma exposure, and of these, 20% screened positive for PTSD.
Overall, 10% of participants screened positive for PTSD by the end of the internship year, compared with a 12-month PTSD prevalence of 3.6% in the general population.
“Work-related trauma exposure and PTSD are common and underdiscussed phenomena among intern physicians,” lead author Mary Vance, MD, assistant professor of psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Md., said in an interview.
“I urge medical educators and policy makers to include this topic in their discussions about physician well-being and to implement effective interventions to mitigate the impact of work-related trauma and PTSD among physician trainees,” she said.
The study was published online June 8 in JAMA Network Open.
Burnout, depression, suicide
“Burnout, depression, and suicide are increasingly recognized as occupational mental health hazards among health care professionals, including physicians,” Dr. Vance said.
“However, in my professional experience as a physician and educator, despite observing anecdotal evidence among my peers and trainees that this is also an issue,” she added.
This gap prompted her “to investigate rates of work-related trauma exposure and PTSD among physicians.”
The researchers sent emails to 4,350 individuals during academic year 2018-2019, 2 months prior to starting internships. Of these, 2,129 agreed to participate and 1,134 (58.6% female, 61.6% non-Hispanic White; mean age, 27.52) completed the study.
Prior to beginning internship, participants completed a baseline survey that assessed demographic characteristics as well as medical education and psychological and psychosocial factors.
Participants completed follow-up surveys sent by email at 3, 6, 9, and 12 months of the internship year. The surveys assessed stressful life events, concern over perceived medical errors in the past 3 months, and number of hours worked over the past week.
At month 12, current PTSD and symptoms of depression and anxiety were also assessed using the Primary Care PTSD Screen for DSM-5, the 9-item Patient Health Questionnaire, and the Generalized Anxiety Disorder 7-item scale, respectively.
Participants were asked to self-report whether they ever had an episode of depression and to complete the Risky Families Questionnaire to assess if they had experienced childhood abuse, neglect, and family conflict. Additionally, they completed an 11-item scale developed specifically for the study regarding recent stressful events.
‘Crucible’ year
A total of 56.4% of respondents reported work-related trauma exposure, and among these, 19.0% screened positive for PTSD. One-tenth (10.8%) of the entire sample screened positive for PTSD by the end of internship year, which is three times higher than the 12-month prevalence of PTSD in the general population (3.6%), the authors noted.
Trauma exposure differed by specialty, ranging from 43.1% in anesthesiology to 72.4% in emergency medicine. Of the respondents in internal medicine, surgery, and medicine/pediatrics, 56.6%, 63.3%, and 71%, respectively, reported work-related trauma exposure.
Work-related PTSD also differed by specialty, ranging from 7.5% in ob.gyn. to 30.0% in pediatrics. Of respondents in internal medicine and family practice, 23.9% and 25.9%, respectively, reported work-related PTSD.
Dr. Vance called the intern year “a crucible, during which newly minted doctors receive intensive on-the-job training at the front lines of patient care [and] work long hours in rapidly shifting environments, often caring for critically ill patients.”
Work-related trauma exposure “is more likely to occur during this high-stress internship year than during the same year in the general population,” she said.
She noted that the “issue of workplace trauma and PTSD among health care workers became even more salient during the height of COVID,” adding that she expects it “to remain a pressure issue for healthcare workers in the post-COVID era.”
Call to action
Commenting on the study David A. Marcus, MD, chair, GME Physician Well-Being Committee, Northwell Health, New Hyde Park, N.Y., noted the study’s “relatively low response rate” is a “significant limitation” of the study.
An additional limitation is the lack of a baseline PTSD assessment, said Dr. Marcus, an assistant professor at Hofstra University, Hempstead, N.Y., who was not involved in the research.
Nevertheless, the “overall prevalence [of work-related PTSD] should serve as a call to action for physician leaders and for leaders in academic medicine,” he said.
Additionally, the study “reminds us that trauma-informed care should be an essential part of mental health support services provided to trainees and to physicians in general,” Dr. Marcus stated.
Also commenting on the study, Lotte N. Dyrbye, MD, professor of medicine and medical education, Mayo Clinic, Rochester, Minn., agreed.
“Organizational strategies should include system-level interventions to reduce the risk of frightening, horrible, or traumatic events from occurring in the workplace in the first place, as well as faculty development efforts to upskill teaching faculty in their ability to support trainees when such events do occur,” she said.
These approaches “should coincide with organizational efforts to support individual trainees by providing adequate time off after traumatic events, ensuring trainees can access affordable mental healthcare, and reducing other barriers to appropriate help-seeking, such as stigma, and efforts to build a culture of well-being,” suggested Dr. Dyrbye, who is codirector of the Mayo Clinic Program on Physician Wellbeing and was not involved in the study.
The study was supported by grants from the Blue Cross Blue Shield Foundation of Michigan and National Institutes of Health. Dr. Vance and coauthors, Dr. Marcus, and Dr. Dyrbye reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Work-related posttraumatic stress disorder is three times higher in interns than the general population, new research shows.
Investigators assessed PTSD in more than 1,100 physicians at the end of their internship year and found that a little over half reported work-related trauma exposure, and of these, 20% screened positive for PTSD.
Overall, 10% of participants screened positive for PTSD by the end of the internship year, compared with a 12-month PTSD prevalence of 3.6% in the general population.
“Work-related trauma exposure and PTSD are common and underdiscussed phenomena among intern physicians,” lead author Mary Vance, MD, assistant professor of psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Md., said in an interview.
“I urge medical educators and policy makers to include this topic in their discussions about physician well-being and to implement effective interventions to mitigate the impact of work-related trauma and PTSD among physician trainees,” she said.
The study was published online June 8 in JAMA Network Open.
Burnout, depression, suicide
“Burnout, depression, and suicide are increasingly recognized as occupational mental health hazards among health care professionals, including physicians,” Dr. Vance said.
“However, in my professional experience as a physician and educator, despite observing anecdotal evidence among my peers and trainees that this is also an issue,” she added.
This gap prompted her “to investigate rates of work-related trauma exposure and PTSD among physicians.”
The researchers sent emails to 4,350 individuals during academic year 2018-2019, 2 months prior to starting internships. Of these, 2,129 agreed to participate and 1,134 (58.6% female, 61.6% non-Hispanic White; mean age, 27.52) completed the study.
Prior to beginning internship, participants completed a baseline survey that assessed demographic characteristics as well as medical education and psychological and psychosocial factors.
Participants completed follow-up surveys sent by email at 3, 6, 9, and 12 months of the internship year. The surveys assessed stressful life events, concern over perceived medical errors in the past 3 months, and number of hours worked over the past week.
At month 12, current PTSD and symptoms of depression and anxiety were also assessed using the Primary Care PTSD Screen for DSM-5, the 9-item Patient Health Questionnaire, and the Generalized Anxiety Disorder 7-item scale, respectively.
Participants were asked to self-report whether they ever had an episode of depression and to complete the Risky Families Questionnaire to assess if they had experienced childhood abuse, neglect, and family conflict. Additionally, they completed an 11-item scale developed specifically for the study regarding recent stressful events.
‘Crucible’ year
A total of 56.4% of respondents reported work-related trauma exposure, and among these, 19.0% screened positive for PTSD. One-tenth (10.8%) of the entire sample screened positive for PTSD by the end of internship year, which is three times higher than the 12-month prevalence of PTSD in the general population (3.6%), the authors noted.
Trauma exposure differed by specialty, ranging from 43.1% in anesthesiology to 72.4% in emergency medicine. Of the respondents in internal medicine, surgery, and medicine/pediatrics, 56.6%, 63.3%, and 71%, respectively, reported work-related trauma exposure.
Work-related PTSD also differed by specialty, ranging from 7.5% in ob.gyn. to 30.0% in pediatrics. Of respondents in internal medicine and family practice, 23.9% and 25.9%, respectively, reported work-related PTSD.
Dr. Vance called the intern year “a crucible, during which newly minted doctors receive intensive on-the-job training at the front lines of patient care [and] work long hours in rapidly shifting environments, often caring for critically ill patients.”
Work-related trauma exposure “is more likely to occur during this high-stress internship year than during the same year in the general population,” she said.
She noted that the “issue of workplace trauma and PTSD among health care workers became even more salient during the height of COVID,” adding that she expects it “to remain a pressure issue for healthcare workers in the post-COVID era.”
Call to action
Commenting on the study David A. Marcus, MD, chair, GME Physician Well-Being Committee, Northwell Health, New Hyde Park, N.Y., noted the study’s “relatively low response rate” is a “significant limitation” of the study.
An additional limitation is the lack of a baseline PTSD assessment, said Dr. Marcus, an assistant professor at Hofstra University, Hempstead, N.Y., who was not involved in the research.
Nevertheless, the “overall prevalence [of work-related PTSD] should serve as a call to action for physician leaders and for leaders in academic medicine,” he said.
Additionally, the study “reminds us that trauma-informed care should be an essential part of mental health support services provided to trainees and to physicians in general,” Dr. Marcus stated.
Also commenting on the study, Lotte N. Dyrbye, MD, professor of medicine and medical education, Mayo Clinic, Rochester, Minn., agreed.
“Organizational strategies should include system-level interventions to reduce the risk of frightening, horrible, or traumatic events from occurring in the workplace in the first place, as well as faculty development efforts to upskill teaching faculty in their ability to support trainees when such events do occur,” she said.
These approaches “should coincide with organizational efforts to support individual trainees by providing adequate time off after traumatic events, ensuring trainees can access affordable mental healthcare, and reducing other barriers to appropriate help-seeking, such as stigma, and efforts to build a culture of well-being,” suggested Dr. Dyrbye, who is codirector of the Mayo Clinic Program on Physician Wellbeing and was not involved in the study.
The study was supported by grants from the Blue Cross Blue Shield Foundation of Michigan and National Institutes of Health. Dr. Vance and coauthors, Dr. Marcus, and Dr. Dyrbye reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Low-dose nitrous oxide shows benefit for resistant depression
A 1-hour treatment with a low concentration of nitrous oxide, commonly known as “laughing gas,” appears to relieve symptoms of treatment-resistant major depression (TRMD), with effects lasting as long as several weeks, new research suggests.
In a trial with a crossover design, investigators randomly assigned 28 patients with severe TRMD to receive a single 1-hour inhalation of placebo or nitrous oxide once a month over a 3-month period. Participants received an inhalation of placebo; a 25% concentration of nitrous oxide; and a 50% concentration of nitrous oxide. Sessions were conducted 4 weeks apart.
Both doses of nitrous oxide were associated with substantial improvement in depressive symptoms for roughly 85% of participants. However, the 25% concentration had a lower risk for adverse effects, which included sedation, nausea, and mild dissociation, compared to the 50% concentration.
“Twenty-five percent nitrous oxide has similar efficacy, compared to 50% nitrous oxide, and reduced side effects fourfold,” lead author Peter Nagele, MD, MSc, chair and professor of anesthesia and critical care, University of Chicago, said in an interview.
“We also observed that many patients had a 2-week improvement of depressive symptoms after a nitrous oxide treatment,” said Dr. Nagele, who also is professor of psychiatry and behavioral neuroscience.
The study was published online June 9 in Science Translational Medicine.
Further refinement
A previous proof-of-principle study conducted by the same researchers demonstrated that a 1-hour inhalation of 50% nitrous oxide had rapid antidepressant effects for patients with TRMD.
The current phase 2 trial “is a follow-up study to our earlier 2015 pilot trial and was designed to further refine the dose of nitrous oxide needed for antidepressant efficacy,” Dr. Nagele said.
“An important secondary aim [of the current study] was to determine whether a lower dose – 25% – would reduce side effects, and a third aim was to determine how long the antidepressants effects last,” he explained.
To investigate, the researchers enrolled 28 patients (median [interquartile range (IQR)] age 39 years [26-68 years]; 71% women; 96% White) to have three inhalation sessions (placebo, 25%, and 50% nitrous oxide) at 4-week intervals. Twenty patients completed all three inhalation sessions, and four completed ≥1 treatment.
Participants had “sustained and refractory depressive illness,” with a mean illness lifetime duration of 17.5 years and an extensive history of antidepressant drug failure (median, 4.5 [2-10] adequate-dose/duration antidepressants).
Some patients had undergone vagus nerve stimulation, electroconvulsive therapy, or repetitive transcranial magnetic stimulation, or had received ketamine (4%, 8%, 13%, and 8%, respectively).
The primary outcome was improvement on the 21-item Hamilton Depression rating Scale (HDRS-21) score over a 2-week observation period.
‘Stronger evidence’
Compared to placebo, nitrous oxide significantly improved depressive symptoms (P = .01). There was no significant difference between the 25% and the 50% concentrations (P = .58).
The estimated difference in HDRS-21 scores between the placebo and various treatment groups are shown in the following table.
To ensure there where were carryover effects between the two doses, the researchers performed an analysis to ascertain whether order of receipt of the higher dose was related to the 2-week HDRS-21 score; they found no significant effect of trial order (P = .22).
The 20 patients who completed the entire course of treatment “experienced a clinically significant improvement in depressive symptoms from a median baseline HDRS-21 score of 20.5 (IQR, 19.0 to 25.5) to 8.5 (IQR, 2.0 to 16.0) at study completion, corresponding to a median change of −11.0 points (IQR, −3.3 to −14.0 points; P < .0001) after the 3-month study period,” the investigators noted.
The types of treatment response and improvement in depressive symptoms from baseline to study completion are listed in the table below.
There were statistically significant differences in adverse events between the two treatment doses; 47 events occurred following inhalation of the 50% concentration, compared to 11 after inhalation of the 25% concentration. There were six adverse events after inhalation of placebo (P < .0001).
“None of the adverse events were serious, and nearly all occurred either during or immediately after the treatment session and resolved within several hours,” the authors reported.
“We need to be remindful that – despite the exciting results of the study – the study was small and cannot be considered definitive evidence; as such, it is too early to advocate for the use of nitrous oxide in everyday clinical practice,” Dr. Nagele said.
Nevertheless, on the basis of the current findings, he stated.
Rapid-acting antidepressants
Commenting on the study in an interview, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the Mood Disorders Psychopharmacology Unit at Toronto Western Hospital, noted that the research into nitrous oxide is “part of an interest in rapid-acting antidepressants.”
Dr. McIntyre, also the chairman and executive director of the Brain and Cognition Discovery Foundation, Toronto, who was not involved with the study, found it “interesting” that “almost 20% of the sample had previously had suboptimal outcomes to ketamine and/or neurostimulation, meaning these patients had serious refractory illness, but the benefit [of nitrous oxide] was sustained at 2 weeks.”
Studies of the use of nitrous oxide for patients with bipolar depression “would be warranted, since it appears generally safe and well tolerated,” said Dr. McIntyre, director of the Depression and Bipolar Support Alliance.
The study was sponsored by an award to Dr. Nagele from the NARSAD Independent Investigator Award from the Brain and Behavior Research Foundation and an award to Dr. Nagele and other coauthors from the Taylor Family Institute for Innovative Psychiatric Research at Washington University in St. Louis. Dr. Nagele receives funding from the National Institute of Mental Health the American Foundation for Prevention of Suicide, and the Brain and Behavior Research Foundation; has received research funding and honoraria from Roche Diagnostics and Abbott Diagnostics; and has previously filed for intellectual property protection related to the use of nitrous oxide in major depression. The other authors’ disclosures are listed on the original article. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation; speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and Abbvie. Dr. McIntyre is also CEO of AltMed.
A version of this article first appeared on Medscape.com.
A 1-hour treatment with a low concentration of nitrous oxide, commonly known as “laughing gas,” appears to relieve symptoms of treatment-resistant major depression (TRMD), with effects lasting as long as several weeks, new research suggests.
In a trial with a crossover design, investigators randomly assigned 28 patients with severe TRMD to receive a single 1-hour inhalation of placebo or nitrous oxide once a month over a 3-month period. Participants received an inhalation of placebo; a 25% concentration of nitrous oxide; and a 50% concentration of nitrous oxide. Sessions were conducted 4 weeks apart.
Both doses of nitrous oxide were associated with substantial improvement in depressive symptoms for roughly 85% of participants. However, the 25% concentration had a lower risk for adverse effects, which included sedation, nausea, and mild dissociation, compared to the 50% concentration.
“Twenty-five percent nitrous oxide has similar efficacy, compared to 50% nitrous oxide, and reduced side effects fourfold,” lead author Peter Nagele, MD, MSc, chair and professor of anesthesia and critical care, University of Chicago, said in an interview.
“We also observed that many patients had a 2-week improvement of depressive symptoms after a nitrous oxide treatment,” said Dr. Nagele, who also is professor of psychiatry and behavioral neuroscience.
The study was published online June 9 in Science Translational Medicine.
Further refinement
A previous proof-of-principle study conducted by the same researchers demonstrated that a 1-hour inhalation of 50% nitrous oxide had rapid antidepressant effects for patients with TRMD.
The current phase 2 trial “is a follow-up study to our earlier 2015 pilot trial and was designed to further refine the dose of nitrous oxide needed for antidepressant efficacy,” Dr. Nagele said.
“An important secondary aim [of the current study] was to determine whether a lower dose – 25% – would reduce side effects, and a third aim was to determine how long the antidepressants effects last,” he explained.
To investigate, the researchers enrolled 28 patients (median [interquartile range (IQR)] age 39 years [26-68 years]; 71% women; 96% White) to have three inhalation sessions (placebo, 25%, and 50% nitrous oxide) at 4-week intervals. Twenty patients completed all three inhalation sessions, and four completed ≥1 treatment.
Participants had “sustained and refractory depressive illness,” with a mean illness lifetime duration of 17.5 years and an extensive history of antidepressant drug failure (median, 4.5 [2-10] adequate-dose/duration antidepressants).
Some patients had undergone vagus nerve stimulation, electroconvulsive therapy, or repetitive transcranial magnetic stimulation, or had received ketamine (4%, 8%, 13%, and 8%, respectively).
The primary outcome was improvement on the 21-item Hamilton Depression rating Scale (HDRS-21) score over a 2-week observation period.
‘Stronger evidence’
Compared to placebo, nitrous oxide significantly improved depressive symptoms (P = .01). There was no significant difference between the 25% and the 50% concentrations (P = .58).
The estimated difference in HDRS-21 scores between the placebo and various treatment groups are shown in the following table.
To ensure there where were carryover effects between the two doses, the researchers performed an analysis to ascertain whether order of receipt of the higher dose was related to the 2-week HDRS-21 score; they found no significant effect of trial order (P = .22).
The 20 patients who completed the entire course of treatment “experienced a clinically significant improvement in depressive symptoms from a median baseline HDRS-21 score of 20.5 (IQR, 19.0 to 25.5) to 8.5 (IQR, 2.0 to 16.0) at study completion, corresponding to a median change of −11.0 points (IQR, −3.3 to −14.0 points; P < .0001) after the 3-month study period,” the investigators noted.
The types of treatment response and improvement in depressive symptoms from baseline to study completion are listed in the table below.
There were statistically significant differences in adverse events between the two treatment doses; 47 events occurred following inhalation of the 50% concentration, compared to 11 after inhalation of the 25% concentration. There were six adverse events after inhalation of placebo (P < .0001).
“None of the adverse events were serious, and nearly all occurred either during or immediately after the treatment session and resolved within several hours,” the authors reported.
“We need to be remindful that – despite the exciting results of the study – the study was small and cannot be considered definitive evidence; as such, it is too early to advocate for the use of nitrous oxide in everyday clinical practice,” Dr. Nagele said.
Nevertheless, on the basis of the current findings, he stated.
Rapid-acting antidepressants
Commenting on the study in an interview, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the Mood Disorders Psychopharmacology Unit at Toronto Western Hospital, noted that the research into nitrous oxide is “part of an interest in rapid-acting antidepressants.”
Dr. McIntyre, also the chairman and executive director of the Brain and Cognition Discovery Foundation, Toronto, who was not involved with the study, found it “interesting” that “almost 20% of the sample had previously had suboptimal outcomes to ketamine and/or neurostimulation, meaning these patients had serious refractory illness, but the benefit [of nitrous oxide] was sustained at 2 weeks.”
Studies of the use of nitrous oxide for patients with bipolar depression “would be warranted, since it appears generally safe and well tolerated,” said Dr. McIntyre, director of the Depression and Bipolar Support Alliance.
The study was sponsored by an award to Dr. Nagele from the NARSAD Independent Investigator Award from the Brain and Behavior Research Foundation and an award to Dr. Nagele and other coauthors from the Taylor Family Institute for Innovative Psychiatric Research at Washington University in St. Louis. Dr. Nagele receives funding from the National Institute of Mental Health the American Foundation for Prevention of Suicide, and the Brain and Behavior Research Foundation; has received research funding and honoraria from Roche Diagnostics and Abbott Diagnostics; and has previously filed for intellectual property protection related to the use of nitrous oxide in major depression. The other authors’ disclosures are listed on the original article. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation; speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and Abbvie. Dr. McIntyre is also CEO of AltMed.
A version of this article first appeared on Medscape.com.
A 1-hour treatment with a low concentration of nitrous oxide, commonly known as “laughing gas,” appears to relieve symptoms of treatment-resistant major depression (TRMD), with effects lasting as long as several weeks, new research suggests.
In a trial with a crossover design, investigators randomly assigned 28 patients with severe TRMD to receive a single 1-hour inhalation of placebo or nitrous oxide once a month over a 3-month period. Participants received an inhalation of placebo; a 25% concentration of nitrous oxide; and a 50% concentration of nitrous oxide. Sessions were conducted 4 weeks apart.
Both doses of nitrous oxide were associated with substantial improvement in depressive symptoms for roughly 85% of participants. However, the 25% concentration had a lower risk for adverse effects, which included sedation, nausea, and mild dissociation, compared to the 50% concentration.
“Twenty-five percent nitrous oxide has similar efficacy, compared to 50% nitrous oxide, and reduced side effects fourfold,” lead author Peter Nagele, MD, MSc, chair and professor of anesthesia and critical care, University of Chicago, said in an interview.
“We also observed that many patients had a 2-week improvement of depressive symptoms after a nitrous oxide treatment,” said Dr. Nagele, who also is professor of psychiatry and behavioral neuroscience.
The study was published online June 9 in Science Translational Medicine.
Further refinement
A previous proof-of-principle study conducted by the same researchers demonstrated that a 1-hour inhalation of 50% nitrous oxide had rapid antidepressant effects for patients with TRMD.
The current phase 2 trial “is a follow-up study to our earlier 2015 pilot trial and was designed to further refine the dose of nitrous oxide needed for antidepressant efficacy,” Dr. Nagele said.
“An important secondary aim [of the current study] was to determine whether a lower dose – 25% – would reduce side effects, and a third aim was to determine how long the antidepressants effects last,” he explained.
To investigate, the researchers enrolled 28 patients (median [interquartile range (IQR)] age 39 years [26-68 years]; 71% women; 96% White) to have three inhalation sessions (placebo, 25%, and 50% nitrous oxide) at 4-week intervals. Twenty patients completed all three inhalation sessions, and four completed ≥1 treatment.
Participants had “sustained and refractory depressive illness,” with a mean illness lifetime duration of 17.5 years and an extensive history of antidepressant drug failure (median, 4.5 [2-10] adequate-dose/duration antidepressants).
Some patients had undergone vagus nerve stimulation, electroconvulsive therapy, or repetitive transcranial magnetic stimulation, or had received ketamine (4%, 8%, 13%, and 8%, respectively).
The primary outcome was improvement on the 21-item Hamilton Depression rating Scale (HDRS-21) score over a 2-week observation period.
‘Stronger evidence’
Compared to placebo, nitrous oxide significantly improved depressive symptoms (P = .01). There was no significant difference between the 25% and the 50% concentrations (P = .58).
The estimated difference in HDRS-21 scores between the placebo and various treatment groups are shown in the following table.
To ensure there where were carryover effects between the two doses, the researchers performed an analysis to ascertain whether order of receipt of the higher dose was related to the 2-week HDRS-21 score; they found no significant effect of trial order (P = .22).
The 20 patients who completed the entire course of treatment “experienced a clinically significant improvement in depressive symptoms from a median baseline HDRS-21 score of 20.5 (IQR, 19.0 to 25.5) to 8.5 (IQR, 2.0 to 16.0) at study completion, corresponding to a median change of −11.0 points (IQR, −3.3 to −14.0 points; P < .0001) after the 3-month study period,” the investigators noted.
The types of treatment response and improvement in depressive symptoms from baseline to study completion are listed in the table below.
There were statistically significant differences in adverse events between the two treatment doses; 47 events occurred following inhalation of the 50% concentration, compared to 11 after inhalation of the 25% concentration. There were six adverse events after inhalation of placebo (P < .0001).
“None of the adverse events were serious, and nearly all occurred either during or immediately after the treatment session and resolved within several hours,” the authors reported.
“We need to be remindful that – despite the exciting results of the study – the study was small and cannot be considered definitive evidence; as such, it is too early to advocate for the use of nitrous oxide in everyday clinical practice,” Dr. Nagele said.
Nevertheless, on the basis of the current findings, he stated.
Rapid-acting antidepressants
Commenting on the study in an interview, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the Mood Disorders Psychopharmacology Unit at Toronto Western Hospital, noted that the research into nitrous oxide is “part of an interest in rapid-acting antidepressants.”
Dr. McIntyre, also the chairman and executive director of the Brain and Cognition Discovery Foundation, Toronto, who was not involved with the study, found it “interesting” that “almost 20% of the sample had previously had suboptimal outcomes to ketamine and/or neurostimulation, meaning these patients had serious refractory illness, but the benefit [of nitrous oxide] was sustained at 2 weeks.”
Studies of the use of nitrous oxide for patients with bipolar depression “would be warranted, since it appears generally safe and well tolerated,” said Dr. McIntyre, director of the Depression and Bipolar Support Alliance.
The study was sponsored by an award to Dr. Nagele from the NARSAD Independent Investigator Award from the Brain and Behavior Research Foundation and an award to Dr. Nagele and other coauthors from the Taylor Family Institute for Innovative Psychiatric Research at Washington University in St. Louis. Dr. Nagele receives funding from the National Institute of Mental Health the American Foundation for Prevention of Suicide, and the Brain and Behavior Research Foundation; has received research funding and honoraria from Roche Diagnostics and Abbott Diagnostics; and has previously filed for intellectual property protection related to the use of nitrous oxide in major depression. The other authors’ disclosures are listed on the original article. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation; speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and Abbvie. Dr. McIntyre is also CEO of AltMed.
A version of this article first appeared on Medscape.com.
Child suicides drive Colorado hospital to declare state of emergency
On May 25, Jena Hausmann, CEO of Children’s Hospital Colorado, Aurora, declared a state of emergency in youth mental health in response to an astronomical increase in pediatric mental health cases, including suicide, which has overwhelmed the institution.
From April 2019 to April 2021, the demand for pediatric behavioral health treatment at the hospital system increased by 90%. In Colorado, suicide is now the number one cause of death among youth and occurs in children as young as 10 years of age.
“Now we are seeing our pediatric emergency departments and our inpatient units overrun with kids attempting suicide and suffering from other forms of major mental health illness,” Dr. Hausmann said in a press release.
“We had to draw attention to what we’re seeing in our hospital and our community on an everyday basis – an unprecedented number of suicidal children who need acute treatment for behavioral health problems – and when I say ‘unprecedented,’ I’m serious – I’ve been in pediatrics for two decades and have never seen anything like this before,” David Brumbaugh, MD, a pediatric gastroenterologist and chief medical officer for Children’s Colorado, told this news organization.
Christine Crawford, MD, associate medical director of the National Alliance on Mental Illness, stated in an interview that she “commends the CEO of the hospital for making this announcement, because it is outrageous to see what is happening with more and more children with significant psychiatric symptoms who are not getting adequate care.”
Jenna Glover, PhD, child psychologist and director of psychology training at Children’s Hospital, said that during the past decade, there has been a steady increase in depression, anxiety, and suicide among youth in Colorado. Suicide, she added, is now the number one cause of death in youth, “so we were already in a state of crisis.” She added that COVID-19 was “the straw that broke the camel’s back.”
“In January to April of this year, behavioral health ED visits to Children’s Hospital were 72% higher than they were 2 years ago at this time,” she said. “Colorado Springs had a 145% increase for ED behavioral health visits during the first 4 months of 2021, compared to the first 4 months of 2020.”
COVID’s impact
Other problems that have been “skyrocketing” in youth are self-harm, substance use, and eating disorders. Younger children are experiencing an increase in behavioral problems, including developmental regression, such as tantrums, and problems with sleeping, toileting, and eating, Dr. Glover noted.
The youth mental health crisis has mushroomed, although social distancing requirements are now beginning to ease and we are in the “home stretch of the pandemic,” Dr. Brumbaugh said.
One possible reason “is that we took kids out of their normal routines, social circles, friendships, etc., for 12 months, and that was the limit of their physiological or mental resistance, and they got to the end of their rope,” he speculated.
Dr. Glover said, “Kids are burned out, and although they’re asking to return to their life, they don’t feel they have the resources. They feel so behind; they don’t know how to catch up.”
Dr. Brumbaugh said that there are not enough child psychiatrists to provide outpatient services or enough inpatient beds for children in crisis.
“This is an unacceptable situation. We would never allow a child with leukemia or appendicitis to go several weeks without treatment,” he said.
Community donors have come forward, enabling an anticipated 50% increase in Children’s Hospital’s mental health outpatient, inpatient, and day services by March 2022.
“On a hospital level, we are continuing to do things to expand access to care, like opening units that provide different levels of care for patients with psychiatric problems, as well as expanding into areas that are more rural,” Dr. Glover said.
However, the “blueprint is not in action yet, and a lot of money still needs to be allocated. A workforce has to be created, because there are not enough clinicians to fill these roles,” she added.
Chronic underfunding
Dr. Brumbaugh said Colorado has always had a “relatively underfunded behavioral health system for kids.” A 2021 report by
However, Dr. Glover noted that Colorado is “not exceptional.” The increased vulnerability to youth mental illness and suicide is characteristic of other mountain states, which have larger rural areas, less access to care, and increased access to guns, she said.
Mass shootings may have amped up stress levels. “For some kids, this is happening in their schools or towns, and they feel traumatized and unsafe,” Dr. Glover added.
Dr. Crawford, who is an assistant professor of psychiatry at Boston University, also pointed out that the mental health crisis in youth is not unique to Colorado.
“Throughout the country, we’ve seen these colliding pandemics – inadequate mental health resources for children and COVID-19, which exacerbated the existing mental health crisis,” she said.
“The pandemic led to an increase in telehealth services, making individual and group psychotherapy available to kids in areas that never had access to these before, which is a ‘silver lining’ of the pandemic,” Dr. Glover said.
Dr. Crawford is “encouraged that we are having more conversations about pediatric mental health, because the pandemic amplified what was already going on and made it impossible to ignore.”
Screening is essential
Screening for mental health problems should be at the top of the mind of pediatricians and other clinicians who work with children, Dr. Glover said.
“Pediatricians are in the best place to catch potentially suicidal kids, because they are more likely to see these kids than therapists,” she noted.
She suggested using a rapid screen for depression, such as the Patient Health Questionnaire-9 (PHQ-9) modified for adolescents. Parents can also fill out a PHQ-9 for younger children and even for themselves.
“Depression, anxiety, and suicidality affect the whole family, so screening for these conditions in adults will benefit the children too,” she said. Teachers should also “be aware of what depression and anxiety symptoms look like in kids, because sometimes they can manifest more as irritability,” Dr. Glover added.
Policymakers and insurers need to prioritize pediatric mental health when determining allocation of health care, said Dr. Crawford.
“Financial incentives should be provided for hospitals to want to reserve beds for psychiatric patients, and in the outpatient setting, we also need to look at the payment structure of psychiatric visits,” she added.
Many psychiatrists do not want to accept insurance because of the increased bureaucracy and low reimbursement rates of insurance companies, and families cannot afford to pay out of pocket, “so we really need to look at the insurance issue at a policy level,” Dr. Crawford said.
Dr. Brumbaugh, Dr. Glover, and Dr. Crawford have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
On May 25, Jena Hausmann, CEO of Children’s Hospital Colorado, Aurora, declared a state of emergency in youth mental health in response to an astronomical increase in pediatric mental health cases, including suicide, which has overwhelmed the institution.
From April 2019 to April 2021, the demand for pediatric behavioral health treatment at the hospital system increased by 90%. In Colorado, suicide is now the number one cause of death among youth and occurs in children as young as 10 years of age.
“Now we are seeing our pediatric emergency departments and our inpatient units overrun with kids attempting suicide and suffering from other forms of major mental health illness,” Dr. Hausmann said in a press release.
“We had to draw attention to what we’re seeing in our hospital and our community on an everyday basis – an unprecedented number of suicidal children who need acute treatment for behavioral health problems – and when I say ‘unprecedented,’ I’m serious – I’ve been in pediatrics for two decades and have never seen anything like this before,” David Brumbaugh, MD, a pediatric gastroenterologist and chief medical officer for Children’s Colorado, told this news organization.
Christine Crawford, MD, associate medical director of the National Alliance on Mental Illness, stated in an interview that she “commends the CEO of the hospital for making this announcement, because it is outrageous to see what is happening with more and more children with significant psychiatric symptoms who are not getting adequate care.”
Jenna Glover, PhD, child psychologist and director of psychology training at Children’s Hospital, said that during the past decade, there has been a steady increase in depression, anxiety, and suicide among youth in Colorado. Suicide, she added, is now the number one cause of death in youth, “so we were already in a state of crisis.” She added that COVID-19 was “the straw that broke the camel’s back.”
“In January to April of this year, behavioral health ED visits to Children’s Hospital were 72% higher than they were 2 years ago at this time,” she said. “Colorado Springs had a 145% increase for ED behavioral health visits during the first 4 months of 2021, compared to the first 4 months of 2020.”
COVID’s impact
Other problems that have been “skyrocketing” in youth are self-harm, substance use, and eating disorders. Younger children are experiencing an increase in behavioral problems, including developmental regression, such as tantrums, and problems with sleeping, toileting, and eating, Dr. Glover noted.
The youth mental health crisis has mushroomed, although social distancing requirements are now beginning to ease and we are in the “home stretch of the pandemic,” Dr. Brumbaugh said.
One possible reason “is that we took kids out of their normal routines, social circles, friendships, etc., for 12 months, and that was the limit of their physiological or mental resistance, and they got to the end of their rope,” he speculated.
Dr. Glover said, “Kids are burned out, and although they’re asking to return to their life, they don’t feel they have the resources. They feel so behind; they don’t know how to catch up.”
Dr. Brumbaugh said that there are not enough child psychiatrists to provide outpatient services or enough inpatient beds for children in crisis.
“This is an unacceptable situation. We would never allow a child with leukemia or appendicitis to go several weeks without treatment,” he said.
Community donors have come forward, enabling an anticipated 50% increase in Children’s Hospital’s mental health outpatient, inpatient, and day services by March 2022.
“On a hospital level, we are continuing to do things to expand access to care, like opening units that provide different levels of care for patients with psychiatric problems, as well as expanding into areas that are more rural,” Dr. Glover said.
However, the “blueprint is not in action yet, and a lot of money still needs to be allocated. A workforce has to be created, because there are not enough clinicians to fill these roles,” she added.
Chronic underfunding
Dr. Brumbaugh said Colorado has always had a “relatively underfunded behavioral health system for kids.” A 2021 report by
However, Dr. Glover noted that Colorado is “not exceptional.” The increased vulnerability to youth mental illness and suicide is characteristic of other mountain states, which have larger rural areas, less access to care, and increased access to guns, she said.
Mass shootings may have amped up stress levels. “For some kids, this is happening in their schools or towns, and they feel traumatized and unsafe,” Dr. Glover added.
Dr. Crawford, who is an assistant professor of psychiatry at Boston University, also pointed out that the mental health crisis in youth is not unique to Colorado.
“Throughout the country, we’ve seen these colliding pandemics – inadequate mental health resources for children and COVID-19, which exacerbated the existing mental health crisis,” she said.
“The pandemic led to an increase in telehealth services, making individual and group psychotherapy available to kids in areas that never had access to these before, which is a ‘silver lining’ of the pandemic,” Dr. Glover said.
Dr. Crawford is “encouraged that we are having more conversations about pediatric mental health, because the pandemic amplified what was already going on and made it impossible to ignore.”
Screening is essential
Screening for mental health problems should be at the top of the mind of pediatricians and other clinicians who work with children, Dr. Glover said.
“Pediatricians are in the best place to catch potentially suicidal kids, because they are more likely to see these kids than therapists,” she noted.
She suggested using a rapid screen for depression, such as the Patient Health Questionnaire-9 (PHQ-9) modified for adolescents. Parents can also fill out a PHQ-9 for younger children and even for themselves.
“Depression, anxiety, and suicidality affect the whole family, so screening for these conditions in adults will benefit the children too,” she said. Teachers should also “be aware of what depression and anxiety symptoms look like in kids, because sometimes they can manifest more as irritability,” Dr. Glover added.
Policymakers and insurers need to prioritize pediatric mental health when determining allocation of health care, said Dr. Crawford.
“Financial incentives should be provided for hospitals to want to reserve beds for psychiatric patients, and in the outpatient setting, we also need to look at the payment structure of psychiatric visits,” she added.
Many psychiatrists do not want to accept insurance because of the increased bureaucracy and low reimbursement rates of insurance companies, and families cannot afford to pay out of pocket, “so we really need to look at the insurance issue at a policy level,” Dr. Crawford said.
Dr. Brumbaugh, Dr. Glover, and Dr. Crawford have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
On May 25, Jena Hausmann, CEO of Children’s Hospital Colorado, Aurora, declared a state of emergency in youth mental health in response to an astronomical increase in pediatric mental health cases, including suicide, which has overwhelmed the institution.
From April 2019 to April 2021, the demand for pediatric behavioral health treatment at the hospital system increased by 90%. In Colorado, suicide is now the number one cause of death among youth and occurs in children as young as 10 years of age.
“Now we are seeing our pediatric emergency departments and our inpatient units overrun with kids attempting suicide and suffering from other forms of major mental health illness,” Dr. Hausmann said in a press release.
“We had to draw attention to what we’re seeing in our hospital and our community on an everyday basis – an unprecedented number of suicidal children who need acute treatment for behavioral health problems – and when I say ‘unprecedented,’ I’m serious – I’ve been in pediatrics for two decades and have never seen anything like this before,” David Brumbaugh, MD, a pediatric gastroenterologist and chief medical officer for Children’s Colorado, told this news organization.
Christine Crawford, MD, associate medical director of the National Alliance on Mental Illness, stated in an interview that she “commends the CEO of the hospital for making this announcement, because it is outrageous to see what is happening with more and more children with significant psychiatric symptoms who are not getting adequate care.”
Jenna Glover, PhD, child psychologist and director of psychology training at Children’s Hospital, said that during the past decade, there has been a steady increase in depression, anxiety, and suicide among youth in Colorado. Suicide, she added, is now the number one cause of death in youth, “so we were already in a state of crisis.” She added that COVID-19 was “the straw that broke the camel’s back.”
“In January to April of this year, behavioral health ED visits to Children’s Hospital were 72% higher than they were 2 years ago at this time,” she said. “Colorado Springs had a 145% increase for ED behavioral health visits during the first 4 months of 2021, compared to the first 4 months of 2020.”
COVID’s impact
Other problems that have been “skyrocketing” in youth are self-harm, substance use, and eating disorders. Younger children are experiencing an increase in behavioral problems, including developmental regression, such as tantrums, and problems with sleeping, toileting, and eating, Dr. Glover noted.
The youth mental health crisis has mushroomed, although social distancing requirements are now beginning to ease and we are in the “home stretch of the pandemic,” Dr. Brumbaugh said.
One possible reason “is that we took kids out of their normal routines, social circles, friendships, etc., for 12 months, and that was the limit of their physiological or mental resistance, and they got to the end of their rope,” he speculated.
Dr. Glover said, “Kids are burned out, and although they’re asking to return to their life, they don’t feel they have the resources. They feel so behind; they don’t know how to catch up.”
Dr. Brumbaugh said that there are not enough child psychiatrists to provide outpatient services or enough inpatient beds for children in crisis.
“This is an unacceptable situation. We would never allow a child with leukemia or appendicitis to go several weeks without treatment,” he said.
Community donors have come forward, enabling an anticipated 50% increase in Children’s Hospital’s mental health outpatient, inpatient, and day services by March 2022.
“On a hospital level, we are continuing to do things to expand access to care, like opening units that provide different levels of care for patients with psychiatric problems, as well as expanding into areas that are more rural,” Dr. Glover said.
However, the “blueprint is not in action yet, and a lot of money still needs to be allocated. A workforce has to be created, because there are not enough clinicians to fill these roles,” she added.
Chronic underfunding
Dr. Brumbaugh said Colorado has always had a “relatively underfunded behavioral health system for kids.” A 2021 report by
However, Dr. Glover noted that Colorado is “not exceptional.” The increased vulnerability to youth mental illness and suicide is characteristic of other mountain states, which have larger rural areas, less access to care, and increased access to guns, she said.
Mass shootings may have amped up stress levels. “For some kids, this is happening in their schools or towns, and they feel traumatized and unsafe,” Dr. Glover added.
Dr. Crawford, who is an assistant professor of psychiatry at Boston University, also pointed out that the mental health crisis in youth is not unique to Colorado.
“Throughout the country, we’ve seen these colliding pandemics – inadequate mental health resources for children and COVID-19, which exacerbated the existing mental health crisis,” she said.
“The pandemic led to an increase in telehealth services, making individual and group psychotherapy available to kids in areas that never had access to these before, which is a ‘silver lining’ of the pandemic,” Dr. Glover said.
Dr. Crawford is “encouraged that we are having more conversations about pediatric mental health, because the pandemic amplified what was already going on and made it impossible to ignore.”
Screening is essential
Screening for mental health problems should be at the top of the mind of pediatricians and other clinicians who work with children, Dr. Glover said.
“Pediatricians are in the best place to catch potentially suicidal kids, because they are more likely to see these kids than therapists,” she noted.
She suggested using a rapid screen for depression, such as the Patient Health Questionnaire-9 (PHQ-9) modified for adolescents. Parents can also fill out a PHQ-9 for younger children and even for themselves.
“Depression, anxiety, and suicidality affect the whole family, so screening for these conditions in adults will benefit the children too,” she said. Teachers should also “be aware of what depression and anxiety symptoms look like in kids, because sometimes they can manifest more as irritability,” Dr. Glover added.
Policymakers and insurers need to prioritize pediatric mental health when determining allocation of health care, said Dr. Crawford.
“Financial incentives should be provided for hospitals to want to reserve beds for psychiatric patients, and in the outpatient setting, we also need to look at the payment structure of psychiatric visits,” she added.
Many psychiatrists do not want to accept insurance because of the increased bureaucracy and low reimbursement rates of insurance companies, and families cannot afford to pay out of pocket, “so we really need to look at the insurance issue at a policy level,” Dr. Crawford said.
Dr. Brumbaugh, Dr. Glover, and Dr. Crawford have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Emotional support animals help lick symptoms of depression, anxiety in serious mental illness
Use of emotional support animals (ESAs) yields quantifiable reductions in depression, anxiety, and loneliness for patients with serious mental illness (SMI) who live alone, early research suggests.
Investigators followed 11 community-dwelling adults with SMI who were paired with a shelter dog or cat for 1 year. Participants’ depression, anxiety, and loneliness were assessed at baseline and 12 months after receipt of their ESAs.
At regular home visits during the study, participants also underwent saliva testing before playing with their pets and after 10 minutes of enjoyable pet interaction to assess levels of oxytocin – a biomarker associated with bonding – as well as cortisol and alpha amylase, which are markers of stress.
Significant reductions in measures of anxiety, depression, and loneliness were found between baseline and 12 months for all participants. Moreover, there was a pattern of an increase in levels of oxytocin and a decrease in levels of cortisol after 10 minutes of ESA interaction, but the degree of change did not reach statistical significance.
“Although this was a small pilot study and the findings are correlational, rather than causal, we can nevertheless say from the self-report of this group of participants and from the data collected that having an emotional support animal was beneficial to their mental health,” lead author Janet Hoy-Gerlach, PhD, professor of social work, University of Toledo (Ohio), said in an interview.
“We feel this data is a strong justification for additional study, and we hope that it will be a catalyst for future research with larger samples and more rigorous methodology,” said Dr. Hoy-Gerlach, author of “Human-Animal Interaction: A Social Work Guide,” published by NASW Press in 2017.
The study was published online May 20 in Human Animal Interaction Bulletin.
Everyday interactions
An ESA is a “companion animal (pet) who helps to reduce disability-related impairment for a particular person through the animal’s presence and everyday interactions,” the authors wrote.
Unlike service animals, which perform specific functions, ESAs “provide benefits that fall along the same dimensions as the benefits of pets – physical, social, emotional, and psychological – and there is research supporting the role that animals can play in each of these arenas,” Dr. Hoy-Gerlach said.
ESAs require no special training. All that is needed is a letter from a medical or mental health professional “that the individual meets the definition of ‘disability’ under the Fair Housing Act and a companion animal is a needed disability-ameliorating accommodation and should be allowed in buildings that don’t ordinarily permit pets,” she noted.
There is currently no peer-reviewed research that focuses explicitly on the impact of ESAs in individuals with SMI. To investigate, the researchers turned to the Hope and Recovery Pet Program (HARP) – a community partnership of the University of Toledo, the Toledo Humane Society, and ProMedica, a large regional nonprofit Toledo-based health care system – that pairs community-living individuals who have depression and/or anxiety with shelter animals that require adoption. The program pays for pet food, supplies, and veterinary care for those unable to afford these.
Participants (n = 11; mean age, 53.67 years; 78% women) were recruited from the HARP program. Participants were required to be psychiatrically stable, have stable housing, live alone, be at risk for social isolation, have low income, be sober, and have no history of violence. Their primary diagnoses were major depressive disorder, bipolar disorder, and schizoaffective disorder (63%, 18%, and 18%, respectively).
Six participants adopted a cat, and five adopted a dog.
Prior to ESA adoption and at 12 months, participants completed the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), and the UCLA Loneliness Scale Version 3.
Prior to ESA adoption and at 1, 3, 6, 9, and 12 months, saliva samples were collected from participants by researchers at the beginning of a home visit and then after 10 minutes of “focused pleasant interaction” with the ESA. The saliva was tested for oxytocin, alpha amylase, and cortisol.
Motivation, comfort, calm
The researchers found statistically significant decreases in UCLA Loneliness Scale scores from pre-ESA (mean [SD],59.20 [9.47]) to 12 months (49.90 [13.66], P = .004). The eta-squared statistic (.62) indicated a large effect size.
For 18 of the 20 items on the loneliness scale, mean values were lower after the intervention than before the intervention. Of these, four were statistically significant.
A statistically significant decrease in BDI total scores was also seen from pre-ESA to 12 months (21.09 [8.43] to 14.64 [7.03], respectively; P = .03). The eta-squared statistic (.41) indicated a large effect size.
Of the 21 items on the BDI scale, the mean value was lower for 19 after the intervention. Of these, five were statistically significant.
Similarly, a statistically significant decrease in BAI score was found from pre-ESA to 12 months (23.55 [9.81] to 17.73 [11.79], P = .049). The eta-squared statistic (.36) indicated a large effect size, although there were no statistically significant changes in individual item scores.
The researchers found “observable patterns” of decreases in cortisol and increases in oxytocin after the 10-minute enjoyable ESA interactions. The highest oxytocin increase occurred at 12 months; however, these improvements did not reach statistical significance.
Participants offered open-ended statements about the positive impact of their ESA on their mental health, Dr. Hoy-Gerlach said. “For example, they described feeling motivated to take better care of themselves because their ESA needed them. Some described feeling ‘comforted,’ distracted from symptoms, soothed, and calmed.
“There is definitely a place for ESAs, especially with mental health post pandemic, when we need all the resources that we can for those who can benefit,” she added.
Postpandemic mental health
Commenting on the study for this news organization, Christine Crawford, MD, MPH, assistant professor of psychiatry, Boston University, observed that ESAs “are not on the radar for a lot of clinicians, and a lot of clinicians don’t know about the science [supporting their use] or what an emotional support pet entails.
“ besides traditional forms of treatment, such as medication and therapy. Even a little relief is important, and having an emotional support pet is a good option,” said Dr. Crawford, associate medical director of the National Alliance on Mental Illness. She was not involved with the study.
The Kenneth A. Scott Charitable Trust provided grant funding. Dr. Hoy-Gerlach, her coauthors, and Dr. Crawford have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Use of emotional support animals (ESAs) yields quantifiable reductions in depression, anxiety, and loneliness for patients with serious mental illness (SMI) who live alone, early research suggests.
Investigators followed 11 community-dwelling adults with SMI who were paired with a shelter dog or cat for 1 year. Participants’ depression, anxiety, and loneliness were assessed at baseline and 12 months after receipt of their ESAs.
At regular home visits during the study, participants also underwent saliva testing before playing with their pets and after 10 minutes of enjoyable pet interaction to assess levels of oxytocin – a biomarker associated with bonding – as well as cortisol and alpha amylase, which are markers of stress.
Significant reductions in measures of anxiety, depression, and loneliness were found between baseline and 12 months for all participants. Moreover, there was a pattern of an increase in levels of oxytocin and a decrease in levels of cortisol after 10 minutes of ESA interaction, but the degree of change did not reach statistical significance.
“Although this was a small pilot study and the findings are correlational, rather than causal, we can nevertheless say from the self-report of this group of participants and from the data collected that having an emotional support animal was beneficial to their mental health,” lead author Janet Hoy-Gerlach, PhD, professor of social work, University of Toledo (Ohio), said in an interview.
“We feel this data is a strong justification for additional study, and we hope that it will be a catalyst for future research with larger samples and more rigorous methodology,” said Dr. Hoy-Gerlach, author of “Human-Animal Interaction: A Social Work Guide,” published by NASW Press in 2017.
The study was published online May 20 in Human Animal Interaction Bulletin.
Everyday interactions
An ESA is a “companion animal (pet) who helps to reduce disability-related impairment for a particular person through the animal’s presence and everyday interactions,” the authors wrote.
Unlike service animals, which perform specific functions, ESAs “provide benefits that fall along the same dimensions as the benefits of pets – physical, social, emotional, and psychological – and there is research supporting the role that animals can play in each of these arenas,” Dr. Hoy-Gerlach said.
ESAs require no special training. All that is needed is a letter from a medical or mental health professional “that the individual meets the definition of ‘disability’ under the Fair Housing Act and a companion animal is a needed disability-ameliorating accommodation and should be allowed in buildings that don’t ordinarily permit pets,” she noted.
There is currently no peer-reviewed research that focuses explicitly on the impact of ESAs in individuals with SMI. To investigate, the researchers turned to the Hope and Recovery Pet Program (HARP) – a community partnership of the University of Toledo, the Toledo Humane Society, and ProMedica, a large regional nonprofit Toledo-based health care system – that pairs community-living individuals who have depression and/or anxiety with shelter animals that require adoption. The program pays for pet food, supplies, and veterinary care for those unable to afford these.
Participants (n = 11; mean age, 53.67 years; 78% women) were recruited from the HARP program. Participants were required to be psychiatrically stable, have stable housing, live alone, be at risk for social isolation, have low income, be sober, and have no history of violence. Their primary diagnoses were major depressive disorder, bipolar disorder, and schizoaffective disorder (63%, 18%, and 18%, respectively).
Six participants adopted a cat, and five adopted a dog.
Prior to ESA adoption and at 12 months, participants completed the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), and the UCLA Loneliness Scale Version 3.
Prior to ESA adoption and at 1, 3, 6, 9, and 12 months, saliva samples were collected from participants by researchers at the beginning of a home visit and then after 10 minutes of “focused pleasant interaction” with the ESA. The saliva was tested for oxytocin, alpha amylase, and cortisol.
Motivation, comfort, calm
The researchers found statistically significant decreases in UCLA Loneliness Scale scores from pre-ESA (mean [SD],59.20 [9.47]) to 12 months (49.90 [13.66], P = .004). The eta-squared statistic (.62) indicated a large effect size.
For 18 of the 20 items on the loneliness scale, mean values were lower after the intervention than before the intervention. Of these, four were statistically significant.
A statistically significant decrease in BDI total scores was also seen from pre-ESA to 12 months (21.09 [8.43] to 14.64 [7.03], respectively; P = .03). The eta-squared statistic (.41) indicated a large effect size.
Of the 21 items on the BDI scale, the mean value was lower for 19 after the intervention. Of these, five were statistically significant.
Similarly, a statistically significant decrease in BAI score was found from pre-ESA to 12 months (23.55 [9.81] to 17.73 [11.79], P = .049). The eta-squared statistic (.36) indicated a large effect size, although there were no statistically significant changes in individual item scores.
The researchers found “observable patterns” of decreases in cortisol and increases in oxytocin after the 10-minute enjoyable ESA interactions. The highest oxytocin increase occurred at 12 months; however, these improvements did not reach statistical significance.
Participants offered open-ended statements about the positive impact of their ESA on their mental health, Dr. Hoy-Gerlach said. “For example, they described feeling motivated to take better care of themselves because their ESA needed them. Some described feeling ‘comforted,’ distracted from symptoms, soothed, and calmed.
“There is definitely a place for ESAs, especially with mental health post pandemic, when we need all the resources that we can for those who can benefit,” she added.
Postpandemic mental health
Commenting on the study for this news organization, Christine Crawford, MD, MPH, assistant professor of psychiatry, Boston University, observed that ESAs “are not on the radar for a lot of clinicians, and a lot of clinicians don’t know about the science [supporting their use] or what an emotional support pet entails.
“ besides traditional forms of treatment, such as medication and therapy. Even a little relief is important, and having an emotional support pet is a good option,” said Dr. Crawford, associate medical director of the National Alliance on Mental Illness. She was not involved with the study.
The Kenneth A. Scott Charitable Trust provided grant funding. Dr. Hoy-Gerlach, her coauthors, and Dr. Crawford have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Use of emotional support animals (ESAs) yields quantifiable reductions in depression, anxiety, and loneliness for patients with serious mental illness (SMI) who live alone, early research suggests.
Investigators followed 11 community-dwelling adults with SMI who were paired with a shelter dog or cat for 1 year. Participants’ depression, anxiety, and loneliness were assessed at baseline and 12 months after receipt of their ESAs.
At regular home visits during the study, participants also underwent saliva testing before playing with their pets and after 10 minutes of enjoyable pet interaction to assess levels of oxytocin – a biomarker associated with bonding – as well as cortisol and alpha amylase, which are markers of stress.
Significant reductions in measures of anxiety, depression, and loneliness were found between baseline and 12 months for all participants. Moreover, there was a pattern of an increase in levels of oxytocin and a decrease in levels of cortisol after 10 minutes of ESA interaction, but the degree of change did not reach statistical significance.
“Although this was a small pilot study and the findings are correlational, rather than causal, we can nevertheless say from the self-report of this group of participants and from the data collected that having an emotional support animal was beneficial to their mental health,” lead author Janet Hoy-Gerlach, PhD, professor of social work, University of Toledo (Ohio), said in an interview.
“We feel this data is a strong justification for additional study, and we hope that it will be a catalyst for future research with larger samples and more rigorous methodology,” said Dr. Hoy-Gerlach, author of “Human-Animal Interaction: A Social Work Guide,” published by NASW Press in 2017.
The study was published online May 20 in Human Animal Interaction Bulletin.
Everyday interactions
An ESA is a “companion animal (pet) who helps to reduce disability-related impairment for a particular person through the animal’s presence and everyday interactions,” the authors wrote.
Unlike service animals, which perform specific functions, ESAs “provide benefits that fall along the same dimensions as the benefits of pets – physical, social, emotional, and psychological – and there is research supporting the role that animals can play in each of these arenas,” Dr. Hoy-Gerlach said.
ESAs require no special training. All that is needed is a letter from a medical or mental health professional “that the individual meets the definition of ‘disability’ under the Fair Housing Act and a companion animal is a needed disability-ameliorating accommodation and should be allowed in buildings that don’t ordinarily permit pets,” she noted.
There is currently no peer-reviewed research that focuses explicitly on the impact of ESAs in individuals with SMI. To investigate, the researchers turned to the Hope and Recovery Pet Program (HARP) – a community partnership of the University of Toledo, the Toledo Humane Society, and ProMedica, a large regional nonprofit Toledo-based health care system – that pairs community-living individuals who have depression and/or anxiety with shelter animals that require adoption. The program pays for pet food, supplies, and veterinary care for those unable to afford these.
Participants (n = 11; mean age, 53.67 years; 78% women) were recruited from the HARP program. Participants were required to be psychiatrically stable, have stable housing, live alone, be at risk for social isolation, have low income, be sober, and have no history of violence. Their primary diagnoses were major depressive disorder, bipolar disorder, and schizoaffective disorder (63%, 18%, and 18%, respectively).
Six participants adopted a cat, and five adopted a dog.
Prior to ESA adoption and at 12 months, participants completed the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), and the UCLA Loneliness Scale Version 3.
Prior to ESA adoption and at 1, 3, 6, 9, and 12 months, saliva samples were collected from participants by researchers at the beginning of a home visit and then after 10 minutes of “focused pleasant interaction” with the ESA. The saliva was tested for oxytocin, alpha amylase, and cortisol.
Motivation, comfort, calm
The researchers found statistically significant decreases in UCLA Loneliness Scale scores from pre-ESA (mean [SD],59.20 [9.47]) to 12 months (49.90 [13.66], P = .004). The eta-squared statistic (.62) indicated a large effect size.
For 18 of the 20 items on the loneliness scale, mean values were lower after the intervention than before the intervention. Of these, four were statistically significant.
A statistically significant decrease in BDI total scores was also seen from pre-ESA to 12 months (21.09 [8.43] to 14.64 [7.03], respectively; P = .03). The eta-squared statistic (.41) indicated a large effect size.
Of the 21 items on the BDI scale, the mean value was lower for 19 after the intervention. Of these, five were statistically significant.
Similarly, a statistically significant decrease in BAI score was found from pre-ESA to 12 months (23.55 [9.81] to 17.73 [11.79], P = .049). The eta-squared statistic (.36) indicated a large effect size, although there were no statistically significant changes in individual item scores.
The researchers found “observable patterns” of decreases in cortisol and increases in oxytocin after the 10-minute enjoyable ESA interactions. The highest oxytocin increase occurred at 12 months; however, these improvements did not reach statistical significance.
Participants offered open-ended statements about the positive impact of their ESA on their mental health, Dr. Hoy-Gerlach said. “For example, they described feeling motivated to take better care of themselves because their ESA needed them. Some described feeling ‘comforted,’ distracted from symptoms, soothed, and calmed.
“There is definitely a place for ESAs, especially with mental health post pandemic, when we need all the resources that we can for those who can benefit,” she added.
Postpandemic mental health
Commenting on the study for this news organization, Christine Crawford, MD, MPH, assistant professor of psychiatry, Boston University, observed that ESAs “are not on the radar for a lot of clinicians, and a lot of clinicians don’t know about the science [supporting their use] or what an emotional support pet entails.
“ besides traditional forms of treatment, such as medication and therapy. Even a little relief is important, and having an emotional support pet is a good option,” said Dr. Crawford, associate medical director of the National Alliance on Mental Illness. She was not involved with the study.
The Kenneth A. Scott Charitable Trust provided grant funding. Dr. Hoy-Gerlach, her coauthors, and Dr. Crawford have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Suicide risk prediction tools fail people of color
Current models used to predict suicide risk fall short for racialized populations including Black, Indigenous, and people of color (BIPOC), new research shows.
Investigators developed two suicide prediction models to examine whether these types of tools are accurate in their predictive abilities, or whether they are flawed.
They found both prediction models failed to identify high-risk BIPOC individuals. In the first model, nearly half of outpatient visits followed by suicide were identified in White patients versus only 7% of visits followed by suicide in BIPOC patients. The second model had a sensitivity of 41% for White patients, but just 3% for Black patients and 7% for American Indian/Alaskan Native patients.
“You don’t know whether a prediction model will be useful or harmful until it’s evaluated. The take-home message of our study is this: You have to look,” lead author Yates Coley, PhD, assistant investigator, Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.
The study was published online April 28, 2021, in JAMA Psychiatry.
Racial inequities
Suicide risk prediction models have been “developed and validated in several settings” and are now in regular use at the Veterans Health Administration, HealthPartners, and Kaiser Permanente, the authors wrote.
But the performance of suicide risk prediction models, while accurate in the overall population, “remains unexamined” in particular subpopulations, they noted.
“Health records data reflect existing racial and ethnic inequities in health care access, quality, and outcomes; and prediction models using health records data may perpetuate these disparities by presuming that past healthcare patterns accurately reflect actual needs,” Dr. Coley said.
Dr. Coley and associates “wanted to make sure that any suicide prediction model we implemented in clinical care reduced health disparities rather than exacerbated them.”
To investigate, researchers examined all outpatient mental health visits to seven large integrated health care systems by patients 13 years and older (n = 13,980,570 visits by 1,422,534 patients; 64% female, mean age, 42 years). The study spanned from Jan. 1, 2009, to Sept. 30, 2017, with follow-up through Dec. 31, 2017.
In particular, researchers looked at suicides that took place within 90 days following the outpatient visit.
Researchers used two prediction models: logistic regression with LASSO (Least Absolute Shrinkage and Selection Operator) variable selection and random forest technique, a “tree-based method that explores interactions between predictors (including those with race and ethnicity) in estimating probability of an outcome.”
The models considered prespecified interactions between predictors, including prior diagnoses, suicide attempts, and PHQ-9 [Patient Health Questionnaire–9] responses, and race and ethnicity data.
Researchers evaluated performance of the prediction models in the overall validation set and within subgroups defined by race/ethnicity.
The area under the curve measured model discrimination, and sensitivity was estimated for global and race/ethnicity-specific thresholds.
‘Unacceptable’ scenario
Within the total population, there were 768 deaths by suicide within 90 days of 3,143 visits. Suicide rates were highest for visits by patients with no recorded race/ethnicity, followed by visits by Asian, White, American Indian/Alaskan Native, Hispanic, and Black patients.
Both models showed “high” AUC sensitivity for White, Hispanic, and Asian patients but “poor” AUC sensitivity for BIPOC and patients without recorded race/ethnicity, the authors reported.
“Implementation of prediction models has to be considered in the broader context of unmet health care needs,” said Dr. Coley.
“In our specific example of suicide prediction, BIPOC populations already face substantial barriers in accessing quality mental health care and, as a result, have poorer outcomes, and using either of the suicide prediction models examined in our study will provide less benefit to already-underserved populations and widen existing care gaps,” a scenario Dr. Coley said is “unacceptable.”
“ she added.
Biased algorithms
Commenting on the study, Jonathan Singer, PhD, LCSW, associate professor at Loyola University, Chicago, described it as an “important contribution because it points to a systemic problem and also to the fact that the algorithms we create are biased, created by humans, and humans are biased.”
Although the study focused on the health care system, Dr. Singer believes the findings have implications for individual clinicians.
“If clinicians may be biased against identifying suicide risk in Black and Native American patients, they may attribute suicidal risk to something else. For example, we know that in Black Americans, expressions of intense emotions are oftentimes interpreted as aggression or being threatening, as opposed to indicators of sadness or fear,” noted Dr. Singer, who is also president of the American Academy of Suicidology and was not involved with the study,
“Clinicians who misinterpret these intense emotions are less likely to identify a Black client or patient who is suicidal,” Dr. Singer said.
The research was supported by the Mental Health Research Network from the National Institute of Mental Health. Dr. Coley has reported receiving support through a grant from the Agency for Healthcare Research and Quality. Dr. Singer reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Current models used to predict suicide risk fall short for racialized populations including Black, Indigenous, and people of color (BIPOC), new research shows.
Investigators developed two suicide prediction models to examine whether these types of tools are accurate in their predictive abilities, or whether they are flawed.
They found both prediction models failed to identify high-risk BIPOC individuals. In the first model, nearly half of outpatient visits followed by suicide were identified in White patients versus only 7% of visits followed by suicide in BIPOC patients. The second model had a sensitivity of 41% for White patients, but just 3% for Black patients and 7% for American Indian/Alaskan Native patients.
“You don’t know whether a prediction model will be useful or harmful until it’s evaluated. The take-home message of our study is this: You have to look,” lead author Yates Coley, PhD, assistant investigator, Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.
The study was published online April 28, 2021, in JAMA Psychiatry.
Racial inequities
Suicide risk prediction models have been “developed and validated in several settings” and are now in regular use at the Veterans Health Administration, HealthPartners, and Kaiser Permanente, the authors wrote.
But the performance of suicide risk prediction models, while accurate in the overall population, “remains unexamined” in particular subpopulations, they noted.
“Health records data reflect existing racial and ethnic inequities in health care access, quality, and outcomes; and prediction models using health records data may perpetuate these disparities by presuming that past healthcare patterns accurately reflect actual needs,” Dr. Coley said.
Dr. Coley and associates “wanted to make sure that any suicide prediction model we implemented in clinical care reduced health disparities rather than exacerbated them.”
To investigate, researchers examined all outpatient mental health visits to seven large integrated health care systems by patients 13 years and older (n = 13,980,570 visits by 1,422,534 patients; 64% female, mean age, 42 years). The study spanned from Jan. 1, 2009, to Sept. 30, 2017, with follow-up through Dec. 31, 2017.
In particular, researchers looked at suicides that took place within 90 days following the outpatient visit.
Researchers used two prediction models: logistic regression with LASSO (Least Absolute Shrinkage and Selection Operator) variable selection and random forest technique, a “tree-based method that explores interactions between predictors (including those with race and ethnicity) in estimating probability of an outcome.”
The models considered prespecified interactions between predictors, including prior diagnoses, suicide attempts, and PHQ-9 [Patient Health Questionnaire–9] responses, and race and ethnicity data.
Researchers evaluated performance of the prediction models in the overall validation set and within subgroups defined by race/ethnicity.
The area under the curve measured model discrimination, and sensitivity was estimated for global and race/ethnicity-specific thresholds.
‘Unacceptable’ scenario
Within the total population, there were 768 deaths by suicide within 90 days of 3,143 visits. Suicide rates were highest for visits by patients with no recorded race/ethnicity, followed by visits by Asian, White, American Indian/Alaskan Native, Hispanic, and Black patients.
Both models showed “high” AUC sensitivity for White, Hispanic, and Asian patients but “poor” AUC sensitivity for BIPOC and patients without recorded race/ethnicity, the authors reported.
“Implementation of prediction models has to be considered in the broader context of unmet health care needs,” said Dr. Coley.
“In our specific example of suicide prediction, BIPOC populations already face substantial barriers in accessing quality mental health care and, as a result, have poorer outcomes, and using either of the suicide prediction models examined in our study will provide less benefit to already-underserved populations and widen existing care gaps,” a scenario Dr. Coley said is “unacceptable.”
“ she added.
Biased algorithms
Commenting on the study, Jonathan Singer, PhD, LCSW, associate professor at Loyola University, Chicago, described it as an “important contribution because it points to a systemic problem and also to the fact that the algorithms we create are biased, created by humans, and humans are biased.”
Although the study focused on the health care system, Dr. Singer believes the findings have implications for individual clinicians.
“If clinicians may be biased against identifying suicide risk in Black and Native American patients, they may attribute suicidal risk to something else. For example, we know that in Black Americans, expressions of intense emotions are oftentimes interpreted as aggression or being threatening, as opposed to indicators of sadness or fear,” noted Dr. Singer, who is also president of the American Academy of Suicidology and was not involved with the study,
“Clinicians who misinterpret these intense emotions are less likely to identify a Black client or patient who is suicidal,” Dr. Singer said.
The research was supported by the Mental Health Research Network from the National Institute of Mental Health. Dr. Coley has reported receiving support through a grant from the Agency for Healthcare Research and Quality. Dr. Singer reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Current models used to predict suicide risk fall short for racialized populations including Black, Indigenous, and people of color (BIPOC), new research shows.
Investigators developed two suicide prediction models to examine whether these types of tools are accurate in their predictive abilities, or whether they are flawed.
They found both prediction models failed to identify high-risk BIPOC individuals. In the first model, nearly half of outpatient visits followed by suicide were identified in White patients versus only 7% of visits followed by suicide in BIPOC patients. The second model had a sensitivity of 41% for White patients, but just 3% for Black patients and 7% for American Indian/Alaskan Native patients.
“You don’t know whether a prediction model will be useful or harmful until it’s evaluated. The take-home message of our study is this: You have to look,” lead author Yates Coley, PhD, assistant investigator, Kaiser Permanente Washington Health Research Institute, Seattle, said in an interview.
The study was published online April 28, 2021, in JAMA Psychiatry.
Racial inequities
Suicide risk prediction models have been “developed and validated in several settings” and are now in regular use at the Veterans Health Administration, HealthPartners, and Kaiser Permanente, the authors wrote.
But the performance of suicide risk prediction models, while accurate in the overall population, “remains unexamined” in particular subpopulations, they noted.
“Health records data reflect existing racial and ethnic inequities in health care access, quality, and outcomes; and prediction models using health records data may perpetuate these disparities by presuming that past healthcare patterns accurately reflect actual needs,” Dr. Coley said.
Dr. Coley and associates “wanted to make sure that any suicide prediction model we implemented in clinical care reduced health disparities rather than exacerbated them.”
To investigate, researchers examined all outpatient mental health visits to seven large integrated health care systems by patients 13 years and older (n = 13,980,570 visits by 1,422,534 patients; 64% female, mean age, 42 years). The study spanned from Jan. 1, 2009, to Sept. 30, 2017, with follow-up through Dec. 31, 2017.
In particular, researchers looked at suicides that took place within 90 days following the outpatient visit.
Researchers used two prediction models: logistic regression with LASSO (Least Absolute Shrinkage and Selection Operator) variable selection and random forest technique, a “tree-based method that explores interactions between predictors (including those with race and ethnicity) in estimating probability of an outcome.”
The models considered prespecified interactions between predictors, including prior diagnoses, suicide attempts, and PHQ-9 [Patient Health Questionnaire–9] responses, and race and ethnicity data.
Researchers evaluated performance of the prediction models in the overall validation set and within subgroups defined by race/ethnicity.
The area under the curve measured model discrimination, and sensitivity was estimated for global and race/ethnicity-specific thresholds.
‘Unacceptable’ scenario
Within the total population, there were 768 deaths by suicide within 90 days of 3,143 visits. Suicide rates were highest for visits by patients with no recorded race/ethnicity, followed by visits by Asian, White, American Indian/Alaskan Native, Hispanic, and Black patients.
Both models showed “high” AUC sensitivity for White, Hispanic, and Asian patients but “poor” AUC sensitivity for BIPOC and patients without recorded race/ethnicity, the authors reported.
“Implementation of prediction models has to be considered in the broader context of unmet health care needs,” said Dr. Coley.
“In our specific example of suicide prediction, BIPOC populations already face substantial barriers in accessing quality mental health care and, as a result, have poorer outcomes, and using either of the suicide prediction models examined in our study will provide less benefit to already-underserved populations and widen existing care gaps,” a scenario Dr. Coley said is “unacceptable.”
“ she added.
Biased algorithms
Commenting on the study, Jonathan Singer, PhD, LCSW, associate professor at Loyola University, Chicago, described it as an “important contribution because it points to a systemic problem and also to the fact that the algorithms we create are biased, created by humans, and humans are biased.”
Although the study focused on the health care system, Dr. Singer believes the findings have implications for individual clinicians.
“If clinicians may be biased against identifying suicide risk in Black and Native American patients, they may attribute suicidal risk to something else. For example, we know that in Black Americans, expressions of intense emotions are oftentimes interpreted as aggression or being threatening, as opposed to indicators of sadness or fear,” noted Dr. Singer, who is also president of the American Academy of Suicidology and was not involved with the study,
“Clinicians who misinterpret these intense emotions are less likely to identify a Black client or patient who is suicidal,” Dr. Singer said.
The research was supported by the Mental Health Research Network from the National Institute of Mental Health. Dr. Coley has reported receiving support through a grant from the Agency for Healthcare Research and Quality. Dr. Singer reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nurses or physicians: Who are at highest suicide risk?
Female nurses are at significantly greater risk of dying by suicide than physicians in findings that contradict previous research suggesting doctors are at greatest risk.
Results of a large retrospective cohort study show that nurses of both sexes were 18% more likely to die by suicide, compared with individuals in the general population. In addition, compared with female physicians, the suicide risk among female nurses was 70% higher.
“The main takeaway is that the risk of suicide among nurses is twice that of the general population and even higher than that among physicians, a population known to be at high risk,” lead author Matthew Davis, MPH, PhD, associate professor, department of systems, populations, and leadership, University of Michigan, Ann Arbor, said in an interview.
The study was published online April 14, 2021, in JAMA Psychiatry.
Focus on physicians
Compared with the general public, health care workers are at higher risk for suicide, but most studies of suicide have focused on physicians, Dr. Davis said.
Although “there were several older studies hinting that there might be a difference in suicide risk among nurses,” the data were insufficient to “make an overall conclusion,” he noted.
For that reason, his group “set out to make the best estimates possible” by using a large dataset from the National Violent Death Reporting System of the Centers for Disease Control and Prevention spanning the years 2007-2018 and focusing on suicides by individuals aged 30 years and older (n = 159,372 suicides).
Additional workforce data were acquired from the Bureau of Labor Statistics and the Association of Medical Colleges State Physician Workforce Data.
An important area of focus was method of suicide.
“ and know how to use them to overdose, which also increases their risk,” Dr. Davis said in a press release.
Enormous job strain
The researchers identified 2,374 suicides among nurses, 857 suicides among physicians, and 156,141 suicides in the general population.
Compared with the general population, nurses who died by suicide were more likely to be women, less racially diverse (non-Hispanic White), and more likely to have been married.
Rates of suicide were higher among nurses than among the general population, with a sex-adjusted incidence for 2017-2018 of 23.8 per 100,000 versus 20.1 per 100,000 (relative risk, 1.18; 95% confidence interval, 1.03-1.36).
The difference between suicide rates among female nurses and among women in the general population was even more striking: In 2017-2018, the suicide incidence among nurses was 17.1 per 100,000 versus 8.6 per 100,000 in the population at large (RR, 1.99; 95% CI, 1.82-2.18).
“In absolute terms, being a female nurse was associated with an additional 8.5 suicides per 100,000 (7.0-10.0), compared with the general population,” the authors reported.
In contrast, overall physician suicide rates were not statistically different from those of the general population (RR, 1.01; 95% CI, 0.79-1.30) except during the period 2011-2012 (11.7 per 100,000; 95% CI, 6.6-16.8 vs. 7.5 per 100,000; 95% CI, 7.2-7.7).
Clinicians of both sexes were more likely to use poisoning and less likely to use a firearm, compared with individuals in the general population who died by suicide. For example, 24.9% (23.5%-26.4%) of nurse suicides involved poisoning, compared to 16.8% (16.6%-17.0%) of suicides in the general population.
Toxicology reports showed that the presence of antidepressants, benzodiazepines, barbiturates, and opiates was more common in clinician suicides than suicides in the general population.
Dr. Davis suggested the higher risk for suicide among nurses, compared with physicians, might be attributed to “high job demands – for example, nurses provide the majority of bedside care, work long shifts in stressful environments, and have less autonomy.
“Health care workers and friends and family of health care workers need to be aware of mental health issues and suicide risk that can be associated with the job and, most importantly, recognize those who may be struggling and encourage them to get help by calling the National Suicide Prevention Lifeline,” he said.
Other potential contributors include “avoidance of mental health services due to stigma and greater access to the means to commit suicide via medication,” Dr. Davis noted.
Benchmark research
Commenting on the study, Constance Guille, MD, MSCR, professor in the department of psychiatry and behavioral science, Medical University of South Carolina, Charleston, noted that nurses are “predominantly female” and that women tend to be twice as likely as men to experience depression, which is a major risk factor for suicide. Thus, this population is particularly vulnerable.
One reason the investigators did not find that suicide rates were higher among physicians is that the health care professionals whom the researchers studied were older than 30 years. Thus, the study “excludes younger physicians in early practice or training, who likely do have higher suicide rates than the general population,” she suggested.
Dr. Guille, who is the author of an accompanying editorial and was not involved with the study, recommended “taking a public health approach, implementing preventative interventions, identifying people at high risk, providing treatment for health care professionals struggling with mental health problems, and destigmatizing help seeking.”
She encouraged clinicians to “reach out to colleagues who are struggling in a way to help them seek services and check in with them because it’s helpful when peers reach out.”
Dr. Davis noted that these disturbing trends will likely increase in the aftermath of the COVID-19 pandemic. “The pandemic has placed enormous strain on the health care workforce, and we fear this may have made the situation even worse.”
The current findings “will serve as a benchmark for future comparisons,” he said.
No source of funding for the study was reported. Dr. Davis has received consulting fees as a statistical reviewer for the journal Regional Anesthesia and Pain Medicine. His coauthors disclosed no relevant financial relationships. Dr. Guille has received grants from the National Institute on Drug Abuse, the American Foundation on Suicide Prevention, and the Duke Endowment and serves on the advisory board and speakers bureau of Sage Therapeutics.
A version of this article first appeared on Medscape.com.
Female nurses are at significantly greater risk of dying by suicide than physicians in findings that contradict previous research suggesting doctors are at greatest risk.
Results of a large retrospective cohort study show that nurses of both sexes were 18% more likely to die by suicide, compared with individuals in the general population. In addition, compared with female physicians, the suicide risk among female nurses was 70% higher.
“The main takeaway is that the risk of suicide among nurses is twice that of the general population and even higher than that among physicians, a population known to be at high risk,” lead author Matthew Davis, MPH, PhD, associate professor, department of systems, populations, and leadership, University of Michigan, Ann Arbor, said in an interview.
The study was published online April 14, 2021, in JAMA Psychiatry.
Focus on physicians
Compared with the general public, health care workers are at higher risk for suicide, but most studies of suicide have focused on physicians, Dr. Davis said.
Although “there were several older studies hinting that there might be a difference in suicide risk among nurses,” the data were insufficient to “make an overall conclusion,” he noted.
For that reason, his group “set out to make the best estimates possible” by using a large dataset from the National Violent Death Reporting System of the Centers for Disease Control and Prevention spanning the years 2007-2018 and focusing on suicides by individuals aged 30 years and older (n = 159,372 suicides).
Additional workforce data were acquired from the Bureau of Labor Statistics and the Association of Medical Colleges State Physician Workforce Data.
An important area of focus was method of suicide.
“ and know how to use them to overdose, which also increases their risk,” Dr. Davis said in a press release.
Enormous job strain
The researchers identified 2,374 suicides among nurses, 857 suicides among physicians, and 156,141 suicides in the general population.
Compared with the general population, nurses who died by suicide were more likely to be women, less racially diverse (non-Hispanic White), and more likely to have been married.
Rates of suicide were higher among nurses than among the general population, with a sex-adjusted incidence for 2017-2018 of 23.8 per 100,000 versus 20.1 per 100,000 (relative risk, 1.18; 95% confidence interval, 1.03-1.36).
The difference between suicide rates among female nurses and among women in the general population was even more striking: In 2017-2018, the suicide incidence among nurses was 17.1 per 100,000 versus 8.6 per 100,000 in the population at large (RR, 1.99; 95% CI, 1.82-2.18).
“In absolute terms, being a female nurse was associated with an additional 8.5 suicides per 100,000 (7.0-10.0), compared with the general population,” the authors reported.
In contrast, overall physician suicide rates were not statistically different from those of the general population (RR, 1.01; 95% CI, 0.79-1.30) except during the period 2011-2012 (11.7 per 100,000; 95% CI, 6.6-16.8 vs. 7.5 per 100,000; 95% CI, 7.2-7.7).
Clinicians of both sexes were more likely to use poisoning and less likely to use a firearm, compared with individuals in the general population who died by suicide. For example, 24.9% (23.5%-26.4%) of nurse suicides involved poisoning, compared to 16.8% (16.6%-17.0%) of suicides in the general population.
Toxicology reports showed that the presence of antidepressants, benzodiazepines, barbiturates, and opiates was more common in clinician suicides than suicides in the general population.
Dr. Davis suggested the higher risk for suicide among nurses, compared with physicians, might be attributed to “high job demands – for example, nurses provide the majority of bedside care, work long shifts in stressful environments, and have less autonomy.
“Health care workers and friends and family of health care workers need to be aware of mental health issues and suicide risk that can be associated with the job and, most importantly, recognize those who may be struggling and encourage them to get help by calling the National Suicide Prevention Lifeline,” he said.
Other potential contributors include “avoidance of mental health services due to stigma and greater access to the means to commit suicide via medication,” Dr. Davis noted.
Benchmark research
Commenting on the study, Constance Guille, MD, MSCR, professor in the department of psychiatry and behavioral science, Medical University of South Carolina, Charleston, noted that nurses are “predominantly female” and that women tend to be twice as likely as men to experience depression, which is a major risk factor for suicide. Thus, this population is particularly vulnerable.
One reason the investigators did not find that suicide rates were higher among physicians is that the health care professionals whom the researchers studied were older than 30 years. Thus, the study “excludes younger physicians in early practice or training, who likely do have higher suicide rates than the general population,” she suggested.
Dr. Guille, who is the author of an accompanying editorial and was not involved with the study, recommended “taking a public health approach, implementing preventative interventions, identifying people at high risk, providing treatment for health care professionals struggling with mental health problems, and destigmatizing help seeking.”
She encouraged clinicians to “reach out to colleagues who are struggling in a way to help them seek services and check in with them because it’s helpful when peers reach out.”
Dr. Davis noted that these disturbing trends will likely increase in the aftermath of the COVID-19 pandemic. “The pandemic has placed enormous strain on the health care workforce, and we fear this may have made the situation even worse.”
The current findings “will serve as a benchmark for future comparisons,” he said.
No source of funding for the study was reported. Dr. Davis has received consulting fees as a statistical reviewer for the journal Regional Anesthesia and Pain Medicine. His coauthors disclosed no relevant financial relationships. Dr. Guille has received grants from the National Institute on Drug Abuse, the American Foundation on Suicide Prevention, and the Duke Endowment and serves on the advisory board and speakers bureau of Sage Therapeutics.
A version of this article first appeared on Medscape.com.
Female nurses are at significantly greater risk of dying by suicide than physicians in findings that contradict previous research suggesting doctors are at greatest risk.
Results of a large retrospective cohort study show that nurses of both sexes were 18% more likely to die by suicide, compared with individuals in the general population. In addition, compared with female physicians, the suicide risk among female nurses was 70% higher.
“The main takeaway is that the risk of suicide among nurses is twice that of the general population and even higher than that among physicians, a population known to be at high risk,” lead author Matthew Davis, MPH, PhD, associate professor, department of systems, populations, and leadership, University of Michigan, Ann Arbor, said in an interview.
The study was published online April 14, 2021, in JAMA Psychiatry.
Focus on physicians
Compared with the general public, health care workers are at higher risk for suicide, but most studies of suicide have focused on physicians, Dr. Davis said.
Although “there were several older studies hinting that there might be a difference in suicide risk among nurses,” the data were insufficient to “make an overall conclusion,” he noted.
For that reason, his group “set out to make the best estimates possible” by using a large dataset from the National Violent Death Reporting System of the Centers for Disease Control and Prevention spanning the years 2007-2018 and focusing on suicides by individuals aged 30 years and older (n = 159,372 suicides).
Additional workforce data were acquired from the Bureau of Labor Statistics and the Association of Medical Colleges State Physician Workforce Data.
An important area of focus was method of suicide.
“ and know how to use them to overdose, which also increases their risk,” Dr. Davis said in a press release.
Enormous job strain
The researchers identified 2,374 suicides among nurses, 857 suicides among physicians, and 156,141 suicides in the general population.
Compared with the general population, nurses who died by suicide were more likely to be women, less racially diverse (non-Hispanic White), and more likely to have been married.
Rates of suicide were higher among nurses than among the general population, with a sex-adjusted incidence for 2017-2018 of 23.8 per 100,000 versus 20.1 per 100,000 (relative risk, 1.18; 95% confidence interval, 1.03-1.36).
The difference between suicide rates among female nurses and among women in the general population was even more striking: In 2017-2018, the suicide incidence among nurses was 17.1 per 100,000 versus 8.6 per 100,000 in the population at large (RR, 1.99; 95% CI, 1.82-2.18).
“In absolute terms, being a female nurse was associated with an additional 8.5 suicides per 100,000 (7.0-10.0), compared with the general population,” the authors reported.
In contrast, overall physician suicide rates were not statistically different from those of the general population (RR, 1.01; 95% CI, 0.79-1.30) except during the period 2011-2012 (11.7 per 100,000; 95% CI, 6.6-16.8 vs. 7.5 per 100,000; 95% CI, 7.2-7.7).
Clinicians of both sexes were more likely to use poisoning and less likely to use a firearm, compared with individuals in the general population who died by suicide. For example, 24.9% (23.5%-26.4%) of nurse suicides involved poisoning, compared to 16.8% (16.6%-17.0%) of suicides in the general population.
Toxicology reports showed that the presence of antidepressants, benzodiazepines, barbiturates, and opiates was more common in clinician suicides than suicides in the general population.
Dr. Davis suggested the higher risk for suicide among nurses, compared with physicians, might be attributed to “high job demands – for example, nurses provide the majority of bedside care, work long shifts in stressful environments, and have less autonomy.
“Health care workers and friends and family of health care workers need to be aware of mental health issues and suicide risk that can be associated with the job and, most importantly, recognize those who may be struggling and encourage them to get help by calling the National Suicide Prevention Lifeline,” he said.
Other potential contributors include “avoidance of mental health services due to stigma and greater access to the means to commit suicide via medication,” Dr. Davis noted.
Benchmark research
Commenting on the study, Constance Guille, MD, MSCR, professor in the department of psychiatry and behavioral science, Medical University of South Carolina, Charleston, noted that nurses are “predominantly female” and that women tend to be twice as likely as men to experience depression, which is a major risk factor for suicide. Thus, this population is particularly vulnerable.
One reason the investigators did not find that suicide rates were higher among physicians is that the health care professionals whom the researchers studied were older than 30 years. Thus, the study “excludes younger physicians in early practice or training, who likely do have higher suicide rates than the general population,” she suggested.
Dr. Guille, who is the author of an accompanying editorial and was not involved with the study, recommended “taking a public health approach, implementing preventative interventions, identifying people at high risk, providing treatment for health care professionals struggling with mental health problems, and destigmatizing help seeking.”
She encouraged clinicians to “reach out to colleagues who are struggling in a way to help them seek services and check in with them because it’s helpful when peers reach out.”
Dr. Davis noted that these disturbing trends will likely increase in the aftermath of the COVID-19 pandemic. “The pandemic has placed enormous strain on the health care workforce, and we fear this may have made the situation even worse.”
The current findings “will serve as a benchmark for future comparisons,” he said.
No source of funding for the study was reported. Dr. Davis has received consulting fees as a statistical reviewer for the journal Regional Anesthesia and Pain Medicine. His coauthors disclosed no relevant financial relationships. Dr. Guille has received grants from the National Institute on Drug Abuse, the American Foundation on Suicide Prevention, and the Duke Endowment and serves on the advisory board and speakers bureau of Sage Therapeutics.
A version of this article first appeared on Medscape.com.