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Novel drug may lower agitation, aggression in multiple psychiatric disorders
The novel lysine-specific demethylase 1 inhibitor vafidemstat (ORY-2001, Oryzon Genomics) is effective for treating agitation and aggression across a number of psychiatric disorders, new research suggests.
The REIMAGINE trial included 30 patients with autism spectrum disorder (ASD), ADHD, or borderline personality disorder (BPD). Results showed significant improvements after 8 weeks in general functioning and agitation-aggression scores for all three disorders.
The study “supports vafidemstat as an emerging therapeutic option to treat aggression-agitation, as well as the nonaggression features of psychiatric diseases with high unmet medical need,” lead researcher Roger Bullock, MD, Oryzon Genomics, Corneliá De Llobregat, Spain, told Medscape Medical News.
Bullock added.
However, another expert urged prudence when interpreting the findings.
“The study results must be viewed with caution, given the inherent limitations of an open-label trial, small sample size, and weak rationale for the sample selection,” said Nathan Kolla, MD, PhD, a psychiatrist at the University of Toronto, Canada, who was not involved with the research.
The findings were presented at the European Psychiatric Association (EPA) 2020 Congress, which was held online this year because of the COVID-19 pandemic.
Little evidence available
“Epigenetic mechanisms have been proposed in many psychiatric conditions, but so far, little clinical evidence is available,” Bullock said during his presentation.
In preclinical models, vafidemstat has been associated with a reduction in aggressive behavior “and the normal response to stress of immediate early genes in the prefrontal cortex” via the modification of gene transcription, noted Bullock.
“This new approach makes it a good candidate to look at aggression in multiple psychiatric and CNS conditions,” he added.
REIMAGINE was a phase 2a open-label trial that included 30 patients (53% women; mean age, 33.5 years; 87% White) with psychiatric disorders who had significant or persistent agitation or aggression that was disruptive of the patients› daily life.
Among the participants, 12 had BPD, 11 had ADHD, and seven had ASD. All were treated with vafidemstat 1.2 mg for 8 weeks.
In all, 23 patients completed all 8 weeks of treatment, including nine patients with BPD, eight with ADHD, and six with ASD.
Results showed that the study drug was well tolerated, with no serious adverse events reported and no patients withdrawing because of safety-related events.
The most common adverse events were headache (20%) and insomnia (10%), which resolved without intervention or treatment modification.
Significantly improved scores
Across the whole cohort, the drug was associated with significant reductions in scores over baseline on the Clinical Global Impression–Severity (CGI-S) and CGI-Improvement (CGI-I) scales. There were also significant improvements for Neuropsychiatric Inventory (NPI) total scores and agitation-aggression scores (P < .001 for comparisons).
Similar results were observed with respect to individual diagnoses, albeit at varying degrees of significance for each scale.
Patients with BPD experienced significant reductions in scores on the Borderline Personality Disorder Checklist (BPDCL) (P < .01). Patients with ADHD experienced reductions on the ADHD Rating Scale (P < .05).
Patients with BPD also experienced reductions in suicidal ideation, as measured with the Columbia Suicide Severity Rating Scale (P < .01). That is “the only cohort where this trait is relevant,” the researchers note.
In addition, significant correlations were shown between NPI total scores and scores on the BPDCL after treatment with vafidemstat (P = .015), as well as between NPI agitation-aggression scores and both CGI-I (P = .008) and CGI-S scores (P = .0001).
“This convergence of signals in scales of different nature and scope support the pharmacological role of vafidemstat in controlling aggression-agitation in different psychiatric conditions,” the investigators note.
Bullock added that further randomized placebo-controlled clinical trials “to confirm vafidemstat’s potential to treat aggression-agitation in psychiatric disorders are now planned.”
First up will be PORTICO, which is planned to start over the coming months in Spain and will include patients with BPD.
Several limitations
Commenting on the study for Medscape Medical News, Kolla, who is also a researcher at the Center for Addiction and Mental Health, noted that REIMAGINE was originally designed to test vafidemstat for the treatment of agitation and aggression in patients with Alzheimer’s disease (AD).
“It seems peculiar that the study investigators would choose to examine three additional psychiatric disorders that bear little resemblance to AD in terms of phenomenology. Additionally, the etiological underpinnings of the three disorders likely differ markedly from AD,” said Kolla, who was not involved with the research.
In addition, the “very small” sample size in each group makes it difficult to interpret the investigators’ conclusions, he noted.
There are also “many more sophisticated scales” to assess agitation and aggression than what were used in the study, he added.
Kolla also questioned the notion that a drug such as vafidemstat satisfies an unmet clinical need for the treatment of aggression and agitation.
Trials that “purport to reduce aggression in these populations often provide some level of global improvement in functioning that may appear as if they directly treat agitation or aggression,” he said. “However, no drug has ever been developed that directly reduces aggression and agitation.”
That means that, for now, there is insufficient evidence to “conclude that vafidemstat overcomes the unmet medical need of treating aggression/agitation,” he said.
For Kolla, the concept of a psychiatric drug that works by effecting epigenetic changes to the genome is also questionable, although such mechanisms may “play a role in the salubrious effects of certain mood stabilizers or antipsychotics for which better-defined mechanisms of action have been established.”
The study was funded by Oryzon Genomics. Bullock and the other investigators are employees of Oryzon Genomics.
This article first appeared on Medscape.com.
The novel lysine-specific demethylase 1 inhibitor vafidemstat (ORY-2001, Oryzon Genomics) is effective for treating agitation and aggression across a number of psychiatric disorders, new research suggests.
The REIMAGINE trial included 30 patients with autism spectrum disorder (ASD), ADHD, or borderline personality disorder (BPD). Results showed significant improvements after 8 weeks in general functioning and agitation-aggression scores for all three disorders.
The study “supports vafidemstat as an emerging therapeutic option to treat aggression-agitation, as well as the nonaggression features of psychiatric diseases with high unmet medical need,” lead researcher Roger Bullock, MD, Oryzon Genomics, Corneliá De Llobregat, Spain, told Medscape Medical News.
Bullock added.
However, another expert urged prudence when interpreting the findings.
“The study results must be viewed with caution, given the inherent limitations of an open-label trial, small sample size, and weak rationale for the sample selection,” said Nathan Kolla, MD, PhD, a psychiatrist at the University of Toronto, Canada, who was not involved with the research.
The findings were presented at the European Psychiatric Association (EPA) 2020 Congress, which was held online this year because of the COVID-19 pandemic.
Little evidence available
“Epigenetic mechanisms have been proposed in many psychiatric conditions, but so far, little clinical evidence is available,” Bullock said during his presentation.
In preclinical models, vafidemstat has been associated with a reduction in aggressive behavior “and the normal response to stress of immediate early genes in the prefrontal cortex” via the modification of gene transcription, noted Bullock.
“This new approach makes it a good candidate to look at aggression in multiple psychiatric and CNS conditions,” he added.
REIMAGINE was a phase 2a open-label trial that included 30 patients (53% women; mean age, 33.5 years; 87% White) with psychiatric disorders who had significant or persistent agitation or aggression that was disruptive of the patients› daily life.
Among the participants, 12 had BPD, 11 had ADHD, and seven had ASD. All were treated with vafidemstat 1.2 mg for 8 weeks.
In all, 23 patients completed all 8 weeks of treatment, including nine patients with BPD, eight with ADHD, and six with ASD.
Results showed that the study drug was well tolerated, with no serious adverse events reported and no patients withdrawing because of safety-related events.
The most common adverse events were headache (20%) and insomnia (10%), which resolved without intervention or treatment modification.
Significantly improved scores
Across the whole cohort, the drug was associated with significant reductions in scores over baseline on the Clinical Global Impression–Severity (CGI-S) and CGI-Improvement (CGI-I) scales. There were also significant improvements for Neuropsychiatric Inventory (NPI) total scores and agitation-aggression scores (P < .001 for comparisons).
Similar results were observed with respect to individual diagnoses, albeit at varying degrees of significance for each scale.
Patients with BPD experienced significant reductions in scores on the Borderline Personality Disorder Checklist (BPDCL) (P < .01). Patients with ADHD experienced reductions on the ADHD Rating Scale (P < .05).
Patients with BPD also experienced reductions in suicidal ideation, as measured with the Columbia Suicide Severity Rating Scale (P < .01). That is “the only cohort where this trait is relevant,” the researchers note.
In addition, significant correlations were shown between NPI total scores and scores on the BPDCL after treatment with vafidemstat (P = .015), as well as between NPI agitation-aggression scores and both CGI-I (P = .008) and CGI-S scores (P = .0001).
“This convergence of signals in scales of different nature and scope support the pharmacological role of vafidemstat in controlling aggression-agitation in different psychiatric conditions,” the investigators note.
Bullock added that further randomized placebo-controlled clinical trials “to confirm vafidemstat’s potential to treat aggression-agitation in psychiatric disorders are now planned.”
First up will be PORTICO, which is planned to start over the coming months in Spain and will include patients with BPD.
Several limitations
Commenting on the study for Medscape Medical News, Kolla, who is also a researcher at the Center for Addiction and Mental Health, noted that REIMAGINE was originally designed to test vafidemstat for the treatment of agitation and aggression in patients with Alzheimer’s disease (AD).
“It seems peculiar that the study investigators would choose to examine three additional psychiatric disorders that bear little resemblance to AD in terms of phenomenology. Additionally, the etiological underpinnings of the three disorders likely differ markedly from AD,” said Kolla, who was not involved with the research.
In addition, the “very small” sample size in each group makes it difficult to interpret the investigators’ conclusions, he noted.
There are also “many more sophisticated scales” to assess agitation and aggression than what were used in the study, he added.
Kolla also questioned the notion that a drug such as vafidemstat satisfies an unmet clinical need for the treatment of aggression and agitation.
Trials that “purport to reduce aggression in these populations often provide some level of global improvement in functioning that may appear as if they directly treat agitation or aggression,” he said. “However, no drug has ever been developed that directly reduces aggression and agitation.”
That means that, for now, there is insufficient evidence to “conclude that vafidemstat overcomes the unmet medical need of treating aggression/agitation,” he said.
For Kolla, the concept of a psychiatric drug that works by effecting epigenetic changes to the genome is also questionable, although such mechanisms may “play a role in the salubrious effects of certain mood stabilizers or antipsychotics for which better-defined mechanisms of action have been established.”
The study was funded by Oryzon Genomics. Bullock and the other investigators are employees of Oryzon Genomics.
This article first appeared on Medscape.com.
The novel lysine-specific demethylase 1 inhibitor vafidemstat (ORY-2001, Oryzon Genomics) is effective for treating agitation and aggression across a number of psychiatric disorders, new research suggests.
The REIMAGINE trial included 30 patients with autism spectrum disorder (ASD), ADHD, or borderline personality disorder (BPD). Results showed significant improvements after 8 weeks in general functioning and agitation-aggression scores for all three disorders.
The study “supports vafidemstat as an emerging therapeutic option to treat aggression-agitation, as well as the nonaggression features of psychiatric diseases with high unmet medical need,” lead researcher Roger Bullock, MD, Oryzon Genomics, Corneliá De Llobregat, Spain, told Medscape Medical News.
Bullock added.
However, another expert urged prudence when interpreting the findings.
“The study results must be viewed with caution, given the inherent limitations of an open-label trial, small sample size, and weak rationale for the sample selection,” said Nathan Kolla, MD, PhD, a psychiatrist at the University of Toronto, Canada, who was not involved with the research.
The findings were presented at the European Psychiatric Association (EPA) 2020 Congress, which was held online this year because of the COVID-19 pandemic.
Little evidence available
“Epigenetic mechanisms have been proposed in many psychiatric conditions, but so far, little clinical evidence is available,” Bullock said during his presentation.
In preclinical models, vafidemstat has been associated with a reduction in aggressive behavior “and the normal response to stress of immediate early genes in the prefrontal cortex” via the modification of gene transcription, noted Bullock.
“This new approach makes it a good candidate to look at aggression in multiple psychiatric and CNS conditions,” he added.
REIMAGINE was a phase 2a open-label trial that included 30 patients (53% women; mean age, 33.5 years; 87% White) with psychiatric disorders who had significant or persistent agitation or aggression that was disruptive of the patients› daily life.
Among the participants, 12 had BPD, 11 had ADHD, and seven had ASD. All were treated with vafidemstat 1.2 mg for 8 weeks.
In all, 23 patients completed all 8 weeks of treatment, including nine patients with BPD, eight with ADHD, and six with ASD.
Results showed that the study drug was well tolerated, with no serious adverse events reported and no patients withdrawing because of safety-related events.
The most common adverse events were headache (20%) and insomnia (10%), which resolved without intervention or treatment modification.
Significantly improved scores
Across the whole cohort, the drug was associated with significant reductions in scores over baseline on the Clinical Global Impression–Severity (CGI-S) and CGI-Improvement (CGI-I) scales. There were also significant improvements for Neuropsychiatric Inventory (NPI) total scores and agitation-aggression scores (P < .001 for comparisons).
Similar results were observed with respect to individual diagnoses, albeit at varying degrees of significance for each scale.
Patients with BPD experienced significant reductions in scores on the Borderline Personality Disorder Checklist (BPDCL) (P < .01). Patients with ADHD experienced reductions on the ADHD Rating Scale (P < .05).
Patients with BPD also experienced reductions in suicidal ideation, as measured with the Columbia Suicide Severity Rating Scale (P < .01). That is “the only cohort where this trait is relevant,” the researchers note.
In addition, significant correlations were shown between NPI total scores and scores on the BPDCL after treatment with vafidemstat (P = .015), as well as between NPI agitation-aggression scores and both CGI-I (P = .008) and CGI-S scores (P = .0001).
“This convergence of signals in scales of different nature and scope support the pharmacological role of vafidemstat in controlling aggression-agitation in different psychiatric conditions,” the investigators note.
Bullock added that further randomized placebo-controlled clinical trials “to confirm vafidemstat’s potential to treat aggression-agitation in psychiatric disorders are now planned.”
First up will be PORTICO, which is planned to start over the coming months in Spain and will include patients with BPD.
Several limitations
Commenting on the study for Medscape Medical News, Kolla, who is also a researcher at the Center for Addiction and Mental Health, noted that REIMAGINE was originally designed to test vafidemstat for the treatment of agitation and aggression in patients with Alzheimer’s disease (AD).
“It seems peculiar that the study investigators would choose to examine three additional psychiatric disorders that bear little resemblance to AD in terms of phenomenology. Additionally, the etiological underpinnings of the three disorders likely differ markedly from AD,” said Kolla, who was not involved with the research.
In addition, the “very small” sample size in each group makes it difficult to interpret the investigators’ conclusions, he noted.
There are also “many more sophisticated scales” to assess agitation and aggression than what were used in the study, he added.
Kolla also questioned the notion that a drug such as vafidemstat satisfies an unmet clinical need for the treatment of aggression and agitation.
Trials that “purport to reduce aggression in these populations often provide some level of global improvement in functioning that may appear as if they directly treat agitation or aggression,” he said. “However, no drug has ever been developed that directly reduces aggression and agitation.”
That means that, for now, there is insufficient evidence to “conclude that vafidemstat overcomes the unmet medical need of treating aggression/agitation,” he said.
For Kolla, the concept of a psychiatric drug that works by effecting epigenetic changes to the genome is also questionable, although such mechanisms may “play a role in the salubrious effects of certain mood stabilizers or antipsychotics for which better-defined mechanisms of action have been established.”
The study was funded by Oryzon Genomics. Bullock and the other investigators are employees of Oryzon Genomics.
This article first appeared on Medscape.com.
Heavy toll from ongoing cancer referral delays
Delays in cancer referrals caused by the COVID-19 pandemic and the ensuing shutdown in cancer services will lead to thousands of additional deaths and tens of thousands of life-years lost, suggest two new modeling studies from the United Kingdom.
Clearing the backlog in cancer diagnoses will require a coordinated effort from the government and the National Health Service (NHS), say the authors, inasmuch as services were already running at “full capacity” before the pandemic.
Both studies were published in The Lancet Oncology on July 20.
When the UK-wide lockdown to combat the COVID-19 pandemic was implemented on March 23, cancer screening and routine outpatient referrals in the NHS were suspended, and treatment of cancer patients either halted or slowed down.
Moreover, because of physical distancing measures, which are expected to continue for up to a year, urgent 3-week referrals for suspected cancer cases have fallen by as much as 80%.
To estimate the potential impact on cancer deaths, Ajay Aggarwal, MD, from the London School of Hygiene and Tropical Medicine, United Kingdom, and colleagues conducted a population-based modeling study.
They collected data on 32,583 patients with breast cancer, 24,975 with colorectal cancer, 6744 with esophageal cancer, and 29,305 with lung cancer. Patients were diagnosed between 2010 and 2012 and were followed to 2015.
The investigators used that data to estimate the impact of diagnostic delays resulting from 12 months of physical distancing.
For breast cancer, this would lead to a 7.9%-9.6% increase in the number of cancer deaths within 5 years after diagnosis, or to 281-344 additional deaths.
For colorectal cancer, there would be a 15.3%-16.7% increase in mortality over 5 years, or an additional 1,445-1,563 deaths.
For lung cancer, there would a 4.8%-5.3% increase in mortality, or an additional 1235-1372 deaths.
For esophageal cancer, the mortality increase over 5 years would be 5.8%-6.0%, leading to 330-342 additional deaths.
Across the four tumor types, 59,204-63,229 life-years would be lost because of physical distancing compared to the prepandemic era.
Resources need to be increased
These additional deaths are not inevitable, the researchers suggest.
To prevent the increase in colorectal cancer deaths, for example, Aggarwal said, “It is vital that more resources are made urgently available for endoscopy and colonoscopy services, which are managing significant backlogs currently.
“Whilst currently attention is being focused on diagnostic pathways where cancer is suspected, the issue is that a significant number of cancers are diagnosed in patients awaiting investigation for symptoms not considered related to be cancer,” he added in a statement.
“Therefore we need a whole system approach to avoid the predicted excess deaths.”
Coauthor Bernard Rachet, PhD, also from the London School of Hygiene and Tropical Medicine, added that “to absorb the cancer patient backlog, the healthcare community also needs to establish clear criteria to prioritise patients on clinical grounds, in order to maintain equitability in care delivery.”
It will not be easy “to pin down the exact number of additional cancer deaths we expect to see over the coming years, but studies like this help us to understand the devastating long-term effect a pandemic like COVID-19 will have on the lives of thousands of cancer patients,” commented Michelle Mitchell, chief executive of Cancer Research UK.
Underlining the “enormous backlog” of cancer care that has built up during the pandemic, she said: “Diagnosing and treating people swiftly is vital to give people with cancer the greatest chances of survival.
“The government must work closely with the NHS to ensure it has sufficient staff and equipment to clear the backlog while giving patients the care that they need, quickly and safely,” Mitchell added.
Increasing resources will not be easy. In an accompanying editorial, William Hamilton, MD, PhD, University of Exeter, United Kingdom, warns that many NHS imaging departments, for example, were “working at full capacity before the COVID-19 pandemic.”
Consequently, they “might not be able to meet the increase in demand” resulting from the backlog in patients, especially as “the need to keep patients separate and to clean equipment has reduced their efficiency.
“The UK has had a long-term shortage of diagnostic capacity, although this shortage is not simply of equipment, but also of personnel, which is not so easily improved,” he cautions.
Another study, similar estimates
For the second study, Clare Turnbull, PhD, Institute of Cancer Research, London, and colleagues obtained age- and stage-stratified 10-year cancer survival estimates for patients in England diagnosed with 20 common tumor types between 2008 and 2017.
They also gathered data on cancer diagnoses made via urgent 2-week referrals between 2013 and 2016. They estimate that 6,281 patients were diagnosed with cancer of stages I-III per month.
Of those, 1,691 (27%) would die within 10 years of their diagnosis, they found.
They then calculated that delays in 2-week referrals during a 3-month lockdown would lead to an average delay in presentation of 2 months per patient.
A resulting 25% backlog in referrals would lead to 181 additional lives and 3,316 life-years lost. With a 75% backlog in referrals, an additional 276 lives and 5,075 life-years would be lost.
The team says that additional diagnostic delays spread over 3-8 months after the lockdown could increase the impact of a 25% backlog in referrals to 401 additional lives and 14,873 life-years lost.
For a 75% backlog in referrals, the additional lives lost would rise to 1,231, and the number of life-years lost would reach 22,635.
“Substantial additional deaths from diagnostic delays on top of those expected from delays in presentation – because many people are simply too afraid to visit their GP or hospital – are likely, especially if rapid provision of additional capacity, including technical provision and increased staffing, is not forthcoming,” Turnbull commented in a statement.
The study by Aggarwal and colleagues was funded by the U.K. Research and Innovation Economic and Social Research Council. Several of the researchers were supported by Cancer Research UK and Breast Cancer Now. Turnbull reports receiving support from the Movember Foundation.
This article first appeared on Medscape.com.
Delays in cancer referrals caused by the COVID-19 pandemic and the ensuing shutdown in cancer services will lead to thousands of additional deaths and tens of thousands of life-years lost, suggest two new modeling studies from the United Kingdom.
Clearing the backlog in cancer diagnoses will require a coordinated effort from the government and the National Health Service (NHS), say the authors, inasmuch as services were already running at “full capacity” before the pandemic.
Both studies were published in The Lancet Oncology on July 20.
When the UK-wide lockdown to combat the COVID-19 pandemic was implemented on March 23, cancer screening and routine outpatient referrals in the NHS were suspended, and treatment of cancer patients either halted or slowed down.
Moreover, because of physical distancing measures, which are expected to continue for up to a year, urgent 3-week referrals for suspected cancer cases have fallen by as much as 80%.
To estimate the potential impact on cancer deaths, Ajay Aggarwal, MD, from the London School of Hygiene and Tropical Medicine, United Kingdom, and colleagues conducted a population-based modeling study.
They collected data on 32,583 patients with breast cancer, 24,975 with colorectal cancer, 6744 with esophageal cancer, and 29,305 with lung cancer. Patients were diagnosed between 2010 and 2012 and were followed to 2015.
The investigators used that data to estimate the impact of diagnostic delays resulting from 12 months of physical distancing.
For breast cancer, this would lead to a 7.9%-9.6% increase in the number of cancer deaths within 5 years after diagnosis, or to 281-344 additional deaths.
For colorectal cancer, there would be a 15.3%-16.7% increase in mortality over 5 years, or an additional 1,445-1,563 deaths.
For lung cancer, there would a 4.8%-5.3% increase in mortality, or an additional 1235-1372 deaths.
For esophageal cancer, the mortality increase over 5 years would be 5.8%-6.0%, leading to 330-342 additional deaths.
Across the four tumor types, 59,204-63,229 life-years would be lost because of physical distancing compared to the prepandemic era.
Resources need to be increased
These additional deaths are not inevitable, the researchers suggest.
To prevent the increase in colorectal cancer deaths, for example, Aggarwal said, “It is vital that more resources are made urgently available for endoscopy and colonoscopy services, which are managing significant backlogs currently.
“Whilst currently attention is being focused on diagnostic pathways where cancer is suspected, the issue is that a significant number of cancers are diagnosed in patients awaiting investigation for symptoms not considered related to be cancer,” he added in a statement.
“Therefore we need a whole system approach to avoid the predicted excess deaths.”
Coauthor Bernard Rachet, PhD, also from the London School of Hygiene and Tropical Medicine, added that “to absorb the cancer patient backlog, the healthcare community also needs to establish clear criteria to prioritise patients on clinical grounds, in order to maintain equitability in care delivery.”
It will not be easy “to pin down the exact number of additional cancer deaths we expect to see over the coming years, but studies like this help us to understand the devastating long-term effect a pandemic like COVID-19 will have on the lives of thousands of cancer patients,” commented Michelle Mitchell, chief executive of Cancer Research UK.
Underlining the “enormous backlog” of cancer care that has built up during the pandemic, she said: “Diagnosing and treating people swiftly is vital to give people with cancer the greatest chances of survival.
“The government must work closely with the NHS to ensure it has sufficient staff and equipment to clear the backlog while giving patients the care that they need, quickly and safely,” Mitchell added.
Increasing resources will not be easy. In an accompanying editorial, William Hamilton, MD, PhD, University of Exeter, United Kingdom, warns that many NHS imaging departments, for example, were “working at full capacity before the COVID-19 pandemic.”
Consequently, they “might not be able to meet the increase in demand” resulting from the backlog in patients, especially as “the need to keep patients separate and to clean equipment has reduced their efficiency.
“The UK has had a long-term shortage of diagnostic capacity, although this shortage is not simply of equipment, but also of personnel, which is not so easily improved,” he cautions.
Another study, similar estimates
For the second study, Clare Turnbull, PhD, Institute of Cancer Research, London, and colleagues obtained age- and stage-stratified 10-year cancer survival estimates for patients in England diagnosed with 20 common tumor types between 2008 and 2017.
They also gathered data on cancer diagnoses made via urgent 2-week referrals between 2013 and 2016. They estimate that 6,281 patients were diagnosed with cancer of stages I-III per month.
Of those, 1,691 (27%) would die within 10 years of their diagnosis, they found.
They then calculated that delays in 2-week referrals during a 3-month lockdown would lead to an average delay in presentation of 2 months per patient.
A resulting 25% backlog in referrals would lead to 181 additional lives and 3,316 life-years lost. With a 75% backlog in referrals, an additional 276 lives and 5,075 life-years would be lost.
The team says that additional diagnostic delays spread over 3-8 months after the lockdown could increase the impact of a 25% backlog in referrals to 401 additional lives and 14,873 life-years lost.
For a 75% backlog in referrals, the additional lives lost would rise to 1,231, and the number of life-years lost would reach 22,635.
“Substantial additional deaths from diagnostic delays on top of those expected from delays in presentation – because many people are simply too afraid to visit their GP or hospital – are likely, especially if rapid provision of additional capacity, including technical provision and increased staffing, is not forthcoming,” Turnbull commented in a statement.
The study by Aggarwal and colleagues was funded by the U.K. Research and Innovation Economic and Social Research Council. Several of the researchers were supported by Cancer Research UK and Breast Cancer Now. Turnbull reports receiving support from the Movember Foundation.
This article first appeared on Medscape.com.
Delays in cancer referrals caused by the COVID-19 pandemic and the ensuing shutdown in cancer services will lead to thousands of additional deaths and tens of thousands of life-years lost, suggest two new modeling studies from the United Kingdom.
Clearing the backlog in cancer diagnoses will require a coordinated effort from the government and the National Health Service (NHS), say the authors, inasmuch as services were already running at “full capacity” before the pandemic.
Both studies were published in The Lancet Oncology on July 20.
When the UK-wide lockdown to combat the COVID-19 pandemic was implemented on March 23, cancer screening and routine outpatient referrals in the NHS were suspended, and treatment of cancer patients either halted or slowed down.
Moreover, because of physical distancing measures, which are expected to continue for up to a year, urgent 3-week referrals for suspected cancer cases have fallen by as much as 80%.
To estimate the potential impact on cancer deaths, Ajay Aggarwal, MD, from the London School of Hygiene and Tropical Medicine, United Kingdom, and colleagues conducted a population-based modeling study.
They collected data on 32,583 patients with breast cancer, 24,975 with colorectal cancer, 6744 with esophageal cancer, and 29,305 with lung cancer. Patients were diagnosed between 2010 and 2012 and were followed to 2015.
The investigators used that data to estimate the impact of diagnostic delays resulting from 12 months of physical distancing.
For breast cancer, this would lead to a 7.9%-9.6% increase in the number of cancer deaths within 5 years after diagnosis, or to 281-344 additional deaths.
For colorectal cancer, there would be a 15.3%-16.7% increase in mortality over 5 years, or an additional 1,445-1,563 deaths.
For lung cancer, there would a 4.8%-5.3% increase in mortality, or an additional 1235-1372 deaths.
For esophageal cancer, the mortality increase over 5 years would be 5.8%-6.0%, leading to 330-342 additional deaths.
Across the four tumor types, 59,204-63,229 life-years would be lost because of physical distancing compared to the prepandemic era.
Resources need to be increased
These additional deaths are not inevitable, the researchers suggest.
To prevent the increase in colorectal cancer deaths, for example, Aggarwal said, “It is vital that more resources are made urgently available for endoscopy and colonoscopy services, which are managing significant backlogs currently.
“Whilst currently attention is being focused on diagnostic pathways where cancer is suspected, the issue is that a significant number of cancers are diagnosed in patients awaiting investigation for symptoms not considered related to be cancer,” he added in a statement.
“Therefore we need a whole system approach to avoid the predicted excess deaths.”
Coauthor Bernard Rachet, PhD, also from the London School of Hygiene and Tropical Medicine, added that “to absorb the cancer patient backlog, the healthcare community also needs to establish clear criteria to prioritise patients on clinical grounds, in order to maintain equitability in care delivery.”
It will not be easy “to pin down the exact number of additional cancer deaths we expect to see over the coming years, but studies like this help us to understand the devastating long-term effect a pandemic like COVID-19 will have on the lives of thousands of cancer patients,” commented Michelle Mitchell, chief executive of Cancer Research UK.
Underlining the “enormous backlog” of cancer care that has built up during the pandemic, she said: “Diagnosing and treating people swiftly is vital to give people with cancer the greatest chances of survival.
“The government must work closely with the NHS to ensure it has sufficient staff and equipment to clear the backlog while giving patients the care that they need, quickly and safely,” Mitchell added.
Increasing resources will not be easy. In an accompanying editorial, William Hamilton, MD, PhD, University of Exeter, United Kingdom, warns that many NHS imaging departments, for example, were “working at full capacity before the COVID-19 pandemic.”
Consequently, they “might not be able to meet the increase in demand” resulting from the backlog in patients, especially as “the need to keep patients separate and to clean equipment has reduced their efficiency.
“The UK has had a long-term shortage of diagnostic capacity, although this shortage is not simply of equipment, but also of personnel, which is not so easily improved,” he cautions.
Another study, similar estimates
For the second study, Clare Turnbull, PhD, Institute of Cancer Research, London, and colleagues obtained age- and stage-stratified 10-year cancer survival estimates for patients in England diagnosed with 20 common tumor types between 2008 and 2017.
They also gathered data on cancer diagnoses made via urgent 2-week referrals between 2013 and 2016. They estimate that 6,281 patients were diagnosed with cancer of stages I-III per month.
Of those, 1,691 (27%) would die within 10 years of their diagnosis, they found.
They then calculated that delays in 2-week referrals during a 3-month lockdown would lead to an average delay in presentation of 2 months per patient.
A resulting 25% backlog in referrals would lead to 181 additional lives and 3,316 life-years lost. With a 75% backlog in referrals, an additional 276 lives and 5,075 life-years would be lost.
The team says that additional diagnostic delays spread over 3-8 months after the lockdown could increase the impact of a 25% backlog in referrals to 401 additional lives and 14,873 life-years lost.
For a 75% backlog in referrals, the additional lives lost would rise to 1,231, and the number of life-years lost would reach 22,635.
“Substantial additional deaths from diagnostic delays on top of those expected from delays in presentation – because many people are simply too afraid to visit their GP or hospital – are likely, especially if rapid provision of additional capacity, including technical provision and increased staffing, is not forthcoming,” Turnbull commented in a statement.
The study by Aggarwal and colleagues was funded by the U.K. Research and Innovation Economic and Social Research Council. Several of the researchers were supported by Cancer Research UK and Breast Cancer Now. Turnbull reports receiving support from the Movember Foundation.
This article first appeared on Medscape.com.
No ‘tidal wave’ of new mental illness; pandemic exacerbates preexisting conditions
The COVID-19 pandemic and resulting lockdown are associated with increased depression and lower levels of life satisfaction – but primarily in specific demographic and socioeconomic groups, new research shows.
A survey of more than 72,000 individuals in the United Kingdom shows that young adults, Interestingly, anxiety increased during the lead-up to the lockdown for the overall group but decreased during the lockdown itself.
A second survey showed that the pandemic triggered poorer mental health among more than 1,400 patients with mental illness or their caregivers. However, individuals found ways of coping despite the increased stress.
Commenting on the findings, David Spiegel, MD, professor and associate chair of psychiatry and behavioral sciences and director of the Center on Stress and Health at Stanford (Calif.) University, noted that expectations of a “tidal wave” of mental health problems during the pandemic may have been wide of the mark.
Instead, the pandemic seems to have caused “an exacerbation” of preexisting mental health conditions, Dr. Spiegel said in an interview.
The studies were presented during a dedicated session at the European Psychiatric Association 2020 Congress, which was virtual this year because of COVID-19.
Underrepresented groups
The first presentation was given by Daisy Fancourt, PhD, associate professor of psychobiology and epidemiology, University College London. She described the COVID-19 Social Study, which included more than 72,000 individuals.
Participants were recruited via research databases, media communications, and “more targeted sampling at underrepresented groups, including people from low educational backgrounds and low-income households,” Dr. Fancourt noted.
The respondents took part in the study once a week. This resulted in more than 500,000 completed surveys at a rate of between 3,000 and 6,000 responses per day. Sixteen weeks of data have been gathered so far.
The samples were weighted so they “aligned with population proportions in the U.K. for demographic factors such as age, ethnicity, gender, geographical location, and educational attainment,” said Dr. Fancourt.
Results showed that mental health decreased in the lead-up to lockdown, with decreases in happiness and increases in fear, stress, and sadness.
At the start of lockdown, approximately 60% of people reported that they were stressed about COVID-19 itself, whether catching it or becoming seriously ill. During lockdown, there was little change in levels of depression, but anxiety decreased and life satisfaction increased during this period.
‘We’re not all in this together’
The lower stress level wasn’t surprising, “because people were at home much more. But what is particularly surprising is that it’s continued to drop even though lockdown easing has now been taking place for a number of weeks,” Dr. Fancourt said.
“A big question is: Has mental health been equally affected across this period? And our data seem to suggest that’s very much not the case,” she added.
After assessing different demographic and socioeconomic groups, the investigators found that participants aged 18-29 years had much higher levels of anxiety, depression, and thoughts of death or self-harm and much lower levels of life satisfaction than older participants.
A similar pattern was found for lower-income groups in comparison with those earning more and for individuals in Black, Asian, and minority ethnic groups, compared with White individuals.
For patients who had been diagnosed with a mental illness, levels of depression, anxiety, and thoughts of death or self-harm, as well as life satisfaction, generally ran parallel to those of the general population, although at a far worse level.
Overall, the results suggest that “we’ve not all been ‘in this together,’ as we heard in some of the media,” Dr. Fancourt said. “In fact, it’s been a very different experience, depending on people’s demographic and socioeconomic characteristics.”
Increased loneliness, economic worry
Further analysis into loneliness showed that twice as many respondents described themselves as lonely during the COVID-19 pandemic in comparison with beforehand (18.3% vs. 8.5%).
There was very little improvement in loneliness across the study period, “so whilst it might be higher than normal, we’ve not really seen any reduction, even when there’s been easing of lockdown,” Dr. Fancourt said.
A possible reason could be that some of the most lonely respondents were not able to come out of lockdown because of being in a higher-risk group, she noted.
As with the main findings, loneliness during the pandemic was worse for younger adults as well as for those of low income, those who lived alone, and those who had a mental illness.
The researchers assessed lower socioeconomic position (SEP), which was defined by several indicators: annual household income less than £30,000 (about $38,000), high school or lower education, being unemployed, renting instead of owning one’s own home, or living in overcrowded accommodations
During the COVID-19 epidemic, having a lower SEP was associated with a 50%-100% increased risk of losing work in comparison with having a higher SEP. There was also a 300% increased risk of being unable to pay bills and a 600%-800% increased risk of not being able to access essentials, such as medication or sufficient food.
Interestingly, worrying about potential adversities during the pandemic had a similar impact on anxiety and depression. “In other words, worrying about what might be about to happen seems to be as bad for mental health as those things actually happening,” Dr. Fancourt said.
The majority of participants did not feel in control of their future plans and felt more out of control of their employment and mental health than they did their physical health.
Individuals aged 18-29 years felt least in control over finances, relationships, future plans, and mental health. Those aged 60 years or older were the most likely to report feeling in control on all measures.
Puzzling results
Dr. Spiegel described the results as “a little puzzling in some ways.” He noted that the easing of discomfort that participants felt during lockdown suggests that the idea of a lockdown being a terrible thing “is not necessarily the case.”
“People realize that their lives and lifestyles are being threatened, and it can be actually comforting to be doing something, even if what you’re doing is rather uncomfortable and disruptive of life,” said Dr. Spiegel, who was not involved with the research.
The lockdown may have led people “to think a little more deeply about what matters to them in life,” he added.
A big message from the study is that “the most anxious and depressed were young people in their late teens to late 20s,” Dr. Spiegel noted. That’s when individuals are most sociable, when they form their own social networks, and when they look for partners.
“What’s a little scarier is they also had higher levels of thoughts of death and self-harm and less life satisfaction. So I think the consequences of social disruption were most profound in this study for people for whom social life is the most important,” said Dr. Spiegel.
However, Roxane Cohen Silver, PhD, professor of psychological science, medicine, and public health, University of California, Irvine, noted that, despite the large number of participants, the study’s methodology left many questions unanswered.
She explained that to make sound public policy recommendations, “one needs to pay a great deal of attention to the methods that are used in collecting those data.” From the available information, the degree to which the sample is representative and the participation rate are unclear, which leaves the study open to selection bias, despite the weighting the researchers performed to generate the results.
“The methodological soundness of the studies on the mental health effect of COVID are just as important, I believe, as they are when we’re trying to understand the effect of treatment or a drug,” Dr. Cohen Silver said.
Relief during the pandemic?
The second presentation was given by Sara Simblett, PhD, department of psychology, King’s College London, who described the Coronavirus Outbreak Psychological Experiences study.
This was a two-part investigation in which 31 semistructured interviews with users of mental health services and carers formed the basis of a qualitative survey. It examined the impact of the pandemic on thoughts, emotions, behaviors, and life situations.
The survey was advertised via social media and mental health charities, yielding a total of 1,402 responses. These included responses from 968 individuals who had experience of a mental health condition. Of these, 266 were currently using mental health services, and 189 were informal carers.
Of those, 46.8% met the case threshold for anxiety, 40.3% met the threshold for depression, and 45.3% were determined to have “low resilience.”
The COVID-19 pandemic triggered poorer mental health in the majority of respondents, at 60.8% among those with a preexisting mental health condition and 64.1% among informal carers.
This was reflected in 95.3% of respondents saying that things were uncertain, 81.3% saying they felt restricted by the pandemic, and 71.9% saying that their day was less structured.
However, the survey also revealed that 79.8% felt relieved during the pandemic, 82.1% said that their memory was “much better,” and 62.9% found it easier to concentrate and make plans.
In addition, many people turned to coping mechanisms; 74.7% looked to religion and spirituality as a source of support, and 64.2% used health and wellness apps.
The COVID-19 Social Study is funded by the Wellcome Trust and the Nuffield Foundation. The Coronavirus Outbreak Psychological Experiences study is a collaboration with the McPin Foundation. The investigators and commentators reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The COVID-19 pandemic and resulting lockdown are associated with increased depression and lower levels of life satisfaction – but primarily in specific demographic and socioeconomic groups, new research shows.
A survey of more than 72,000 individuals in the United Kingdom shows that young adults, Interestingly, anxiety increased during the lead-up to the lockdown for the overall group but decreased during the lockdown itself.
A second survey showed that the pandemic triggered poorer mental health among more than 1,400 patients with mental illness or their caregivers. However, individuals found ways of coping despite the increased stress.
Commenting on the findings, David Spiegel, MD, professor and associate chair of psychiatry and behavioral sciences and director of the Center on Stress and Health at Stanford (Calif.) University, noted that expectations of a “tidal wave” of mental health problems during the pandemic may have been wide of the mark.
Instead, the pandemic seems to have caused “an exacerbation” of preexisting mental health conditions, Dr. Spiegel said in an interview.
The studies were presented during a dedicated session at the European Psychiatric Association 2020 Congress, which was virtual this year because of COVID-19.
Underrepresented groups
The first presentation was given by Daisy Fancourt, PhD, associate professor of psychobiology and epidemiology, University College London. She described the COVID-19 Social Study, which included more than 72,000 individuals.
Participants were recruited via research databases, media communications, and “more targeted sampling at underrepresented groups, including people from low educational backgrounds and low-income households,” Dr. Fancourt noted.
The respondents took part in the study once a week. This resulted in more than 500,000 completed surveys at a rate of between 3,000 and 6,000 responses per day. Sixteen weeks of data have been gathered so far.
The samples were weighted so they “aligned with population proportions in the U.K. for demographic factors such as age, ethnicity, gender, geographical location, and educational attainment,” said Dr. Fancourt.
Results showed that mental health decreased in the lead-up to lockdown, with decreases in happiness and increases in fear, stress, and sadness.
At the start of lockdown, approximately 60% of people reported that they were stressed about COVID-19 itself, whether catching it or becoming seriously ill. During lockdown, there was little change in levels of depression, but anxiety decreased and life satisfaction increased during this period.
‘We’re not all in this together’
The lower stress level wasn’t surprising, “because people were at home much more. But what is particularly surprising is that it’s continued to drop even though lockdown easing has now been taking place for a number of weeks,” Dr. Fancourt said.
“A big question is: Has mental health been equally affected across this period? And our data seem to suggest that’s very much not the case,” she added.
After assessing different demographic and socioeconomic groups, the investigators found that participants aged 18-29 years had much higher levels of anxiety, depression, and thoughts of death or self-harm and much lower levels of life satisfaction than older participants.
A similar pattern was found for lower-income groups in comparison with those earning more and for individuals in Black, Asian, and minority ethnic groups, compared with White individuals.
For patients who had been diagnosed with a mental illness, levels of depression, anxiety, and thoughts of death or self-harm, as well as life satisfaction, generally ran parallel to those of the general population, although at a far worse level.
Overall, the results suggest that “we’ve not all been ‘in this together,’ as we heard in some of the media,” Dr. Fancourt said. “In fact, it’s been a very different experience, depending on people’s demographic and socioeconomic characteristics.”
Increased loneliness, economic worry
Further analysis into loneliness showed that twice as many respondents described themselves as lonely during the COVID-19 pandemic in comparison with beforehand (18.3% vs. 8.5%).
There was very little improvement in loneliness across the study period, “so whilst it might be higher than normal, we’ve not really seen any reduction, even when there’s been easing of lockdown,” Dr. Fancourt said.
A possible reason could be that some of the most lonely respondents were not able to come out of lockdown because of being in a higher-risk group, she noted.
As with the main findings, loneliness during the pandemic was worse for younger adults as well as for those of low income, those who lived alone, and those who had a mental illness.
The researchers assessed lower socioeconomic position (SEP), which was defined by several indicators: annual household income less than £30,000 (about $38,000), high school or lower education, being unemployed, renting instead of owning one’s own home, or living in overcrowded accommodations
During the COVID-19 epidemic, having a lower SEP was associated with a 50%-100% increased risk of losing work in comparison with having a higher SEP. There was also a 300% increased risk of being unable to pay bills and a 600%-800% increased risk of not being able to access essentials, such as medication or sufficient food.
Interestingly, worrying about potential adversities during the pandemic had a similar impact on anxiety and depression. “In other words, worrying about what might be about to happen seems to be as bad for mental health as those things actually happening,” Dr. Fancourt said.
The majority of participants did not feel in control of their future plans and felt more out of control of their employment and mental health than they did their physical health.
Individuals aged 18-29 years felt least in control over finances, relationships, future plans, and mental health. Those aged 60 years or older were the most likely to report feeling in control on all measures.
Puzzling results
Dr. Spiegel described the results as “a little puzzling in some ways.” He noted that the easing of discomfort that participants felt during lockdown suggests that the idea of a lockdown being a terrible thing “is not necessarily the case.”
“People realize that their lives and lifestyles are being threatened, and it can be actually comforting to be doing something, even if what you’re doing is rather uncomfortable and disruptive of life,” said Dr. Spiegel, who was not involved with the research.
The lockdown may have led people “to think a little more deeply about what matters to them in life,” he added.
A big message from the study is that “the most anxious and depressed were young people in their late teens to late 20s,” Dr. Spiegel noted. That’s when individuals are most sociable, when they form their own social networks, and when they look for partners.
“What’s a little scarier is they also had higher levels of thoughts of death and self-harm and less life satisfaction. So I think the consequences of social disruption were most profound in this study for people for whom social life is the most important,” said Dr. Spiegel.
However, Roxane Cohen Silver, PhD, professor of psychological science, medicine, and public health, University of California, Irvine, noted that, despite the large number of participants, the study’s methodology left many questions unanswered.
She explained that to make sound public policy recommendations, “one needs to pay a great deal of attention to the methods that are used in collecting those data.” From the available information, the degree to which the sample is representative and the participation rate are unclear, which leaves the study open to selection bias, despite the weighting the researchers performed to generate the results.
“The methodological soundness of the studies on the mental health effect of COVID are just as important, I believe, as they are when we’re trying to understand the effect of treatment or a drug,” Dr. Cohen Silver said.
Relief during the pandemic?
The second presentation was given by Sara Simblett, PhD, department of psychology, King’s College London, who described the Coronavirus Outbreak Psychological Experiences study.
This was a two-part investigation in which 31 semistructured interviews with users of mental health services and carers formed the basis of a qualitative survey. It examined the impact of the pandemic on thoughts, emotions, behaviors, and life situations.
The survey was advertised via social media and mental health charities, yielding a total of 1,402 responses. These included responses from 968 individuals who had experience of a mental health condition. Of these, 266 were currently using mental health services, and 189 were informal carers.
Of those, 46.8% met the case threshold for anxiety, 40.3% met the threshold for depression, and 45.3% were determined to have “low resilience.”
The COVID-19 pandemic triggered poorer mental health in the majority of respondents, at 60.8% among those with a preexisting mental health condition and 64.1% among informal carers.
This was reflected in 95.3% of respondents saying that things were uncertain, 81.3% saying they felt restricted by the pandemic, and 71.9% saying that their day was less structured.
However, the survey also revealed that 79.8% felt relieved during the pandemic, 82.1% said that their memory was “much better,” and 62.9% found it easier to concentrate and make plans.
In addition, many people turned to coping mechanisms; 74.7% looked to religion and spirituality as a source of support, and 64.2% used health and wellness apps.
The COVID-19 Social Study is funded by the Wellcome Trust and the Nuffield Foundation. The Coronavirus Outbreak Psychological Experiences study is a collaboration with the McPin Foundation. The investigators and commentators reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The COVID-19 pandemic and resulting lockdown are associated with increased depression and lower levels of life satisfaction – but primarily in specific demographic and socioeconomic groups, new research shows.
A survey of more than 72,000 individuals in the United Kingdom shows that young adults, Interestingly, anxiety increased during the lead-up to the lockdown for the overall group but decreased during the lockdown itself.
A second survey showed that the pandemic triggered poorer mental health among more than 1,400 patients with mental illness or their caregivers. However, individuals found ways of coping despite the increased stress.
Commenting on the findings, David Spiegel, MD, professor and associate chair of psychiatry and behavioral sciences and director of the Center on Stress and Health at Stanford (Calif.) University, noted that expectations of a “tidal wave” of mental health problems during the pandemic may have been wide of the mark.
Instead, the pandemic seems to have caused “an exacerbation” of preexisting mental health conditions, Dr. Spiegel said in an interview.
The studies were presented during a dedicated session at the European Psychiatric Association 2020 Congress, which was virtual this year because of COVID-19.
Underrepresented groups
The first presentation was given by Daisy Fancourt, PhD, associate professor of psychobiology and epidemiology, University College London. She described the COVID-19 Social Study, which included more than 72,000 individuals.
Participants were recruited via research databases, media communications, and “more targeted sampling at underrepresented groups, including people from low educational backgrounds and low-income households,” Dr. Fancourt noted.
The respondents took part in the study once a week. This resulted in more than 500,000 completed surveys at a rate of between 3,000 and 6,000 responses per day. Sixteen weeks of data have been gathered so far.
The samples were weighted so they “aligned with population proportions in the U.K. for demographic factors such as age, ethnicity, gender, geographical location, and educational attainment,” said Dr. Fancourt.
Results showed that mental health decreased in the lead-up to lockdown, with decreases in happiness and increases in fear, stress, and sadness.
At the start of lockdown, approximately 60% of people reported that they were stressed about COVID-19 itself, whether catching it or becoming seriously ill. During lockdown, there was little change in levels of depression, but anxiety decreased and life satisfaction increased during this period.
‘We’re not all in this together’
The lower stress level wasn’t surprising, “because people were at home much more. But what is particularly surprising is that it’s continued to drop even though lockdown easing has now been taking place for a number of weeks,” Dr. Fancourt said.
“A big question is: Has mental health been equally affected across this period? And our data seem to suggest that’s very much not the case,” she added.
After assessing different demographic and socioeconomic groups, the investigators found that participants aged 18-29 years had much higher levels of anxiety, depression, and thoughts of death or self-harm and much lower levels of life satisfaction than older participants.
A similar pattern was found for lower-income groups in comparison with those earning more and for individuals in Black, Asian, and minority ethnic groups, compared with White individuals.
For patients who had been diagnosed with a mental illness, levels of depression, anxiety, and thoughts of death or self-harm, as well as life satisfaction, generally ran parallel to those of the general population, although at a far worse level.
Overall, the results suggest that “we’ve not all been ‘in this together,’ as we heard in some of the media,” Dr. Fancourt said. “In fact, it’s been a very different experience, depending on people’s demographic and socioeconomic characteristics.”
Increased loneliness, economic worry
Further analysis into loneliness showed that twice as many respondents described themselves as lonely during the COVID-19 pandemic in comparison with beforehand (18.3% vs. 8.5%).
There was very little improvement in loneliness across the study period, “so whilst it might be higher than normal, we’ve not really seen any reduction, even when there’s been easing of lockdown,” Dr. Fancourt said.
A possible reason could be that some of the most lonely respondents were not able to come out of lockdown because of being in a higher-risk group, she noted.
As with the main findings, loneliness during the pandemic was worse for younger adults as well as for those of low income, those who lived alone, and those who had a mental illness.
The researchers assessed lower socioeconomic position (SEP), which was defined by several indicators: annual household income less than £30,000 (about $38,000), high school or lower education, being unemployed, renting instead of owning one’s own home, or living in overcrowded accommodations
During the COVID-19 epidemic, having a lower SEP was associated with a 50%-100% increased risk of losing work in comparison with having a higher SEP. There was also a 300% increased risk of being unable to pay bills and a 600%-800% increased risk of not being able to access essentials, such as medication or sufficient food.
Interestingly, worrying about potential adversities during the pandemic had a similar impact on anxiety and depression. “In other words, worrying about what might be about to happen seems to be as bad for mental health as those things actually happening,” Dr. Fancourt said.
The majority of participants did not feel in control of their future plans and felt more out of control of their employment and mental health than they did their physical health.
Individuals aged 18-29 years felt least in control over finances, relationships, future plans, and mental health. Those aged 60 years or older were the most likely to report feeling in control on all measures.
Puzzling results
Dr. Spiegel described the results as “a little puzzling in some ways.” He noted that the easing of discomfort that participants felt during lockdown suggests that the idea of a lockdown being a terrible thing “is not necessarily the case.”
“People realize that their lives and lifestyles are being threatened, and it can be actually comforting to be doing something, even if what you’re doing is rather uncomfortable and disruptive of life,” said Dr. Spiegel, who was not involved with the research.
The lockdown may have led people “to think a little more deeply about what matters to them in life,” he added.
A big message from the study is that “the most anxious and depressed were young people in their late teens to late 20s,” Dr. Spiegel noted. That’s when individuals are most sociable, when they form their own social networks, and when they look for partners.
“What’s a little scarier is they also had higher levels of thoughts of death and self-harm and less life satisfaction. So I think the consequences of social disruption were most profound in this study for people for whom social life is the most important,” said Dr. Spiegel.
However, Roxane Cohen Silver, PhD, professor of psychological science, medicine, and public health, University of California, Irvine, noted that, despite the large number of participants, the study’s methodology left many questions unanswered.
She explained that to make sound public policy recommendations, “one needs to pay a great deal of attention to the methods that are used in collecting those data.” From the available information, the degree to which the sample is representative and the participation rate are unclear, which leaves the study open to selection bias, despite the weighting the researchers performed to generate the results.
“The methodological soundness of the studies on the mental health effect of COVID are just as important, I believe, as they are when we’re trying to understand the effect of treatment or a drug,” Dr. Cohen Silver said.
Relief during the pandemic?
The second presentation was given by Sara Simblett, PhD, department of psychology, King’s College London, who described the Coronavirus Outbreak Psychological Experiences study.
This was a two-part investigation in which 31 semistructured interviews with users of mental health services and carers formed the basis of a qualitative survey. It examined the impact of the pandemic on thoughts, emotions, behaviors, and life situations.
The survey was advertised via social media and mental health charities, yielding a total of 1,402 responses. These included responses from 968 individuals who had experience of a mental health condition. Of these, 266 were currently using mental health services, and 189 were informal carers.
Of those, 46.8% met the case threshold for anxiety, 40.3% met the threshold for depression, and 45.3% were determined to have “low resilience.”
The COVID-19 pandemic triggered poorer mental health in the majority of respondents, at 60.8% among those with a preexisting mental health condition and 64.1% among informal carers.
This was reflected in 95.3% of respondents saying that things were uncertain, 81.3% saying they felt restricted by the pandemic, and 71.9% saying that their day was less structured.
However, the survey also revealed that 79.8% felt relieved during the pandemic, 82.1% said that their memory was “much better,” and 62.9% found it easier to concentrate and make plans.
In addition, many people turned to coping mechanisms; 74.7% looked to religion and spirituality as a source of support, and 64.2% used health and wellness apps.
The COVID-19 Social Study is funded by the Wellcome Trust and the Nuffield Foundation. The Coronavirus Outbreak Psychological Experiences study is a collaboration with the McPin Foundation. The investigators and commentators reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM EPA 2020
ECT more effective for psychotic vs. nonpsychotic depression?
For patients with psychotic depression, response to treatment, remission rates, and cognitive improvement are better following electroconvulsive therapy (ECT) than for patients with nonpsychotic depression, results from a new study suggest.
However, findings from another study suggest that at least some of these differences may be because psychotic patients are referred for ECT earlier in the disease course.
Both studies were presented at the European Psychiatric Association 2020 Congress, which was held online this year because of the COVID-19 pandemic.
Limited, old evidence
The first study was led by Christopher Yi Wen Chan, MD, Institute of Mental Health, Singapore. The investigators stated that they have “often observed” superior remission rates with ECT in psychotic versus nonpsychotic depression. However, the evidence base is “limited and mostly more than 10 years old.”
They conducted a retrospective case-control study that included 160 patients – 50 with psychotic depression, and 110 with nonpsychotic depression. All patients had a primary diagnosis of unipolar major depressive disorder and underwent ECT at a tertiary psychiatric institute between January 2016 and January 2018.
Baseline characteristics of the two groups were similar, although patients with psychosis were more likely to have had an involuntary hospital admission and to have had higher baseline scores on the Montreal Cognitive Assessment (MoCA) and Clinical Global Impression–Severity scale (CGI-S) than nonpsychotic patients.
Response rates to ECT were significantly higher for the patients with psychotic depression than for those with nonpsychotic depression (79% vs. 51%; P = .009), as were remission rates (71% vs. 36%; P = .001).
Both groups showed significant improvement following ECT in Montgomery-Åsberg Depression Rating Scale, CGI, and quality-of-life scores.
However, only the participants with psychotic depression showed a significant improvement in MoCA total score (P = .038), as well as on attention (P = .024), language (P = .008), and orientation (P = .021) subdomains.
Psychotic depression markers?
For the second study, a team led by Aida De Arriba Arnau, MD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, retrospectively analyzed 66 patients with depression who had received ECT. Of these, 26 had psychotic depression, and 40 had nonpsychotic depression.
Response rates were again higher in patients with psychotic vs nonpsychotic depression (92.3% vs. 85.0%). A similar number of sessions was needed to achieve a response.
Improvements in Hamilton Depression Rating Scale scores were significant between the two groups from the start of treatment, although the difference became nonsignificant at week 6.
Arriba Arnau said that there were some notable differences between patients with psychotic depression and those with nonpsychotic depression. For example, the former had “poor functionality, shorter episode duration, and less pharmacological resistance before receiving ECT,” she said.
“So we hypothesized that they might be referred more promptly to ECT treatment,” she added.
The psychotic depression group was significantly older than the group with nonpsychotic depression, at an average of 67.81 years vs 58.96 years.
They also “showed more illness severity and cognitive disturbances at baseline and ... required less anesthetic doses and higher initial stimulus intensity,» Arriba Arnau noted.
“All these features could be the markers of psychotic depression as an entity,” she said. However, the potential impact of age on these differences should be “further studied.”
She added that other aspects, such as age at onset and number of previous episodes, were similar between the groups.
Confirmatory data
Commenting on the findings for Medscape Medical News, Georgios Petrides, MD, associate professor of psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, East Garden City, New York, noted that differences in response to ECT between patients with psychotic depression and those with nonpsychotic depression are “well known.”
However, “it’s actually good to present more data that confirm what people are doing in clinical practice,” said Petrides, who was not involved with the research.
Petrides noted that some guidelines recommend ECT as first-line treatment for psychotic depression.
“For nonpsychotic depression, we’d try medications, psychotherapy, and everything else first,” he said. He noted that the current results are “a good replication of what is known so far.”
As to why ECT should be more effective for patients with psychotic depression, he said, “A lot of people think that the biology of psychotic depression is different from the biology of nonpsychotic depression.”
Petrides added.
That ECT is more effective in psychotic depression is an “indirect point of evidence” to support that theory.
One aspect that has traditionally dogged the use of ECT has been the stigma that surrounds the procedure, Petrides noted. That’s “always an issue, but it’s getting less and less over time,” he said.
He added that ECT is extremely safe and that it is associated with the “lowest mortality for any procedure performed under general anesthesia,” which helps to reduce the stigma around it, he noted.
The study authors and Petrides have reported no relevant financial relationships.
This article first appeared on Medscape.com.
For patients with psychotic depression, response to treatment, remission rates, and cognitive improvement are better following electroconvulsive therapy (ECT) than for patients with nonpsychotic depression, results from a new study suggest.
However, findings from another study suggest that at least some of these differences may be because psychotic patients are referred for ECT earlier in the disease course.
Both studies were presented at the European Psychiatric Association 2020 Congress, which was held online this year because of the COVID-19 pandemic.
Limited, old evidence
The first study was led by Christopher Yi Wen Chan, MD, Institute of Mental Health, Singapore. The investigators stated that they have “often observed” superior remission rates with ECT in psychotic versus nonpsychotic depression. However, the evidence base is “limited and mostly more than 10 years old.”
They conducted a retrospective case-control study that included 160 patients – 50 with psychotic depression, and 110 with nonpsychotic depression. All patients had a primary diagnosis of unipolar major depressive disorder and underwent ECT at a tertiary psychiatric institute between January 2016 and January 2018.
Baseline characteristics of the two groups were similar, although patients with psychosis were more likely to have had an involuntary hospital admission and to have had higher baseline scores on the Montreal Cognitive Assessment (MoCA) and Clinical Global Impression–Severity scale (CGI-S) than nonpsychotic patients.
Response rates to ECT were significantly higher for the patients with psychotic depression than for those with nonpsychotic depression (79% vs. 51%; P = .009), as were remission rates (71% vs. 36%; P = .001).
Both groups showed significant improvement following ECT in Montgomery-Åsberg Depression Rating Scale, CGI, and quality-of-life scores.
However, only the participants with psychotic depression showed a significant improvement in MoCA total score (P = .038), as well as on attention (P = .024), language (P = .008), and orientation (P = .021) subdomains.
Psychotic depression markers?
For the second study, a team led by Aida De Arriba Arnau, MD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, retrospectively analyzed 66 patients with depression who had received ECT. Of these, 26 had psychotic depression, and 40 had nonpsychotic depression.
Response rates were again higher in patients with psychotic vs nonpsychotic depression (92.3% vs. 85.0%). A similar number of sessions was needed to achieve a response.
Improvements in Hamilton Depression Rating Scale scores were significant between the two groups from the start of treatment, although the difference became nonsignificant at week 6.
Arriba Arnau said that there were some notable differences between patients with psychotic depression and those with nonpsychotic depression. For example, the former had “poor functionality, shorter episode duration, and less pharmacological resistance before receiving ECT,” she said.
“So we hypothesized that they might be referred more promptly to ECT treatment,” she added.
The psychotic depression group was significantly older than the group with nonpsychotic depression, at an average of 67.81 years vs 58.96 years.
They also “showed more illness severity and cognitive disturbances at baseline and ... required less anesthetic doses and higher initial stimulus intensity,» Arriba Arnau noted.
“All these features could be the markers of psychotic depression as an entity,” she said. However, the potential impact of age on these differences should be “further studied.”
She added that other aspects, such as age at onset and number of previous episodes, were similar between the groups.
Confirmatory data
Commenting on the findings for Medscape Medical News, Georgios Petrides, MD, associate professor of psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, East Garden City, New York, noted that differences in response to ECT between patients with psychotic depression and those with nonpsychotic depression are “well known.”
However, “it’s actually good to present more data that confirm what people are doing in clinical practice,” said Petrides, who was not involved with the research.
Petrides noted that some guidelines recommend ECT as first-line treatment for psychotic depression.
“For nonpsychotic depression, we’d try medications, psychotherapy, and everything else first,” he said. He noted that the current results are “a good replication of what is known so far.”
As to why ECT should be more effective for patients with psychotic depression, he said, “A lot of people think that the biology of psychotic depression is different from the biology of nonpsychotic depression.”
Petrides added.
That ECT is more effective in psychotic depression is an “indirect point of evidence” to support that theory.
One aspect that has traditionally dogged the use of ECT has been the stigma that surrounds the procedure, Petrides noted. That’s “always an issue, but it’s getting less and less over time,” he said.
He added that ECT is extremely safe and that it is associated with the “lowest mortality for any procedure performed under general anesthesia,” which helps to reduce the stigma around it, he noted.
The study authors and Petrides have reported no relevant financial relationships.
This article first appeared on Medscape.com.
For patients with psychotic depression, response to treatment, remission rates, and cognitive improvement are better following electroconvulsive therapy (ECT) than for patients with nonpsychotic depression, results from a new study suggest.
However, findings from another study suggest that at least some of these differences may be because psychotic patients are referred for ECT earlier in the disease course.
Both studies were presented at the European Psychiatric Association 2020 Congress, which was held online this year because of the COVID-19 pandemic.
Limited, old evidence
The first study was led by Christopher Yi Wen Chan, MD, Institute of Mental Health, Singapore. The investigators stated that they have “often observed” superior remission rates with ECT in psychotic versus nonpsychotic depression. However, the evidence base is “limited and mostly more than 10 years old.”
They conducted a retrospective case-control study that included 160 patients – 50 with psychotic depression, and 110 with nonpsychotic depression. All patients had a primary diagnosis of unipolar major depressive disorder and underwent ECT at a tertiary psychiatric institute between January 2016 and January 2018.
Baseline characteristics of the two groups were similar, although patients with psychosis were more likely to have had an involuntary hospital admission and to have had higher baseline scores on the Montreal Cognitive Assessment (MoCA) and Clinical Global Impression–Severity scale (CGI-S) than nonpsychotic patients.
Response rates to ECT were significantly higher for the patients with psychotic depression than for those with nonpsychotic depression (79% vs. 51%; P = .009), as were remission rates (71% vs. 36%; P = .001).
Both groups showed significant improvement following ECT in Montgomery-Åsberg Depression Rating Scale, CGI, and quality-of-life scores.
However, only the participants with psychotic depression showed a significant improvement in MoCA total score (P = .038), as well as on attention (P = .024), language (P = .008), and orientation (P = .021) subdomains.
Psychotic depression markers?
For the second study, a team led by Aida De Arriba Arnau, MD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, retrospectively analyzed 66 patients with depression who had received ECT. Of these, 26 had psychotic depression, and 40 had nonpsychotic depression.
Response rates were again higher in patients with psychotic vs nonpsychotic depression (92.3% vs. 85.0%). A similar number of sessions was needed to achieve a response.
Improvements in Hamilton Depression Rating Scale scores were significant between the two groups from the start of treatment, although the difference became nonsignificant at week 6.
Arriba Arnau said that there were some notable differences between patients with psychotic depression and those with nonpsychotic depression. For example, the former had “poor functionality, shorter episode duration, and less pharmacological resistance before receiving ECT,” she said.
“So we hypothesized that they might be referred more promptly to ECT treatment,” she added.
The psychotic depression group was significantly older than the group with nonpsychotic depression, at an average of 67.81 years vs 58.96 years.
They also “showed more illness severity and cognitive disturbances at baseline and ... required less anesthetic doses and higher initial stimulus intensity,» Arriba Arnau noted.
“All these features could be the markers of psychotic depression as an entity,” she said. However, the potential impact of age on these differences should be “further studied.”
She added that other aspects, such as age at onset and number of previous episodes, were similar between the groups.
Confirmatory data
Commenting on the findings for Medscape Medical News, Georgios Petrides, MD, associate professor of psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, East Garden City, New York, noted that differences in response to ECT between patients with psychotic depression and those with nonpsychotic depression are “well known.”
However, “it’s actually good to present more data that confirm what people are doing in clinical practice,” said Petrides, who was not involved with the research.
Petrides noted that some guidelines recommend ECT as first-line treatment for psychotic depression.
“For nonpsychotic depression, we’d try medications, psychotherapy, and everything else first,” he said. He noted that the current results are “a good replication of what is known so far.”
As to why ECT should be more effective for patients with psychotic depression, he said, “A lot of people think that the biology of psychotic depression is different from the biology of nonpsychotic depression.”
Petrides added.
That ECT is more effective in psychotic depression is an “indirect point of evidence” to support that theory.
One aspect that has traditionally dogged the use of ECT has been the stigma that surrounds the procedure, Petrides noted. That’s “always an issue, but it’s getting less and less over time,” he said.
He added that ECT is extremely safe and that it is associated with the “lowest mortality for any procedure performed under general anesthesia,” which helps to reduce the stigma around it, he noted.
The study authors and Petrides have reported no relevant financial relationships.
This article first appeared on Medscape.com.
Device improves physical exam completion rates in serious mental illness
Using a simple point-of-care (POC) finger prick device to measure blood glucose and lipid levels significantly increases rates of physical health checkups for patients with severe mental illness, new research shows.
In a UK pilot study, use of the Afinion 2 device (Abbott) was associated with a doubling of completed physical health checkups.
However, the effect only occurred in early-intervention services, in which clinicians may feel physical health checkups are most beneficial. This underlines the importance of staff training and payment incentives, the researchers note.
“Clearly, convenience is a great thing about these devices” for both the patient and the mental health clinician, Joseph Butler, MD, a psychiatry trainee at the University of Oxford, United Kingdom, told Medscape Medical News.
He noted that blood test results are rapid, which facilitates immediate discussion of a health management plan.
These tests are “independent from the lab, they’re independent from the general practitioner, and so in terms of convenience, we think it wins on both fronts,” Butler said.
The findings were scheduled to be presented at the Congress of the Schizophrenia International Research Society (SIRS) 2020, but the meeting was canceled because of the coronavirus pandemic.
Poor heart health
Previous research has shown that life expectancy of patients with severe mental illness is 15 to 20 years less than that of the general population, mostly because of complications from poor cardiovascular health.
In the United Kingdom, physical healthcare for patients with serious mental illness is provided by primary care clinicians and community mental health teams (CMHTs). The National Institute for Health and Care Excellence recommends an annual physical examination.
However, a recent audit in the south of England indicated that only 38% of patients with severe mental illness underwent complete physical examinations, primarily because blood glucose and lipid test panels had been omitted.
The researchers note that patients are typically advised to visit their general practitioner for blood tests, “which can be a challenge” for those with severe mental illness.
The Cardiovascular Monitoring in Mental Health (CARMEN) project involved distributing the Afinion 2 device for use in two CMHTs in Oxfordshire, United Kingdom, for 6 months. One CMHT was an early-intervention service, and the other was an adult mental health service.
Care coordinators received training on how to use the device as well as ongoing support to facilitate engagement with the device.
Rates of completion of blood testing and full physical examinations were compared between the intervention CMHTs and two matched control services – an early-intervention group, and an adult metal health services group in Buckinghamshire, a neighboring county.
Better completion rates
The investigators found that .
In contrast, the percentage of physical examinations that were completed remained low in the control CMHT early-intervention service, at just 7.8%.
Direct comparison between the two services showed that use of the POC device was associated with a significant increase in the number of complete physical examinations, at a relative rate of 5.18 (P < .001).
Results were similar when the investigators examined rates at which A1c and lipid panels were completed.
However, there was no difference in completion of physical examinations in the adult mental health service group, for which rates were comparable to those in the control service.
Butler speculated that the way health checkups are funded in the United Kingdom might have contributed to the poor results with the device in the adult mental health service.
In early-intervention services, there is increased awareness of the importance of physical examinations, and funding is contingent on whether clinicians persuade patients to have the examinations.
Overall, the findings show that use of a POC device for physical examinations is acceptable to patients who have severe mental illness as well as to mental health care clinicians, the investigators note.
“In teams where it is well adopted, POC testing can improve physical health check completion...although our qualitative findings highlight important considerations for maximizing clinician engagement,” they add.
The researchers plan to repeat the study across the whole of the south of England, with early-intervention services in the west equipped with POC devices and those in the east serving as controls.
Similar findings
Commenting on the findings for Medscape Medical News, Joe Parks, MD, vice president and practice improvement and medical director at the National Council for Behavioral Health, Washington, DC, noted that he and his colleagues conducted a similar study in the mid-2000s.
Starting in 2004, they distributed a POC finger prick test device for use by community mental health teams to measure blood glucose and lipid levels.
“We required as a condition of payment that the providers get these lab results for everybody they served and report them centrally. Then, we databased them and benchmarked them, and we were able to show significant reductions in HbA1c’s over time,” said Parks, who was not involved with the current research.
Moreover, that program achieved corresponding savings of $23 to $24 million, he noted.
Although his study and the current study show that POC devices work, he emphasized that it’s not enough to make the devices available to clinicians.
“You also have to ensure the providers put it in their clinic workflows and use it with everybody. To do that, it really helps if you have the providers report the results, then give them report cards so they can see who’s doing it and who isn’t,” Parks said.
It wasn’t surprising that in the current study, the introduction of the POC device made less of an impact in the adult community services, he noted.
Although weight reduction is much slower in that setting, “you can still get better control of their lipids and HbA1c›s, and you get at their weight over time. You just have to program for that, too,» said Parks.
He added that it’s hard to achieve weight reduction of more than 5% or 10%, but many of these patients need a 25% to 30% reduction. “The only thing that’s going to get that is bariatric surgery,” he noted.
POC devices are not widely used in the United States.
“The payer paying for the care basically has to insist that [it] be used and then provide the machine and train the staff to use it,” Parks said.
It requires payers “to get actually involved in how providers organize and manage care, which they tend to not like to do. It’s silly because the only way any payer has to make anybody better is through the provider,” he noted.
Parks added that to increase uptake beyond the “motivated few” requires that it be made part of the workflow and not left up to clinician discretion.
The study was funded by the National Institute for Health Research. Butler and Parks have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Using a simple point-of-care (POC) finger prick device to measure blood glucose and lipid levels significantly increases rates of physical health checkups for patients with severe mental illness, new research shows.
In a UK pilot study, use of the Afinion 2 device (Abbott) was associated with a doubling of completed physical health checkups.
However, the effect only occurred in early-intervention services, in which clinicians may feel physical health checkups are most beneficial. This underlines the importance of staff training and payment incentives, the researchers note.
“Clearly, convenience is a great thing about these devices” for both the patient and the mental health clinician, Joseph Butler, MD, a psychiatry trainee at the University of Oxford, United Kingdom, told Medscape Medical News.
He noted that blood test results are rapid, which facilitates immediate discussion of a health management plan.
These tests are “independent from the lab, they’re independent from the general practitioner, and so in terms of convenience, we think it wins on both fronts,” Butler said.
The findings were scheduled to be presented at the Congress of the Schizophrenia International Research Society (SIRS) 2020, but the meeting was canceled because of the coronavirus pandemic.
Poor heart health
Previous research has shown that life expectancy of patients with severe mental illness is 15 to 20 years less than that of the general population, mostly because of complications from poor cardiovascular health.
In the United Kingdom, physical healthcare for patients with serious mental illness is provided by primary care clinicians and community mental health teams (CMHTs). The National Institute for Health and Care Excellence recommends an annual physical examination.
However, a recent audit in the south of England indicated that only 38% of patients with severe mental illness underwent complete physical examinations, primarily because blood glucose and lipid test panels had been omitted.
The researchers note that patients are typically advised to visit their general practitioner for blood tests, “which can be a challenge” for those with severe mental illness.
The Cardiovascular Monitoring in Mental Health (CARMEN) project involved distributing the Afinion 2 device for use in two CMHTs in Oxfordshire, United Kingdom, for 6 months. One CMHT was an early-intervention service, and the other was an adult mental health service.
Care coordinators received training on how to use the device as well as ongoing support to facilitate engagement with the device.
Rates of completion of blood testing and full physical examinations were compared between the intervention CMHTs and two matched control services – an early-intervention group, and an adult metal health services group in Buckinghamshire, a neighboring county.
Better completion rates
The investigators found that .
In contrast, the percentage of physical examinations that were completed remained low in the control CMHT early-intervention service, at just 7.8%.
Direct comparison between the two services showed that use of the POC device was associated with a significant increase in the number of complete physical examinations, at a relative rate of 5.18 (P < .001).
Results were similar when the investigators examined rates at which A1c and lipid panels were completed.
However, there was no difference in completion of physical examinations in the adult mental health service group, for which rates were comparable to those in the control service.
Butler speculated that the way health checkups are funded in the United Kingdom might have contributed to the poor results with the device in the adult mental health service.
In early-intervention services, there is increased awareness of the importance of physical examinations, and funding is contingent on whether clinicians persuade patients to have the examinations.
Overall, the findings show that use of a POC device for physical examinations is acceptable to patients who have severe mental illness as well as to mental health care clinicians, the investigators note.
“In teams where it is well adopted, POC testing can improve physical health check completion...although our qualitative findings highlight important considerations for maximizing clinician engagement,” they add.
The researchers plan to repeat the study across the whole of the south of England, with early-intervention services in the west equipped with POC devices and those in the east serving as controls.
Similar findings
Commenting on the findings for Medscape Medical News, Joe Parks, MD, vice president and practice improvement and medical director at the National Council for Behavioral Health, Washington, DC, noted that he and his colleagues conducted a similar study in the mid-2000s.
Starting in 2004, they distributed a POC finger prick test device for use by community mental health teams to measure blood glucose and lipid levels.
“We required as a condition of payment that the providers get these lab results for everybody they served and report them centrally. Then, we databased them and benchmarked them, and we were able to show significant reductions in HbA1c’s over time,” said Parks, who was not involved with the current research.
Moreover, that program achieved corresponding savings of $23 to $24 million, he noted.
Although his study and the current study show that POC devices work, he emphasized that it’s not enough to make the devices available to clinicians.
“You also have to ensure the providers put it in their clinic workflows and use it with everybody. To do that, it really helps if you have the providers report the results, then give them report cards so they can see who’s doing it and who isn’t,” Parks said.
It wasn’t surprising that in the current study, the introduction of the POC device made less of an impact in the adult community services, he noted.
Although weight reduction is much slower in that setting, “you can still get better control of their lipids and HbA1c›s, and you get at their weight over time. You just have to program for that, too,» said Parks.
He added that it’s hard to achieve weight reduction of more than 5% or 10%, but many of these patients need a 25% to 30% reduction. “The only thing that’s going to get that is bariatric surgery,” he noted.
POC devices are not widely used in the United States.
“The payer paying for the care basically has to insist that [it] be used and then provide the machine and train the staff to use it,” Parks said.
It requires payers “to get actually involved in how providers organize and manage care, which they tend to not like to do. It’s silly because the only way any payer has to make anybody better is through the provider,” he noted.
Parks added that to increase uptake beyond the “motivated few” requires that it be made part of the workflow and not left up to clinician discretion.
The study was funded by the National Institute for Health Research. Butler and Parks have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Using a simple point-of-care (POC) finger prick device to measure blood glucose and lipid levels significantly increases rates of physical health checkups for patients with severe mental illness, new research shows.
In a UK pilot study, use of the Afinion 2 device (Abbott) was associated with a doubling of completed physical health checkups.
However, the effect only occurred in early-intervention services, in which clinicians may feel physical health checkups are most beneficial. This underlines the importance of staff training and payment incentives, the researchers note.
“Clearly, convenience is a great thing about these devices” for both the patient and the mental health clinician, Joseph Butler, MD, a psychiatry trainee at the University of Oxford, United Kingdom, told Medscape Medical News.
He noted that blood test results are rapid, which facilitates immediate discussion of a health management plan.
These tests are “independent from the lab, they’re independent from the general practitioner, and so in terms of convenience, we think it wins on both fronts,” Butler said.
The findings were scheduled to be presented at the Congress of the Schizophrenia International Research Society (SIRS) 2020, but the meeting was canceled because of the coronavirus pandemic.
Poor heart health
Previous research has shown that life expectancy of patients with severe mental illness is 15 to 20 years less than that of the general population, mostly because of complications from poor cardiovascular health.
In the United Kingdom, physical healthcare for patients with serious mental illness is provided by primary care clinicians and community mental health teams (CMHTs). The National Institute for Health and Care Excellence recommends an annual physical examination.
However, a recent audit in the south of England indicated that only 38% of patients with severe mental illness underwent complete physical examinations, primarily because blood glucose and lipid test panels had been omitted.
The researchers note that patients are typically advised to visit their general practitioner for blood tests, “which can be a challenge” for those with severe mental illness.
The Cardiovascular Monitoring in Mental Health (CARMEN) project involved distributing the Afinion 2 device for use in two CMHTs in Oxfordshire, United Kingdom, for 6 months. One CMHT was an early-intervention service, and the other was an adult mental health service.
Care coordinators received training on how to use the device as well as ongoing support to facilitate engagement with the device.
Rates of completion of blood testing and full physical examinations were compared between the intervention CMHTs and two matched control services – an early-intervention group, and an adult metal health services group in Buckinghamshire, a neighboring county.
Better completion rates
The investigators found that .
In contrast, the percentage of physical examinations that were completed remained low in the control CMHT early-intervention service, at just 7.8%.
Direct comparison between the two services showed that use of the POC device was associated with a significant increase in the number of complete physical examinations, at a relative rate of 5.18 (P < .001).
Results were similar when the investigators examined rates at which A1c and lipid panels were completed.
However, there was no difference in completion of physical examinations in the adult mental health service group, for which rates were comparable to those in the control service.
Butler speculated that the way health checkups are funded in the United Kingdom might have contributed to the poor results with the device in the adult mental health service.
In early-intervention services, there is increased awareness of the importance of physical examinations, and funding is contingent on whether clinicians persuade patients to have the examinations.
Overall, the findings show that use of a POC device for physical examinations is acceptable to patients who have severe mental illness as well as to mental health care clinicians, the investigators note.
“In teams where it is well adopted, POC testing can improve physical health check completion...although our qualitative findings highlight important considerations for maximizing clinician engagement,” they add.
The researchers plan to repeat the study across the whole of the south of England, with early-intervention services in the west equipped with POC devices and those in the east serving as controls.
Similar findings
Commenting on the findings for Medscape Medical News, Joe Parks, MD, vice president and practice improvement and medical director at the National Council for Behavioral Health, Washington, DC, noted that he and his colleagues conducted a similar study in the mid-2000s.
Starting in 2004, they distributed a POC finger prick test device for use by community mental health teams to measure blood glucose and lipid levels.
“We required as a condition of payment that the providers get these lab results for everybody they served and report them centrally. Then, we databased them and benchmarked them, and we were able to show significant reductions in HbA1c’s over time,” said Parks, who was not involved with the current research.
Moreover, that program achieved corresponding savings of $23 to $24 million, he noted.
Although his study and the current study show that POC devices work, he emphasized that it’s not enough to make the devices available to clinicians.
“You also have to ensure the providers put it in their clinic workflows and use it with everybody. To do that, it really helps if you have the providers report the results, then give them report cards so they can see who’s doing it and who isn’t,” Parks said.
It wasn’t surprising that in the current study, the introduction of the POC device made less of an impact in the adult community services, he noted.
Although weight reduction is much slower in that setting, “you can still get better control of their lipids and HbA1c›s, and you get at their weight over time. You just have to program for that, too,» said Parks.
He added that it’s hard to achieve weight reduction of more than 5% or 10%, but many of these patients need a 25% to 30% reduction. “The only thing that’s going to get that is bariatric surgery,” he noted.
POC devices are not widely used in the United States.
“The payer paying for the care basically has to insist that [it] be used and then provide the machine and train the staff to use it,” Parks said.
It requires payers “to get actually involved in how providers organize and manage care, which they tend to not like to do. It’s silly because the only way any payer has to make anybody better is through the provider,” he noted.
Parks added that to increase uptake beyond the “motivated few” requires that it be made part of the workflow and not left up to clinician discretion.
The study was funded by the National Institute for Health Research. Butler and Parks have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM SIRS 2020
Psychiatry trainees subjected to high levels of physical, sexual, verbal abuse from patients
More than 80% of psychiatric trainees have experienced some kind of verbal, physical, or sexual assault from patients, and approximately one-third have been physically attacked multiple times, new survey results show.
Such incidents, said study investigator Victor Pereira-Sanchez, MD, from the department of child and adolescent psychiatry at New York University take a toll on the trainees’ well-being and may ultimately affect the quality of patient care.
“The extent of violence against psychiatric trainees is alarming and calls for the implementation of effective training, prevention, and intervention measures,” Dr. Pereira-Sanchez said in an interview.
The findings were presented at the European Psychiatric Association (EPA) 2020 Congress, which was virtual this year because of the COVID-19 pandemic.
Widespread problem
Violence against health care professionals is widespread among clinicians in EDs with psychiatry trainees “more exposed and vulnerable,” Dr. Pereira-Sanchez said during his presentation.
In 2017, the European Federation of Psychiatric Trainees established a group of researchers to describe “the extent and consequences of violence against psychiatric trainees in Europe and beyond,” he said. The group developed a 15-item questionnaire asking young clinicians about experiences of physical, sexual, and verbal assault at work. The survey was posted online by partner institutions via social media.
A total of 827 psychiatric trainees, the majority of whom were from France and the United Kingdom, completed the survey. Respondents had an average age of 31 years, and 68% were women. On average, respondents had completed 51.3% of their psychiatric training.
with 92.0% reporting verbal assaults, 44.1% physical assaults, and 9.3% sexual assaults. In addition, 14.2% had been assaulted once, 51.9% had been assaulted two to five times, and 33.9% had been assaulted more than five times during their training. Results also showed that assaults were more likely to occur on an inpatient ward (63.4%) or the ED (56.9%), although 37.2% occurred in an outpatient setting and 4.2% in community settings. The majority of respondents (69.0%) did not report their assaults, and 67.3% did not call police or security personnel.
The most common emotions experienced by trainees following an assault were fear, rage, and anxiety. Guilt, sadness, feeling unsupported, and self-doubt were also reported.
Dr. Pereira-Sanchez noted the low rate of reported assaults is likely because trainees view it as “part of the job to get insulted, it’s part of the job to suffer minor physical violence.”
Individuals who did report assaults tended to be those who had been assaulted more than five times and those who felt more anxiety, rage, and fear.
“Basically, those who experience more emotional consequences and physical consequences tend to report more,” he said.
In addition, trainees tended to report assaults if they worked in an institution that provided protocols and training in prevention and management of patient aggression.
However, he added, most respondents reported they were not aware of their center’s protocols with respect to assaults and were not trained in the management or prevention of patient violence.
Management tools key
Commenting on the study in an interview, Renee Binder, MD, professor of psychiatry at University of California, San Francisco, said the findings show that, “when patients are out of control, they may act inappropriately, including verbal, physical, and sexual assaults.”
Consequently, “clinicians should be prepared and have management tools,” said Dr. Binder, who was not involved in the research.
She noted that derogatory statements and racial slurs were included among the verbal assaults, which is particularly common in inpatient units and EDs where “patients may be acutely psychotic or manic and out of control,” she said.
However, Dr. Binder pointed out that the investigators did not separate mild and more severe forms of physical and sexual assault.
“If the authors had more finely separated out the types of physical and sexual assaults, they probably would have found that mild types of assaults are much more common than more severe assaults,” she said.
Dr. Pereira-Sanchez’s fellowship program is funded by Fundacion Alicia Koplowitz. He and Dr. Binder have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
More than 80% of psychiatric trainees have experienced some kind of verbal, physical, or sexual assault from patients, and approximately one-third have been physically attacked multiple times, new survey results show.
Such incidents, said study investigator Victor Pereira-Sanchez, MD, from the department of child and adolescent psychiatry at New York University take a toll on the trainees’ well-being and may ultimately affect the quality of patient care.
“The extent of violence against psychiatric trainees is alarming and calls for the implementation of effective training, prevention, and intervention measures,” Dr. Pereira-Sanchez said in an interview.
The findings were presented at the European Psychiatric Association (EPA) 2020 Congress, which was virtual this year because of the COVID-19 pandemic.
Widespread problem
Violence against health care professionals is widespread among clinicians in EDs with psychiatry trainees “more exposed and vulnerable,” Dr. Pereira-Sanchez said during his presentation.
In 2017, the European Federation of Psychiatric Trainees established a group of researchers to describe “the extent and consequences of violence against psychiatric trainees in Europe and beyond,” he said. The group developed a 15-item questionnaire asking young clinicians about experiences of physical, sexual, and verbal assault at work. The survey was posted online by partner institutions via social media.
A total of 827 psychiatric trainees, the majority of whom were from France and the United Kingdom, completed the survey. Respondents had an average age of 31 years, and 68% were women. On average, respondents had completed 51.3% of their psychiatric training.
with 92.0% reporting verbal assaults, 44.1% physical assaults, and 9.3% sexual assaults. In addition, 14.2% had been assaulted once, 51.9% had been assaulted two to five times, and 33.9% had been assaulted more than five times during their training. Results also showed that assaults were more likely to occur on an inpatient ward (63.4%) or the ED (56.9%), although 37.2% occurred in an outpatient setting and 4.2% in community settings. The majority of respondents (69.0%) did not report their assaults, and 67.3% did not call police or security personnel.
The most common emotions experienced by trainees following an assault were fear, rage, and anxiety. Guilt, sadness, feeling unsupported, and self-doubt were also reported.
Dr. Pereira-Sanchez noted the low rate of reported assaults is likely because trainees view it as “part of the job to get insulted, it’s part of the job to suffer minor physical violence.”
Individuals who did report assaults tended to be those who had been assaulted more than five times and those who felt more anxiety, rage, and fear.
“Basically, those who experience more emotional consequences and physical consequences tend to report more,” he said.
In addition, trainees tended to report assaults if they worked in an institution that provided protocols and training in prevention and management of patient aggression.
However, he added, most respondents reported they were not aware of their center’s protocols with respect to assaults and were not trained in the management or prevention of patient violence.
Management tools key
Commenting on the study in an interview, Renee Binder, MD, professor of psychiatry at University of California, San Francisco, said the findings show that, “when patients are out of control, they may act inappropriately, including verbal, physical, and sexual assaults.”
Consequently, “clinicians should be prepared and have management tools,” said Dr. Binder, who was not involved in the research.
She noted that derogatory statements and racial slurs were included among the verbal assaults, which is particularly common in inpatient units and EDs where “patients may be acutely psychotic or manic and out of control,” she said.
However, Dr. Binder pointed out that the investigators did not separate mild and more severe forms of physical and sexual assault.
“If the authors had more finely separated out the types of physical and sexual assaults, they probably would have found that mild types of assaults are much more common than more severe assaults,” she said.
Dr. Pereira-Sanchez’s fellowship program is funded by Fundacion Alicia Koplowitz. He and Dr. Binder have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
More than 80% of psychiatric trainees have experienced some kind of verbal, physical, or sexual assault from patients, and approximately one-third have been physically attacked multiple times, new survey results show.
Such incidents, said study investigator Victor Pereira-Sanchez, MD, from the department of child and adolescent psychiatry at New York University take a toll on the trainees’ well-being and may ultimately affect the quality of patient care.
“The extent of violence against psychiatric trainees is alarming and calls for the implementation of effective training, prevention, and intervention measures,” Dr. Pereira-Sanchez said in an interview.
The findings were presented at the European Psychiatric Association (EPA) 2020 Congress, which was virtual this year because of the COVID-19 pandemic.
Widespread problem
Violence against health care professionals is widespread among clinicians in EDs with psychiatry trainees “more exposed and vulnerable,” Dr. Pereira-Sanchez said during his presentation.
In 2017, the European Federation of Psychiatric Trainees established a group of researchers to describe “the extent and consequences of violence against psychiatric trainees in Europe and beyond,” he said. The group developed a 15-item questionnaire asking young clinicians about experiences of physical, sexual, and verbal assault at work. The survey was posted online by partner institutions via social media.
A total of 827 psychiatric trainees, the majority of whom were from France and the United Kingdom, completed the survey. Respondents had an average age of 31 years, and 68% were women. On average, respondents had completed 51.3% of their psychiatric training.
with 92.0% reporting verbal assaults, 44.1% physical assaults, and 9.3% sexual assaults. In addition, 14.2% had been assaulted once, 51.9% had been assaulted two to five times, and 33.9% had been assaulted more than five times during their training. Results also showed that assaults were more likely to occur on an inpatient ward (63.4%) or the ED (56.9%), although 37.2% occurred in an outpatient setting and 4.2% in community settings. The majority of respondents (69.0%) did not report their assaults, and 67.3% did not call police or security personnel.
The most common emotions experienced by trainees following an assault were fear, rage, and anxiety. Guilt, sadness, feeling unsupported, and self-doubt were also reported.
Dr. Pereira-Sanchez noted the low rate of reported assaults is likely because trainees view it as “part of the job to get insulted, it’s part of the job to suffer minor physical violence.”
Individuals who did report assaults tended to be those who had been assaulted more than five times and those who felt more anxiety, rage, and fear.
“Basically, those who experience more emotional consequences and physical consequences tend to report more,” he said.
In addition, trainees tended to report assaults if they worked in an institution that provided protocols and training in prevention and management of patient aggression.
However, he added, most respondents reported they were not aware of their center’s protocols with respect to assaults and were not trained in the management or prevention of patient violence.
Management tools key
Commenting on the study in an interview, Renee Binder, MD, professor of psychiatry at University of California, San Francisco, said the findings show that, “when patients are out of control, they may act inappropriately, including verbal, physical, and sexual assaults.”
Consequently, “clinicians should be prepared and have management tools,” said Dr. Binder, who was not involved in the research.
She noted that derogatory statements and racial slurs were included among the verbal assaults, which is particularly common in inpatient units and EDs where “patients may be acutely psychotic or manic and out of control,” she said.
However, Dr. Binder pointed out that the investigators did not separate mild and more severe forms of physical and sexual assault.
“If the authors had more finely separated out the types of physical and sexual assaults, they probably would have found that mild types of assaults are much more common than more severe assaults,” she said.
Dr. Pereira-Sanchez’s fellowship program is funded by Fundacion Alicia Koplowitz. He and Dr. Binder have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Caution urged for antidepressant use in bipolar depression
Although patients with bipolar disorder commonly experience depressive symptoms, clinicians should be very cautious about treating them with antidepressants, especially as monotherapy, experts asserted in a recent debate on the topic as part of the European Psychiatric Association (EPA) 2020 Congress.
At the Congress, which was virtual this year because of the COVID-19 pandemic, psychiatric experts said that clinicians should also screen patients for mixed symptoms that are better treated with mood stabilizers. These same experts also raised concerns over long-term antidepressant use, recommending continued use only in patients who relapse after stopping antidepressants.
Isabella Pacchiarotti, MD, PhD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, argued against the use of antidepressants in treating bipolar disorder; Guy Goodwin, PhD, however, took the “pro” stance.
Goodwin, a professor of psychiatry at the University of Oxford in the UK, admitted that there is a “paucity of data” on the role of antidepressants in bipolar disorder.
Nevertheless, there are “circumstances that one really has to treat with antidepressants simply because other things have been tried and have not worked,” he told conference attendees.
Challenging, Controversial Topic
The debate was chaired by Eduard Vieta, MD, PhD, chair of the Department of Psychiatry and Psychology at the University of Barcelona Hospital Clinic, Spain.
Vieta said the question over whether antidepressants should be used in the depressive phase of bipolar illness is “perhaps the most challenging ... especially in the area of bipolar disorder.”
At the beginning of the presentation, Vieta asked the audience for their opinion in order to have a “baseline” for the debate: among 164 respondents, 73% were in favor of using antidepressants in bipolar depression.
“Clearly there is a majority, so Isabella [Dr Pacchiarotti] is going to have a hard time improving these numbers,” Vieta noted.
Up first, Pacchiarotti began by noting that this topic remains “an area of big controversy.” However, the real question “should not be the pros and cons of antidepressants but more when and how to use them.»
Of the three phases of bipolar disorder, acute depression «poses the greatest difficulties,» she added.
This is because of the relative paucity of studies in the area, the often heated debates on the specific role of antidepressants, the discrepancy in conclusions between meta-analyses, and the currently approved therapeutic options being associated with “not very high response rates,” Pacchiarotti said.
The diagnostic criteria for unipolar and bipolar depression are “basically the same,” she noted. However, it’s important to be able to distinguish between the two conditions, as up to one fifth of patients with unipolar depression suffer from undiagnosed bipolar disorder, she explained.
Moreover, several studies have identified key symptoms in bipolar depression, such as hyperphagia and hypersomnia, increased anxiety, and psychotic and psychomotor symptoms.
As previously reported by Medscape Medical News, a task force report was released in 2013 by the International Society for Bipolar Disorder (ISBD) on antidepressant use in bipolar disorders. Pacchiarotti and Goodwin were among the report’s authors, which concluded that available evidence on this issue is methodologically weak.
This is largely because of a lack of placebo-controlled studies in this patient population (bipolar depression, alongside suicidal ideation, is often an exclusion criteria in clinical antidepressant trials).
Many guidelines consequently do not consider antidepressants to be a first-line option as monotherapy in bipolar depression, although some name the drugs as second- or third-line options.
In 2013, the ISBD recommended that antidepressant monotherapy should be “avoided” in bipolar I disorder; and in bipolar I and II depression, the treatment should be accompanied by at least two concomitant core manic symptoms.
“What Has Changed?”
Antidepressants should be used “only if there is a history of a positive response,” whereas maintenance therapy should be considered if a patient relapses into a depressive episode after stopping the drugs, the report notes.
Pacchiarotti noted that since the recommendations were published nothing has changed, noting that antidepressant efficacy in bipolar depression “remains unproven.”
The issue is not whether antidepressants are effective in bipolar depression but rather are there subpopulations where these medications are helpful or harmful, she added.
The key to understanding the heterogeneity of responses to antidepressants, she said, is the concept of a bipolar spectrum and a dimensional approach to distinguishing between bipolar disorder and unipolar depression.
In addition, the definition of a mixed episode in the DSM-IV-TR differs from that of an episode with mixed characteristics in the DSM-5, which Pacchiarotti said offers a better understanding of the phenomenon while seemingly disposing with the idea of mixed depression.
Based on previous research, there is some suggestion that a depressive state exists between major depressive disorder and bipolar I disorder with mixed features, and hypomania state between bipolar II and I disorder, also with mixed features.
Pacchiarotti said the role of antidepressants in the treatment of bipolar depression remains “controversial” and there is a need for both short- and long-term studies of their use in both bipolar I and bipolar II disorder with real-world inclusion criteria.
The concept of a bipolar spectrum needs to be considered a more “dimensional approach” to depression, with mixed features seen as a “transversal” contraindication for antidepressant use, she concluded.
In Favor — With Caveats
Taking the opposite position and arguing in favor of antidepressant use, albeit cautiously, Goodwin said previous work has shown that stable patients with bipolar disorder experience depression of variable severity about 50% of the time.
The truth is that patients do not have a depressive episode for extended periods but instead have depressive symptoms, he said. “So how we manage and treat depression really matters.”
In an analysis, Goodwin and his colleagues estimated that the cost of bipolar disorder is approximately £12,600 ($16,000) per patient per year, of which only 30.6% is attributable to healthcare costs and 68.1% to indirect costs. This means the impact on the patient is also felt by society.
He agreed with Pacchiarotti’s assertion of a bipolar spectrum and the need for a dimensional approach.
“All the patients along the spectrum have the symptoms of depression and they differ in the extent to which they show symptoms of mania, which will include irritability,” he added.
Goodwin argued that there is no evidence to suggest that the depression experienced at one end of the scale is any different from that at the other. However, safety issues around antidepressant use “really relate to the additional symptoms you see with increasing evidence of bipolarity.”
In addition, the whole discussion is confounded by comorbidity, “with symptoms that sometimes coalesce into our concept of borderline personality disorder” or attention deficit hyperactivity disorder, he said.
Goodwin said there is “very little doubt” that antidepressants have an effect vs placebo. “The argument is over whether the effect is large and whether we should regard it as clinically significant.”
He noted that previous studies have shown a range of effect sizes with antidepressants, but the “massive” confidence intervals mean that “one is free to believe pretty much what one likes.”
The only antidepressant medication that is statistically significantly different from placebo is fluoxetine combined with olanzapine. However, that conclusion is based on “little data,” said Goodwin.
In terms of long-term management, there is “extremely little” randomized data for maintenance treatment with antidepressants in bipolar disorder. “So this does not support” long-term use, he added.
Still, although choice of antidepressant remains a guess, there is “just about support” for using them, Goodwin noted.
He urged clinicians not to dismiss antidepressant use, but to use them only where there is a clinical need and for as little time as possible. Patients with bipolar disorder should continue to take antidepressants if they relapse after they come off these medications.
However, all of that sits “in contrast” to how they’re currently used in clinical practice, Goodwin said.
Caution Urged
After the debate, the audience was asked to vote again. This time, The remaining 12% voted against the practice.
Summarizing the discussion, Vieta said that “we should be cautious” when using antidepressants in bipolar depression. However, “we should be able to use them when necessary,” he added.
Although their use as monotherapy is not best practice, especially in bipolar I disorder, there may be a subset of bipolar II patients in whom monotherapy “might still be acceptable; but I don’t think it’s a good idea,” Vieta said.
He added that clinicians should very carefully screen for mixed symptoms, which call for the prescription of other drugs, such as olanzapine and fluoxetine.
“The other important message is that we have to be even more cautious in the long term with the use of antidepressants, and we should be able to use them when there is a comorbidity” that calls for their use, Vieta concluded.
Pacchiarotti reported having received speaker fees and educational grants from Adamed, AstraZeneca, Janssen-Cilag, and Lundbeck. Goodwin reported having received honoraria from Angellini, Medscape, Pfizer, Servier, Shire, and Sun; having shares in P1vital Products; past employment as medical director of P1vital Products; and advisory board membership for Compass Pathways, Minerva, MSD, Novartis, Lundbeck, Sage, Servier, and Shire. Vieta has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Although patients with bipolar disorder commonly experience depressive symptoms, clinicians should be very cautious about treating them with antidepressants, especially as monotherapy, experts asserted in a recent debate on the topic as part of the European Psychiatric Association (EPA) 2020 Congress.
At the Congress, which was virtual this year because of the COVID-19 pandemic, psychiatric experts said that clinicians should also screen patients for mixed symptoms that are better treated with mood stabilizers. These same experts also raised concerns over long-term antidepressant use, recommending continued use only in patients who relapse after stopping antidepressants.
Isabella Pacchiarotti, MD, PhD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, argued against the use of antidepressants in treating bipolar disorder; Guy Goodwin, PhD, however, took the “pro” stance.
Goodwin, a professor of psychiatry at the University of Oxford in the UK, admitted that there is a “paucity of data” on the role of antidepressants in bipolar disorder.
Nevertheless, there are “circumstances that one really has to treat with antidepressants simply because other things have been tried and have not worked,” he told conference attendees.
Challenging, Controversial Topic
The debate was chaired by Eduard Vieta, MD, PhD, chair of the Department of Psychiatry and Psychology at the University of Barcelona Hospital Clinic, Spain.
Vieta said the question over whether antidepressants should be used in the depressive phase of bipolar illness is “perhaps the most challenging ... especially in the area of bipolar disorder.”
At the beginning of the presentation, Vieta asked the audience for their opinion in order to have a “baseline” for the debate: among 164 respondents, 73% were in favor of using antidepressants in bipolar depression.
“Clearly there is a majority, so Isabella [Dr Pacchiarotti] is going to have a hard time improving these numbers,” Vieta noted.
Up first, Pacchiarotti began by noting that this topic remains “an area of big controversy.” However, the real question “should not be the pros and cons of antidepressants but more when and how to use them.»
Of the three phases of bipolar disorder, acute depression «poses the greatest difficulties,» she added.
This is because of the relative paucity of studies in the area, the often heated debates on the specific role of antidepressants, the discrepancy in conclusions between meta-analyses, and the currently approved therapeutic options being associated with “not very high response rates,” Pacchiarotti said.
The diagnostic criteria for unipolar and bipolar depression are “basically the same,” she noted. However, it’s important to be able to distinguish between the two conditions, as up to one fifth of patients with unipolar depression suffer from undiagnosed bipolar disorder, she explained.
Moreover, several studies have identified key symptoms in bipolar depression, such as hyperphagia and hypersomnia, increased anxiety, and psychotic and psychomotor symptoms.
As previously reported by Medscape Medical News, a task force report was released in 2013 by the International Society for Bipolar Disorder (ISBD) on antidepressant use in bipolar disorders. Pacchiarotti and Goodwin were among the report’s authors, which concluded that available evidence on this issue is methodologically weak.
This is largely because of a lack of placebo-controlled studies in this patient population (bipolar depression, alongside suicidal ideation, is often an exclusion criteria in clinical antidepressant trials).
Many guidelines consequently do not consider antidepressants to be a first-line option as monotherapy in bipolar depression, although some name the drugs as second- or third-line options.
In 2013, the ISBD recommended that antidepressant monotherapy should be “avoided” in bipolar I disorder; and in bipolar I and II depression, the treatment should be accompanied by at least two concomitant core manic symptoms.
“What Has Changed?”
Antidepressants should be used “only if there is a history of a positive response,” whereas maintenance therapy should be considered if a patient relapses into a depressive episode after stopping the drugs, the report notes.
Pacchiarotti noted that since the recommendations were published nothing has changed, noting that antidepressant efficacy in bipolar depression “remains unproven.”
The issue is not whether antidepressants are effective in bipolar depression but rather are there subpopulations where these medications are helpful or harmful, she added.
The key to understanding the heterogeneity of responses to antidepressants, she said, is the concept of a bipolar spectrum and a dimensional approach to distinguishing between bipolar disorder and unipolar depression.
In addition, the definition of a mixed episode in the DSM-IV-TR differs from that of an episode with mixed characteristics in the DSM-5, which Pacchiarotti said offers a better understanding of the phenomenon while seemingly disposing with the idea of mixed depression.
Based on previous research, there is some suggestion that a depressive state exists between major depressive disorder and bipolar I disorder with mixed features, and hypomania state between bipolar II and I disorder, also with mixed features.
Pacchiarotti said the role of antidepressants in the treatment of bipolar depression remains “controversial” and there is a need for both short- and long-term studies of their use in both bipolar I and bipolar II disorder with real-world inclusion criteria.
The concept of a bipolar spectrum needs to be considered a more “dimensional approach” to depression, with mixed features seen as a “transversal” contraindication for antidepressant use, she concluded.
In Favor — With Caveats
Taking the opposite position and arguing in favor of antidepressant use, albeit cautiously, Goodwin said previous work has shown that stable patients with bipolar disorder experience depression of variable severity about 50% of the time.
The truth is that patients do not have a depressive episode for extended periods but instead have depressive symptoms, he said. “So how we manage and treat depression really matters.”
In an analysis, Goodwin and his colleagues estimated that the cost of bipolar disorder is approximately £12,600 ($16,000) per patient per year, of which only 30.6% is attributable to healthcare costs and 68.1% to indirect costs. This means the impact on the patient is also felt by society.
He agreed with Pacchiarotti’s assertion of a bipolar spectrum and the need for a dimensional approach.
“All the patients along the spectrum have the symptoms of depression and they differ in the extent to which they show symptoms of mania, which will include irritability,” he added.
Goodwin argued that there is no evidence to suggest that the depression experienced at one end of the scale is any different from that at the other. However, safety issues around antidepressant use “really relate to the additional symptoms you see with increasing evidence of bipolarity.”
In addition, the whole discussion is confounded by comorbidity, “with symptoms that sometimes coalesce into our concept of borderline personality disorder” or attention deficit hyperactivity disorder, he said.
Goodwin said there is “very little doubt” that antidepressants have an effect vs placebo. “The argument is over whether the effect is large and whether we should regard it as clinically significant.”
He noted that previous studies have shown a range of effect sizes with antidepressants, but the “massive” confidence intervals mean that “one is free to believe pretty much what one likes.”
The only antidepressant medication that is statistically significantly different from placebo is fluoxetine combined with olanzapine. However, that conclusion is based on “little data,” said Goodwin.
In terms of long-term management, there is “extremely little” randomized data for maintenance treatment with antidepressants in bipolar disorder. “So this does not support” long-term use, he added.
Still, although choice of antidepressant remains a guess, there is “just about support” for using them, Goodwin noted.
He urged clinicians not to dismiss antidepressant use, but to use them only where there is a clinical need and for as little time as possible. Patients with bipolar disorder should continue to take antidepressants if they relapse after they come off these medications.
However, all of that sits “in contrast” to how they’re currently used in clinical practice, Goodwin said.
Caution Urged
After the debate, the audience was asked to vote again. This time, The remaining 12% voted against the practice.
Summarizing the discussion, Vieta said that “we should be cautious” when using antidepressants in bipolar depression. However, “we should be able to use them when necessary,” he added.
Although their use as monotherapy is not best practice, especially in bipolar I disorder, there may be a subset of bipolar II patients in whom monotherapy “might still be acceptable; but I don’t think it’s a good idea,” Vieta said.
He added that clinicians should very carefully screen for mixed symptoms, which call for the prescription of other drugs, such as olanzapine and fluoxetine.
“The other important message is that we have to be even more cautious in the long term with the use of antidepressants, and we should be able to use them when there is a comorbidity” that calls for their use, Vieta concluded.
Pacchiarotti reported having received speaker fees and educational grants from Adamed, AstraZeneca, Janssen-Cilag, and Lundbeck. Goodwin reported having received honoraria from Angellini, Medscape, Pfizer, Servier, Shire, and Sun; having shares in P1vital Products; past employment as medical director of P1vital Products; and advisory board membership for Compass Pathways, Minerva, MSD, Novartis, Lundbeck, Sage, Servier, and Shire. Vieta has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Although patients with bipolar disorder commonly experience depressive symptoms, clinicians should be very cautious about treating them with antidepressants, especially as monotherapy, experts asserted in a recent debate on the topic as part of the European Psychiatric Association (EPA) 2020 Congress.
At the Congress, which was virtual this year because of the COVID-19 pandemic, psychiatric experts said that clinicians should also screen patients for mixed symptoms that are better treated with mood stabilizers. These same experts also raised concerns over long-term antidepressant use, recommending continued use only in patients who relapse after stopping antidepressants.
Isabella Pacchiarotti, MD, PhD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, argued against the use of antidepressants in treating bipolar disorder; Guy Goodwin, PhD, however, took the “pro” stance.
Goodwin, a professor of psychiatry at the University of Oxford in the UK, admitted that there is a “paucity of data” on the role of antidepressants in bipolar disorder.
Nevertheless, there are “circumstances that one really has to treat with antidepressants simply because other things have been tried and have not worked,” he told conference attendees.
Challenging, Controversial Topic
The debate was chaired by Eduard Vieta, MD, PhD, chair of the Department of Psychiatry and Psychology at the University of Barcelona Hospital Clinic, Spain.
Vieta said the question over whether antidepressants should be used in the depressive phase of bipolar illness is “perhaps the most challenging ... especially in the area of bipolar disorder.”
At the beginning of the presentation, Vieta asked the audience for their opinion in order to have a “baseline” for the debate: among 164 respondents, 73% were in favor of using antidepressants in bipolar depression.
“Clearly there is a majority, so Isabella [Dr Pacchiarotti] is going to have a hard time improving these numbers,” Vieta noted.
Up first, Pacchiarotti began by noting that this topic remains “an area of big controversy.” However, the real question “should not be the pros and cons of antidepressants but more when and how to use them.»
Of the three phases of bipolar disorder, acute depression «poses the greatest difficulties,» she added.
This is because of the relative paucity of studies in the area, the often heated debates on the specific role of antidepressants, the discrepancy in conclusions between meta-analyses, and the currently approved therapeutic options being associated with “not very high response rates,” Pacchiarotti said.
The diagnostic criteria for unipolar and bipolar depression are “basically the same,” she noted. However, it’s important to be able to distinguish between the two conditions, as up to one fifth of patients with unipolar depression suffer from undiagnosed bipolar disorder, she explained.
Moreover, several studies have identified key symptoms in bipolar depression, such as hyperphagia and hypersomnia, increased anxiety, and psychotic and psychomotor symptoms.
As previously reported by Medscape Medical News, a task force report was released in 2013 by the International Society for Bipolar Disorder (ISBD) on antidepressant use in bipolar disorders. Pacchiarotti and Goodwin were among the report’s authors, which concluded that available evidence on this issue is methodologically weak.
This is largely because of a lack of placebo-controlled studies in this patient population (bipolar depression, alongside suicidal ideation, is often an exclusion criteria in clinical antidepressant trials).
Many guidelines consequently do not consider antidepressants to be a first-line option as monotherapy in bipolar depression, although some name the drugs as second- or third-line options.
In 2013, the ISBD recommended that antidepressant monotherapy should be “avoided” in bipolar I disorder; and in bipolar I and II depression, the treatment should be accompanied by at least two concomitant core manic symptoms.
“What Has Changed?”
Antidepressants should be used “only if there is a history of a positive response,” whereas maintenance therapy should be considered if a patient relapses into a depressive episode after stopping the drugs, the report notes.
Pacchiarotti noted that since the recommendations were published nothing has changed, noting that antidepressant efficacy in bipolar depression “remains unproven.”
The issue is not whether antidepressants are effective in bipolar depression but rather are there subpopulations where these medications are helpful or harmful, she added.
The key to understanding the heterogeneity of responses to antidepressants, she said, is the concept of a bipolar spectrum and a dimensional approach to distinguishing between bipolar disorder and unipolar depression.
In addition, the definition of a mixed episode in the DSM-IV-TR differs from that of an episode with mixed characteristics in the DSM-5, which Pacchiarotti said offers a better understanding of the phenomenon while seemingly disposing with the idea of mixed depression.
Based on previous research, there is some suggestion that a depressive state exists between major depressive disorder and bipolar I disorder with mixed features, and hypomania state between bipolar II and I disorder, also with mixed features.
Pacchiarotti said the role of antidepressants in the treatment of bipolar depression remains “controversial” and there is a need for both short- and long-term studies of their use in both bipolar I and bipolar II disorder with real-world inclusion criteria.
The concept of a bipolar spectrum needs to be considered a more “dimensional approach” to depression, with mixed features seen as a “transversal” contraindication for antidepressant use, she concluded.
In Favor — With Caveats
Taking the opposite position and arguing in favor of antidepressant use, albeit cautiously, Goodwin said previous work has shown that stable patients with bipolar disorder experience depression of variable severity about 50% of the time.
The truth is that patients do not have a depressive episode for extended periods but instead have depressive symptoms, he said. “So how we manage and treat depression really matters.”
In an analysis, Goodwin and his colleagues estimated that the cost of bipolar disorder is approximately £12,600 ($16,000) per patient per year, of which only 30.6% is attributable to healthcare costs and 68.1% to indirect costs. This means the impact on the patient is also felt by society.
He agreed with Pacchiarotti’s assertion of a bipolar spectrum and the need for a dimensional approach.
“All the patients along the spectrum have the symptoms of depression and they differ in the extent to which they show symptoms of mania, which will include irritability,” he added.
Goodwin argued that there is no evidence to suggest that the depression experienced at one end of the scale is any different from that at the other. However, safety issues around antidepressant use “really relate to the additional symptoms you see with increasing evidence of bipolarity.”
In addition, the whole discussion is confounded by comorbidity, “with symptoms that sometimes coalesce into our concept of borderline personality disorder” or attention deficit hyperactivity disorder, he said.
Goodwin said there is “very little doubt” that antidepressants have an effect vs placebo. “The argument is over whether the effect is large and whether we should regard it as clinically significant.”
He noted that previous studies have shown a range of effect sizes with antidepressants, but the “massive” confidence intervals mean that “one is free to believe pretty much what one likes.”
The only antidepressant medication that is statistically significantly different from placebo is fluoxetine combined with olanzapine. However, that conclusion is based on “little data,” said Goodwin.
In terms of long-term management, there is “extremely little” randomized data for maintenance treatment with antidepressants in bipolar disorder. “So this does not support” long-term use, he added.
Still, although choice of antidepressant remains a guess, there is “just about support” for using them, Goodwin noted.
He urged clinicians not to dismiss antidepressant use, but to use them only where there is a clinical need and for as little time as possible. Patients with bipolar disorder should continue to take antidepressants if they relapse after they come off these medications.
However, all of that sits “in contrast” to how they’re currently used in clinical practice, Goodwin said.
Caution Urged
After the debate, the audience was asked to vote again. This time, The remaining 12% voted against the practice.
Summarizing the discussion, Vieta said that “we should be cautious” when using antidepressants in bipolar depression. However, “we should be able to use them when necessary,” he added.
Although their use as monotherapy is not best practice, especially in bipolar I disorder, there may be a subset of bipolar II patients in whom monotherapy “might still be acceptable; but I don’t think it’s a good idea,” Vieta said.
He added that clinicians should very carefully screen for mixed symptoms, which call for the prescription of other drugs, such as olanzapine and fluoxetine.
“The other important message is that we have to be even more cautious in the long term with the use of antidepressants, and we should be able to use them when there is a comorbidity” that calls for their use, Vieta concluded.
Pacchiarotti reported having received speaker fees and educational grants from Adamed, AstraZeneca, Janssen-Cilag, and Lundbeck. Goodwin reported having received honoraria from Angellini, Medscape, Pfizer, Servier, Shire, and Sun; having shares in P1vital Products; past employment as medical director of P1vital Products; and advisory board membership for Compass Pathways, Minerva, MSD, Novartis, Lundbeck, Sage, Servier, and Shire. Vieta has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Family environment important in early psychosis outcomes
Family environment may influence subsequent functional outcomes in patients with first-episode psychosis, new research suggests.
A study of more than 300 patients with first-episode psychosis (FEP) showed that although family environment was not associated with functioning at initial presentation, an interaction developed over time that could have “important implications for early interventions for both patients and caregivers,” investigators reported.
study coinvestigator Norma Verdolini, MD, PhD, bipolar and depressive disorders unit, hospital Clinic Barcelona, University of Barcelona, said in an interview.
The findings were scheduled to be presented at the Congress of the Schizophrenia International Research Society 2020, but the meeting was canceled because of the coronavirus pandemic.
FAST measures
Previous research has shown that family environment influences the development of psychotic symptoms, with negative family environmental factors associated with poor prognoses.
Conversely, one study indicated that a positive family environment is linked to greater improvement in negative and disorganized symptoms in adolescents at imminent risk for psychosis onset.
However, the current investigators noted that the impact of family environment on longitudinal functioning in individuals presenting with FEP is unclear.
To investigate further, they conducted an analysis as part of the PEPs study, which included 335 patients with FEP and 253 healthy controls. Functioning was measured using the Functional Assessment Short Test (FAST), and family environmental styles were evaluated using the Family Environment Scale (FES), which assesses “emotional climate” of a family across 10 domains.
At baseline, the mean total FAST score was 27.8 in patients with FEP versus 3.5 in the healthy controls, indicating substantially worse functioning among the patients. Linear regression analysis indicated that at baseline there was no significant association between aspects of family environment on the FES and functional scores.
Patients were assessed again at 2 years, by which point 283 had been diagnosed with psychotic disorders and 52 with bipolar disorder. The mean total FAST scores were 20.98 among patients with psychotic disorders and 13.8 in those with bipolar disorder.
Family conflict
Results showed that, among those with bipolar disorder, worse functioning on FAST at 2 years was significantly associated with higher rates of open expression of conflict in the family (P = .004).
In patients with psychotic disorders, worse functioning was significantly associated with lower rates of participation in social activities (P = .006) and an achievement-oriented family environment (P = .039). Worse functioning in patients with psychotic disorders was also significantly associated with higher rates of religious practice and values (P = .003).
Dr. Verdolini noted the reason family environment does not appear to have an impact at initial FEP presentation may be that the “first kick” is given by an individual’s genetic liability for psychiatric disorders in combination with the family environment. In reality, the two are intertwined, especially when considering what it means to a family to have one member with a psychiatric disorder, which “will have an impact on the family environment.”
Dr. Verdolini added: “This is not actually the objective family environment,” but the perceived family environment.
“So maybe in the following 2 years the patient who experiences a first episode of psychosis may change their idea of the family environment itself,” she noted. She added that at her institution psychoeducation is offered to FEP patients’ families.
‘Interesting’ findings
Commenting on the study, Nicole Kozloff, MD, from the child, youth, and emerging adult program at the Centre for Addiction and Mental Health in Toronto, said one limitation of the study is that it’s not clear what care patients received – or who in the family completed the FES.
It is also important to note that “measures of association do not necessarily imply that one factor caused the other factor,” said Dr. Kozloff, who was not involved in the research. “For example, it may be that, among people with bipolar disorder, open expression of conflict in the family can lead to worse functioning, or that worse functioning can lead to more conflict in the family.”
Nevertheless, Dr. Kozloff described the finding of an emerging association between the family environment and functioning over time as “interesting.”
When young people with FEP enter treatment, “they have reached a crisis point and are functioning poorly,” she noted.
“It could be that there is less to differentiate among levels of functioning at treatment entry but, after 2 years, the individuals have separated into those who have been responsive to treatment and are functioning well, and those who continue to have functional challenges. And this is where we start to see a relationship with family environment emerge,” Dr. Kozloff said.
She also agreed with Dr. Verdolini’s take on the findings, and that family psychoeducation “can reduce relapse rates in schizophrenia and the emotional burden on the family.”
“We also know that having family involvement in care is one of the most robust predictors that young people with psychosis will remain engaged in mental health services,” she said.
Teaching families about psychosis and its treatment, about problem-solving and communication skills, and providing support to ensure that family members know how to get help in a crisis, “is a key part of comprehensive early psychosis intervention,” Dr. Kozloff said. “It is good for the patient and good for the family, and allows the clinicians to provide better care.”
Articulates clinical practice findings
Also commenting on the results, Brian O’Donoghue, MD, PhD, senior clinical research fellow at Orygen, the National Centre of Excellence in Youth Mental Health in Melbourne, described the research as important, adding that the study highlights the need for sufficient follow-up.
“It makes sense that the involvement of family over time has a strong impact upon outcome and functioning,” he said in an interview.
“These research findings articulate what we see in clinical practice, so it is good to see that it is captured,” added Dr. O’Donoghue, who was not associated with the study.
He noted that it is common for family involvement to influence outcome, especially if the family is positively involved. “It is invaluable toward their recovery. However, conversely, if there are ongoing family stressors, then this can be a trigger for relapse or lack of improvement.”
Overall, the results “really emphasize that the family needs to be involved in care.”
The Early Psychosis Prevention and Intervention Centre where Dr. O’Donoghue is a consultant psychiatrist offers a psychoeducational course “to inform families about psychosis, treatment, and how they can support their family members.”
“We also have family peer support workers and family therapists, which are essential to the service and for the young person’s recovery,” Dr. O’Donoghue said.
The investigators and Dr. O’Donoghue disclosed no relevant financial relationships. Dr. Kozloff reported receiving research funding from the CAMH Foundation, Brain & Behavior Research Foundation, Canadian Institutes of Health Research, and AFP Innovation Fund; honoraria from Humber River Hospital, the University of Calgary (Alta.), and the Canadian Consortium for Early Intervention in Psychosis; and salary support from Inner City Health Associates.
A version of this article originally appeared on Medscape.com.
Family environment may influence subsequent functional outcomes in patients with first-episode psychosis, new research suggests.
A study of more than 300 patients with first-episode psychosis (FEP) showed that although family environment was not associated with functioning at initial presentation, an interaction developed over time that could have “important implications for early interventions for both patients and caregivers,” investigators reported.
study coinvestigator Norma Verdolini, MD, PhD, bipolar and depressive disorders unit, hospital Clinic Barcelona, University of Barcelona, said in an interview.
The findings were scheduled to be presented at the Congress of the Schizophrenia International Research Society 2020, but the meeting was canceled because of the coronavirus pandemic.
FAST measures
Previous research has shown that family environment influences the development of psychotic symptoms, with negative family environmental factors associated with poor prognoses.
Conversely, one study indicated that a positive family environment is linked to greater improvement in negative and disorganized symptoms in adolescents at imminent risk for psychosis onset.
However, the current investigators noted that the impact of family environment on longitudinal functioning in individuals presenting with FEP is unclear.
To investigate further, they conducted an analysis as part of the PEPs study, which included 335 patients with FEP and 253 healthy controls. Functioning was measured using the Functional Assessment Short Test (FAST), and family environmental styles were evaluated using the Family Environment Scale (FES), which assesses “emotional climate” of a family across 10 domains.
At baseline, the mean total FAST score was 27.8 in patients with FEP versus 3.5 in the healthy controls, indicating substantially worse functioning among the patients. Linear regression analysis indicated that at baseline there was no significant association between aspects of family environment on the FES and functional scores.
Patients were assessed again at 2 years, by which point 283 had been diagnosed with psychotic disorders and 52 with bipolar disorder. The mean total FAST scores were 20.98 among patients with psychotic disorders and 13.8 in those with bipolar disorder.
Family conflict
Results showed that, among those with bipolar disorder, worse functioning on FAST at 2 years was significantly associated with higher rates of open expression of conflict in the family (P = .004).
In patients with psychotic disorders, worse functioning was significantly associated with lower rates of participation in social activities (P = .006) and an achievement-oriented family environment (P = .039). Worse functioning in patients with psychotic disorders was also significantly associated with higher rates of religious practice and values (P = .003).
Dr. Verdolini noted the reason family environment does not appear to have an impact at initial FEP presentation may be that the “first kick” is given by an individual’s genetic liability for psychiatric disorders in combination with the family environment. In reality, the two are intertwined, especially when considering what it means to a family to have one member with a psychiatric disorder, which “will have an impact on the family environment.”
Dr. Verdolini added: “This is not actually the objective family environment,” but the perceived family environment.
“So maybe in the following 2 years the patient who experiences a first episode of psychosis may change their idea of the family environment itself,” she noted. She added that at her institution psychoeducation is offered to FEP patients’ families.
‘Interesting’ findings
Commenting on the study, Nicole Kozloff, MD, from the child, youth, and emerging adult program at the Centre for Addiction and Mental Health in Toronto, said one limitation of the study is that it’s not clear what care patients received – or who in the family completed the FES.
It is also important to note that “measures of association do not necessarily imply that one factor caused the other factor,” said Dr. Kozloff, who was not involved in the research. “For example, it may be that, among people with bipolar disorder, open expression of conflict in the family can lead to worse functioning, or that worse functioning can lead to more conflict in the family.”
Nevertheless, Dr. Kozloff described the finding of an emerging association between the family environment and functioning over time as “interesting.”
When young people with FEP enter treatment, “they have reached a crisis point and are functioning poorly,” she noted.
“It could be that there is less to differentiate among levels of functioning at treatment entry but, after 2 years, the individuals have separated into those who have been responsive to treatment and are functioning well, and those who continue to have functional challenges. And this is where we start to see a relationship with family environment emerge,” Dr. Kozloff said.
She also agreed with Dr. Verdolini’s take on the findings, and that family psychoeducation “can reduce relapse rates in schizophrenia and the emotional burden on the family.”
“We also know that having family involvement in care is one of the most robust predictors that young people with psychosis will remain engaged in mental health services,” she said.
Teaching families about psychosis and its treatment, about problem-solving and communication skills, and providing support to ensure that family members know how to get help in a crisis, “is a key part of comprehensive early psychosis intervention,” Dr. Kozloff said. “It is good for the patient and good for the family, and allows the clinicians to provide better care.”
Articulates clinical practice findings
Also commenting on the results, Brian O’Donoghue, MD, PhD, senior clinical research fellow at Orygen, the National Centre of Excellence in Youth Mental Health in Melbourne, described the research as important, adding that the study highlights the need for sufficient follow-up.
“It makes sense that the involvement of family over time has a strong impact upon outcome and functioning,” he said in an interview.
“These research findings articulate what we see in clinical practice, so it is good to see that it is captured,” added Dr. O’Donoghue, who was not associated with the study.
He noted that it is common for family involvement to influence outcome, especially if the family is positively involved. “It is invaluable toward their recovery. However, conversely, if there are ongoing family stressors, then this can be a trigger for relapse or lack of improvement.”
Overall, the results “really emphasize that the family needs to be involved in care.”
The Early Psychosis Prevention and Intervention Centre where Dr. O’Donoghue is a consultant psychiatrist offers a psychoeducational course “to inform families about psychosis, treatment, and how they can support their family members.”
“We also have family peer support workers and family therapists, which are essential to the service and for the young person’s recovery,” Dr. O’Donoghue said.
The investigators and Dr. O’Donoghue disclosed no relevant financial relationships. Dr. Kozloff reported receiving research funding from the CAMH Foundation, Brain & Behavior Research Foundation, Canadian Institutes of Health Research, and AFP Innovation Fund; honoraria from Humber River Hospital, the University of Calgary (Alta.), and the Canadian Consortium for Early Intervention in Psychosis; and salary support from Inner City Health Associates.
A version of this article originally appeared on Medscape.com.
Family environment may influence subsequent functional outcomes in patients with first-episode psychosis, new research suggests.
A study of more than 300 patients with first-episode psychosis (FEP) showed that although family environment was not associated with functioning at initial presentation, an interaction developed over time that could have “important implications for early interventions for both patients and caregivers,” investigators reported.
study coinvestigator Norma Verdolini, MD, PhD, bipolar and depressive disorders unit, hospital Clinic Barcelona, University of Barcelona, said in an interview.
The findings were scheduled to be presented at the Congress of the Schizophrenia International Research Society 2020, but the meeting was canceled because of the coronavirus pandemic.
FAST measures
Previous research has shown that family environment influences the development of psychotic symptoms, with negative family environmental factors associated with poor prognoses.
Conversely, one study indicated that a positive family environment is linked to greater improvement in negative and disorganized symptoms in adolescents at imminent risk for psychosis onset.
However, the current investigators noted that the impact of family environment on longitudinal functioning in individuals presenting with FEP is unclear.
To investigate further, they conducted an analysis as part of the PEPs study, which included 335 patients with FEP and 253 healthy controls. Functioning was measured using the Functional Assessment Short Test (FAST), and family environmental styles were evaluated using the Family Environment Scale (FES), which assesses “emotional climate” of a family across 10 domains.
At baseline, the mean total FAST score was 27.8 in patients with FEP versus 3.5 in the healthy controls, indicating substantially worse functioning among the patients. Linear regression analysis indicated that at baseline there was no significant association between aspects of family environment on the FES and functional scores.
Patients were assessed again at 2 years, by which point 283 had been diagnosed with psychotic disorders and 52 with bipolar disorder. The mean total FAST scores were 20.98 among patients with psychotic disorders and 13.8 in those with bipolar disorder.
Family conflict
Results showed that, among those with bipolar disorder, worse functioning on FAST at 2 years was significantly associated with higher rates of open expression of conflict in the family (P = .004).
In patients with psychotic disorders, worse functioning was significantly associated with lower rates of participation in social activities (P = .006) and an achievement-oriented family environment (P = .039). Worse functioning in patients with psychotic disorders was also significantly associated with higher rates of religious practice and values (P = .003).
Dr. Verdolini noted the reason family environment does not appear to have an impact at initial FEP presentation may be that the “first kick” is given by an individual’s genetic liability for psychiatric disorders in combination with the family environment. In reality, the two are intertwined, especially when considering what it means to a family to have one member with a psychiatric disorder, which “will have an impact on the family environment.”
Dr. Verdolini added: “This is not actually the objective family environment,” but the perceived family environment.
“So maybe in the following 2 years the patient who experiences a first episode of psychosis may change their idea of the family environment itself,” she noted. She added that at her institution psychoeducation is offered to FEP patients’ families.
‘Interesting’ findings
Commenting on the study, Nicole Kozloff, MD, from the child, youth, and emerging adult program at the Centre for Addiction and Mental Health in Toronto, said one limitation of the study is that it’s not clear what care patients received – or who in the family completed the FES.
It is also important to note that “measures of association do not necessarily imply that one factor caused the other factor,” said Dr. Kozloff, who was not involved in the research. “For example, it may be that, among people with bipolar disorder, open expression of conflict in the family can lead to worse functioning, or that worse functioning can lead to more conflict in the family.”
Nevertheless, Dr. Kozloff described the finding of an emerging association between the family environment and functioning over time as “interesting.”
When young people with FEP enter treatment, “they have reached a crisis point and are functioning poorly,” she noted.
“It could be that there is less to differentiate among levels of functioning at treatment entry but, after 2 years, the individuals have separated into those who have been responsive to treatment and are functioning well, and those who continue to have functional challenges. And this is where we start to see a relationship with family environment emerge,” Dr. Kozloff said.
She also agreed with Dr. Verdolini’s take on the findings, and that family psychoeducation “can reduce relapse rates in schizophrenia and the emotional burden on the family.”
“We also know that having family involvement in care is one of the most robust predictors that young people with psychosis will remain engaged in mental health services,” she said.
Teaching families about psychosis and its treatment, about problem-solving and communication skills, and providing support to ensure that family members know how to get help in a crisis, “is a key part of comprehensive early psychosis intervention,” Dr. Kozloff said. “It is good for the patient and good for the family, and allows the clinicians to provide better care.”
Articulates clinical practice findings
Also commenting on the results, Brian O’Donoghue, MD, PhD, senior clinical research fellow at Orygen, the National Centre of Excellence in Youth Mental Health in Melbourne, described the research as important, adding that the study highlights the need for sufficient follow-up.
“It makes sense that the involvement of family over time has a strong impact upon outcome and functioning,” he said in an interview.
“These research findings articulate what we see in clinical practice, so it is good to see that it is captured,” added Dr. O’Donoghue, who was not associated with the study.
He noted that it is common for family involvement to influence outcome, especially if the family is positively involved. “It is invaluable toward their recovery. However, conversely, if there are ongoing family stressors, then this can be a trigger for relapse or lack of improvement.”
Overall, the results “really emphasize that the family needs to be involved in care.”
The Early Psychosis Prevention and Intervention Centre where Dr. O’Donoghue is a consultant psychiatrist offers a psychoeducational course “to inform families about psychosis, treatment, and how they can support their family members.”
“We also have family peer support workers and family therapists, which are essential to the service and for the young person’s recovery,” Dr. O’Donoghue said.
The investigators and Dr. O’Donoghue disclosed no relevant financial relationships. Dr. Kozloff reported receiving research funding from the CAMH Foundation, Brain & Behavior Research Foundation, Canadian Institutes of Health Research, and AFP Innovation Fund; honoraria from Humber River Hospital, the University of Calgary (Alta.), and the Canadian Consortium for Early Intervention in Psychosis; and salary support from Inner City Health Associates.
A version of this article originally appeared on Medscape.com.
FROM SIRS 2020
Drug-drug interactions to avoid in patients with GI cancer
warned a leading expert in the field.
Rachel P. Riechelmann, MD, AC Camargo Cancer Center, São Paulo, Brazil, was delivering a keynote speech during the ESMO 22nd World Congress on Gastrointestinal Cancer Virtual Experience on July 4.
One of the drug-drug interactions that can have a deleterious effect on patients with GI cancers is that occurring between proton pump inhibitors (PPIs), such as omeprazole, and chemotherapy regimens containing capecitabine, she said.
She cited clinical trial data showing that the use of PPIs can increase the risk for progression in colorectal cancer patients being treated with adjuvant CapeOx (capecitabine with oxaliplatin) or FOLFOX (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin). Further clinical trial data from the LOGIC trial show that PPIs have a significant effect on both progression-free and overall survival in HER2+ gastric cancer patients being treated with CapOx with or without lapatinib.
Commenting on the presentation on Twitter, Jose Fernando Moura, MD, PhD, Medical Oncology, Real Hospital Português, Recife, Brazil, agreed that it is better to avoid PPIs during chemotherapy for colorectal and gastrointestinal tumors.
Benedikt Westphalen, MD, PhD, coordinator, molecular oncology, University of Munich Comprehensive Cancer Center, Munich, Germany, replied that the data presented by Dr. Riechelmann are “clearly interesting.”
He added his own checklist of things to consider in regard to drug-drug interactions, including changes in drug levels, the effect on the microbiome, and gender differences.
Previous studies, including many from Dr. Riechelmann’s group, have indicated that potential drug-drug interactions occur in about two thirds of inpatients and in approximately one third of outpatients.
The frequency of clinically relevant drug interactions in oncology patients enrolled in clinical trials is “not that high,” however, at between 3% and 17%, depending on the mechanism of interaction, she commented.
“But it should be zero, because all clinical trials have a list of combinations that should not be prescribed and drugs that should be avoided,” she added.
There have been very few studies on the occurrence of drug-drug interactions in oncology patients in the real world, Dr. Riechelmann commented.
One study suggested that 4% of oncology deaths in hospitals were due to adverse drug reactions or interactions. Another study, conducted by Dr. Riechelmann’s team, suggested that 2% of nonelective hospitalizations among oncology patients were for drug-drug interactions.
She said that common potential drug interactions in oncology involve the use of aspirin, warfarin, beta blockers, and corticosteroids.
She also singled out olaparib (Lynparza, AstraZeneca) as an interesting case. Coadministration of drugs that act as CYP3A4 inhibitors or inducers can effect exposure to this drug; itraconazole significantly increases exposure, and rifampin significantly reduces exposure.
Avoiding interactions
In conclusion, Dr. Riechelmann made a series of recommendations for avoiding dangerous drug-drug interactions in cancer patients, the first of which is to avoid polypharmacy in the first place.
She also suggested that high-risk patients, such as those taking many drugs and who have comorbid illness, should be screened for potential drug interactions, and attention should be paid to “dangerous” combinations.
Combinations to avoid include those of two drugs that each prolong the QT interval. These include quinolones, azithromycin, and clarithromycin.
“I think every one of us has to develop our own list of dangerous combinations” that should be avoided if possible, she said. If their use is necessary, patients should be informed of the potential risk and should be monitored closely for adverse events.
No funding for the study has been reported. The investigators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
warned a leading expert in the field.
Rachel P. Riechelmann, MD, AC Camargo Cancer Center, São Paulo, Brazil, was delivering a keynote speech during the ESMO 22nd World Congress on Gastrointestinal Cancer Virtual Experience on July 4.
One of the drug-drug interactions that can have a deleterious effect on patients with GI cancers is that occurring between proton pump inhibitors (PPIs), such as omeprazole, and chemotherapy regimens containing capecitabine, she said.
She cited clinical trial data showing that the use of PPIs can increase the risk for progression in colorectal cancer patients being treated with adjuvant CapeOx (capecitabine with oxaliplatin) or FOLFOX (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin). Further clinical trial data from the LOGIC trial show that PPIs have a significant effect on both progression-free and overall survival in HER2+ gastric cancer patients being treated with CapOx with or without lapatinib.
Commenting on the presentation on Twitter, Jose Fernando Moura, MD, PhD, Medical Oncology, Real Hospital Português, Recife, Brazil, agreed that it is better to avoid PPIs during chemotherapy for colorectal and gastrointestinal tumors.
Benedikt Westphalen, MD, PhD, coordinator, molecular oncology, University of Munich Comprehensive Cancer Center, Munich, Germany, replied that the data presented by Dr. Riechelmann are “clearly interesting.”
He added his own checklist of things to consider in regard to drug-drug interactions, including changes in drug levels, the effect on the microbiome, and gender differences.
Previous studies, including many from Dr. Riechelmann’s group, have indicated that potential drug-drug interactions occur in about two thirds of inpatients and in approximately one third of outpatients.
The frequency of clinically relevant drug interactions in oncology patients enrolled in clinical trials is “not that high,” however, at between 3% and 17%, depending on the mechanism of interaction, she commented.
“But it should be zero, because all clinical trials have a list of combinations that should not be prescribed and drugs that should be avoided,” she added.
There have been very few studies on the occurrence of drug-drug interactions in oncology patients in the real world, Dr. Riechelmann commented.
One study suggested that 4% of oncology deaths in hospitals were due to adverse drug reactions or interactions. Another study, conducted by Dr. Riechelmann’s team, suggested that 2% of nonelective hospitalizations among oncology patients were for drug-drug interactions.
She said that common potential drug interactions in oncology involve the use of aspirin, warfarin, beta blockers, and corticosteroids.
She also singled out olaparib (Lynparza, AstraZeneca) as an interesting case. Coadministration of drugs that act as CYP3A4 inhibitors or inducers can effect exposure to this drug; itraconazole significantly increases exposure, and rifampin significantly reduces exposure.
Avoiding interactions
In conclusion, Dr. Riechelmann made a series of recommendations for avoiding dangerous drug-drug interactions in cancer patients, the first of which is to avoid polypharmacy in the first place.
She also suggested that high-risk patients, such as those taking many drugs and who have comorbid illness, should be screened for potential drug interactions, and attention should be paid to “dangerous” combinations.
Combinations to avoid include those of two drugs that each prolong the QT interval. These include quinolones, azithromycin, and clarithromycin.
“I think every one of us has to develop our own list of dangerous combinations” that should be avoided if possible, she said. If their use is necessary, patients should be informed of the potential risk and should be monitored closely for adverse events.
No funding for the study has been reported. The investigators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
warned a leading expert in the field.
Rachel P. Riechelmann, MD, AC Camargo Cancer Center, São Paulo, Brazil, was delivering a keynote speech during the ESMO 22nd World Congress on Gastrointestinal Cancer Virtual Experience on July 4.
One of the drug-drug interactions that can have a deleterious effect on patients with GI cancers is that occurring between proton pump inhibitors (PPIs), such as omeprazole, and chemotherapy regimens containing capecitabine, she said.
She cited clinical trial data showing that the use of PPIs can increase the risk for progression in colorectal cancer patients being treated with adjuvant CapeOx (capecitabine with oxaliplatin) or FOLFOX (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin). Further clinical trial data from the LOGIC trial show that PPIs have a significant effect on both progression-free and overall survival in HER2+ gastric cancer patients being treated with CapOx with or without lapatinib.
Commenting on the presentation on Twitter, Jose Fernando Moura, MD, PhD, Medical Oncology, Real Hospital Português, Recife, Brazil, agreed that it is better to avoid PPIs during chemotherapy for colorectal and gastrointestinal tumors.
Benedikt Westphalen, MD, PhD, coordinator, molecular oncology, University of Munich Comprehensive Cancer Center, Munich, Germany, replied that the data presented by Dr. Riechelmann are “clearly interesting.”
He added his own checklist of things to consider in regard to drug-drug interactions, including changes in drug levels, the effect on the microbiome, and gender differences.
Previous studies, including many from Dr. Riechelmann’s group, have indicated that potential drug-drug interactions occur in about two thirds of inpatients and in approximately one third of outpatients.
The frequency of clinically relevant drug interactions in oncology patients enrolled in clinical trials is “not that high,” however, at between 3% and 17%, depending on the mechanism of interaction, she commented.
“But it should be zero, because all clinical trials have a list of combinations that should not be prescribed and drugs that should be avoided,” she added.
There have been very few studies on the occurrence of drug-drug interactions in oncology patients in the real world, Dr. Riechelmann commented.
One study suggested that 4% of oncology deaths in hospitals were due to adverse drug reactions or interactions. Another study, conducted by Dr. Riechelmann’s team, suggested that 2% of nonelective hospitalizations among oncology patients were for drug-drug interactions.
She said that common potential drug interactions in oncology involve the use of aspirin, warfarin, beta blockers, and corticosteroids.
She also singled out olaparib (Lynparza, AstraZeneca) as an interesting case. Coadministration of drugs that act as CYP3A4 inhibitors or inducers can effect exposure to this drug; itraconazole significantly increases exposure, and rifampin significantly reduces exposure.
Avoiding interactions
In conclusion, Dr. Riechelmann made a series of recommendations for avoiding dangerous drug-drug interactions in cancer patients, the first of which is to avoid polypharmacy in the first place.
She also suggested that high-risk patients, such as those taking many drugs and who have comorbid illness, should be screened for potential drug interactions, and attention should be paid to “dangerous” combinations.
Combinations to avoid include those of two drugs that each prolong the QT interval. These include quinolones, azithromycin, and clarithromycin.
“I think every one of us has to develop our own list of dangerous combinations” that should be avoided if possible, she said. If their use is necessary, patients should be informed of the potential risk and should be monitored closely for adverse events.
No funding for the study has been reported. The investigators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Entrectinib results emphasize need for NTRK detection
Although fusions in the neurotrophic receptor tyrosine kinase (NTRK) gene are rare in gastrointestinal carcinomas (found in fewer than 5% of cases), they should be looked for, inasmuch as treatment with the TRK inhibitor entrectinib (Rozlytrek, Genentech/Roche) can achieve robust and durable responses, say researchers.
This point was made during several presentations at the virtual World Conference on Gastrointestinal Cancer (WCGC) 2020 on July 1.
Entrectinib and similar agents that act on NTRK fusion genes are described as tumor agnostic, in that they are biomarkers that define the cancer rather than the organ of origin.
The Food and Drug Administration last year granted accelerated approval of entrectinib for patients with locally advanced or metastatic NTRK-expressing solid tumors that have progressed following prior therapies. The drug can also be used as a first-line treatment when there are no effective therapies.
At the meeting, Manish R. Patel, MD, Department of Medicine, University of Minnesota, Minneapolis, and colleagues presented combined results from the ALKA-372-001, STARTRK-1, and STARTRK-2 studies of entrectinib.
They identified 12 gastrointestinal carcinoma patients among 74 adults with locally advanced/metastatic NTRK fusion positive, TRK inhibitor-naive solid tumors who had undergone at least 6 months of follow-up.
Many of these 12 patients had colorectal cancer (58%) or pancreatic cancer (24%).
Treatment with entrectinib elicited an overall response rate of 50%, which consisted entirely of partial responses.
The median duration of response was 12.9 months, which was largely driven by a median duration of response of 15.1 months among colorectal cancer patients, vs 10.0 months among pancreatic cancer patients and 9.3 months in the patient with cholangiocarcinoma.
The median progression-free survival was 7.1 months across the whole cohort. It was 8.0 months for pancreatic cancer patients and 12.0 months for the patient with cholangiocarcinoma.
The median overall survival was 16 months.
Dr. Patel said that this “demonstrates that entrectinib induces durable and clinically meaningful systemic responses in patients with gastrointestinal carcinomas harboring NTRK fusions.”
He noted that entrectinib is “overall very well tolerated, with very few dose interruptions or reductions, and the discontinuation rate was very low.” The majority of adverse events were of grade 1/2. The most common event was change in taste, which occurred in 37.3% of patients. There were no treatment-related deaths.
“The main take-away point from this abstract is that, though they are rare, if we identify patients with NTRK fusions during the course of the disease, we can offer them benefit from entrectinib, and I would argue that ... we should be screening patients for NTRK fusions much more frequently,” Dr. Patel added.
In the second study, a Belgian team performed immunohistochemistry (IHC) analysis followed by next-generation sequencing on archived samples of biliopancreatic cancers to determine the prevalence of NTRK fusions.
They found just one fusion among almost 150 biliary tract cancers and none in nearly 300 pancreatic adenocarcinomas.
Lead author Anne Demols, MD, PhD, Department of Gastroenterology and Gastrointestinal Oncology, CUB Hôpital Erasme, Brussels, Belgium, said the results show that, “consistent” with their low frequency in solid tumors, NTRK gene fusions are “also rare” in biliopancreatic cancers.
“Given this low frequency, testing and identification are of high clinical importance, due to possible treatment with pan-TRK inhibitors,” she said.
She added that a two-step diagnosis is recommended, in that it is both “time saving” and economical, and that next-generation sequencing is “mandatory” to confirm a positive result on IHC.
For discussant Juan W. Valle, MD, professor of medical oncology at the University of Manchester, United Kingdom, the results of the second study reinforce the take-home message of the first.
He said that “two-step diagnosis can preselect patients suitable for next-generation sequencing assay, and what we saw from the previous [study] is that the therapeutic implications make this an important diagnosis.”
Valle noted that there is an “immortal time bias” in the trial analysis, because patients had to be well enough to undergo at least 6 months of follow-up, and that “future work will focus on the best platform to use for known, as well as the identification of new, fusion partners.”
He highlighted the “improved response rate and progression-free survival” achieved with entrectinib among patients with gastrointestinal cancers harboring NTRK fusions, which will benefit patient outcomes.
Pashtoon Kasi, MD, a gastrointestinal oncologist at the University of Iowa Holden Comprehensive Cancer Center, Iowa City, commented on Twitter that, for him, the results were more than just about the impressive response rate but how “brisk, robust, and durable these tend to be.”
In his experience, even patients with stage IV disease who have responded to entrectinib have been able to undergo “secondary ‘curative’ resections.”
The ALKA-372-001, STARTRK-1 and STARTRK-2 studies were sponsored by F. Hoffmann-La Roche. The study by Demols and colleagues was funded by a research grant from Bayer Health. Dr. Patel reports relationships with Nektar Therapeutic, MSD, and Fate Therapeutics. Demols reports relationships with Bayer, Ipsen, Vifor, Servier and Roche. Dr. Valle reports relationships with numerous companies.
This article first appeared on Medscape.com.
Although fusions in the neurotrophic receptor tyrosine kinase (NTRK) gene are rare in gastrointestinal carcinomas (found in fewer than 5% of cases), they should be looked for, inasmuch as treatment with the TRK inhibitor entrectinib (Rozlytrek, Genentech/Roche) can achieve robust and durable responses, say researchers.
This point was made during several presentations at the virtual World Conference on Gastrointestinal Cancer (WCGC) 2020 on July 1.
Entrectinib and similar agents that act on NTRK fusion genes are described as tumor agnostic, in that they are biomarkers that define the cancer rather than the organ of origin.
The Food and Drug Administration last year granted accelerated approval of entrectinib for patients with locally advanced or metastatic NTRK-expressing solid tumors that have progressed following prior therapies. The drug can also be used as a first-line treatment when there are no effective therapies.
At the meeting, Manish R. Patel, MD, Department of Medicine, University of Minnesota, Minneapolis, and colleagues presented combined results from the ALKA-372-001, STARTRK-1, and STARTRK-2 studies of entrectinib.
They identified 12 gastrointestinal carcinoma patients among 74 adults with locally advanced/metastatic NTRK fusion positive, TRK inhibitor-naive solid tumors who had undergone at least 6 months of follow-up.
Many of these 12 patients had colorectal cancer (58%) or pancreatic cancer (24%).
Treatment with entrectinib elicited an overall response rate of 50%, which consisted entirely of partial responses.
The median duration of response was 12.9 months, which was largely driven by a median duration of response of 15.1 months among colorectal cancer patients, vs 10.0 months among pancreatic cancer patients and 9.3 months in the patient with cholangiocarcinoma.
The median progression-free survival was 7.1 months across the whole cohort. It was 8.0 months for pancreatic cancer patients and 12.0 months for the patient with cholangiocarcinoma.
The median overall survival was 16 months.
Dr. Patel said that this “demonstrates that entrectinib induces durable and clinically meaningful systemic responses in patients with gastrointestinal carcinomas harboring NTRK fusions.”
He noted that entrectinib is “overall very well tolerated, with very few dose interruptions or reductions, and the discontinuation rate was very low.” The majority of adverse events were of grade 1/2. The most common event was change in taste, which occurred in 37.3% of patients. There were no treatment-related deaths.
“The main take-away point from this abstract is that, though they are rare, if we identify patients with NTRK fusions during the course of the disease, we can offer them benefit from entrectinib, and I would argue that ... we should be screening patients for NTRK fusions much more frequently,” Dr. Patel added.
In the second study, a Belgian team performed immunohistochemistry (IHC) analysis followed by next-generation sequencing on archived samples of biliopancreatic cancers to determine the prevalence of NTRK fusions.
They found just one fusion among almost 150 biliary tract cancers and none in nearly 300 pancreatic adenocarcinomas.
Lead author Anne Demols, MD, PhD, Department of Gastroenterology and Gastrointestinal Oncology, CUB Hôpital Erasme, Brussels, Belgium, said the results show that, “consistent” with their low frequency in solid tumors, NTRK gene fusions are “also rare” in biliopancreatic cancers.
“Given this low frequency, testing and identification are of high clinical importance, due to possible treatment with pan-TRK inhibitors,” she said.
She added that a two-step diagnosis is recommended, in that it is both “time saving” and economical, and that next-generation sequencing is “mandatory” to confirm a positive result on IHC.
For discussant Juan W. Valle, MD, professor of medical oncology at the University of Manchester, United Kingdom, the results of the second study reinforce the take-home message of the first.
He said that “two-step diagnosis can preselect patients suitable for next-generation sequencing assay, and what we saw from the previous [study] is that the therapeutic implications make this an important diagnosis.”
Valle noted that there is an “immortal time bias” in the trial analysis, because patients had to be well enough to undergo at least 6 months of follow-up, and that “future work will focus on the best platform to use for known, as well as the identification of new, fusion partners.”
He highlighted the “improved response rate and progression-free survival” achieved with entrectinib among patients with gastrointestinal cancers harboring NTRK fusions, which will benefit patient outcomes.
Pashtoon Kasi, MD, a gastrointestinal oncologist at the University of Iowa Holden Comprehensive Cancer Center, Iowa City, commented on Twitter that, for him, the results were more than just about the impressive response rate but how “brisk, robust, and durable these tend to be.”
In his experience, even patients with stage IV disease who have responded to entrectinib have been able to undergo “secondary ‘curative’ resections.”
The ALKA-372-001, STARTRK-1 and STARTRK-2 studies were sponsored by F. Hoffmann-La Roche. The study by Demols and colleagues was funded by a research grant from Bayer Health. Dr. Patel reports relationships with Nektar Therapeutic, MSD, and Fate Therapeutics. Demols reports relationships with Bayer, Ipsen, Vifor, Servier and Roche. Dr. Valle reports relationships with numerous companies.
This article first appeared on Medscape.com.
Although fusions in the neurotrophic receptor tyrosine kinase (NTRK) gene are rare in gastrointestinal carcinomas (found in fewer than 5% of cases), they should be looked for, inasmuch as treatment with the TRK inhibitor entrectinib (Rozlytrek, Genentech/Roche) can achieve robust and durable responses, say researchers.
This point was made during several presentations at the virtual World Conference on Gastrointestinal Cancer (WCGC) 2020 on July 1.
Entrectinib and similar agents that act on NTRK fusion genes are described as tumor agnostic, in that they are biomarkers that define the cancer rather than the organ of origin.
The Food and Drug Administration last year granted accelerated approval of entrectinib for patients with locally advanced or metastatic NTRK-expressing solid tumors that have progressed following prior therapies. The drug can also be used as a first-line treatment when there are no effective therapies.
At the meeting, Manish R. Patel, MD, Department of Medicine, University of Minnesota, Minneapolis, and colleagues presented combined results from the ALKA-372-001, STARTRK-1, and STARTRK-2 studies of entrectinib.
They identified 12 gastrointestinal carcinoma patients among 74 adults with locally advanced/metastatic NTRK fusion positive, TRK inhibitor-naive solid tumors who had undergone at least 6 months of follow-up.
Many of these 12 patients had colorectal cancer (58%) or pancreatic cancer (24%).
Treatment with entrectinib elicited an overall response rate of 50%, which consisted entirely of partial responses.
The median duration of response was 12.9 months, which was largely driven by a median duration of response of 15.1 months among colorectal cancer patients, vs 10.0 months among pancreatic cancer patients and 9.3 months in the patient with cholangiocarcinoma.
The median progression-free survival was 7.1 months across the whole cohort. It was 8.0 months for pancreatic cancer patients and 12.0 months for the patient with cholangiocarcinoma.
The median overall survival was 16 months.
Dr. Patel said that this “demonstrates that entrectinib induces durable and clinically meaningful systemic responses in patients with gastrointestinal carcinomas harboring NTRK fusions.”
He noted that entrectinib is “overall very well tolerated, with very few dose interruptions or reductions, and the discontinuation rate was very low.” The majority of adverse events were of grade 1/2. The most common event was change in taste, which occurred in 37.3% of patients. There were no treatment-related deaths.
“The main take-away point from this abstract is that, though they are rare, if we identify patients with NTRK fusions during the course of the disease, we can offer them benefit from entrectinib, and I would argue that ... we should be screening patients for NTRK fusions much more frequently,” Dr. Patel added.
In the second study, a Belgian team performed immunohistochemistry (IHC) analysis followed by next-generation sequencing on archived samples of biliopancreatic cancers to determine the prevalence of NTRK fusions.
They found just one fusion among almost 150 biliary tract cancers and none in nearly 300 pancreatic adenocarcinomas.
Lead author Anne Demols, MD, PhD, Department of Gastroenterology and Gastrointestinal Oncology, CUB Hôpital Erasme, Brussels, Belgium, said the results show that, “consistent” with their low frequency in solid tumors, NTRK gene fusions are “also rare” in biliopancreatic cancers.
“Given this low frequency, testing and identification are of high clinical importance, due to possible treatment with pan-TRK inhibitors,” she said.
She added that a two-step diagnosis is recommended, in that it is both “time saving” and economical, and that next-generation sequencing is “mandatory” to confirm a positive result on IHC.
For discussant Juan W. Valle, MD, professor of medical oncology at the University of Manchester, United Kingdom, the results of the second study reinforce the take-home message of the first.
He said that “two-step diagnosis can preselect patients suitable for next-generation sequencing assay, and what we saw from the previous [study] is that the therapeutic implications make this an important diagnosis.”
Valle noted that there is an “immortal time bias” in the trial analysis, because patients had to be well enough to undergo at least 6 months of follow-up, and that “future work will focus on the best platform to use for known, as well as the identification of new, fusion partners.”
He highlighted the “improved response rate and progression-free survival” achieved with entrectinib among patients with gastrointestinal cancers harboring NTRK fusions, which will benefit patient outcomes.
Pashtoon Kasi, MD, a gastrointestinal oncologist at the University of Iowa Holden Comprehensive Cancer Center, Iowa City, commented on Twitter that, for him, the results were more than just about the impressive response rate but how “brisk, robust, and durable these tend to be.”
In his experience, even patients with stage IV disease who have responded to entrectinib have been able to undergo “secondary ‘curative’ resections.”
The ALKA-372-001, STARTRK-1 and STARTRK-2 studies were sponsored by F. Hoffmann-La Roche. The study by Demols and colleagues was funded by a research grant from Bayer Health. Dr. Patel reports relationships with Nektar Therapeutic, MSD, and Fate Therapeutics. Demols reports relationships with Bayer, Ipsen, Vifor, Servier and Roche. Dr. Valle reports relationships with numerous companies.
This article first appeared on Medscape.com.