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University to train ‘trip facilitators’ for psychedelic therapy
The UC Berkeley Center for the Science of Psychedelics (BCSP) training program aims to create a cadre of facilitators who will be ready to help if, and when, substances such as psilocybin, MDMA, and LSD are approved in the United States, Tina Trujillo, PhD, an associate professor at UC Berkeley’s School of Education, told reporters at a press briefing.
Hallucinogenic drugs are on the Drug Enforcement Administration’s (DEA) Schedule I list because they are considered to have no currently accepted medical use and high abuse potential. But there has been an explosion of research into psychedelics – combined with therapy – as treatment for severe depression, posttraumatic stress disorder, substance-use disorder, and other mental health conditions. Some 100 clinical trials are underway.
“The estimates are that we’re going to need 100,000 trained psychedelic facilitators once psilocybin and MDMA are approved by the [U.S. Food and Drug Administration] FDA, which is expected to happen within the next 5 years or so,” said Michael Pollan, co-founder of the BCSP. He is author of “How to Change Your Mind,” a 2018 book about psychedelics, which has been adapted into a four-part docuseries currently streaming on Netflix.
Nine-month program
The first 24 trainees – a mix of physicians, nurses, psychotherapists, and social workers – will undergo 9 months of education and preparation in “the technical, the cultural, the mystical, and the ethical dimensions of psychedelic facilitation,” said Dr. Trujillo.
The BCSP’s Certificate Program in Psychedelic Facilitation will have “an emphasis on both western science and spiritual care traditions,” she said.
Trainees will receive 150 instructional hours and a 25-hour practicum and will take part in a final 5-day retreat. The program will initially focus only on psilocybin, in part because the BCSP is involved in several FDA-approved trials testing the drug.
In one study – which aims to enroll participants in the fall – researchers will use functional MRI to examine the neural correlates of the psychedelic experience in individuals receiving low-dose psilocybin.
Eligible trainees will have an opportunity to participate in the Berkeley psilocybin trials and “increase their first-hand knowledge,” Dr. Trujillo said.
At the conclusion of the training, students will receive a certificate, “not a license or sanction to go off and practice,” she said. She noted that eventually, when facilitation is legal, certificate holders will be able to practice in clinical research settings or in health care settings.
Growing acceptance in psychiatry
Mr. Pollan said there has been a radical change in acceptance of psychedelics as potential therapies.
“The shift from destroyer of young minds in the ‘60s to effective medicine in the 2020s is as sudden as it is confusing for many people,” he said. He noted that the Berkeley center hopes to provide evidence-based information for journalists, the public, and clinicians.
He said that after his book was released, he expected pushback from “mainstream psychiatry.” Instead, he was invited to give grand rounds talks. Psychiatrists are “very open to the potential of psychedelics,” Mr. Pollan said.
“The reason for that, quite frankly, is because they are desperate,” he said. “The tools of conventional psychiatry to deal with things like depression and anxiety and addiction are not very good, and some of them are failing,” he said.
Mr. Pollan cited some other indicators of acceptance. In Oregon, beginning in 2023, psilocybin will be available to anyone older than 21 years but only for use in licensed facilities with licensed facilitators, and the substance must be produced by a licensed manufacturer.
In November, Colorado will ask voters whether they want to follow the Oregon model and legalize psilocybin. If approved, another Colorado ballot initiative would decriminalize possession.
Mr. Pollan noted that Cory Booker, the Democratic Senator from New Jersey, and Rand Paul, a conservative Republican Senator from Kentucky, have found a common cause, introducing legislation to let select terminally ill patients have access to psychedelics and other Schedule I drugs.
Some 400 companies are conducting research on psychedelics. Researchers must have a license from the DEA to obtain and study the substances, Andrea Gomez, assistant professor of neurobiology at UC Berkeley, told reporters.
She said growing interest in the potential of these drugs might lead more researchers to “jump through the hoops” to get the licenses. The floodgates would truly open if the National Institutes of Health started funding studies, she said.
A version of this article first appeared on Medscape.com.
The UC Berkeley Center for the Science of Psychedelics (BCSP) training program aims to create a cadre of facilitators who will be ready to help if, and when, substances such as psilocybin, MDMA, and LSD are approved in the United States, Tina Trujillo, PhD, an associate professor at UC Berkeley’s School of Education, told reporters at a press briefing.
Hallucinogenic drugs are on the Drug Enforcement Administration’s (DEA) Schedule I list because they are considered to have no currently accepted medical use and high abuse potential. But there has been an explosion of research into psychedelics – combined with therapy – as treatment for severe depression, posttraumatic stress disorder, substance-use disorder, and other mental health conditions. Some 100 clinical trials are underway.
“The estimates are that we’re going to need 100,000 trained psychedelic facilitators once psilocybin and MDMA are approved by the [U.S. Food and Drug Administration] FDA, which is expected to happen within the next 5 years or so,” said Michael Pollan, co-founder of the BCSP. He is author of “How to Change Your Mind,” a 2018 book about psychedelics, which has been adapted into a four-part docuseries currently streaming on Netflix.
Nine-month program
The first 24 trainees – a mix of physicians, nurses, psychotherapists, and social workers – will undergo 9 months of education and preparation in “the technical, the cultural, the mystical, and the ethical dimensions of psychedelic facilitation,” said Dr. Trujillo.
The BCSP’s Certificate Program in Psychedelic Facilitation will have “an emphasis on both western science and spiritual care traditions,” she said.
Trainees will receive 150 instructional hours and a 25-hour practicum and will take part in a final 5-day retreat. The program will initially focus only on psilocybin, in part because the BCSP is involved in several FDA-approved trials testing the drug.
In one study – which aims to enroll participants in the fall – researchers will use functional MRI to examine the neural correlates of the psychedelic experience in individuals receiving low-dose psilocybin.
Eligible trainees will have an opportunity to participate in the Berkeley psilocybin trials and “increase their first-hand knowledge,” Dr. Trujillo said.
At the conclusion of the training, students will receive a certificate, “not a license or sanction to go off and practice,” she said. She noted that eventually, when facilitation is legal, certificate holders will be able to practice in clinical research settings or in health care settings.
Growing acceptance in psychiatry
Mr. Pollan said there has been a radical change in acceptance of psychedelics as potential therapies.
“The shift from destroyer of young minds in the ‘60s to effective medicine in the 2020s is as sudden as it is confusing for many people,” he said. He noted that the Berkeley center hopes to provide evidence-based information for journalists, the public, and clinicians.
He said that after his book was released, he expected pushback from “mainstream psychiatry.” Instead, he was invited to give grand rounds talks. Psychiatrists are “very open to the potential of psychedelics,” Mr. Pollan said.
“The reason for that, quite frankly, is because they are desperate,” he said. “The tools of conventional psychiatry to deal with things like depression and anxiety and addiction are not very good, and some of them are failing,” he said.
Mr. Pollan cited some other indicators of acceptance. In Oregon, beginning in 2023, psilocybin will be available to anyone older than 21 years but only for use in licensed facilities with licensed facilitators, and the substance must be produced by a licensed manufacturer.
In November, Colorado will ask voters whether they want to follow the Oregon model and legalize psilocybin. If approved, another Colorado ballot initiative would decriminalize possession.
Mr. Pollan noted that Cory Booker, the Democratic Senator from New Jersey, and Rand Paul, a conservative Republican Senator from Kentucky, have found a common cause, introducing legislation to let select terminally ill patients have access to psychedelics and other Schedule I drugs.
Some 400 companies are conducting research on psychedelics. Researchers must have a license from the DEA to obtain and study the substances, Andrea Gomez, assistant professor of neurobiology at UC Berkeley, told reporters.
She said growing interest in the potential of these drugs might lead more researchers to “jump through the hoops” to get the licenses. The floodgates would truly open if the National Institutes of Health started funding studies, she said.
A version of this article first appeared on Medscape.com.
The UC Berkeley Center for the Science of Psychedelics (BCSP) training program aims to create a cadre of facilitators who will be ready to help if, and when, substances such as psilocybin, MDMA, and LSD are approved in the United States, Tina Trujillo, PhD, an associate professor at UC Berkeley’s School of Education, told reporters at a press briefing.
Hallucinogenic drugs are on the Drug Enforcement Administration’s (DEA) Schedule I list because they are considered to have no currently accepted medical use and high abuse potential. But there has been an explosion of research into psychedelics – combined with therapy – as treatment for severe depression, posttraumatic stress disorder, substance-use disorder, and other mental health conditions. Some 100 clinical trials are underway.
“The estimates are that we’re going to need 100,000 trained psychedelic facilitators once psilocybin and MDMA are approved by the [U.S. Food and Drug Administration] FDA, which is expected to happen within the next 5 years or so,” said Michael Pollan, co-founder of the BCSP. He is author of “How to Change Your Mind,” a 2018 book about psychedelics, which has been adapted into a four-part docuseries currently streaming on Netflix.
Nine-month program
The first 24 trainees – a mix of physicians, nurses, psychotherapists, and social workers – will undergo 9 months of education and preparation in “the technical, the cultural, the mystical, and the ethical dimensions of psychedelic facilitation,” said Dr. Trujillo.
The BCSP’s Certificate Program in Psychedelic Facilitation will have “an emphasis on both western science and spiritual care traditions,” she said.
Trainees will receive 150 instructional hours and a 25-hour practicum and will take part in a final 5-day retreat. The program will initially focus only on psilocybin, in part because the BCSP is involved in several FDA-approved trials testing the drug.
In one study – which aims to enroll participants in the fall – researchers will use functional MRI to examine the neural correlates of the psychedelic experience in individuals receiving low-dose psilocybin.
Eligible trainees will have an opportunity to participate in the Berkeley psilocybin trials and “increase their first-hand knowledge,” Dr. Trujillo said.
At the conclusion of the training, students will receive a certificate, “not a license or sanction to go off and practice,” she said. She noted that eventually, when facilitation is legal, certificate holders will be able to practice in clinical research settings or in health care settings.
Growing acceptance in psychiatry
Mr. Pollan said there has been a radical change in acceptance of psychedelics as potential therapies.
“The shift from destroyer of young minds in the ‘60s to effective medicine in the 2020s is as sudden as it is confusing for many people,” he said. He noted that the Berkeley center hopes to provide evidence-based information for journalists, the public, and clinicians.
He said that after his book was released, he expected pushback from “mainstream psychiatry.” Instead, he was invited to give grand rounds talks. Psychiatrists are “very open to the potential of psychedelics,” Mr. Pollan said.
“The reason for that, quite frankly, is because they are desperate,” he said. “The tools of conventional psychiatry to deal with things like depression and anxiety and addiction are not very good, and some of them are failing,” he said.
Mr. Pollan cited some other indicators of acceptance. In Oregon, beginning in 2023, psilocybin will be available to anyone older than 21 years but only for use in licensed facilities with licensed facilitators, and the substance must be produced by a licensed manufacturer.
In November, Colorado will ask voters whether they want to follow the Oregon model and legalize psilocybin. If approved, another Colorado ballot initiative would decriminalize possession.
Mr. Pollan noted that Cory Booker, the Democratic Senator from New Jersey, and Rand Paul, a conservative Republican Senator from Kentucky, have found a common cause, introducing legislation to let select terminally ill patients have access to psychedelics and other Schedule I drugs.
Some 400 companies are conducting research on psychedelics. Researchers must have a license from the DEA to obtain and study the substances, Andrea Gomez, assistant professor of neurobiology at UC Berkeley, told reporters.
She said growing interest in the potential of these drugs might lead more researchers to “jump through the hoops” to get the licenses. The floodgates would truly open if the National Institutes of Health started funding studies, she said.
A version of this article first appeared on Medscape.com.
Sexual assault flagged as a possible psychosis trigger
A new study sheds light on some of the risk factors for the development of psychosis, including the potentially causative role of sexual assault.
Investigators conducted an exposome-wide association analysis on more than 155,000 individuals. Of more than 140 correlates of psychotic experiences that they identified, they narrowed it down to 36 variables, which they further explored using Mendelian randomization analysis.
On the other hand, having experienced a physical violent crime, cannabis use, and prolonged worry after embarrassment showed a pleiotropic association and appeared to be an aftereffect of psychotic experience.
“From a public health perspective, we need more investment in comprehensive strategies to prevent traumatic experiences at the population level to decrease the burden of psychosis,” senior author Sinan Gülöksüz, MD, PhD, associate professor in the department of psychiatry and neuropsychiatry, Maastricht University Medical Center, the Netherlands, said in an interview.
“From a clinical perspective, clinicians should be aware of the harmful influence of traumatic experiences on mental health and address this through interventions such as trauma-informed care,” he said.
The study was published online in JAMA Psychiatry.
‘Disentangling’ cause and effect
“Previous research has shown associations between psychosis and a few environmental factors, such as substance use, urbanicity, pregnancy complications, and traumatic experiences, but research has so far investigated only a few specific environmental factors by singling them out in individual studies,” Dr. Gülöksüz said.
“Yet, environment is a much more complex and interactive network that includes many factors shaping our health – where we live, what we eat, our lifestyle preferences and habits such as exercise and smoking, and our social surrounding,” he continued. “Rarely has it been possible to understand whether these environmental factors have causal roles in developing psychosis.”
To investigate the question, the researchers turned to the UK Biobank, one of the largest population-based datasets in the world. The current study focused on individuals with completed data on mental questionnaires that assessed psychotic experiences (n = 155,247; mean [SD] age, 55.94 [7.74] years; 57% female).
They began by conducting an exposome-wide association study, using logistic regression analyses with psychotic experiences as the outcome and adjusting all analyses for age and sex.
“Initially, we identified many associations between environmental factors and psychotic experiences in this large cohort,” Dr. Gülöksüz reported.
In the final multivariable model, variables associated with psychotic experiences were further analyzed using “genetically informed approaches to probe potential associations.”
The researchers utilized Mendelian randomization (MR) methodology “to disentangle cause and effect in this observational study,” Dr. Gülöksüz said. “This method reduces confounding and reverse causation in observational studies by using genetic variants that have been passed on from generation to generation randomly as instruments.”
MR analysis “has allowed us to assess whether these associations reflect potentially causal influences of environmental factors on psychotic experiences,” he added.
Well-studied and unexplored risk factors
The researchers identified 162 variables associated with psychotic experiences in the discovery dataset and were able to replicate 148. When these 148 variables were subjected to multivariable analyses, 36 were found to be statistically significantly associated with psychotic experiences. Of these variables, 28 had “significant genetic overlap” with psychotic experiences.
When the researchers conducted one-sample MR analyses, they found forward associations with three variables and reverse associations with three variables.
Forward associations were found with ever having experienced sexual assault (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.14-1.52; P = 2.67), and forward associations (with pleiotropy) were found with ever having experienced a physically violent crime and risk-taking behavior (OR, 1.25, 95% CI, 1.11-1.41; P = 3.28 and OR, 1.21, 95% CI, 1.08-1.35; P = 1.34, respectively).
“The allele scores for these 3 variables explained 0.03% to 0.23% variance of the corresponding variable” and the F statistics “ranged from 21.53 to 181.84, indicating that the results did not suffer from a weak-instrument bias,” the authors reported.
The researchers calculated an instrument based on increasing psychotic experiences risk allele scores and found that these scores explained 0.14% variance of psychotic experiences (F statistic, 19.26).
Using that calculation, they found a reverse association with having experienced a physically violent crime (OR, 1.08; 95% CI, 1.04-1.13; P = 3.92 × 10-4), cannabis use (OR, 1.11; 95% CI, 1.06-1.15; P = 2.64 × 10-6), and worrying too long after embarrassment (OR, 1.06; 95% CI, 1.03-1.10; P = 3.96 × 10-4). They then validated these associations.
The presence of all five correlates was associated with tenfold increased odds of psychotic experiences (OR, 10.63; 95% CI, 8.27-13.65, P = 1.2 × 10-114).
“Associations with psychotic experiences were found with both well-studied and unexplored multiple correlated variables,” the authors stated.
Era of ‘big data’
In a comment, Chirag Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, who was not involved with the study, said he thought the study was “a nice example of a data-driven and comprehensive study of the environment coupled with attempts to triangulate evidence from genetics, made possible by biobank data.
“To guide public health policies and implementation of prevention strategies for psychosis, we need more systematic analyses and triangulate evidence with genetically informed methods to identify potentially modifiable risk factors in the era of ‘big data,’ ” he said.
“For instance, traumatic experiences contribute to poor mental and physical health, including psychosis,” Dr. Gülöksüz added.
The Kootstra Talent Fellowship, the Ophelia Research Project, and the Vidi Award from the Netherlands Scientific Organization provided funding to individual investigators. Dr. Gülöksüz and coauthors declared no relevant financial conflicts. Dr. Patel served as a reviewer on the study.
A version of this article first appeared on Medscape.com.
A new study sheds light on some of the risk factors for the development of psychosis, including the potentially causative role of sexual assault.
Investigators conducted an exposome-wide association analysis on more than 155,000 individuals. Of more than 140 correlates of psychotic experiences that they identified, they narrowed it down to 36 variables, which they further explored using Mendelian randomization analysis.
On the other hand, having experienced a physical violent crime, cannabis use, and prolonged worry after embarrassment showed a pleiotropic association and appeared to be an aftereffect of psychotic experience.
“From a public health perspective, we need more investment in comprehensive strategies to prevent traumatic experiences at the population level to decrease the burden of psychosis,” senior author Sinan Gülöksüz, MD, PhD, associate professor in the department of psychiatry and neuropsychiatry, Maastricht University Medical Center, the Netherlands, said in an interview.
“From a clinical perspective, clinicians should be aware of the harmful influence of traumatic experiences on mental health and address this through interventions such as trauma-informed care,” he said.
The study was published online in JAMA Psychiatry.
‘Disentangling’ cause and effect
“Previous research has shown associations between psychosis and a few environmental factors, such as substance use, urbanicity, pregnancy complications, and traumatic experiences, but research has so far investigated only a few specific environmental factors by singling them out in individual studies,” Dr. Gülöksüz said.
“Yet, environment is a much more complex and interactive network that includes many factors shaping our health – where we live, what we eat, our lifestyle preferences and habits such as exercise and smoking, and our social surrounding,” he continued. “Rarely has it been possible to understand whether these environmental factors have causal roles in developing psychosis.”
To investigate the question, the researchers turned to the UK Biobank, one of the largest population-based datasets in the world. The current study focused on individuals with completed data on mental questionnaires that assessed psychotic experiences (n = 155,247; mean [SD] age, 55.94 [7.74] years; 57% female).
They began by conducting an exposome-wide association study, using logistic regression analyses with psychotic experiences as the outcome and adjusting all analyses for age and sex.
“Initially, we identified many associations between environmental factors and psychotic experiences in this large cohort,” Dr. Gülöksüz reported.
In the final multivariable model, variables associated with psychotic experiences were further analyzed using “genetically informed approaches to probe potential associations.”
The researchers utilized Mendelian randomization (MR) methodology “to disentangle cause and effect in this observational study,” Dr. Gülöksüz said. “This method reduces confounding and reverse causation in observational studies by using genetic variants that have been passed on from generation to generation randomly as instruments.”
MR analysis “has allowed us to assess whether these associations reflect potentially causal influences of environmental factors on psychotic experiences,” he added.
Well-studied and unexplored risk factors
The researchers identified 162 variables associated with psychotic experiences in the discovery dataset and were able to replicate 148. When these 148 variables were subjected to multivariable analyses, 36 were found to be statistically significantly associated with psychotic experiences. Of these variables, 28 had “significant genetic overlap” with psychotic experiences.
When the researchers conducted one-sample MR analyses, they found forward associations with three variables and reverse associations with three variables.
Forward associations were found with ever having experienced sexual assault (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.14-1.52; P = 2.67), and forward associations (with pleiotropy) were found with ever having experienced a physically violent crime and risk-taking behavior (OR, 1.25, 95% CI, 1.11-1.41; P = 3.28 and OR, 1.21, 95% CI, 1.08-1.35; P = 1.34, respectively).
“The allele scores for these 3 variables explained 0.03% to 0.23% variance of the corresponding variable” and the F statistics “ranged from 21.53 to 181.84, indicating that the results did not suffer from a weak-instrument bias,” the authors reported.
The researchers calculated an instrument based on increasing psychotic experiences risk allele scores and found that these scores explained 0.14% variance of psychotic experiences (F statistic, 19.26).
Using that calculation, they found a reverse association with having experienced a physically violent crime (OR, 1.08; 95% CI, 1.04-1.13; P = 3.92 × 10-4), cannabis use (OR, 1.11; 95% CI, 1.06-1.15; P = 2.64 × 10-6), and worrying too long after embarrassment (OR, 1.06; 95% CI, 1.03-1.10; P = 3.96 × 10-4). They then validated these associations.
The presence of all five correlates was associated with tenfold increased odds of psychotic experiences (OR, 10.63; 95% CI, 8.27-13.65, P = 1.2 × 10-114).
“Associations with psychotic experiences were found with both well-studied and unexplored multiple correlated variables,” the authors stated.
Era of ‘big data’
In a comment, Chirag Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, who was not involved with the study, said he thought the study was “a nice example of a data-driven and comprehensive study of the environment coupled with attempts to triangulate evidence from genetics, made possible by biobank data.
“To guide public health policies and implementation of prevention strategies for psychosis, we need more systematic analyses and triangulate evidence with genetically informed methods to identify potentially modifiable risk factors in the era of ‘big data,’ ” he said.
“For instance, traumatic experiences contribute to poor mental and physical health, including psychosis,” Dr. Gülöksüz added.
The Kootstra Talent Fellowship, the Ophelia Research Project, and the Vidi Award from the Netherlands Scientific Organization provided funding to individual investigators. Dr. Gülöksüz and coauthors declared no relevant financial conflicts. Dr. Patel served as a reviewer on the study.
A version of this article first appeared on Medscape.com.
A new study sheds light on some of the risk factors for the development of psychosis, including the potentially causative role of sexual assault.
Investigators conducted an exposome-wide association analysis on more than 155,000 individuals. Of more than 140 correlates of psychotic experiences that they identified, they narrowed it down to 36 variables, which they further explored using Mendelian randomization analysis.
On the other hand, having experienced a physical violent crime, cannabis use, and prolonged worry after embarrassment showed a pleiotropic association and appeared to be an aftereffect of psychotic experience.
“From a public health perspective, we need more investment in comprehensive strategies to prevent traumatic experiences at the population level to decrease the burden of psychosis,” senior author Sinan Gülöksüz, MD, PhD, associate professor in the department of psychiatry and neuropsychiatry, Maastricht University Medical Center, the Netherlands, said in an interview.
“From a clinical perspective, clinicians should be aware of the harmful influence of traumatic experiences on mental health and address this through interventions such as trauma-informed care,” he said.
The study was published online in JAMA Psychiatry.
‘Disentangling’ cause and effect
“Previous research has shown associations between psychosis and a few environmental factors, such as substance use, urbanicity, pregnancy complications, and traumatic experiences, but research has so far investigated only a few specific environmental factors by singling them out in individual studies,” Dr. Gülöksüz said.
“Yet, environment is a much more complex and interactive network that includes many factors shaping our health – where we live, what we eat, our lifestyle preferences and habits such as exercise and smoking, and our social surrounding,” he continued. “Rarely has it been possible to understand whether these environmental factors have causal roles in developing psychosis.”
To investigate the question, the researchers turned to the UK Biobank, one of the largest population-based datasets in the world. The current study focused on individuals with completed data on mental questionnaires that assessed psychotic experiences (n = 155,247; mean [SD] age, 55.94 [7.74] years; 57% female).
They began by conducting an exposome-wide association study, using logistic regression analyses with psychotic experiences as the outcome and adjusting all analyses for age and sex.
“Initially, we identified many associations between environmental factors and psychotic experiences in this large cohort,” Dr. Gülöksüz reported.
In the final multivariable model, variables associated with psychotic experiences were further analyzed using “genetically informed approaches to probe potential associations.”
The researchers utilized Mendelian randomization (MR) methodology “to disentangle cause and effect in this observational study,” Dr. Gülöksüz said. “This method reduces confounding and reverse causation in observational studies by using genetic variants that have been passed on from generation to generation randomly as instruments.”
MR analysis “has allowed us to assess whether these associations reflect potentially causal influences of environmental factors on psychotic experiences,” he added.
Well-studied and unexplored risk factors
The researchers identified 162 variables associated with psychotic experiences in the discovery dataset and were able to replicate 148. When these 148 variables were subjected to multivariable analyses, 36 were found to be statistically significantly associated with psychotic experiences. Of these variables, 28 had “significant genetic overlap” with psychotic experiences.
When the researchers conducted one-sample MR analyses, they found forward associations with three variables and reverse associations with three variables.
Forward associations were found with ever having experienced sexual assault (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.14-1.52; P = 2.67), and forward associations (with pleiotropy) were found with ever having experienced a physically violent crime and risk-taking behavior (OR, 1.25, 95% CI, 1.11-1.41; P = 3.28 and OR, 1.21, 95% CI, 1.08-1.35; P = 1.34, respectively).
“The allele scores for these 3 variables explained 0.03% to 0.23% variance of the corresponding variable” and the F statistics “ranged from 21.53 to 181.84, indicating that the results did not suffer from a weak-instrument bias,” the authors reported.
The researchers calculated an instrument based on increasing psychotic experiences risk allele scores and found that these scores explained 0.14% variance of psychotic experiences (F statistic, 19.26).
Using that calculation, they found a reverse association with having experienced a physically violent crime (OR, 1.08; 95% CI, 1.04-1.13; P = 3.92 × 10-4), cannabis use (OR, 1.11; 95% CI, 1.06-1.15; P = 2.64 × 10-6), and worrying too long after embarrassment (OR, 1.06; 95% CI, 1.03-1.10; P = 3.96 × 10-4). They then validated these associations.
The presence of all five correlates was associated with tenfold increased odds of psychotic experiences (OR, 10.63; 95% CI, 8.27-13.65, P = 1.2 × 10-114).
“Associations with psychotic experiences were found with both well-studied and unexplored multiple correlated variables,” the authors stated.
Era of ‘big data’
In a comment, Chirag Patel, PhD, associate professor of biomedical informatics at Harvard Medical School, Boston, who was not involved with the study, said he thought the study was “a nice example of a data-driven and comprehensive study of the environment coupled with attempts to triangulate evidence from genetics, made possible by biobank data.
“To guide public health policies and implementation of prevention strategies for psychosis, we need more systematic analyses and triangulate evidence with genetically informed methods to identify potentially modifiable risk factors in the era of ‘big data,’ ” he said.
“For instance, traumatic experiences contribute to poor mental and physical health, including psychosis,” Dr. Gülöksüz added.
The Kootstra Talent Fellowship, the Ophelia Research Project, and the Vidi Award from the Netherlands Scientific Organization provided funding to individual investigators. Dr. Gülöksüz and coauthors declared no relevant financial conflicts. Dr. Patel served as a reviewer on the study.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY
Skin-picking, hair-pulling disorders: Diagnostic criteria, prevalence, and treatment
INDIANAPOLIS –
And while both body-focused repetitive behavior disorders affect a greater proportion of females than males, “we have no current information that is useful about what hormonal influences may or may not play in terms of picking and pulling behaviors,” Jon E. Grant, MD, JD, MPH, professor of psychiatry and behavioral neuroscience at the University of Chicago, said at the annual meeting of the Society for Pediatric Dermatology. “On a cognitive level, affected children and adolescents often have impaired inhibitory control but they are often 1-2 standard deviations above average IQ. They have Type A personalities [and are] very driven young kids. They also do not tolerate any down time or boredom. They need to be doing something all the time.”
According to the DSM-5, the diagnostic criteria for skin picking includes recurrent skin picking that results in skin lesions and is not attributable to another medical condition or substance. It also involves repeated attempts to decrease or stop the behavior and causes clinically significant distress or impairment.
“The other medical condition that we are interested in is the misuse of or dependence upon amphetamines or other prescription-based or illicit stimulants,” Dr. Grant said. “I saw a young man who was using about 600 mg of Ritalin a day, and he was picking all over the place. He did not have a primary skin disorder.”
The lifetime prevalence of skin picking disorder ranges between 1.4% and 5.4% of the general population. However, about 63% of people in a community sample endorsed some form of skin picking, and in a study of 105 college students, almost 40% said they picked their skin and had noticeable tissue damage as a result.
“Skin picking is not the same as self-injury,” Dr. Grant said. “It is also not simply an anxiety disorder. Anxiety will make people who pick worse, so people will say that they pick when they’re under stress. I can give them benzodiazepines and they’re still going to pick.”
Animal and human studies demonstrate that skin picking and hair pulling primarily affect females. “You will encounter young boys that pick and pull, but it largely affects females, and it tends to start around puberty,” he said. “Picking can have an onset after the age of 30, which is quite uncommon.”
From a cognitive standpoint, pathological skin pickers demonstrate impaired inhibitory control, impaired stop signal reaction time, increased rates of negative urgency (a tendency to act impulsively in response to negative emotions), and increased rates of positive urgency (a tendency to act impulsively in response to exciting or pleasurable emotions).
Trichotillomania
The lifetime prevalence of trichotillomania ranges between 0.6% and 3.9%. The onset is typically from ages 10-13 years, and the mean duration of illness is 22 years.
The DSM-5 criteria for trichotillomania are similar to that of skin-picking disorder, “although we don’t really worry about the substance use issue with people who pull their hair,” Dr. Grant said. “It doesn’t seem to have a correlation.” In addition, sometimes, children “will worsen pulling or picking when they have co-occurring ADHD and they’ve been started on a stimulant, even at a typical dose. For kids who have those issues, we prefer to try nonstimulant options for their ADHD such as bupropion or atomoxetine.”
Individuals with trichotillomania also tend to have low self-esteem and increased social anxiety, he added, and about one-third report low or very low quality of life. “When you notice alopecia, particularly in young girls who often have longer hair, up to 20% will eat their hair,” Dr. Grant said. “We don’t know why. It’s not related to vitamin deficiencies; it’s not a pica type of iron deficiency. There seems to be a shame piece about eating one’s own hair, but it’s important to assess that. Ask about constipation or overflow incontinence because they can get a bezoar, which can rupture” and can be fatal.
Skin-picking disorder and trichotillomania co-occur in up to 20% of cases. “When they do it tends to be a more difficult problem,” he said. These patients often come for mental health care because of depression, and most, he added, say “I don’t think I would be depressed if I wasn’t covered with excoriations or missing most of my hair.”
Treatment for both conditions
According to Dr. Grant, the treatment of choice for skin-picking disorder and trichotillomania is a specific psychotherapy known as “habit reversal therapy,” which involves helping the patient gain better self-control. The drawback is that it’s difficult to find someone trained in habit reversal therapy, “who know anything about skin picking and hair pulling,” he said. “That has been a huge challenge in the field.”
In his experience, the medical treatment of choice for skin-picking disorder and trichotillomania is N-acetylcysteine, an over-the-counter amino acid and antioxidant, which has been shown to be helpful at a dose of 2,400 mg per day. “Patients report to me that some of the excoriations clear up a little quicker as they’re taking it,” Dr. Grant said.
There may also be a role for antipsychotic therapy, he said, “but because of the associated weight gain with most antipsychotics we prefer not to use them.”
The opioid antagonist naltrexone has been shown to be effective in the subset of patients with skin-picking or hair-pulling disorders whose parents have a substance use disorder, Dr. Grant said. “The thought is that there’s something addictive about this behavior in some kids. These kids will look forward to picking and find it rewarding and exciting.”
Dr. Grant reported having no relevant financial disclosures.
INDIANAPOLIS –
And while both body-focused repetitive behavior disorders affect a greater proportion of females than males, “we have no current information that is useful about what hormonal influences may or may not play in terms of picking and pulling behaviors,” Jon E. Grant, MD, JD, MPH, professor of psychiatry and behavioral neuroscience at the University of Chicago, said at the annual meeting of the Society for Pediatric Dermatology. “On a cognitive level, affected children and adolescents often have impaired inhibitory control but they are often 1-2 standard deviations above average IQ. They have Type A personalities [and are] very driven young kids. They also do not tolerate any down time or boredom. They need to be doing something all the time.”
According to the DSM-5, the diagnostic criteria for skin picking includes recurrent skin picking that results in skin lesions and is not attributable to another medical condition or substance. It also involves repeated attempts to decrease or stop the behavior and causes clinically significant distress or impairment.
“The other medical condition that we are interested in is the misuse of or dependence upon amphetamines or other prescription-based or illicit stimulants,” Dr. Grant said. “I saw a young man who was using about 600 mg of Ritalin a day, and he was picking all over the place. He did not have a primary skin disorder.”
The lifetime prevalence of skin picking disorder ranges between 1.4% and 5.4% of the general population. However, about 63% of people in a community sample endorsed some form of skin picking, and in a study of 105 college students, almost 40% said they picked their skin and had noticeable tissue damage as a result.
“Skin picking is not the same as self-injury,” Dr. Grant said. “It is also not simply an anxiety disorder. Anxiety will make people who pick worse, so people will say that they pick when they’re under stress. I can give them benzodiazepines and they’re still going to pick.”
Animal and human studies demonstrate that skin picking and hair pulling primarily affect females. “You will encounter young boys that pick and pull, but it largely affects females, and it tends to start around puberty,” he said. “Picking can have an onset after the age of 30, which is quite uncommon.”
From a cognitive standpoint, pathological skin pickers demonstrate impaired inhibitory control, impaired stop signal reaction time, increased rates of negative urgency (a tendency to act impulsively in response to negative emotions), and increased rates of positive urgency (a tendency to act impulsively in response to exciting or pleasurable emotions).
Trichotillomania
The lifetime prevalence of trichotillomania ranges between 0.6% and 3.9%. The onset is typically from ages 10-13 years, and the mean duration of illness is 22 years.
The DSM-5 criteria for trichotillomania are similar to that of skin-picking disorder, “although we don’t really worry about the substance use issue with people who pull their hair,” Dr. Grant said. “It doesn’t seem to have a correlation.” In addition, sometimes, children “will worsen pulling or picking when they have co-occurring ADHD and they’ve been started on a stimulant, even at a typical dose. For kids who have those issues, we prefer to try nonstimulant options for their ADHD such as bupropion or atomoxetine.”
Individuals with trichotillomania also tend to have low self-esteem and increased social anxiety, he added, and about one-third report low or very low quality of life. “When you notice alopecia, particularly in young girls who often have longer hair, up to 20% will eat their hair,” Dr. Grant said. “We don’t know why. It’s not related to vitamin deficiencies; it’s not a pica type of iron deficiency. There seems to be a shame piece about eating one’s own hair, but it’s important to assess that. Ask about constipation or overflow incontinence because they can get a bezoar, which can rupture” and can be fatal.
Skin-picking disorder and trichotillomania co-occur in up to 20% of cases. “When they do it tends to be a more difficult problem,” he said. These patients often come for mental health care because of depression, and most, he added, say “I don’t think I would be depressed if I wasn’t covered with excoriations or missing most of my hair.”
Treatment for both conditions
According to Dr. Grant, the treatment of choice for skin-picking disorder and trichotillomania is a specific psychotherapy known as “habit reversal therapy,” which involves helping the patient gain better self-control. The drawback is that it’s difficult to find someone trained in habit reversal therapy, “who know anything about skin picking and hair pulling,” he said. “That has been a huge challenge in the field.”
In his experience, the medical treatment of choice for skin-picking disorder and trichotillomania is N-acetylcysteine, an over-the-counter amino acid and antioxidant, which has been shown to be helpful at a dose of 2,400 mg per day. “Patients report to me that some of the excoriations clear up a little quicker as they’re taking it,” Dr. Grant said.
There may also be a role for antipsychotic therapy, he said, “but because of the associated weight gain with most antipsychotics we prefer not to use them.”
The opioid antagonist naltrexone has been shown to be effective in the subset of patients with skin-picking or hair-pulling disorders whose parents have a substance use disorder, Dr. Grant said. “The thought is that there’s something addictive about this behavior in some kids. These kids will look forward to picking and find it rewarding and exciting.”
Dr. Grant reported having no relevant financial disclosures.
INDIANAPOLIS –
And while both body-focused repetitive behavior disorders affect a greater proportion of females than males, “we have no current information that is useful about what hormonal influences may or may not play in terms of picking and pulling behaviors,” Jon E. Grant, MD, JD, MPH, professor of psychiatry and behavioral neuroscience at the University of Chicago, said at the annual meeting of the Society for Pediatric Dermatology. “On a cognitive level, affected children and adolescents often have impaired inhibitory control but they are often 1-2 standard deviations above average IQ. They have Type A personalities [and are] very driven young kids. They also do not tolerate any down time or boredom. They need to be doing something all the time.”
According to the DSM-5, the diagnostic criteria for skin picking includes recurrent skin picking that results in skin lesions and is not attributable to another medical condition or substance. It also involves repeated attempts to decrease or stop the behavior and causes clinically significant distress or impairment.
“The other medical condition that we are interested in is the misuse of or dependence upon amphetamines or other prescription-based or illicit stimulants,” Dr. Grant said. “I saw a young man who was using about 600 mg of Ritalin a day, and he was picking all over the place. He did not have a primary skin disorder.”
The lifetime prevalence of skin picking disorder ranges between 1.4% and 5.4% of the general population. However, about 63% of people in a community sample endorsed some form of skin picking, and in a study of 105 college students, almost 40% said they picked their skin and had noticeable tissue damage as a result.
“Skin picking is not the same as self-injury,” Dr. Grant said. “It is also not simply an anxiety disorder. Anxiety will make people who pick worse, so people will say that they pick when they’re under stress. I can give them benzodiazepines and they’re still going to pick.”
Animal and human studies demonstrate that skin picking and hair pulling primarily affect females. “You will encounter young boys that pick and pull, but it largely affects females, and it tends to start around puberty,” he said. “Picking can have an onset after the age of 30, which is quite uncommon.”
From a cognitive standpoint, pathological skin pickers demonstrate impaired inhibitory control, impaired stop signal reaction time, increased rates of negative urgency (a tendency to act impulsively in response to negative emotions), and increased rates of positive urgency (a tendency to act impulsively in response to exciting or pleasurable emotions).
Trichotillomania
The lifetime prevalence of trichotillomania ranges between 0.6% and 3.9%. The onset is typically from ages 10-13 years, and the mean duration of illness is 22 years.
The DSM-5 criteria for trichotillomania are similar to that of skin-picking disorder, “although we don’t really worry about the substance use issue with people who pull their hair,” Dr. Grant said. “It doesn’t seem to have a correlation.” In addition, sometimes, children “will worsen pulling or picking when they have co-occurring ADHD and they’ve been started on a stimulant, even at a typical dose. For kids who have those issues, we prefer to try nonstimulant options for their ADHD such as bupropion or atomoxetine.”
Individuals with trichotillomania also tend to have low self-esteem and increased social anxiety, he added, and about one-third report low or very low quality of life. “When you notice alopecia, particularly in young girls who often have longer hair, up to 20% will eat their hair,” Dr. Grant said. “We don’t know why. It’s not related to vitamin deficiencies; it’s not a pica type of iron deficiency. There seems to be a shame piece about eating one’s own hair, but it’s important to assess that. Ask about constipation or overflow incontinence because they can get a bezoar, which can rupture” and can be fatal.
Skin-picking disorder and trichotillomania co-occur in up to 20% of cases. “When they do it tends to be a more difficult problem,” he said. These patients often come for mental health care because of depression, and most, he added, say “I don’t think I would be depressed if I wasn’t covered with excoriations or missing most of my hair.”
Treatment for both conditions
According to Dr. Grant, the treatment of choice for skin-picking disorder and trichotillomania is a specific psychotherapy known as “habit reversal therapy,” which involves helping the patient gain better self-control. The drawback is that it’s difficult to find someone trained in habit reversal therapy, “who know anything about skin picking and hair pulling,” he said. “That has been a huge challenge in the field.”
In his experience, the medical treatment of choice for skin-picking disorder and trichotillomania is N-acetylcysteine, an over-the-counter amino acid and antioxidant, which has been shown to be helpful at a dose of 2,400 mg per day. “Patients report to me that some of the excoriations clear up a little quicker as they’re taking it,” Dr. Grant said.
There may also be a role for antipsychotic therapy, he said, “but because of the associated weight gain with most antipsychotics we prefer not to use them.”
The opioid antagonist naltrexone has been shown to be effective in the subset of patients with skin-picking or hair-pulling disorders whose parents have a substance use disorder, Dr. Grant said. “The thought is that there’s something addictive about this behavior in some kids. These kids will look forward to picking and find it rewarding and exciting.”
Dr. Grant reported having no relevant financial disclosures.
AT SPD 2022
B6 a new approach for depression, anxiety?
Investigators compared supplementation with a 1-month course of vitamin B6 or B12 to supplementation with placebo in almost 500 adults. Results showed that vitamin B6 supplementation was associated with reductions in self-reported anxiety and a trend toward decreased depressive symptoms.
In addition, the vitamin B6 group showed increased levels of gamma-aminobutyric acid (GABA), as indicated by results on a visual test that was administered at the end of the trial. The test results demonstrated subtle changes in participants’ visual performance. The researchers considered this to be consistent with controlled levels of GABA-related brain activity.
However, “before practicing clinicians would recommend taking high doses of vitamin B6, a full-scale clinical trial would have to be carried out to verify the findings, assess any side effects, and find out which types of patients do or don’t benefit,” study investigator David Field, PhD, associate professor, School of Psychological and Clinical Language Sciences, University of Reading (England), told this news organization.
“My relatively small study can only be considered as an initial proof of concept,” Dr. Field said.
The findings were published online in the Journal of Human Psychopharmacology: Clinical and Experimental.
Eat Marmite?
“Recent research has connected mood disorders and some other neuropsychiatric conditions with disturbance in this balance, often in the direction of raised levels of brain activity,” Dr. Field noted.
Vitamin B6 is a coenzyme in the synthesis of GABA, an inhibitory neurotransmitter, from glutamate. Some previous research has suggested that vitamins B6 and B12 have a role in improving mood-related outcomes.
Dr. Field had reviewed a 2017 study of the effects on visual processing of eating Marmite, a type of food spread rich in vitamin B, every day for a few weeks.
“Remarkably, the results of that study suggested that eating Marmite had increased the level of the inhibitory neurotransmitter GABA in the visual part of the brain, damping down the level of neural activity slightly,” he said.
However, Marmite contains other B vitamins and other ingredients that might potentially account for this result, “plus, a lot of people don’t like the taste of Marmite,” Dr. Field noted.
Therefore, he wanted to “find out which individual ingredients were driving the effect, and B6 and B12 were the most plausible candidates.”
He decided to test these vitamins individually and to compare them to placebo. “I added the measures of anxiety and depression that were not in the Marmite study because I reasoned that if GABA levels were altered, this could improve those disorders, because we know that decreased levels of GABA in the brain occur in both of those conditions,” Dr. Field added.
Over the course of 5 years, investigators recruited 478 participants aged 18-58 years (mean age, 23 years; 381 women). Of these, 265 reported having anxiety, and 146 reported having depression.
The study participants were randomly assigned to receive either vitamin B6 (100 mg pyroxidine hydrochloride), vitamin B12 (1,000 mg methylcobalmin), or placebo tablets once daily for a month.
They also completed the Screen for Adult Anxiety Related Disorders (SCAARED) and the Mood and Feelings Questionnaire (MFQ) long version at baseline and following supplementation (“post test”), and they underwent three sensory tests that acted as assays of inhibitory function at post test.
In addition, 307 participants completed the Visual Contrast Sensitivity and Surround Suppression, which “measures the minimum percentage contrast between the lighter and darker regions of a striped pattern that can be detected (called the contrast threshold),” the investigators note.
The contrast threshold was measured with and without a suppressive surround mask that increases the threshold – an effect mediated by GABAergic connections in the visual cortex.
Participants (n = 172) also completed the Binocular Rivalry test and the Tactile Test Battery (n = 180). Both tests are designed to measure responses requiring GABAergic inhibitory activity.
‘Subtle changes’
ANOVA analyses revealed a “highly significant” reduction in anxiety at post test (F[1,173] = 10.03; P = .002; np 2 = .055), driven primarily by reduced anxiety in the B6 group (t[88] = 3.51; P < .001; d = .37). The placebo group also showed some reduction in anxiety, but it was not deemed significant, and the overall interaction itself did not reach significance.
A comparison of the B12 group with the group that received placebo revealed a significant reduction in anxiety at post test (F[1,175] = 4.08; P = .045; np 2 = .023), similarly driven by reduced anxiety in the B12 group (t[89] = 1.84; P = .069; d = .19) – but the interaction was not significant.
Among the B6 group, there was a highly significant reduction in scores on the generalized anxiety disorder and social anxiety subscales of the SCAARED, and there was a trend toward reductions on the other subscales. Among the B12 group, there was a significant reduction only on scores on the separation anxiety subscale. No significant changes were found in the placebo group.
The ANOVA test analysis of the B6 and placebo group data showed “no uniform direction of change” in depression at post test. The researchers found a “tendency” for depression scores to decrease between baseline and post test in the B6 group but to increase in the placebo group – an interaction that “approached” significance (F[1,96] = 3.08; P = .083; np 2 = .031), they report.
The ANOVA analysis of the B12 and placebo group data revealed no significant or trending effects, and the t-test comparing baseline and post-test scores in the B12 group was similarly nonsignificant.
B6 supplementation did change visual contrast thresholds, but only when a suppressive surround was present. There were “no clear effects” of B6 supplementation on other outcome measures, including binocular rivalry reversal rate and the tactile test battery, the investigators note.
“We found that supplementation with B6 produced subtle changes in tests of visual processing in a way that suggested an increase in the level of the inhibitory neurotransmitter GABA,” Dr. Field reported.
Vitamin B6 is a “cofactor for a metabolic pathway in the brain that converts the excitatory neurotransmitter glutamate into the inhibitory/calming GABA,” he said.
“By increasing the quantity of the cofactor, we slightly speed up the rate of this metabolic process, and so you end up with a bit more of the GABA neurotransmitter and a bit less glutamate. The net effect of this is to slightly reduce the amount of activity in the brain,” Dr. Field added.
Most common nutrient deficiency
Carol Johnston, PhD, professor and associate dean for faculty success, College of Health Solutions, Arizona State University, Phoenix, said vitamin B6 is “the most common nutrient deficiency in the United States;” 16% of men and 32% of women are reportedly B6 deficient.
“Young women on birth control are at higher risk for B6 deficiency due to effects of oral contraceptives on B6 metabolism,” whereas vitamin B12 deficiency is more common in older adults, said Dr. Johnston, who was not involved with the study.
The current study’s population mainly consisted of young women, and the interpretation of the data is “limited” because the researchers did not measure blood status for B6 and B12, Dr. Johnston noted. It is possible the sample was low in B6 and that the supplements “improved cognitive measures.”
Because the population was young – no one was older than 60 years – B12 status was likely “adequate in the sample, and supplementation did not have an impact,” she said.
Overall, Dr. Johnston cautioned that it is important to “alert clinicians and the general public about the concerns of overdosing B6.” For example, supplementation at high amounts can cause potentially irreversible sensory neuropathy, she noted.
“The safe upper limit defined by experts is 100 mg per day – the dosage used in this trial. Daily supplementation should not exceed this level,” Dr. Johnston said.
The vitamin tablets used in the study were supplied by Innopure. The investigators and Dr. Johnston have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators compared supplementation with a 1-month course of vitamin B6 or B12 to supplementation with placebo in almost 500 adults. Results showed that vitamin B6 supplementation was associated with reductions in self-reported anxiety and a trend toward decreased depressive symptoms.
In addition, the vitamin B6 group showed increased levels of gamma-aminobutyric acid (GABA), as indicated by results on a visual test that was administered at the end of the trial. The test results demonstrated subtle changes in participants’ visual performance. The researchers considered this to be consistent with controlled levels of GABA-related brain activity.
However, “before practicing clinicians would recommend taking high doses of vitamin B6, a full-scale clinical trial would have to be carried out to verify the findings, assess any side effects, and find out which types of patients do or don’t benefit,” study investigator David Field, PhD, associate professor, School of Psychological and Clinical Language Sciences, University of Reading (England), told this news organization.
“My relatively small study can only be considered as an initial proof of concept,” Dr. Field said.
The findings were published online in the Journal of Human Psychopharmacology: Clinical and Experimental.
Eat Marmite?
“Recent research has connected mood disorders and some other neuropsychiatric conditions with disturbance in this balance, often in the direction of raised levels of brain activity,” Dr. Field noted.
Vitamin B6 is a coenzyme in the synthesis of GABA, an inhibitory neurotransmitter, from glutamate. Some previous research has suggested that vitamins B6 and B12 have a role in improving mood-related outcomes.
Dr. Field had reviewed a 2017 study of the effects on visual processing of eating Marmite, a type of food spread rich in vitamin B, every day for a few weeks.
“Remarkably, the results of that study suggested that eating Marmite had increased the level of the inhibitory neurotransmitter GABA in the visual part of the brain, damping down the level of neural activity slightly,” he said.
However, Marmite contains other B vitamins and other ingredients that might potentially account for this result, “plus, a lot of people don’t like the taste of Marmite,” Dr. Field noted.
Therefore, he wanted to “find out which individual ingredients were driving the effect, and B6 and B12 were the most plausible candidates.”
He decided to test these vitamins individually and to compare them to placebo. “I added the measures of anxiety and depression that were not in the Marmite study because I reasoned that if GABA levels were altered, this could improve those disorders, because we know that decreased levels of GABA in the brain occur in both of those conditions,” Dr. Field added.
Over the course of 5 years, investigators recruited 478 participants aged 18-58 years (mean age, 23 years; 381 women). Of these, 265 reported having anxiety, and 146 reported having depression.
The study participants were randomly assigned to receive either vitamin B6 (100 mg pyroxidine hydrochloride), vitamin B12 (1,000 mg methylcobalmin), or placebo tablets once daily for a month.
They also completed the Screen for Adult Anxiety Related Disorders (SCAARED) and the Mood and Feelings Questionnaire (MFQ) long version at baseline and following supplementation (“post test”), and they underwent three sensory tests that acted as assays of inhibitory function at post test.
In addition, 307 participants completed the Visual Contrast Sensitivity and Surround Suppression, which “measures the minimum percentage contrast between the lighter and darker regions of a striped pattern that can be detected (called the contrast threshold),” the investigators note.
The contrast threshold was measured with and without a suppressive surround mask that increases the threshold – an effect mediated by GABAergic connections in the visual cortex.
Participants (n = 172) also completed the Binocular Rivalry test and the Tactile Test Battery (n = 180). Both tests are designed to measure responses requiring GABAergic inhibitory activity.
‘Subtle changes’
ANOVA analyses revealed a “highly significant” reduction in anxiety at post test (F[1,173] = 10.03; P = .002; np 2 = .055), driven primarily by reduced anxiety in the B6 group (t[88] = 3.51; P < .001; d = .37). The placebo group also showed some reduction in anxiety, but it was not deemed significant, and the overall interaction itself did not reach significance.
A comparison of the B12 group with the group that received placebo revealed a significant reduction in anxiety at post test (F[1,175] = 4.08; P = .045; np 2 = .023), similarly driven by reduced anxiety in the B12 group (t[89] = 1.84; P = .069; d = .19) – but the interaction was not significant.
Among the B6 group, there was a highly significant reduction in scores on the generalized anxiety disorder and social anxiety subscales of the SCAARED, and there was a trend toward reductions on the other subscales. Among the B12 group, there was a significant reduction only on scores on the separation anxiety subscale. No significant changes were found in the placebo group.
The ANOVA test analysis of the B6 and placebo group data showed “no uniform direction of change” in depression at post test. The researchers found a “tendency” for depression scores to decrease between baseline and post test in the B6 group but to increase in the placebo group – an interaction that “approached” significance (F[1,96] = 3.08; P = .083; np 2 = .031), they report.
The ANOVA analysis of the B12 and placebo group data revealed no significant or trending effects, and the t-test comparing baseline and post-test scores in the B12 group was similarly nonsignificant.
B6 supplementation did change visual contrast thresholds, but only when a suppressive surround was present. There were “no clear effects” of B6 supplementation on other outcome measures, including binocular rivalry reversal rate and the tactile test battery, the investigators note.
“We found that supplementation with B6 produced subtle changes in tests of visual processing in a way that suggested an increase in the level of the inhibitory neurotransmitter GABA,” Dr. Field reported.
Vitamin B6 is a “cofactor for a metabolic pathway in the brain that converts the excitatory neurotransmitter glutamate into the inhibitory/calming GABA,” he said.
“By increasing the quantity of the cofactor, we slightly speed up the rate of this metabolic process, and so you end up with a bit more of the GABA neurotransmitter and a bit less glutamate. The net effect of this is to slightly reduce the amount of activity in the brain,” Dr. Field added.
Most common nutrient deficiency
Carol Johnston, PhD, professor and associate dean for faculty success, College of Health Solutions, Arizona State University, Phoenix, said vitamin B6 is “the most common nutrient deficiency in the United States;” 16% of men and 32% of women are reportedly B6 deficient.
“Young women on birth control are at higher risk for B6 deficiency due to effects of oral contraceptives on B6 metabolism,” whereas vitamin B12 deficiency is more common in older adults, said Dr. Johnston, who was not involved with the study.
The current study’s population mainly consisted of young women, and the interpretation of the data is “limited” because the researchers did not measure blood status for B6 and B12, Dr. Johnston noted. It is possible the sample was low in B6 and that the supplements “improved cognitive measures.”
Because the population was young – no one was older than 60 years – B12 status was likely “adequate in the sample, and supplementation did not have an impact,” she said.
Overall, Dr. Johnston cautioned that it is important to “alert clinicians and the general public about the concerns of overdosing B6.” For example, supplementation at high amounts can cause potentially irreversible sensory neuropathy, she noted.
“The safe upper limit defined by experts is 100 mg per day – the dosage used in this trial. Daily supplementation should not exceed this level,” Dr. Johnston said.
The vitamin tablets used in the study were supplied by Innopure. The investigators and Dr. Johnston have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators compared supplementation with a 1-month course of vitamin B6 or B12 to supplementation with placebo in almost 500 adults. Results showed that vitamin B6 supplementation was associated with reductions in self-reported anxiety and a trend toward decreased depressive symptoms.
In addition, the vitamin B6 group showed increased levels of gamma-aminobutyric acid (GABA), as indicated by results on a visual test that was administered at the end of the trial. The test results demonstrated subtle changes in participants’ visual performance. The researchers considered this to be consistent with controlled levels of GABA-related brain activity.
However, “before practicing clinicians would recommend taking high doses of vitamin B6, a full-scale clinical trial would have to be carried out to verify the findings, assess any side effects, and find out which types of patients do or don’t benefit,” study investigator David Field, PhD, associate professor, School of Psychological and Clinical Language Sciences, University of Reading (England), told this news organization.
“My relatively small study can only be considered as an initial proof of concept,” Dr. Field said.
The findings were published online in the Journal of Human Psychopharmacology: Clinical and Experimental.
Eat Marmite?
“Recent research has connected mood disorders and some other neuropsychiatric conditions with disturbance in this balance, often in the direction of raised levels of brain activity,” Dr. Field noted.
Vitamin B6 is a coenzyme in the synthesis of GABA, an inhibitory neurotransmitter, from glutamate. Some previous research has suggested that vitamins B6 and B12 have a role in improving mood-related outcomes.
Dr. Field had reviewed a 2017 study of the effects on visual processing of eating Marmite, a type of food spread rich in vitamin B, every day for a few weeks.
“Remarkably, the results of that study suggested that eating Marmite had increased the level of the inhibitory neurotransmitter GABA in the visual part of the brain, damping down the level of neural activity slightly,” he said.
However, Marmite contains other B vitamins and other ingredients that might potentially account for this result, “plus, a lot of people don’t like the taste of Marmite,” Dr. Field noted.
Therefore, he wanted to “find out which individual ingredients were driving the effect, and B6 and B12 were the most plausible candidates.”
He decided to test these vitamins individually and to compare them to placebo. “I added the measures of anxiety and depression that were not in the Marmite study because I reasoned that if GABA levels were altered, this could improve those disorders, because we know that decreased levels of GABA in the brain occur in both of those conditions,” Dr. Field added.
Over the course of 5 years, investigators recruited 478 participants aged 18-58 years (mean age, 23 years; 381 women). Of these, 265 reported having anxiety, and 146 reported having depression.
The study participants were randomly assigned to receive either vitamin B6 (100 mg pyroxidine hydrochloride), vitamin B12 (1,000 mg methylcobalmin), or placebo tablets once daily for a month.
They also completed the Screen for Adult Anxiety Related Disorders (SCAARED) and the Mood and Feelings Questionnaire (MFQ) long version at baseline and following supplementation (“post test”), and they underwent three sensory tests that acted as assays of inhibitory function at post test.
In addition, 307 participants completed the Visual Contrast Sensitivity and Surround Suppression, which “measures the minimum percentage contrast between the lighter and darker regions of a striped pattern that can be detected (called the contrast threshold),” the investigators note.
The contrast threshold was measured with and without a suppressive surround mask that increases the threshold – an effect mediated by GABAergic connections in the visual cortex.
Participants (n = 172) also completed the Binocular Rivalry test and the Tactile Test Battery (n = 180). Both tests are designed to measure responses requiring GABAergic inhibitory activity.
‘Subtle changes’
ANOVA analyses revealed a “highly significant” reduction in anxiety at post test (F[1,173] = 10.03; P = .002; np 2 = .055), driven primarily by reduced anxiety in the B6 group (t[88] = 3.51; P < .001; d = .37). The placebo group also showed some reduction in anxiety, but it was not deemed significant, and the overall interaction itself did not reach significance.
A comparison of the B12 group with the group that received placebo revealed a significant reduction in anxiety at post test (F[1,175] = 4.08; P = .045; np 2 = .023), similarly driven by reduced anxiety in the B12 group (t[89] = 1.84; P = .069; d = .19) – but the interaction was not significant.
Among the B6 group, there was a highly significant reduction in scores on the generalized anxiety disorder and social anxiety subscales of the SCAARED, and there was a trend toward reductions on the other subscales. Among the B12 group, there was a significant reduction only on scores on the separation anxiety subscale. No significant changes were found in the placebo group.
The ANOVA test analysis of the B6 and placebo group data showed “no uniform direction of change” in depression at post test. The researchers found a “tendency” for depression scores to decrease between baseline and post test in the B6 group but to increase in the placebo group – an interaction that “approached” significance (F[1,96] = 3.08; P = .083; np 2 = .031), they report.
The ANOVA analysis of the B12 and placebo group data revealed no significant or trending effects, and the t-test comparing baseline and post-test scores in the B12 group was similarly nonsignificant.
B6 supplementation did change visual contrast thresholds, but only when a suppressive surround was present. There were “no clear effects” of B6 supplementation on other outcome measures, including binocular rivalry reversal rate and the tactile test battery, the investigators note.
“We found that supplementation with B6 produced subtle changes in tests of visual processing in a way that suggested an increase in the level of the inhibitory neurotransmitter GABA,” Dr. Field reported.
Vitamin B6 is a “cofactor for a metabolic pathway in the brain that converts the excitatory neurotransmitter glutamate into the inhibitory/calming GABA,” he said.
“By increasing the quantity of the cofactor, we slightly speed up the rate of this metabolic process, and so you end up with a bit more of the GABA neurotransmitter and a bit less glutamate. The net effect of this is to slightly reduce the amount of activity in the brain,” Dr. Field added.
Most common nutrient deficiency
Carol Johnston, PhD, professor and associate dean for faculty success, College of Health Solutions, Arizona State University, Phoenix, said vitamin B6 is “the most common nutrient deficiency in the United States;” 16% of men and 32% of women are reportedly B6 deficient.
“Young women on birth control are at higher risk for B6 deficiency due to effects of oral contraceptives on B6 metabolism,” whereas vitamin B12 deficiency is more common in older adults, said Dr. Johnston, who was not involved with the study.
The current study’s population mainly consisted of young women, and the interpretation of the data is “limited” because the researchers did not measure blood status for B6 and B12, Dr. Johnston noted. It is possible the sample was low in B6 and that the supplements “improved cognitive measures.”
Because the population was young – no one was older than 60 years – B12 status was likely “adequate in the sample, and supplementation did not have an impact,” she said.
Overall, Dr. Johnston cautioned that it is important to “alert clinicians and the general public about the concerns of overdosing B6.” For example, supplementation at high amounts can cause potentially irreversible sensory neuropathy, she noted.
“The safe upper limit defined by experts is 100 mg per day – the dosage used in this trial. Daily supplementation should not exceed this level,” Dr. Johnston said.
The vitamin tablets used in the study were supplied by Innopure. The investigators and Dr. Johnston have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Pharmacogenomic testing may curb drug interactions in severe depression
Pharmacogenetic testing, which is used to classify how patients with major depressive disorder (MDD) metabolize medications, reduces adverse drug-gene interactions, new research shows.
In addition, among the intervention group, the rate of remission over 24 weeks was significantly greater.
“These tests can be helpful in rethinking choices of antidepressants, but clinicians should not expect them to be helpful for every patient,” study investigator David W. Oslin, MD, Corporal Michael J. Crescenz VA Medical Center and professor of psychiatry at Perelman School of Medicine, University of Pennsylvania, Philadelphia, said in an interview.
The findings were published online in JAMA.
Less trial and error
Pharmacogenomic testing can provide information to inform drug selection or dosing for patients with a genetic variation that alters pharmacokinetics or pharmacodynamics. Such testing may be particularly useful for patients with MDD, as fewer than 40% of these patients achieve clinical remission after an initial treatment with an antidepressant, the investigators note.
“To get to a treatment that works for an individual, it’s not unusual to have to try two or three or four antidepressants,” said Dr. Oslin. “If we could reduce that variance a little bit with a test like this, that would be huge from a public health perspective.”
The study included 676 physicians and 1,944 adults with MDD (mean age, 48 years; 24% women) who were receiving care at 22 Department of Veterans Affairs medical centers. Eligible patients were set to start a new antidepressant monotherapy, and all underwent a pharmacogenomic test using a cheek swab.
Investigators randomly assigned patients to receive test results when available (pharmacogenomic-guided group) or 24 weeks later (usual-care group). For the former group, clinicians were asked to initiate treatment when test results were available, typically within 2-3 days. For the latter group, they were asked to initiate treatment on a day of randomization.
Assessments included the 9-item Patient Health questionnaire (PHQ-9), scores for which range from 0-27 points, with higher scores indicating worse symptoms.
Of the total patient population, 79% completed the 24-week assessment.
Researchers characterized antidepressant medications on the basis of drug-gene interaction categories: no known interactions, moderate interactions, and substantial interactions.
The co-primary outcomes were treatment initiation within 30 days, determined on the basis of drug-gene interaction categories, and remission from depression symptoms, defined as a PHQ-9 score of less than or equal to 5.
Raters who were blinded to clinical care and study randomization assessed outcomes at 4, 8, 12, 18, and 24 weeks.
Significant impact?
Results showed that the pharmacogenomic-guided group was more likely to receive an antidepressant that had no potential drug-gene interaction, as opposed to one with a moderate/substantial interaction (odds ratio, 4.32; 95% confidence interval, 3.47-5.39; P < .001).
The usual-care group was more likely to receive a drug with mild potential drug-gene interaction (no/moderate interaction vs. substantial interaction: OR, 2.08; 95% CI, 1.52-2.84; P = .005).
For the intervention group, the estimated rates of receiving an antidepressant with no, moderate, and substantial drug-gene interactions were 59.3%, 30.0%, and 10.7%, respectively. For the usual-care group, the estimates were 25.7%, 54.6%, and 19.7%.
The finding that 1 in 5 patients who received usual care were initially given a medication for which there were significant drug-gene interactions means it is “not a rare event,” said Dr. Oslin. “If we can make an impact on 20% of the people we prescribe to, that’s actually pretty big.”
Rates of remission were greater in the pharmacogenomic-guided group over 24 weeks (OR, 1.28; 95% CI, 1.05-1.57; P = .02; absolute risk difference, 2.8%; 95% CI, 0.6%-5.1%).
The secondary outcomes of response to treatment, defined as at least a 50% decrease in PHQ-9 score, also favored the pharmacogenomic-guided group. This was also the case for the secondary outcome of reduction in symptom severity on the PHQ-9 score.
Some physicians have expressed skepticism about pharmacogenomic testing, but the study provides additional evidence of its usefulness, Dr. Oslin noted.
“While I don’t think testing should be standard of practice, I also don’t think we should put barriers into the testing until we can better understand how to target the testing” to those who will benefit the most, he added.
The tests are available at a commercial cost of about $1,000 – which may not be that expensive if testing has a significant impact on a patient’s life, said Dr. Oslin.
Important research, but with several limitations
In an accompanying editorial, Dan V. Iosifescu, MD, associate professor of psychiatry at New York University School of Medicine and director of clinical research at the Nathan Kline Institute for Psychiatric Research, called the study an important addition to the literature on pharmacogenomic testing for patients with MDD.
The study was significantly larger and had broader inclusion criteria and longer follow-up than previous clinical trials and is one of the few investigations not funded by a manufacturer of pharmacogenomic tests, writes Dr. Iosifescu, who was not involved with the research.
However, he notes that an antidepressant was not initiated for 30 days after randomization in 25% of the intervention group and in 31% of the usual-care group, which was “puzzling.” “Because these rates were comparable in the 2 groups, it cannot be explained primarily by the delay of the pharmacogenomic test results in the intervention group,” he writes.
In addition, in the co-primary outcome of symptom remission rate, the difference in clinical improvement in favor of the pharmacogenomic-guided treatment was only “modest” – the gain was of less than 2% in the proportion of patients achieving remission, Dr. Iosifescu adds.
He adds this is “likely not very meaningful clinically despite this difference achieving statistical significance in this large study sample.”
Other potential study limitations he cites include the lack of patient blinding to treatment assignment and the absence of clarity about why rates of MDD response and remission over time were relatively low in both treatment groups.
A possible approach to optimize antidepressant choices could involve integration of pharmacogenomic data into larger predictive models that include clinical and demographic variables, Dr. Iosifescu notes.
“The development of such complex models is challenging, but it is now possible given the recent substantial advances in the proficiency of computational tools,” he writes.
The study was funded by the U.S. Department of Veterans Affairs (VA), Health Services Research and Development Service, and the Mental Illness Research, Education, and Clinical Center at the Corporal Michael J. Crescenz VA Medical Center. Dr. Oslin reports having received grants from the VA Office of Research and Development and Janssen Pharmaceuticals and nonfinancial support from Myriad Genetics during the conduct of the study. Dr. Iosifescu report having received personal fees from Alkermes, Allergan, Axsome, Biogen, the Centers for Psychiatric Excellence, Jazz, Lundbeck, Precision Neuroscience, Sage, and Sunovion and grants from Alkermes, AstraZeneca, Brainsway, Litecure, Neosync, Otsuka, Roche, and Shire.
A version of this article first appeared on Medscape.com.
Pharmacogenetic testing, which is used to classify how patients with major depressive disorder (MDD) metabolize medications, reduces adverse drug-gene interactions, new research shows.
In addition, among the intervention group, the rate of remission over 24 weeks was significantly greater.
“These tests can be helpful in rethinking choices of antidepressants, but clinicians should not expect them to be helpful for every patient,” study investigator David W. Oslin, MD, Corporal Michael J. Crescenz VA Medical Center and professor of psychiatry at Perelman School of Medicine, University of Pennsylvania, Philadelphia, said in an interview.
The findings were published online in JAMA.
Less trial and error
Pharmacogenomic testing can provide information to inform drug selection or dosing for patients with a genetic variation that alters pharmacokinetics or pharmacodynamics. Such testing may be particularly useful for patients with MDD, as fewer than 40% of these patients achieve clinical remission after an initial treatment with an antidepressant, the investigators note.
“To get to a treatment that works for an individual, it’s not unusual to have to try two or three or four antidepressants,” said Dr. Oslin. “If we could reduce that variance a little bit with a test like this, that would be huge from a public health perspective.”
The study included 676 physicians and 1,944 adults with MDD (mean age, 48 years; 24% women) who were receiving care at 22 Department of Veterans Affairs medical centers. Eligible patients were set to start a new antidepressant monotherapy, and all underwent a pharmacogenomic test using a cheek swab.
Investigators randomly assigned patients to receive test results when available (pharmacogenomic-guided group) or 24 weeks later (usual-care group). For the former group, clinicians were asked to initiate treatment when test results were available, typically within 2-3 days. For the latter group, they were asked to initiate treatment on a day of randomization.
Assessments included the 9-item Patient Health questionnaire (PHQ-9), scores for which range from 0-27 points, with higher scores indicating worse symptoms.
Of the total patient population, 79% completed the 24-week assessment.
Researchers characterized antidepressant medications on the basis of drug-gene interaction categories: no known interactions, moderate interactions, and substantial interactions.
The co-primary outcomes were treatment initiation within 30 days, determined on the basis of drug-gene interaction categories, and remission from depression symptoms, defined as a PHQ-9 score of less than or equal to 5.
Raters who were blinded to clinical care and study randomization assessed outcomes at 4, 8, 12, 18, and 24 weeks.
Significant impact?
Results showed that the pharmacogenomic-guided group was more likely to receive an antidepressant that had no potential drug-gene interaction, as opposed to one with a moderate/substantial interaction (odds ratio, 4.32; 95% confidence interval, 3.47-5.39; P < .001).
The usual-care group was more likely to receive a drug with mild potential drug-gene interaction (no/moderate interaction vs. substantial interaction: OR, 2.08; 95% CI, 1.52-2.84; P = .005).
For the intervention group, the estimated rates of receiving an antidepressant with no, moderate, and substantial drug-gene interactions were 59.3%, 30.0%, and 10.7%, respectively. For the usual-care group, the estimates were 25.7%, 54.6%, and 19.7%.
The finding that 1 in 5 patients who received usual care were initially given a medication for which there were significant drug-gene interactions means it is “not a rare event,” said Dr. Oslin. “If we can make an impact on 20% of the people we prescribe to, that’s actually pretty big.”
Rates of remission were greater in the pharmacogenomic-guided group over 24 weeks (OR, 1.28; 95% CI, 1.05-1.57; P = .02; absolute risk difference, 2.8%; 95% CI, 0.6%-5.1%).
The secondary outcomes of response to treatment, defined as at least a 50% decrease in PHQ-9 score, also favored the pharmacogenomic-guided group. This was also the case for the secondary outcome of reduction in symptom severity on the PHQ-9 score.
Some physicians have expressed skepticism about pharmacogenomic testing, but the study provides additional evidence of its usefulness, Dr. Oslin noted.
“While I don’t think testing should be standard of practice, I also don’t think we should put barriers into the testing until we can better understand how to target the testing” to those who will benefit the most, he added.
The tests are available at a commercial cost of about $1,000 – which may not be that expensive if testing has a significant impact on a patient’s life, said Dr. Oslin.
Important research, but with several limitations
In an accompanying editorial, Dan V. Iosifescu, MD, associate professor of psychiatry at New York University School of Medicine and director of clinical research at the Nathan Kline Institute for Psychiatric Research, called the study an important addition to the literature on pharmacogenomic testing for patients with MDD.
The study was significantly larger and had broader inclusion criteria and longer follow-up than previous clinical trials and is one of the few investigations not funded by a manufacturer of pharmacogenomic tests, writes Dr. Iosifescu, who was not involved with the research.
However, he notes that an antidepressant was not initiated for 30 days after randomization in 25% of the intervention group and in 31% of the usual-care group, which was “puzzling.” “Because these rates were comparable in the 2 groups, it cannot be explained primarily by the delay of the pharmacogenomic test results in the intervention group,” he writes.
In addition, in the co-primary outcome of symptom remission rate, the difference in clinical improvement in favor of the pharmacogenomic-guided treatment was only “modest” – the gain was of less than 2% in the proportion of patients achieving remission, Dr. Iosifescu adds.
He adds this is “likely not very meaningful clinically despite this difference achieving statistical significance in this large study sample.”
Other potential study limitations he cites include the lack of patient blinding to treatment assignment and the absence of clarity about why rates of MDD response and remission over time were relatively low in both treatment groups.
A possible approach to optimize antidepressant choices could involve integration of pharmacogenomic data into larger predictive models that include clinical and demographic variables, Dr. Iosifescu notes.
“The development of such complex models is challenging, but it is now possible given the recent substantial advances in the proficiency of computational tools,” he writes.
The study was funded by the U.S. Department of Veterans Affairs (VA), Health Services Research and Development Service, and the Mental Illness Research, Education, and Clinical Center at the Corporal Michael J. Crescenz VA Medical Center. Dr. Oslin reports having received grants from the VA Office of Research and Development and Janssen Pharmaceuticals and nonfinancial support from Myriad Genetics during the conduct of the study. Dr. Iosifescu report having received personal fees from Alkermes, Allergan, Axsome, Biogen, the Centers for Psychiatric Excellence, Jazz, Lundbeck, Precision Neuroscience, Sage, and Sunovion and grants from Alkermes, AstraZeneca, Brainsway, Litecure, Neosync, Otsuka, Roche, and Shire.
A version of this article first appeared on Medscape.com.
Pharmacogenetic testing, which is used to classify how patients with major depressive disorder (MDD) metabolize medications, reduces adverse drug-gene interactions, new research shows.
In addition, among the intervention group, the rate of remission over 24 weeks was significantly greater.
“These tests can be helpful in rethinking choices of antidepressants, but clinicians should not expect them to be helpful for every patient,” study investigator David W. Oslin, MD, Corporal Michael J. Crescenz VA Medical Center and professor of psychiatry at Perelman School of Medicine, University of Pennsylvania, Philadelphia, said in an interview.
The findings were published online in JAMA.
Less trial and error
Pharmacogenomic testing can provide information to inform drug selection or dosing for patients with a genetic variation that alters pharmacokinetics or pharmacodynamics. Such testing may be particularly useful for patients with MDD, as fewer than 40% of these patients achieve clinical remission after an initial treatment with an antidepressant, the investigators note.
“To get to a treatment that works for an individual, it’s not unusual to have to try two or three or four antidepressants,” said Dr. Oslin. “If we could reduce that variance a little bit with a test like this, that would be huge from a public health perspective.”
The study included 676 physicians and 1,944 adults with MDD (mean age, 48 years; 24% women) who were receiving care at 22 Department of Veterans Affairs medical centers. Eligible patients were set to start a new antidepressant monotherapy, and all underwent a pharmacogenomic test using a cheek swab.
Investigators randomly assigned patients to receive test results when available (pharmacogenomic-guided group) or 24 weeks later (usual-care group). For the former group, clinicians were asked to initiate treatment when test results were available, typically within 2-3 days. For the latter group, they were asked to initiate treatment on a day of randomization.
Assessments included the 9-item Patient Health questionnaire (PHQ-9), scores for which range from 0-27 points, with higher scores indicating worse symptoms.
Of the total patient population, 79% completed the 24-week assessment.
Researchers characterized antidepressant medications on the basis of drug-gene interaction categories: no known interactions, moderate interactions, and substantial interactions.
The co-primary outcomes were treatment initiation within 30 days, determined on the basis of drug-gene interaction categories, and remission from depression symptoms, defined as a PHQ-9 score of less than or equal to 5.
Raters who were blinded to clinical care and study randomization assessed outcomes at 4, 8, 12, 18, and 24 weeks.
Significant impact?
Results showed that the pharmacogenomic-guided group was more likely to receive an antidepressant that had no potential drug-gene interaction, as opposed to one with a moderate/substantial interaction (odds ratio, 4.32; 95% confidence interval, 3.47-5.39; P < .001).
The usual-care group was more likely to receive a drug with mild potential drug-gene interaction (no/moderate interaction vs. substantial interaction: OR, 2.08; 95% CI, 1.52-2.84; P = .005).
For the intervention group, the estimated rates of receiving an antidepressant with no, moderate, and substantial drug-gene interactions were 59.3%, 30.0%, and 10.7%, respectively. For the usual-care group, the estimates were 25.7%, 54.6%, and 19.7%.
The finding that 1 in 5 patients who received usual care were initially given a medication for which there were significant drug-gene interactions means it is “not a rare event,” said Dr. Oslin. “If we can make an impact on 20% of the people we prescribe to, that’s actually pretty big.”
Rates of remission were greater in the pharmacogenomic-guided group over 24 weeks (OR, 1.28; 95% CI, 1.05-1.57; P = .02; absolute risk difference, 2.8%; 95% CI, 0.6%-5.1%).
The secondary outcomes of response to treatment, defined as at least a 50% decrease in PHQ-9 score, also favored the pharmacogenomic-guided group. This was also the case for the secondary outcome of reduction in symptom severity on the PHQ-9 score.
Some physicians have expressed skepticism about pharmacogenomic testing, but the study provides additional evidence of its usefulness, Dr. Oslin noted.
“While I don’t think testing should be standard of practice, I also don’t think we should put barriers into the testing until we can better understand how to target the testing” to those who will benefit the most, he added.
The tests are available at a commercial cost of about $1,000 – which may not be that expensive if testing has a significant impact on a patient’s life, said Dr. Oslin.
Important research, but with several limitations
In an accompanying editorial, Dan V. Iosifescu, MD, associate professor of psychiatry at New York University School of Medicine and director of clinical research at the Nathan Kline Institute for Psychiatric Research, called the study an important addition to the literature on pharmacogenomic testing for patients with MDD.
The study was significantly larger and had broader inclusion criteria and longer follow-up than previous clinical trials and is one of the few investigations not funded by a manufacturer of pharmacogenomic tests, writes Dr. Iosifescu, who was not involved with the research.
However, he notes that an antidepressant was not initiated for 30 days after randomization in 25% of the intervention group and in 31% of the usual-care group, which was “puzzling.” “Because these rates were comparable in the 2 groups, it cannot be explained primarily by the delay of the pharmacogenomic test results in the intervention group,” he writes.
In addition, in the co-primary outcome of symptom remission rate, the difference in clinical improvement in favor of the pharmacogenomic-guided treatment was only “modest” – the gain was of less than 2% in the proportion of patients achieving remission, Dr. Iosifescu adds.
He adds this is “likely not very meaningful clinically despite this difference achieving statistical significance in this large study sample.”
Other potential study limitations he cites include the lack of patient blinding to treatment assignment and the absence of clarity about why rates of MDD response and remission over time were relatively low in both treatment groups.
A possible approach to optimize antidepressant choices could involve integration of pharmacogenomic data into larger predictive models that include clinical and demographic variables, Dr. Iosifescu notes.
“The development of such complex models is challenging, but it is now possible given the recent substantial advances in the proficiency of computational tools,” he writes.
The study was funded by the U.S. Department of Veterans Affairs (VA), Health Services Research and Development Service, and the Mental Illness Research, Education, and Clinical Center at the Corporal Michael J. Crescenz VA Medical Center. Dr. Oslin reports having received grants from the VA Office of Research and Development and Janssen Pharmaceuticals and nonfinancial support from Myriad Genetics during the conduct of the study. Dr. Iosifescu report having received personal fees from Alkermes, Allergan, Axsome, Biogen, the Centers for Psychiatric Excellence, Jazz, Lundbeck, Precision Neuroscience, Sage, and Sunovion and grants from Alkermes, AstraZeneca, Brainsway, Litecure, Neosync, Otsuka, Roche, and Shire.
A version of this article first appeared on Medscape.com.
FROM JAMA
Geriatric-Centered Interdisciplinary Care Pathway Reduces Delirium in Hospitalized Older Adults With Traumatic Injury
Study 1 Overview (Park et al)
Objective: To examine whether implementation of a geriatric trauma clinical pathway is associated with reduced rates of delirium in older adults with traumatic injury.
Design: Retrospective case-control study of electronic health records.
Setting and participants: Eligible patients were persons aged 65 years or older who were admitted to the trauma service and did not undergo an operation. A Geriatric Trauma Care Pathway was developed by a multidisciplinary Stanford Quality Pathways team and formally launched on November 1, 2018. The clinical pathway was designed to incorporate geriatric best practices, which included order sets (eg, age-appropriate nonpharmacological interventions and pharmacological dosages), guidelines (eg, Institute for Healthcare Improvement Age-Friendly Health systems 4M framework), automated consultations (comprehensive geriatric assessment), and escalation pathways executed by a multidisciplinary team (eg, pain, bowel, and sleep regulation). The clinical pathway began with admission to the emergency department (ED) (ie, automatic trigger of geriatric trauma care admission order set), daily multidisciplinary team meetings during acute hospitalization, and a transitional care team consultation for postdischarge follow-up or home visit.
Main outcome measures: The primary outcome was delirium as determined by a positive Confusion Assessment Method (CAM) score or a diagnosis of delirium by the clinical team. The secondary outcome was hospital length of stay (LOS). Process measures for pathway compliance (eg, achieving adequate pain control, early mobilization, advance care planning) were assessed. Outcome measures were compared between patients who underwent the Geriatric Trauma Care Pathway intervention (postimplementation group) vs patients who were treated prior to pathway implementation (baseline pre-implementation group).
Main results: Of the 859 eligible patients, 712 were included in the analysis (442 [62.1%] in the baseline pre-implementation group and 270 [37.9%] in the postimplementation group); mean (SD) age was 81.4 (9.1) years, and 394 (55.3%) were women. The injury mechanism was similar between groups, with falls being the most common cause of injury (247 [55.9%] in the baseline group vs 162 [60.0%] in the postimplementation group; P = .43). Injuries as measured by Injury Severity Score (ISS) were minor or moderate in both groups (261 [59.0%] in baseline group vs 168 [62.2%] in postimplementation group; P = .87). The adjusted odds ratio (OR) for delirium in the postimplementation group was lower compared to the baseline pre-implementation group (OR, 0.54; 95% CI, 0.37-0.80; P < .001). Measures of advance care planning in the postimplementation group improved, including more frequent goals-of-care documentation (53.7% in postimplementation group vs 16.7% in baseline group; P < .001) and a shortened time to first goals-of-care discussion upon presenting to the ED (36 hours in postimplementation group vs 50 hours in baseline group; P = .03).
Conclusion: Implementation of a multidisciplinary geriatric trauma clinical pathway for older adults with traumatic injury at a single level I trauma center was associated with reduced rates of delirium.
Study 2 Overview (Bryant et al)
Objective: To determine whether an interdisciplinary care pathway for frail trauma patients can improve in-hospital mortality, complications, and 30-day readmissions.
Design: Retrospective cohort study of frail patients.
Setting and participants: Eligible patients were persons aged 65 years or older who were admitted to the trauma service and survived more than 24 hours; admitted to and discharged from the trauma unit; and determined to be pre-frail or frail by a geriatrician’s assessment. A Frailty Identification and Care Pathway designed to reduce delirium and complications in frail older trauma patients was developed by a multidisciplinary team and implemented in 2016. The standardized evidence-based interdisciplinary care pathway included utilization of order sets and interventions for delirium prevention, early ambulation, bowel and pain regimens, nutrition and physical therapy consults, medication management, care-goal setting, and geriatric assessments.
Main outcome measures: The main outcomes were delirium as determined by a positive CAM score, major complications as defined by the Trauma Quality Improvement Project, in-hospital mortality, and 30-day hospital readmission. Outcome measures were compared between patients who underwent Frailty Identification and Care Pathway intervention (postintervention group) vs patients who were treated prior to pathway implementation (pre-intervention group).
Main results: A total of 269 frail patients were included in the analysis (125 in pre-intervention group vs 144 in postintervention group). Patient demographic and admission characteristics were similar between the 2 groups: mean age was 83.5 (7.1) years, 60.6% were women, and median ISS was 10 (interquartile range [IQR], 9-14). The injury mechanism was similar between groups, with falls accounting for 92.8% and 86.1% of injuries in the pre-intervention and postintervention groups, respectively (P = .07). In univariate analysis, the Frailty Identification and Care Pathway intervention was associated with a significant reduction in delirium (12.5% vs 21.6%, P = .04) and 30-day hospital readmission (2.7% vs 9.6%, P = .01) compared to patients in the pre-intervention group. However, rates of major complications (28.5% vs 28.0%, P = 0.93) and in-hospital mortality (4.2% vs 7.2%, P = .28) were similar between the pre-intervention and postintervention groups. In multivariate logistic regression models adjusted for patient characteristics (age, sex, race, ISS), patients in the postintervention group had lower delirium (OR, 0.44; 95% CI, 0.22-0.88; P = .02) and 30-day hospital readmission (OR, 0.25; 95% CI, 0.07-0.84; P = .02) rates compared to those in the pre-intervention group.
Conclusion: Implementation of an interdisciplinary care protocol for frail geriatric trauma patients significantly decreased their risks for in-hospital delirium and 30-day hospital readmission.
Commentary
Traumatic injuries in older adults are associated with higher morbidity and mortality compared to younger patients, with falls and motor vehicle accidents accounting for a majority of these injuries. Astoundingly, up to one-third of this vulnerable population presenting to hospitals with an ISS greater than 15 may die during hospitalization.1 As a result, a large number of studies and clinical trials have focused on interventions that are designed to reduce fall risks, and hence reduce adverse consequences of traumatic injuries that may arise after falls.2 However, this emphasis on falls prevention has overshadowed a need to develop effective geriatric-centered clinical interventions that aim to improve outcomes in older adults who present to hospitals with traumatic injuries. Furthermore, frailty—a geriatric syndrome indicative of an increased state of vulnerability and predictive of adverse outcomes such as delirium—is highly prevalent in older patients with traumatic injury.3 Thus, there is an urgent need to develop novel, hospital-based, traumatic injury–targeting strategies that incorporate a thoughtful redesign of the care framework that includes evidence-based interventions for geriatric syndromes such as delirium and frailty.
The study reported by Park et al (Study 1) represents the latest effort to evaluate inpatient management strategies designed to improve outcomes in hospitalized older adults who have sustained traumatic injury. Through the implementation of a novel multidisciplinary Geriatric Trauma Care Pathway that incorporates geriatric best practices, this intervention was found to be associated with a 46% lower risk of in-hospital delirium. Because of the inclusion of all age-eligible patients across all strata of traumatic injuries, rather than preselecting for those at the highest risk for poor clinical outcomes, the benefits of this intervention extend to those with minor or moderate injury severity. Furthermore, the improvement in delirium (ie, the primary outcome) is particularly meaningful given that delirium is one of the most common hospital-associated complications that increase hospital LOS, discharge to an institution, and mortality in older adults. Finally, the study’s observed reduced time to a first goals-of-care discussion and increased frequency of goals-of-care documentation after intervention should not be overlooked. The improvements in these 2 process measures are highly significant given that advanced care planning, an intervention that helps to align patients’ values, goals, and treatments, is completed at substantially lower rates in older adults in the acute hospital setting.4
Similarly, in an earlier published study, Bryant and colleagues (Study 2) also show that a geriatric-focused interdisciplinary trauma care pathway is associated with delirium risk reduction in hospitalized older trauma patients. Much like Study 1, the Frailty Identification and Care Pathway utilized in Study 2 is an evidence-based interdisciplinary care pathway that includes the use of geriatric assessments, order sets, and geriatric best practices. Moreover, its exclusive inclusion of pre-frail and frail older patients (ie, those at higher risk for poor outcomes) with moderate injury severity (median ISS of 10 [IQR, 9-14]) suggests that this type of care pathway benefits hospitalized older trauma patients, who are particularly vulnerable to adverse complications such as delirium. Moreover, the successful utilization of the FRAIL questionnaire, a validated frailty screening tool, by surgical residents in the ED to initiate this care pathway demonstrates the feasibility of its use in expediting frailty screening in older patients in trauma care.
Application for Clinical Practice and System Implementation
Findings from the 2 studies discussed in this review indicate that implementation of interdisciplinary clinical care pathways predicated on evidence-based geriatric principles and best practices is a promising approach to reduce delirium in hospitalized older trauma patients. These studies have helped to lay the groundwork in outlining the roadmaps (eg, processes and infrastructures) needed to create such clinical pathways. These key elements include: (1) integration of a multidisciplinary committee (eg, representation from trauma, emergency, and geriatric medicine, nursing, physical and occupational therapy, pharmacy, social work) in pathway design and implementation; (2) adaption of evidence-based geriatric best practices (eg, the Institute for Healthcare Improvement Age-Friendly Health System 4M framework [medication, mentation, mobility, what matters]) to prioritize interventions and to design a pathway that incorporates these features; (3) incorporation of comprehensive geriatric assessment by interdisciplinary providers; (4) utilization of validated clinical instruments to assess physical and cognitive functions, frailty, delirium, and social determinants of health; (5) modification of electronic health record systems to encompass order sets that incorporate evidence-based, nonpharmacological and pharmacological interventions to manage symptoms (eg, delirium, pain, bowel movement, sleep, immobility, polypharmacy) essential to quality geriatric care; and (6) integration of patient and caregiver preferences via goals-of-care discussions and corresponding documentation and communication of these goals.
Additionally, these 2 studies imparted some strategies that may facilitate the implementation of interdisciplinary clinical care pathways in trauma care. Examples of such facilitators include: (1) collaboration with champions within each specialty to reinforce education and buy-in; (2) creation of automatically triggered order sets upon patient presentation to the ED that unites distinct features of clinical pathways; (3) adaption and reorganization of existing hospital infrastructures and resources to meet the needs of clinical pathways implementation (eg, utilizing information technology resources to develop electronic health record order sets; using quality department to develop clinical pathway guidelines and electronic outcome dashboards); and (4) development of individualized patient and caregiver education materials based on care needs (eg, principles of delirium prevention and preservation of mobility during hospitalization) to prepare and engage these stakeholders in patient care and recovery.
Practice Points
- A geriatric interdisciplinary care model can be effectively applied to the management of acute trauma in older patients.
- Interdisciplinary clinical pathways should incorporate geriatric best practices and guidelines and age-appropriate order sets to prioritize and integrate care.
—Fred Ko, MD, MS
1. Hashmi A, Ibrahim-Zada I, Rhee P, et al. Predictors of mortality in geriatric trauma patients: a systematic review and meta-analysis. J Trauma Acute Care Surg. 2014;76(3):894-901. doi:10.1097/TA.0b013e3182ab0763
2. Hopewell S, Adedire O, Copsey BJ, et al. Multifactorial and multiple component interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2018;7(7):CD012221. doi:10.1002/14651858.CD012221.pub2
3. Joseph B, Pandit V, Zangbar B, et al. Superiority of frailty over age in predicting outcomes among geriatric trauma patients: a prospective analysis. JAMA Surg. 2014;149(8):766-772. doi:10.1001/jamasurg.2014.296
4. Hopkins SA, Bentley A, Phillips V, Barclay S. Advance care plans and hospitalized frail older adults: a systematic review. BMJ Support Palliat Care. 2020;10(2):164-174. doi:10.1136/bmjspcare-2019-002093
Study 1 Overview (Park et al)
Objective: To examine whether implementation of a geriatric trauma clinical pathway is associated with reduced rates of delirium in older adults with traumatic injury.
Design: Retrospective case-control study of electronic health records.
Setting and participants: Eligible patients were persons aged 65 years or older who were admitted to the trauma service and did not undergo an operation. A Geriatric Trauma Care Pathway was developed by a multidisciplinary Stanford Quality Pathways team and formally launched on November 1, 2018. The clinical pathway was designed to incorporate geriatric best practices, which included order sets (eg, age-appropriate nonpharmacological interventions and pharmacological dosages), guidelines (eg, Institute for Healthcare Improvement Age-Friendly Health systems 4M framework), automated consultations (comprehensive geriatric assessment), and escalation pathways executed by a multidisciplinary team (eg, pain, bowel, and sleep regulation). The clinical pathway began with admission to the emergency department (ED) (ie, automatic trigger of geriatric trauma care admission order set), daily multidisciplinary team meetings during acute hospitalization, and a transitional care team consultation for postdischarge follow-up or home visit.
Main outcome measures: The primary outcome was delirium as determined by a positive Confusion Assessment Method (CAM) score or a diagnosis of delirium by the clinical team. The secondary outcome was hospital length of stay (LOS). Process measures for pathway compliance (eg, achieving adequate pain control, early mobilization, advance care planning) were assessed. Outcome measures were compared between patients who underwent the Geriatric Trauma Care Pathway intervention (postimplementation group) vs patients who were treated prior to pathway implementation (baseline pre-implementation group).
Main results: Of the 859 eligible patients, 712 were included in the analysis (442 [62.1%] in the baseline pre-implementation group and 270 [37.9%] in the postimplementation group); mean (SD) age was 81.4 (9.1) years, and 394 (55.3%) were women. The injury mechanism was similar between groups, with falls being the most common cause of injury (247 [55.9%] in the baseline group vs 162 [60.0%] in the postimplementation group; P = .43). Injuries as measured by Injury Severity Score (ISS) were minor or moderate in both groups (261 [59.0%] in baseline group vs 168 [62.2%] in postimplementation group; P = .87). The adjusted odds ratio (OR) for delirium in the postimplementation group was lower compared to the baseline pre-implementation group (OR, 0.54; 95% CI, 0.37-0.80; P < .001). Measures of advance care planning in the postimplementation group improved, including more frequent goals-of-care documentation (53.7% in postimplementation group vs 16.7% in baseline group; P < .001) and a shortened time to first goals-of-care discussion upon presenting to the ED (36 hours in postimplementation group vs 50 hours in baseline group; P = .03).
Conclusion: Implementation of a multidisciplinary geriatric trauma clinical pathway for older adults with traumatic injury at a single level I trauma center was associated with reduced rates of delirium.
Study 2 Overview (Bryant et al)
Objective: To determine whether an interdisciplinary care pathway for frail trauma patients can improve in-hospital mortality, complications, and 30-day readmissions.
Design: Retrospective cohort study of frail patients.
Setting and participants: Eligible patients were persons aged 65 years or older who were admitted to the trauma service and survived more than 24 hours; admitted to and discharged from the trauma unit; and determined to be pre-frail or frail by a geriatrician’s assessment. A Frailty Identification and Care Pathway designed to reduce delirium and complications in frail older trauma patients was developed by a multidisciplinary team and implemented in 2016. The standardized evidence-based interdisciplinary care pathway included utilization of order sets and interventions for delirium prevention, early ambulation, bowel and pain regimens, nutrition and physical therapy consults, medication management, care-goal setting, and geriatric assessments.
Main outcome measures: The main outcomes were delirium as determined by a positive CAM score, major complications as defined by the Trauma Quality Improvement Project, in-hospital mortality, and 30-day hospital readmission. Outcome measures were compared between patients who underwent Frailty Identification and Care Pathway intervention (postintervention group) vs patients who were treated prior to pathway implementation (pre-intervention group).
Main results: A total of 269 frail patients were included in the analysis (125 in pre-intervention group vs 144 in postintervention group). Patient demographic and admission characteristics were similar between the 2 groups: mean age was 83.5 (7.1) years, 60.6% were women, and median ISS was 10 (interquartile range [IQR], 9-14). The injury mechanism was similar between groups, with falls accounting for 92.8% and 86.1% of injuries in the pre-intervention and postintervention groups, respectively (P = .07). In univariate analysis, the Frailty Identification and Care Pathway intervention was associated with a significant reduction in delirium (12.5% vs 21.6%, P = .04) and 30-day hospital readmission (2.7% vs 9.6%, P = .01) compared to patients in the pre-intervention group. However, rates of major complications (28.5% vs 28.0%, P = 0.93) and in-hospital mortality (4.2% vs 7.2%, P = .28) were similar between the pre-intervention and postintervention groups. In multivariate logistic regression models adjusted for patient characteristics (age, sex, race, ISS), patients in the postintervention group had lower delirium (OR, 0.44; 95% CI, 0.22-0.88; P = .02) and 30-day hospital readmission (OR, 0.25; 95% CI, 0.07-0.84; P = .02) rates compared to those in the pre-intervention group.
Conclusion: Implementation of an interdisciplinary care protocol for frail geriatric trauma patients significantly decreased their risks for in-hospital delirium and 30-day hospital readmission.
Commentary
Traumatic injuries in older adults are associated with higher morbidity and mortality compared to younger patients, with falls and motor vehicle accidents accounting for a majority of these injuries. Astoundingly, up to one-third of this vulnerable population presenting to hospitals with an ISS greater than 15 may die during hospitalization.1 As a result, a large number of studies and clinical trials have focused on interventions that are designed to reduce fall risks, and hence reduce adverse consequences of traumatic injuries that may arise after falls.2 However, this emphasis on falls prevention has overshadowed a need to develop effective geriatric-centered clinical interventions that aim to improve outcomes in older adults who present to hospitals with traumatic injuries. Furthermore, frailty—a geriatric syndrome indicative of an increased state of vulnerability and predictive of adverse outcomes such as delirium—is highly prevalent in older patients with traumatic injury.3 Thus, there is an urgent need to develop novel, hospital-based, traumatic injury–targeting strategies that incorporate a thoughtful redesign of the care framework that includes evidence-based interventions for geriatric syndromes such as delirium and frailty.
The study reported by Park et al (Study 1) represents the latest effort to evaluate inpatient management strategies designed to improve outcomes in hospitalized older adults who have sustained traumatic injury. Through the implementation of a novel multidisciplinary Geriatric Trauma Care Pathway that incorporates geriatric best practices, this intervention was found to be associated with a 46% lower risk of in-hospital delirium. Because of the inclusion of all age-eligible patients across all strata of traumatic injuries, rather than preselecting for those at the highest risk for poor clinical outcomes, the benefits of this intervention extend to those with minor or moderate injury severity. Furthermore, the improvement in delirium (ie, the primary outcome) is particularly meaningful given that delirium is one of the most common hospital-associated complications that increase hospital LOS, discharge to an institution, and mortality in older adults. Finally, the study’s observed reduced time to a first goals-of-care discussion and increased frequency of goals-of-care documentation after intervention should not be overlooked. The improvements in these 2 process measures are highly significant given that advanced care planning, an intervention that helps to align patients’ values, goals, and treatments, is completed at substantially lower rates in older adults in the acute hospital setting.4
Similarly, in an earlier published study, Bryant and colleagues (Study 2) also show that a geriatric-focused interdisciplinary trauma care pathway is associated with delirium risk reduction in hospitalized older trauma patients. Much like Study 1, the Frailty Identification and Care Pathway utilized in Study 2 is an evidence-based interdisciplinary care pathway that includes the use of geriatric assessments, order sets, and geriatric best practices. Moreover, its exclusive inclusion of pre-frail and frail older patients (ie, those at higher risk for poor outcomes) with moderate injury severity (median ISS of 10 [IQR, 9-14]) suggests that this type of care pathway benefits hospitalized older trauma patients, who are particularly vulnerable to adverse complications such as delirium. Moreover, the successful utilization of the FRAIL questionnaire, a validated frailty screening tool, by surgical residents in the ED to initiate this care pathway demonstrates the feasibility of its use in expediting frailty screening in older patients in trauma care.
Application for Clinical Practice and System Implementation
Findings from the 2 studies discussed in this review indicate that implementation of interdisciplinary clinical care pathways predicated on evidence-based geriatric principles and best practices is a promising approach to reduce delirium in hospitalized older trauma patients. These studies have helped to lay the groundwork in outlining the roadmaps (eg, processes and infrastructures) needed to create such clinical pathways. These key elements include: (1) integration of a multidisciplinary committee (eg, representation from trauma, emergency, and geriatric medicine, nursing, physical and occupational therapy, pharmacy, social work) in pathway design and implementation; (2) adaption of evidence-based geriatric best practices (eg, the Institute for Healthcare Improvement Age-Friendly Health System 4M framework [medication, mentation, mobility, what matters]) to prioritize interventions and to design a pathway that incorporates these features; (3) incorporation of comprehensive geriatric assessment by interdisciplinary providers; (4) utilization of validated clinical instruments to assess physical and cognitive functions, frailty, delirium, and social determinants of health; (5) modification of electronic health record systems to encompass order sets that incorporate evidence-based, nonpharmacological and pharmacological interventions to manage symptoms (eg, delirium, pain, bowel movement, sleep, immobility, polypharmacy) essential to quality geriatric care; and (6) integration of patient and caregiver preferences via goals-of-care discussions and corresponding documentation and communication of these goals.
Additionally, these 2 studies imparted some strategies that may facilitate the implementation of interdisciplinary clinical care pathways in trauma care. Examples of such facilitators include: (1) collaboration with champions within each specialty to reinforce education and buy-in; (2) creation of automatically triggered order sets upon patient presentation to the ED that unites distinct features of clinical pathways; (3) adaption and reorganization of existing hospital infrastructures and resources to meet the needs of clinical pathways implementation (eg, utilizing information technology resources to develop electronic health record order sets; using quality department to develop clinical pathway guidelines and electronic outcome dashboards); and (4) development of individualized patient and caregiver education materials based on care needs (eg, principles of delirium prevention and preservation of mobility during hospitalization) to prepare and engage these stakeholders in patient care and recovery.
Practice Points
- A geriatric interdisciplinary care model can be effectively applied to the management of acute trauma in older patients.
- Interdisciplinary clinical pathways should incorporate geriatric best practices and guidelines and age-appropriate order sets to prioritize and integrate care.
—Fred Ko, MD, MS
Study 1 Overview (Park et al)
Objective: To examine whether implementation of a geriatric trauma clinical pathway is associated with reduced rates of delirium in older adults with traumatic injury.
Design: Retrospective case-control study of electronic health records.
Setting and participants: Eligible patients were persons aged 65 years or older who were admitted to the trauma service and did not undergo an operation. A Geriatric Trauma Care Pathway was developed by a multidisciplinary Stanford Quality Pathways team and formally launched on November 1, 2018. The clinical pathway was designed to incorporate geriatric best practices, which included order sets (eg, age-appropriate nonpharmacological interventions and pharmacological dosages), guidelines (eg, Institute for Healthcare Improvement Age-Friendly Health systems 4M framework), automated consultations (comprehensive geriatric assessment), and escalation pathways executed by a multidisciplinary team (eg, pain, bowel, and sleep regulation). The clinical pathway began with admission to the emergency department (ED) (ie, automatic trigger of geriatric trauma care admission order set), daily multidisciplinary team meetings during acute hospitalization, and a transitional care team consultation for postdischarge follow-up or home visit.
Main outcome measures: The primary outcome was delirium as determined by a positive Confusion Assessment Method (CAM) score or a diagnosis of delirium by the clinical team. The secondary outcome was hospital length of stay (LOS). Process measures for pathway compliance (eg, achieving adequate pain control, early mobilization, advance care planning) were assessed. Outcome measures were compared between patients who underwent the Geriatric Trauma Care Pathway intervention (postimplementation group) vs patients who were treated prior to pathway implementation (baseline pre-implementation group).
Main results: Of the 859 eligible patients, 712 were included in the analysis (442 [62.1%] in the baseline pre-implementation group and 270 [37.9%] in the postimplementation group); mean (SD) age was 81.4 (9.1) years, and 394 (55.3%) were women. The injury mechanism was similar between groups, with falls being the most common cause of injury (247 [55.9%] in the baseline group vs 162 [60.0%] in the postimplementation group; P = .43). Injuries as measured by Injury Severity Score (ISS) were minor or moderate in both groups (261 [59.0%] in baseline group vs 168 [62.2%] in postimplementation group; P = .87). The adjusted odds ratio (OR) for delirium in the postimplementation group was lower compared to the baseline pre-implementation group (OR, 0.54; 95% CI, 0.37-0.80; P < .001). Measures of advance care planning in the postimplementation group improved, including more frequent goals-of-care documentation (53.7% in postimplementation group vs 16.7% in baseline group; P < .001) and a shortened time to first goals-of-care discussion upon presenting to the ED (36 hours in postimplementation group vs 50 hours in baseline group; P = .03).
Conclusion: Implementation of a multidisciplinary geriatric trauma clinical pathway for older adults with traumatic injury at a single level I trauma center was associated with reduced rates of delirium.
Study 2 Overview (Bryant et al)
Objective: To determine whether an interdisciplinary care pathway for frail trauma patients can improve in-hospital mortality, complications, and 30-day readmissions.
Design: Retrospective cohort study of frail patients.
Setting and participants: Eligible patients were persons aged 65 years or older who were admitted to the trauma service and survived more than 24 hours; admitted to and discharged from the trauma unit; and determined to be pre-frail or frail by a geriatrician’s assessment. A Frailty Identification and Care Pathway designed to reduce delirium and complications in frail older trauma patients was developed by a multidisciplinary team and implemented in 2016. The standardized evidence-based interdisciplinary care pathway included utilization of order sets and interventions for delirium prevention, early ambulation, bowel and pain regimens, nutrition and physical therapy consults, medication management, care-goal setting, and geriatric assessments.
Main outcome measures: The main outcomes were delirium as determined by a positive CAM score, major complications as defined by the Trauma Quality Improvement Project, in-hospital mortality, and 30-day hospital readmission. Outcome measures were compared between patients who underwent Frailty Identification and Care Pathway intervention (postintervention group) vs patients who were treated prior to pathway implementation (pre-intervention group).
Main results: A total of 269 frail patients were included in the analysis (125 in pre-intervention group vs 144 in postintervention group). Patient demographic and admission characteristics were similar between the 2 groups: mean age was 83.5 (7.1) years, 60.6% were women, and median ISS was 10 (interquartile range [IQR], 9-14). The injury mechanism was similar between groups, with falls accounting for 92.8% and 86.1% of injuries in the pre-intervention and postintervention groups, respectively (P = .07). In univariate analysis, the Frailty Identification and Care Pathway intervention was associated with a significant reduction in delirium (12.5% vs 21.6%, P = .04) and 30-day hospital readmission (2.7% vs 9.6%, P = .01) compared to patients in the pre-intervention group. However, rates of major complications (28.5% vs 28.0%, P = 0.93) and in-hospital mortality (4.2% vs 7.2%, P = .28) were similar between the pre-intervention and postintervention groups. In multivariate logistic regression models adjusted for patient characteristics (age, sex, race, ISS), patients in the postintervention group had lower delirium (OR, 0.44; 95% CI, 0.22-0.88; P = .02) and 30-day hospital readmission (OR, 0.25; 95% CI, 0.07-0.84; P = .02) rates compared to those in the pre-intervention group.
Conclusion: Implementation of an interdisciplinary care protocol for frail geriatric trauma patients significantly decreased their risks for in-hospital delirium and 30-day hospital readmission.
Commentary
Traumatic injuries in older adults are associated with higher morbidity and mortality compared to younger patients, with falls and motor vehicle accidents accounting for a majority of these injuries. Astoundingly, up to one-third of this vulnerable population presenting to hospitals with an ISS greater than 15 may die during hospitalization.1 As a result, a large number of studies and clinical trials have focused on interventions that are designed to reduce fall risks, and hence reduce adverse consequences of traumatic injuries that may arise after falls.2 However, this emphasis on falls prevention has overshadowed a need to develop effective geriatric-centered clinical interventions that aim to improve outcomes in older adults who present to hospitals with traumatic injuries. Furthermore, frailty—a geriatric syndrome indicative of an increased state of vulnerability and predictive of adverse outcomes such as delirium—is highly prevalent in older patients with traumatic injury.3 Thus, there is an urgent need to develop novel, hospital-based, traumatic injury–targeting strategies that incorporate a thoughtful redesign of the care framework that includes evidence-based interventions for geriatric syndromes such as delirium and frailty.
The study reported by Park et al (Study 1) represents the latest effort to evaluate inpatient management strategies designed to improve outcomes in hospitalized older adults who have sustained traumatic injury. Through the implementation of a novel multidisciplinary Geriatric Trauma Care Pathway that incorporates geriatric best practices, this intervention was found to be associated with a 46% lower risk of in-hospital delirium. Because of the inclusion of all age-eligible patients across all strata of traumatic injuries, rather than preselecting for those at the highest risk for poor clinical outcomes, the benefits of this intervention extend to those with minor or moderate injury severity. Furthermore, the improvement in delirium (ie, the primary outcome) is particularly meaningful given that delirium is one of the most common hospital-associated complications that increase hospital LOS, discharge to an institution, and mortality in older adults. Finally, the study’s observed reduced time to a first goals-of-care discussion and increased frequency of goals-of-care documentation after intervention should not be overlooked. The improvements in these 2 process measures are highly significant given that advanced care planning, an intervention that helps to align patients’ values, goals, and treatments, is completed at substantially lower rates in older adults in the acute hospital setting.4
Similarly, in an earlier published study, Bryant and colleagues (Study 2) also show that a geriatric-focused interdisciplinary trauma care pathway is associated with delirium risk reduction in hospitalized older trauma patients. Much like Study 1, the Frailty Identification and Care Pathway utilized in Study 2 is an evidence-based interdisciplinary care pathway that includes the use of geriatric assessments, order sets, and geriatric best practices. Moreover, its exclusive inclusion of pre-frail and frail older patients (ie, those at higher risk for poor outcomes) with moderate injury severity (median ISS of 10 [IQR, 9-14]) suggests that this type of care pathway benefits hospitalized older trauma patients, who are particularly vulnerable to adverse complications such as delirium. Moreover, the successful utilization of the FRAIL questionnaire, a validated frailty screening tool, by surgical residents in the ED to initiate this care pathway demonstrates the feasibility of its use in expediting frailty screening in older patients in trauma care.
Application for Clinical Practice and System Implementation
Findings from the 2 studies discussed in this review indicate that implementation of interdisciplinary clinical care pathways predicated on evidence-based geriatric principles and best practices is a promising approach to reduce delirium in hospitalized older trauma patients. These studies have helped to lay the groundwork in outlining the roadmaps (eg, processes and infrastructures) needed to create such clinical pathways. These key elements include: (1) integration of a multidisciplinary committee (eg, representation from trauma, emergency, and geriatric medicine, nursing, physical and occupational therapy, pharmacy, social work) in pathway design and implementation; (2) adaption of evidence-based geriatric best practices (eg, the Institute for Healthcare Improvement Age-Friendly Health System 4M framework [medication, mentation, mobility, what matters]) to prioritize interventions and to design a pathway that incorporates these features; (3) incorporation of comprehensive geriatric assessment by interdisciplinary providers; (4) utilization of validated clinical instruments to assess physical and cognitive functions, frailty, delirium, and social determinants of health; (5) modification of electronic health record systems to encompass order sets that incorporate evidence-based, nonpharmacological and pharmacological interventions to manage symptoms (eg, delirium, pain, bowel movement, sleep, immobility, polypharmacy) essential to quality geriatric care; and (6) integration of patient and caregiver preferences via goals-of-care discussions and corresponding documentation and communication of these goals.
Additionally, these 2 studies imparted some strategies that may facilitate the implementation of interdisciplinary clinical care pathways in trauma care. Examples of such facilitators include: (1) collaboration with champions within each specialty to reinforce education and buy-in; (2) creation of automatically triggered order sets upon patient presentation to the ED that unites distinct features of clinical pathways; (3) adaption and reorganization of existing hospital infrastructures and resources to meet the needs of clinical pathways implementation (eg, utilizing information technology resources to develop electronic health record order sets; using quality department to develop clinical pathway guidelines and electronic outcome dashboards); and (4) development of individualized patient and caregiver education materials based on care needs (eg, principles of delirium prevention and preservation of mobility during hospitalization) to prepare and engage these stakeholders in patient care and recovery.
Practice Points
- A geriatric interdisciplinary care model can be effectively applied to the management of acute trauma in older patients.
- Interdisciplinary clinical pathways should incorporate geriatric best practices and guidelines and age-appropriate order sets to prioritize and integrate care.
—Fred Ko, MD, MS
1. Hashmi A, Ibrahim-Zada I, Rhee P, et al. Predictors of mortality in geriatric trauma patients: a systematic review and meta-analysis. J Trauma Acute Care Surg. 2014;76(3):894-901. doi:10.1097/TA.0b013e3182ab0763
2. Hopewell S, Adedire O, Copsey BJ, et al. Multifactorial and multiple component interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2018;7(7):CD012221. doi:10.1002/14651858.CD012221.pub2
3. Joseph B, Pandit V, Zangbar B, et al. Superiority of frailty over age in predicting outcomes among geriatric trauma patients: a prospective analysis. JAMA Surg. 2014;149(8):766-772. doi:10.1001/jamasurg.2014.296
4. Hopkins SA, Bentley A, Phillips V, Barclay S. Advance care plans and hospitalized frail older adults: a systematic review. BMJ Support Palliat Care. 2020;10(2):164-174. doi:10.1136/bmjspcare-2019-002093
1. Hashmi A, Ibrahim-Zada I, Rhee P, et al. Predictors of mortality in geriatric trauma patients: a systematic review and meta-analysis. J Trauma Acute Care Surg. 2014;76(3):894-901. doi:10.1097/TA.0b013e3182ab0763
2. Hopewell S, Adedire O, Copsey BJ, et al. Multifactorial and multiple component interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2018;7(7):CD012221. doi:10.1002/14651858.CD012221.pub2
3. Joseph B, Pandit V, Zangbar B, et al. Superiority of frailty over age in predicting outcomes among geriatric trauma patients: a prospective analysis. JAMA Surg. 2014;149(8):766-772. doi:10.1001/jamasurg.2014.296
4. Hopkins SA, Bentley A, Phillips V, Barclay S. Advance care plans and hospitalized frail older adults: a systematic review. BMJ Support Palliat Care. 2020;10(2):164-174. doi:10.1136/bmjspcare-2019-002093
High rate of mental health problems in transgender children
Transgender children, even those as young as 9 or 10 years old, already show increased susceptibility to mental health problems compared with their cisgender peers, new research suggests.
Investigators assessed a sample of more than 7000 children aged 9-10 years in the general population and found those who reported being transgender scored considerably higher on all six subscales of the DSM-5-oriented Child Behavior Checklist (CBCL).
Transgender children had almost sixfold higher odds of suicidality and over twice the odds of depressive and anxiety problems, compared with cisgender children. Moreover, transgender children displayed higher levels of mental health problems compared with previous studies of transgender children recruited from specialist gender clinics.
“Our findings emphasize the vulnerability of transgender children, including those who may not yet have accessed specialist support,” senior author Kenneth C. Pang, MBBS, BMedSc, PhD, associate professor, Murdoch Children’s Research Institute, University of Melbourne, Royal Children’s Hospital, Australia, told this news organization.
“Clinicians providing general health care to transgender children should keep this vulnerability in mind and proactively address any mental health problems that exist,” he said.
The findings were published online as a research letter in JAMA Network Open.
Higher levels of support?
“We felt this study was important to conduct because previous studies regarding the mental health of transgender children have been drawn from children receiving specialist gender-related care,” Dr. Pang said.
“Transgender children receiving such care are likely to enjoy higher levels of support than those unable to access such services, and this might create differences in mental health,” he added.
To investigate this issue, the researchers turned to participants (n = 7,169; mean age, 10.3 years) in the Adolescent Brain Cognitive Development (ABCD) study.
“The ABCD study is a longitudinal study of over 11,000 children who were recruited to reflect the sociodemographic variation of the U.S. population,” lead author Douglas H. Russell, MSc, a PhD candidate at the University of Melbourne, told this news organization.
To be included in the current study, children had to understand and respond to the question “Are you transgender?”
The researchers compared mental health outcomes between transgender and cisgender children (n = 58 and n = 7,111, respectively) using the CBCL, which study participants had completed at baseline.
Key protective factor
The transgender children recorded higher mean T scores for all six subscales of the CBCL, although all children scored in the references range; and the standardized mean difference was “small.”
Suicidality was measured by summing the two suicide-related items in the parent-report CBCL assessing suicidal ideation and attempts.
“For the CBCL, T scores are calculated for measures that are scored on a continuous scale,” Dr. Pang noted. “Responses to the suicidality questions on the CBCL were assessed in a categorical manner (at risk of suicide vs. not), as previously described by others. So T scores were therefore not able to be calculated.”
When the investigators determined the proportion of cisgender and transgender children who scored in the “borderline” or “clinical” range (T score, 65), they found increased odds of transgender children scoring in that range in all six subscales, as well as suicidality.
The researchers note the results for attention-deficit/hyperactivity disorder and oppositional defiant problems were not statistically significant.
Previous studies that used clinical samples of young transgender children (aged 5 -11 years) reported lower rates of depression and anxiety than what was found in the current study.
“Transgender children in the general population displayed higher levels of mental health problems compared to previous studies of transgender children recruited from specialist gender clinics,” Mr. Russell said.
One reason for that may be children in specialist clinics “are likely to have support from their families (a key protective factor for the mental health of transgender young people); in comparison, many transgender children in the general population lack parental support for their gender,” the investigators wrote.
“Our findings suggest that by 9 to 10 years of age transgender children already show increased susceptibility to mental health problems compared with their cisgender peers, which has important public health implications,” they added.
The researchers noted that whether this susceptibility “is due to stigma, minority stress, discrimination, or gender dysphoria is unclear, but providing appropriate mental health supports to this vulnerable group is paramount.”
“Pathologizing and damaging”
Commenting for this news organiztion, Jack L. Turban, MD, incoming assistant professor of child and adolescent psychiatry, University of California, San Francisco, said that “sadly” the findings are “largely in line with past studies that have shown dramatic mental health disparities” for transgender and gender diverse youth.
“The dramatically elevated odds of suicidality warrants particular public health concern,” said Dr. Turban, who was not involved with the study.
He noted these results “come at a time when transgender youth are under legislative attack in many states throughout the country, and the national rhetoric around them has been pathologizing and damaging.”
Dr. Turban said that he worries “if our national discourse around trans youth doesn’t change soon, that these disparities will worsen.”
Funding was provided to individual investigators by the Hugh Williamson Foundation, the Royal Children’s Hospital foundation, the National Health and Medical Research Council, and the Australian Government Research Training Program Scholarship. Mr. Russell and Dr. Pang reported being members of the Australian Professional Association for Trans Health. Dr. Pang is a member of the World Professional Association for Transgender Health and a member of the editorial board of the journal Transgender Health. Dr. Turban reported textbook royalties from Springer Nature, being on the scientific advisory board of Panorama Global (UpSwing Fund), and payments as an expert witness for the American Civil Liberties Union, Lambda Legal, and Cooley LLP. He has received a pilot research award from AACAP and pharmaceutical partners (Arbor and Pfizer), a research fellowship from the Sorensen Foundation, and freelance payments from the New York Times, the Washington Post, and the Los Angeles Times.
A version of this article first appeared on Medscape.com.
Transgender children, even those as young as 9 or 10 years old, already show increased susceptibility to mental health problems compared with their cisgender peers, new research suggests.
Investigators assessed a sample of more than 7000 children aged 9-10 years in the general population and found those who reported being transgender scored considerably higher on all six subscales of the DSM-5-oriented Child Behavior Checklist (CBCL).
Transgender children had almost sixfold higher odds of suicidality and over twice the odds of depressive and anxiety problems, compared with cisgender children. Moreover, transgender children displayed higher levels of mental health problems compared with previous studies of transgender children recruited from specialist gender clinics.
“Our findings emphasize the vulnerability of transgender children, including those who may not yet have accessed specialist support,” senior author Kenneth C. Pang, MBBS, BMedSc, PhD, associate professor, Murdoch Children’s Research Institute, University of Melbourne, Royal Children’s Hospital, Australia, told this news organization.
“Clinicians providing general health care to transgender children should keep this vulnerability in mind and proactively address any mental health problems that exist,” he said.
The findings were published online as a research letter in JAMA Network Open.
Higher levels of support?
“We felt this study was important to conduct because previous studies regarding the mental health of transgender children have been drawn from children receiving specialist gender-related care,” Dr. Pang said.
“Transgender children receiving such care are likely to enjoy higher levels of support than those unable to access such services, and this might create differences in mental health,” he added.
To investigate this issue, the researchers turned to participants (n = 7,169; mean age, 10.3 years) in the Adolescent Brain Cognitive Development (ABCD) study.
“The ABCD study is a longitudinal study of over 11,000 children who were recruited to reflect the sociodemographic variation of the U.S. population,” lead author Douglas H. Russell, MSc, a PhD candidate at the University of Melbourne, told this news organization.
To be included in the current study, children had to understand and respond to the question “Are you transgender?”
The researchers compared mental health outcomes between transgender and cisgender children (n = 58 and n = 7,111, respectively) using the CBCL, which study participants had completed at baseline.
Key protective factor
The transgender children recorded higher mean T scores for all six subscales of the CBCL, although all children scored in the references range; and the standardized mean difference was “small.”
Suicidality was measured by summing the two suicide-related items in the parent-report CBCL assessing suicidal ideation and attempts.
“For the CBCL, T scores are calculated for measures that are scored on a continuous scale,” Dr. Pang noted. “Responses to the suicidality questions on the CBCL were assessed in a categorical manner (at risk of suicide vs. not), as previously described by others. So T scores were therefore not able to be calculated.”
When the investigators determined the proportion of cisgender and transgender children who scored in the “borderline” or “clinical” range (T score, 65), they found increased odds of transgender children scoring in that range in all six subscales, as well as suicidality.
The researchers note the results for attention-deficit/hyperactivity disorder and oppositional defiant problems were not statistically significant.
Previous studies that used clinical samples of young transgender children (aged 5 -11 years) reported lower rates of depression and anxiety than what was found in the current study.
“Transgender children in the general population displayed higher levels of mental health problems compared to previous studies of transgender children recruited from specialist gender clinics,” Mr. Russell said.
One reason for that may be children in specialist clinics “are likely to have support from their families (a key protective factor for the mental health of transgender young people); in comparison, many transgender children in the general population lack parental support for their gender,” the investigators wrote.
“Our findings suggest that by 9 to 10 years of age transgender children already show increased susceptibility to mental health problems compared with their cisgender peers, which has important public health implications,” they added.
The researchers noted that whether this susceptibility “is due to stigma, minority stress, discrimination, or gender dysphoria is unclear, but providing appropriate mental health supports to this vulnerable group is paramount.”
“Pathologizing and damaging”
Commenting for this news organiztion, Jack L. Turban, MD, incoming assistant professor of child and adolescent psychiatry, University of California, San Francisco, said that “sadly” the findings are “largely in line with past studies that have shown dramatic mental health disparities” for transgender and gender diverse youth.
“The dramatically elevated odds of suicidality warrants particular public health concern,” said Dr. Turban, who was not involved with the study.
He noted these results “come at a time when transgender youth are under legislative attack in many states throughout the country, and the national rhetoric around them has been pathologizing and damaging.”
Dr. Turban said that he worries “if our national discourse around trans youth doesn’t change soon, that these disparities will worsen.”
Funding was provided to individual investigators by the Hugh Williamson Foundation, the Royal Children’s Hospital foundation, the National Health and Medical Research Council, and the Australian Government Research Training Program Scholarship. Mr. Russell and Dr. Pang reported being members of the Australian Professional Association for Trans Health. Dr. Pang is a member of the World Professional Association for Transgender Health and a member of the editorial board of the journal Transgender Health. Dr. Turban reported textbook royalties from Springer Nature, being on the scientific advisory board of Panorama Global (UpSwing Fund), and payments as an expert witness for the American Civil Liberties Union, Lambda Legal, and Cooley LLP. He has received a pilot research award from AACAP and pharmaceutical partners (Arbor and Pfizer), a research fellowship from the Sorensen Foundation, and freelance payments from the New York Times, the Washington Post, and the Los Angeles Times.
A version of this article first appeared on Medscape.com.
Transgender children, even those as young as 9 or 10 years old, already show increased susceptibility to mental health problems compared with their cisgender peers, new research suggests.
Investigators assessed a sample of more than 7000 children aged 9-10 years in the general population and found those who reported being transgender scored considerably higher on all six subscales of the DSM-5-oriented Child Behavior Checklist (CBCL).
Transgender children had almost sixfold higher odds of suicidality and over twice the odds of depressive and anxiety problems, compared with cisgender children. Moreover, transgender children displayed higher levels of mental health problems compared with previous studies of transgender children recruited from specialist gender clinics.
“Our findings emphasize the vulnerability of transgender children, including those who may not yet have accessed specialist support,” senior author Kenneth C. Pang, MBBS, BMedSc, PhD, associate professor, Murdoch Children’s Research Institute, University of Melbourne, Royal Children’s Hospital, Australia, told this news organization.
“Clinicians providing general health care to transgender children should keep this vulnerability in mind and proactively address any mental health problems that exist,” he said.
The findings were published online as a research letter in JAMA Network Open.
Higher levels of support?
“We felt this study was important to conduct because previous studies regarding the mental health of transgender children have been drawn from children receiving specialist gender-related care,” Dr. Pang said.
“Transgender children receiving such care are likely to enjoy higher levels of support than those unable to access such services, and this might create differences in mental health,” he added.
To investigate this issue, the researchers turned to participants (n = 7,169; mean age, 10.3 years) in the Adolescent Brain Cognitive Development (ABCD) study.
“The ABCD study is a longitudinal study of over 11,000 children who were recruited to reflect the sociodemographic variation of the U.S. population,” lead author Douglas H. Russell, MSc, a PhD candidate at the University of Melbourne, told this news organization.
To be included in the current study, children had to understand and respond to the question “Are you transgender?”
The researchers compared mental health outcomes between transgender and cisgender children (n = 58 and n = 7,111, respectively) using the CBCL, which study participants had completed at baseline.
Key protective factor
The transgender children recorded higher mean T scores for all six subscales of the CBCL, although all children scored in the references range; and the standardized mean difference was “small.”
Suicidality was measured by summing the two suicide-related items in the parent-report CBCL assessing suicidal ideation and attempts.
“For the CBCL, T scores are calculated for measures that are scored on a continuous scale,” Dr. Pang noted. “Responses to the suicidality questions on the CBCL were assessed in a categorical manner (at risk of suicide vs. not), as previously described by others. So T scores were therefore not able to be calculated.”
When the investigators determined the proportion of cisgender and transgender children who scored in the “borderline” or “clinical” range (T score, 65), they found increased odds of transgender children scoring in that range in all six subscales, as well as suicidality.
The researchers note the results for attention-deficit/hyperactivity disorder and oppositional defiant problems were not statistically significant.
Previous studies that used clinical samples of young transgender children (aged 5 -11 years) reported lower rates of depression and anxiety than what was found in the current study.
“Transgender children in the general population displayed higher levels of mental health problems compared to previous studies of transgender children recruited from specialist gender clinics,” Mr. Russell said.
One reason for that may be children in specialist clinics “are likely to have support from their families (a key protective factor for the mental health of transgender young people); in comparison, many transgender children in the general population lack parental support for their gender,” the investigators wrote.
“Our findings suggest that by 9 to 10 years of age transgender children already show increased susceptibility to mental health problems compared with their cisgender peers, which has important public health implications,” they added.
The researchers noted that whether this susceptibility “is due to stigma, minority stress, discrimination, or gender dysphoria is unclear, but providing appropriate mental health supports to this vulnerable group is paramount.”
“Pathologizing and damaging”
Commenting for this news organiztion, Jack L. Turban, MD, incoming assistant professor of child and adolescent psychiatry, University of California, San Francisco, said that “sadly” the findings are “largely in line with past studies that have shown dramatic mental health disparities” for transgender and gender diverse youth.
“The dramatically elevated odds of suicidality warrants particular public health concern,” said Dr. Turban, who was not involved with the study.
He noted these results “come at a time when transgender youth are under legislative attack in many states throughout the country, and the national rhetoric around them has been pathologizing and damaging.”
Dr. Turban said that he worries “if our national discourse around trans youth doesn’t change soon, that these disparities will worsen.”
Funding was provided to individual investigators by the Hugh Williamson Foundation, the Royal Children’s Hospital foundation, the National Health and Medical Research Council, and the Australian Government Research Training Program Scholarship. Mr. Russell and Dr. Pang reported being members of the Australian Professional Association for Trans Health. Dr. Pang is a member of the World Professional Association for Transgender Health and a member of the editorial board of the journal Transgender Health. Dr. Turban reported textbook royalties from Springer Nature, being on the scientific advisory board of Panorama Global (UpSwing Fund), and payments as an expert witness for the American Civil Liberties Union, Lambda Legal, and Cooley LLP. He has received a pilot research award from AACAP and pharmaceutical partners (Arbor and Pfizer), a research fellowship from the Sorensen Foundation, and freelance payments from the New York Times, the Washington Post, and the Los Angeles Times.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Guideline advises against depression screening in pregnancy
The Canadian Task Force on Preventive Health Care recommends against the routine screening of all pregnant and postpartum women for depression using a standard questionnaire, according to its new guideline.
The basis for its position is the lack of evidence that such screening “adds value beyond discussions about overall wellbeing, depression, anxiety, and mood that are currently a part of established perinatal clinical care.
“We should not be using a one-size-fits all approach,” lead author Eddy Lang, MD, professor and head of emergency medicine at the Cumming School of Medicine, University of Calgary (Alta.), told this news organization.
Instead, the task force emphasizes regular clinical care, including asking patients about their wellbeing and support systems. The task force categorizes the recommendation as conditional and as having very low-certainty evidence.
The recommendation was published in CMAJ.
One randomized study
The task force is an independent panel of clinicians and scientists that makes recommendations on primary and secondary prevention in primary care. A working group of five members of the task force developed this recommendation with scientific support from Public Health Agency of Canada staff.
In its research, the task force found only one study that showed a benefit of routine depression screening in this population. This study was a randomized controlled trial conducted in Hong Kong. Researchers evaluated 462 postpartum women who were randomly assigned to receive screening with the Edinburgh Postnatal Depression Scale (EPDS) or no screening 2 months post partum.
“We found the effect of screening in this study to be very uncertain for the important outcomes of interest,” said Dr. Lang.
“These included parent-child stress, marital stress, and the number of infant hospital admissions. The effects of screening on all of these outcomes were very uncertain, mainly because it was such a small trial,” he said.
The task force also assessed how pregnant and postpartum women feel about being screened. What these women most wanted was a good relationship with a trusted primary care provider who would initiate discussions about their mental health in a caring atmosphere.
“Although they told us they liked the idea of universal screening, they admitted to their family doctors that they actually preferred to be asked about their wellbeing, [to be asked] how things were going at home, and [to have] a discussion about their mental health and wellbeing, rather than a formal screening process. They felt a discussion about depression with a primary health care provider during the pregnancy and postpartum period is critical,” said Dr. Lang.
Thus, the task force recommends “against instrument-based depression screening using a questionnaire with cutoff score to distinguish ‘screen positive’ and ‘screen negative’ administered to all individuals during pregnancy and the postpartum period (up to 1 year after childbirth).”
Screening remains common
“There’s a lot of uncertainty in the scientific community about whether it’s a good idea to administer a screening test to all pregnant and postpartum women to determine in a systematic way if they might be suffering from depression,” said Dr. Lang.
The task force recommended against screening for depression among perinatal or postpartum women in 2013, but screening is still performed in many provinces, said Dr. Lang.
Dr. Lang emphasized that the recommendation does not apply to usual care, in which the provider asks questions about and discusses a patient’s mental health and proceeds on the basis of their clinical judgment; nor does it apply to diagnostic pathways in which the clinician suspects that the individual may have depression and tests her accordingly.
“What we are saying in our recommendation is that all clinicians should ask about a patient’s wellbeing, about their mood, their anxiety, and these questions are an important part of the clinical assessment of pregnant and postpartum women. But we’re also saying the usefulness of doing so with a questionnaire and using a cutoff score on the questionnaire to decide who needs further assessment or possibly treatment is unproven by the research,” Dr. Lang said.
A growing problem
For Diane Francoeur, MD, CEO of the Society of Obstetricians and Gynecologists of Canada, this is all well and good, but the reality is that such screening is better than nothing.
Quebec is the only Canadian province that conducts universal screening for all pregnant and postpartum women, Dr. Francoeur said in an interview. She was not part of the task force.
“I agree that it should be more than one approach, but the problem is that there is such a shortage of resources. There are many issues that can arise when you follow a woman during her pregnancy,” she said.
Dr. Francoeur said that COVID-19 has been particularly tough on women, including pregnant and postpartum women, who are the most vulnerable.
“Especially during the COVID era, it was astonishing how women were not doing well. Their stress level was so high. We need to have a specific approach dedicated to prenatal mental health, because it’s a problem that is bigger than it used to be,” she said.
Violence against women has increased considerably since the beginning of the COVID-19 pandemic, said Dr. Francoeur. “Many more women have been killed by their partners. We have never seen anything like this before, and I hope we will never see this again,” she said.
“Help was more available a few years ago, but now, it’s really hard if and when you need to have a quick consultation with a specialist and the woman is really depressed. It can take forever. So, it’s okay to screen, but then, what’s next? Who is going to be there to take these women and help them? And we don’t have the answer,” Dr. Francoeur said.
Pregnant and postpartum women who suffer from depression need more than pills, she added. “We reassure them and treat their depression pharmacologically, but it’s also a time to give appropriate support and help them through the pregnancy and get well prepared to receive their newborn, because, as we now know, that first year of life is really important for the child, and the mom needs to be supported.”
Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. Dr. Lang and Dr. Francoeur reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The Canadian Task Force on Preventive Health Care recommends against the routine screening of all pregnant and postpartum women for depression using a standard questionnaire, according to its new guideline.
The basis for its position is the lack of evidence that such screening “adds value beyond discussions about overall wellbeing, depression, anxiety, and mood that are currently a part of established perinatal clinical care.
“We should not be using a one-size-fits all approach,” lead author Eddy Lang, MD, professor and head of emergency medicine at the Cumming School of Medicine, University of Calgary (Alta.), told this news organization.
Instead, the task force emphasizes regular clinical care, including asking patients about their wellbeing and support systems. The task force categorizes the recommendation as conditional and as having very low-certainty evidence.
The recommendation was published in CMAJ.
One randomized study
The task force is an independent panel of clinicians and scientists that makes recommendations on primary and secondary prevention in primary care. A working group of five members of the task force developed this recommendation with scientific support from Public Health Agency of Canada staff.
In its research, the task force found only one study that showed a benefit of routine depression screening in this population. This study was a randomized controlled trial conducted in Hong Kong. Researchers evaluated 462 postpartum women who were randomly assigned to receive screening with the Edinburgh Postnatal Depression Scale (EPDS) or no screening 2 months post partum.
“We found the effect of screening in this study to be very uncertain for the important outcomes of interest,” said Dr. Lang.
“These included parent-child stress, marital stress, and the number of infant hospital admissions. The effects of screening on all of these outcomes were very uncertain, mainly because it was such a small trial,” he said.
The task force also assessed how pregnant and postpartum women feel about being screened. What these women most wanted was a good relationship with a trusted primary care provider who would initiate discussions about their mental health in a caring atmosphere.
“Although they told us they liked the idea of universal screening, they admitted to their family doctors that they actually preferred to be asked about their wellbeing, [to be asked] how things were going at home, and [to have] a discussion about their mental health and wellbeing, rather than a formal screening process. They felt a discussion about depression with a primary health care provider during the pregnancy and postpartum period is critical,” said Dr. Lang.
Thus, the task force recommends “against instrument-based depression screening using a questionnaire with cutoff score to distinguish ‘screen positive’ and ‘screen negative’ administered to all individuals during pregnancy and the postpartum period (up to 1 year after childbirth).”
Screening remains common
“There’s a lot of uncertainty in the scientific community about whether it’s a good idea to administer a screening test to all pregnant and postpartum women to determine in a systematic way if they might be suffering from depression,” said Dr. Lang.
The task force recommended against screening for depression among perinatal or postpartum women in 2013, but screening is still performed in many provinces, said Dr. Lang.
Dr. Lang emphasized that the recommendation does not apply to usual care, in which the provider asks questions about and discusses a patient’s mental health and proceeds on the basis of their clinical judgment; nor does it apply to diagnostic pathways in which the clinician suspects that the individual may have depression and tests her accordingly.
“What we are saying in our recommendation is that all clinicians should ask about a patient’s wellbeing, about their mood, their anxiety, and these questions are an important part of the clinical assessment of pregnant and postpartum women. But we’re also saying the usefulness of doing so with a questionnaire and using a cutoff score on the questionnaire to decide who needs further assessment or possibly treatment is unproven by the research,” Dr. Lang said.
A growing problem
For Diane Francoeur, MD, CEO of the Society of Obstetricians and Gynecologists of Canada, this is all well and good, but the reality is that such screening is better than nothing.
Quebec is the only Canadian province that conducts universal screening for all pregnant and postpartum women, Dr. Francoeur said in an interview. She was not part of the task force.
“I agree that it should be more than one approach, but the problem is that there is such a shortage of resources. There are many issues that can arise when you follow a woman during her pregnancy,” she said.
Dr. Francoeur said that COVID-19 has been particularly tough on women, including pregnant and postpartum women, who are the most vulnerable.
“Especially during the COVID era, it was astonishing how women were not doing well. Their stress level was so high. We need to have a specific approach dedicated to prenatal mental health, because it’s a problem that is bigger than it used to be,” she said.
Violence against women has increased considerably since the beginning of the COVID-19 pandemic, said Dr. Francoeur. “Many more women have been killed by their partners. We have never seen anything like this before, and I hope we will never see this again,” she said.
“Help was more available a few years ago, but now, it’s really hard if and when you need to have a quick consultation with a specialist and the woman is really depressed. It can take forever. So, it’s okay to screen, but then, what’s next? Who is going to be there to take these women and help them? And we don’t have the answer,” Dr. Francoeur said.
Pregnant and postpartum women who suffer from depression need more than pills, she added. “We reassure them and treat their depression pharmacologically, but it’s also a time to give appropriate support and help them through the pregnancy and get well prepared to receive their newborn, because, as we now know, that first year of life is really important for the child, and the mom needs to be supported.”
Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. Dr. Lang and Dr. Francoeur reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The Canadian Task Force on Preventive Health Care recommends against the routine screening of all pregnant and postpartum women for depression using a standard questionnaire, according to its new guideline.
The basis for its position is the lack of evidence that such screening “adds value beyond discussions about overall wellbeing, depression, anxiety, and mood that are currently a part of established perinatal clinical care.
“We should not be using a one-size-fits all approach,” lead author Eddy Lang, MD, professor and head of emergency medicine at the Cumming School of Medicine, University of Calgary (Alta.), told this news organization.
Instead, the task force emphasizes regular clinical care, including asking patients about their wellbeing and support systems. The task force categorizes the recommendation as conditional and as having very low-certainty evidence.
The recommendation was published in CMAJ.
One randomized study
The task force is an independent panel of clinicians and scientists that makes recommendations on primary and secondary prevention in primary care. A working group of five members of the task force developed this recommendation with scientific support from Public Health Agency of Canada staff.
In its research, the task force found only one study that showed a benefit of routine depression screening in this population. This study was a randomized controlled trial conducted in Hong Kong. Researchers evaluated 462 postpartum women who were randomly assigned to receive screening with the Edinburgh Postnatal Depression Scale (EPDS) or no screening 2 months post partum.
“We found the effect of screening in this study to be very uncertain for the important outcomes of interest,” said Dr. Lang.
“These included parent-child stress, marital stress, and the number of infant hospital admissions. The effects of screening on all of these outcomes were very uncertain, mainly because it was such a small trial,” he said.
The task force also assessed how pregnant and postpartum women feel about being screened. What these women most wanted was a good relationship with a trusted primary care provider who would initiate discussions about their mental health in a caring atmosphere.
“Although they told us they liked the idea of universal screening, they admitted to their family doctors that they actually preferred to be asked about their wellbeing, [to be asked] how things were going at home, and [to have] a discussion about their mental health and wellbeing, rather than a formal screening process. They felt a discussion about depression with a primary health care provider during the pregnancy and postpartum period is critical,” said Dr. Lang.
Thus, the task force recommends “against instrument-based depression screening using a questionnaire with cutoff score to distinguish ‘screen positive’ and ‘screen negative’ administered to all individuals during pregnancy and the postpartum period (up to 1 year after childbirth).”
Screening remains common
“There’s a lot of uncertainty in the scientific community about whether it’s a good idea to administer a screening test to all pregnant and postpartum women to determine in a systematic way if they might be suffering from depression,” said Dr. Lang.
The task force recommended against screening for depression among perinatal or postpartum women in 2013, but screening is still performed in many provinces, said Dr. Lang.
Dr. Lang emphasized that the recommendation does not apply to usual care, in which the provider asks questions about and discusses a patient’s mental health and proceeds on the basis of their clinical judgment; nor does it apply to diagnostic pathways in which the clinician suspects that the individual may have depression and tests her accordingly.
“What we are saying in our recommendation is that all clinicians should ask about a patient’s wellbeing, about their mood, their anxiety, and these questions are an important part of the clinical assessment of pregnant and postpartum women. But we’re also saying the usefulness of doing so with a questionnaire and using a cutoff score on the questionnaire to decide who needs further assessment or possibly treatment is unproven by the research,” Dr. Lang said.
A growing problem
For Diane Francoeur, MD, CEO of the Society of Obstetricians and Gynecologists of Canada, this is all well and good, but the reality is that such screening is better than nothing.
Quebec is the only Canadian province that conducts universal screening for all pregnant and postpartum women, Dr. Francoeur said in an interview. She was not part of the task force.
“I agree that it should be more than one approach, but the problem is that there is such a shortage of resources. There are many issues that can arise when you follow a woman during her pregnancy,” she said.
Dr. Francoeur said that COVID-19 has been particularly tough on women, including pregnant and postpartum women, who are the most vulnerable.
“Especially during the COVID era, it was astonishing how women were not doing well. Their stress level was so high. We need to have a specific approach dedicated to prenatal mental health, because it’s a problem that is bigger than it used to be,” she said.
Violence against women has increased considerably since the beginning of the COVID-19 pandemic, said Dr. Francoeur. “Many more women have been killed by their partners. We have never seen anything like this before, and I hope we will never see this again,” she said.
“Help was more available a few years ago, but now, it’s really hard if and when you need to have a quick consultation with a specialist and the woman is really depressed. It can take forever. So, it’s okay to screen, but then, what’s next? Who is going to be there to take these women and help them? And we don’t have the answer,” Dr. Francoeur said.
Pregnant and postpartum women who suffer from depression need more than pills, she added. “We reassure them and treat their depression pharmacologically, but it’s also a time to give appropriate support and help them through the pregnancy and get well prepared to receive their newborn, because, as we now know, that first year of life is really important for the child, and the mom needs to be supported.”
Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. Dr. Lang and Dr. Francoeur reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CMAJ
Legal abortion is a matter of public health
On June 24, the U.S. Supreme Court overturned Roe v. Wade, a decision that was issued in 1973. From now on, each state will be able to choose the laws that it wants to put in place regarding abortion. Several states have already decided to ban abortion altogether. As a physician, but also as a woman, I am stunned to see this opposition to a right that, in my opinion, is also a matter of public health.
International data
In Belgium, voluntary termination of pregnancy (VTP) has been allowed since 1990. Except in the case of a serious medical problem, the abortion must take place before the end of the 12th week after conception. So, 14 weeks from the last menstrual period (LMP).
Beyond that time frame, a VTP can be performed only when the continuation of the pregnancy endangers the health of the woman or when it is certain that the unborn child will be affected by a condition of particular gravity and recognized as incurable at the time of diagnosis. This is referred to as termination for medical reasons (TFMR).
First observation
The annual number of VTPs did not climb following legalization. For the past 20 years in Belgium, that number has remained stable, hovering around 19,000. Abortion continues to be an action – neither trivialized nor minimized – that is difficult for any woman to take, no matter what her reason.
Second observation
Over 60% of women who had an abortion were using a form of contraception. So, while the burden of contraception still rests almost exclusively on the woman, it cannot be said that those who had a VTP did not use some method of birth control.
Even more important, legal abortions have very few complications, either physical or psychological. Studies show that pregnancy itself carries a higher risk for psychopathological manifestations than a VTP. These VTPs are safe, and women quickly recover from them. The most sensitive time seems to be the period before the abortion, and it’s at this stage that most of the psychological and psychopathological manifestations accumulate. The majority of women facing a VTP experience feelings of relief, and only a minority develop psychological problems, usually when there is already a history of mental disorder. The literature shows that the levels of anxiety and depression decrease in the month following the abortion. Being denied a VTP, on the other hand, significantly increases the woman’s risk of developing a mental disorder.
Should a VTP be denied, a woman, if she determines that she doesn’t have any other choice, may then end up turning to a back-alley abortion. The methods used for this are medieval, dangerous, and may not prove successful – things like using chemicals, piercing the amniotic sac with a needle or sharp object (the famous coat hanger), eating or drinking abortifacient herbs, taking large quantities of medication, punching the stomach, falling down stairs, and engaging in intense physical exercise.
From there, these risky methods inevitably lead to numerous complications: Incomplete abortions, infections, septicemia, breakthrough bleeding, subsequent sterility, laceration of the uterine wall, or death.
Around one-third of women who undergo risky abortions develop complications, while less than half receive care.
The World Health Organization estimates that back-alley abortions represent 49% of abortions worldwide. It puts the number of illegal abortions performed each year at 20 million.
Each year, around 60,000 women worldwide die as a result of an unsafe VTP. That’s one woman every 9 minutes. And odds are that these figures are underestimated.
Making the decision to resort to a VTP is always difficult. Ideally, you should be able to discuss it with your partner, when there is one, and with your close friends and family, to have someone go with you as support, to weigh the pros and cons, and to make a choice in line with your convictions and your conscience. But first and foremost, the law must guarantee the right to be able to ask oneself this question, because guaranteeing this right is also guaranteeing the health and safety of women, and that is why this remains a public health imperative.
A version of this article first appeared on Medscape.com. This article was translated from MediQuality.
On June 24, the U.S. Supreme Court overturned Roe v. Wade, a decision that was issued in 1973. From now on, each state will be able to choose the laws that it wants to put in place regarding abortion. Several states have already decided to ban abortion altogether. As a physician, but also as a woman, I am stunned to see this opposition to a right that, in my opinion, is also a matter of public health.
International data
In Belgium, voluntary termination of pregnancy (VTP) has been allowed since 1990. Except in the case of a serious medical problem, the abortion must take place before the end of the 12th week after conception. So, 14 weeks from the last menstrual period (LMP).
Beyond that time frame, a VTP can be performed only when the continuation of the pregnancy endangers the health of the woman or when it is certain that the unborn child will be affected by a condition of particular gravity and recognized as incurable at the time of diagnosis. This is referred to as termination for medical reasons (TFMR).
First observation
The annual number of VTPs did not climb following legalization. For the past 20 years in Belgium, that number has remained stable, hovering around 19,000. Abortion continues to be an action – neither trivialized nor minimized – that is difficult for any woman to take, no matter what her reason.
Second observation
Over 60% of women who had an abortion were using a form of contraception. So, while the burden of contraception still rests almost exclusively on the woman, it cannot be said that those who had a VTP did not use some method of birth control.
Even more important, legal abortions have very few complications, either physical or psychological. Studies show that pregnancy itself carries a higher risk for psychopathological manifestations than a VTP. These VTPs are safe, and women quickly recover from them. The most sensitive time seems to be the period before the abortion, and it’s at this stage that most of the psychological and psychopathological manifestations accumulate. The majority of women facing a VTP experience feelings of relief, and only a minority develop psychological problems, usually when there is already a history of mental disorder. The literature shows that the levels of anxiety and depression decrease in the month following the abortion. Being denied a VTP, on the other hand, significantly increases the woman’s risk of developing a mental disorder.
Should a VTP be denied, a woman, if she determines that she doesn’t have any other choice, may then end up turning to a back-alley abortion. The methods used for this are medieval, dangerous, and may not prove successful – things like using chemicals, piercing the amniotic sac with a needle or sharp object (the famous coat hanger), eating or drinking abortifacient herbs, taking large quantities of medication, punching the stomach, falling down stairs, and engaging in intense physical exercise.
From there, these risky methods inevitably lead to numerous complications: Incomplete abortions, infections, septicemia, breakthrough bleeding, subsequent sterility, laceration of the uterine wall, or death.
Around one-third of women who undergo risky abortions develop complications, while less than half receive care.
The World Health Organization estimates that back-alley abortions represent 49% of abortions worldwide. It puts the number of illegal abortions performed each year at 20 million.
Each year, around 60,000 women worldwide die as a result of an unsafe VTP. That’s one woman every 9 minutes. And odds are that these figures are underestimated.
Making the decision to resort to a VTP is always difficult. Ideally, you should be able to discuss it with your partner, when there is one, and with your close friends and family, to have someone go with you as support, to weigh the pros and cons, and to make a choice in line with your convictions and your conscience. But first and foremost, the law must guarantee the right to be able to ask oneself this question, because guaranteeing this right is also guaranteeing the health and safety of women, and that is why this remains a public health imperative.
A version of this article first appeared on Medscape.com. This article was translated from MediQuality.
On June 24, the U.S. Supreme Court overturned Roe v. Wade, a decision that was issued in 1973. From now on, each state will be able to choose the laws that it wants to put in place regarding abortion. Several states have already decided to ban abortion altogether. As a physician, but also as a woman, I am stunned to see this opposition to a right that, in my opinion, is also a matter of public health.
International data
In Belgium, voluntary termination of pregnancy (VTP) has been allowed since 1990. Except in the case of a serious medical problem, the abortion must take place before the end of the 12th week after conception. So, 14 weeks from the last menstrual period (LMP).
Beyond that time frame, a VTP can be performed only when the continuation of the pregnancy endangers the health of the woman or when it is certain that the unborn child will be affected by a condition of particular gravity and recognized as incurable at the time of diagnosis. This is referred to as termination for medical reasons (TFMR).
First observation
The annual number of VTPs did not climb following legalization. For the past 20 years in Belgium, that number has remained stable, hovering around 19,000. Abortion continues to be an action – neither trivialized nor minimized – that is difficult for any woman to take, no matter what her reason.
Second observation
Over 60% of women who had an abortion were using a form of contraception. So, while the burden of contraception still rests almost exclusively on the woman, it cannot be said that those who had a VTP did not use some method of birth control.
Even more important, legal abortions have very few complications, either physical or psychological. Studies show that pregnancy itself carries a higher risk for psychopathological manifestations than a VTP. These VTPs are safe, and women quickly recover from them. The most sensitive time seems to be the period before the abortion, and it’s at this stage that most of the psychological and psychopathological manifestations accumulate. The majority of women facing a VTP experience feelings of relief, and only a minority develop psychological problems, usually when there is already a history of mental disorder. The literature shows that the levels of anxiety and depression decrease in the month following the abortion. Being denied a VTP, on the other hand, significantly increases the woman’s risk of developing a mental disorder.
Should a VTP be denied, a woman, if she determines that she doesn’t have any other choice, may then end up turning to a back-alley abortion. The methods used for this are medieval, dangerous, and may not prove successful – things like using chemicals, piercing the amniotic sac with a needle or sharp object (the famous coat hanger), eating or drinking abortifacient herbs, taking large quantities of medication, punching the stomach, falling down stairs, and engaging in intense physical exercise.
From there, these risky methods inevitably lead to numerous complications: Incomplete abortions, infections, septicemia, breakthrough bleeding, subsequent sterility, laceration of the uterine wall, or death.
Around one-third of women who undergo risky abortions develop complications, while less than half receive care.
The World Health Organization estimates that back-alley abortions represent 49% of abortions worldwide. It puts the number of illegal abortions performed each year at 20 million.
Each year, around 60,000 women worldwide die as a result of an unsafe VTP. That’s one woman every 9 minutes. And odds are that these figures are underestimated.
Making the decision to resort to a VTP is always difficult. Ideally, you should be able to discuss it with your partner, when there is one, and with your close friends and family, to have someone go with you as support, to weigh the pros and cons, and to make a choice in line with your convictions and your conscience. But first and foremost, the law must guarantee the right to be able to ask oneself this question, because guaranteeing this right is also guaranteeing the health and safety of women, and that is why this remains a public health imperative.
A version of this article first appeared on Medscape.com. This article was translated from MediQuality.
Women with fear of pregnancy call for clinician compassion
Cee Elliot is afraid of pregnancy. The 29-year-old retail manager in Connecticut said she has felt that way since puberty, when she “finally understood” pregnancy and reproduction. Always squeamish around babies and pregnant people, she said, as she learned more about the complications birth can cause, the idea of carrying a child herself became increasingly repulsive.
Later, Ms. Elliot said, she was treated poorly by a partner because of her fears, leading to regular panic attacks. She moved on from that partner, but her fear of pregnancy did not. Along the way, she felt her fears were dismissed by doctors and peers alike.
Tokophobia – a severe fear of childbirth – goes beyond the typical anxieties about birth or pregnancy that women often experience. The condition can intrude on everyday life, crippling social interaction and interrupting regular sleep patterns. Although statistics in the United States don’t exist, as many as 14% of women internationally are thought to have tokophobia.
Although psychiatric treatment focusing on past traumas can help, many women resort to managing the condition themselves. Some seek sterilization, whereas others take multiple forms of contraception simultaneously – combining intrauterine devices and oral birth control, for example, experts said. Some women have sought abortions and some even have attempted suicide rather than face giving birth, according to Leila Frodsham, MbChB, a women’s health expert at King’s College London, who has studied tokophobia.
The International Classification of Diseases added tokophobia to its list of diagnostic codes in 2018. But the Diagnostic and Statistical Manual of Mental Disorders, used by clinicians in the United States, has yet to do the same. Without this designation, some doctors are more inclined to diagnose tokophobia than others, Dr. Frodsham said.
“I think some clinicians struggle to understand how much this condition affects women. There isn’t training in it, and I’d like to see it discussed more,” Dr. Frodsham told this news organization.
Dr. Frodsham said she has seen hundreds of patients seeking help with their fear of pregnancy. Many of these women don’t know that they might have a condition that could benefit from psychiatric treatment.
Tokophobia typically takes two forms: primary, which affects women who have never given birth; and secondary, which stems from a previous traumatic birth experience.
“It’s not the pain of childbirth they are afraid of, but rather their fear comes out of a sense that they lack control over themselves and the situation of being pregnant,” Dr. Frodsham said.
Although the phenomenon has been studied internationally, particularly in Europe, fear of childbirth remains almost entirely unexplored in the United States literature.
One of the only scientific examinations of tokophobia in this country was a 2016 survey of 22 women with the condition by researchers at the University of Michigan, Ann Arbor. Published in the Journal of Obstetric, Gynecology & Neonatal Nursing, the survey found that many of the women expressed concern that their race, gender, or level of income might affect the quality of their care. Some women surveyed said they had experienced traumas directly related to systemic inequalities in the health care system.
Lee Roosevelt, PhD, MPH, CNM, a nurse and midwife and a coauthor of the study, said fear of the health care system, coupled with concern over the loss of bodily autonomy, can foster severe aversion to childbirth. In her experience, she said, clinicians often handle these patients poorly.
“If a woman is making the decision not to have children, we want it to be because she has decided for her, and her body, that it is the right thing,” added Lisa Kane Low, PhD, CNM, professor of obstetrics and gynecology at the University of Michigan, who worked with Dr. Roosevelt on the survey. “She shouldn’t feel the decision is made because she can’t access what she needs or the health care system is unable to provide it.”
Access to midwives, doulas, or therapists trained in trauma counseling can allow women to have a voice in their treatment, Dr. Roosevelt said.
No specific medication exists to treat tokophobia; however, drugs for depression or anxiety sometimes help, Dr. Low said. “Women with tokophobia may not need medication but would benefit from other therapies like desensitization or biobehavioral approaches or combinations of those,” she said.
Treating triggers
According to Dr. Frodsham, women with tokophobia often experience guilt and isolation. They may avoid speaking to women who are pregnant or avoid discussing pregnancy and childbirth, afraid that doing so may trigger their fear.
“They can’t see how they can get close to this catastrophic thing they think is going to happen to them,” she said. “Many of them think they will die.”
Many patients avoid thinking about memories of traumatic events so as to not trigger extreme emotional responses.
Dr. Roosevelt said developing ways to assess and treat tokophobia has become more urgent, since the Supreme Court’s recent decision to overturn Roe v. Wade could lead to more instances of women carrying unwanted pregnancies.
Seeking community
The internet has become a place where women with tokophobia and less severe fears about pregnancy can share their experiences. On the online bulletin board Reddit, r/Tokphobia and r/childfree contain thousands of queries and personal stories about the condition, as well as requests for advice.
Jillian Kilcoyne, who lives in New York and attends college in Michigan, said: “Pregnancy has always freaked me out. A part of me believes it’s a biological injustice that women have to go through such pain and be ignored by the medical community just to give birth.” Ms. Kilcoyne said she has not sought counseling or help from a clinician.
“I’m not sure I even want it,” she told this news organization. “Some people want to get over their phobia because they want families, and others don’t want children at all. I think that those individuals should have the help they need.”
Claudia, a South Carolina resident who asked to be identified only by her first name owing to concerns about her privacy, said her tokophobia began when she started having sex. It grew worse when she developed health conditions that could be exacerbated by pregnancy. She said she stocks up on contraceptives and periodically takes a pregnancy test to ease her nerves.
“This started for me when I realized that having children wasn’t a requirement for life. I didn’t even know there was a name for what I was feeling,” Claudia said in an interview. “So, letting women know they have options, and then not making them feel guilty, or ashamed, is the most important thing. We shouldn’t try to convince women that motherhood is the only, or the correct, path.”
Ms. Elliot urged clinicians to have compassion: “Treat tokophobic patients – especially a pregnant one seeking an abortion – like someone with a life-threatening parasite. Don’t belittle or dismiss them. We’re already going to lose so many lives because of unwanted pregnancies and birth. Don’t add to the number.”
A version of this article first appeared on Medscape.com.
Cee Elliot is afraid of pregnancy. The 29-year-old retail manager in Connecticut said she has felt that way since puberty, when she “finally understood” pregnancy and reproduction. Always squeamish around babies and pregnant people, she said, as she learned more about the complications birth can cause, the idea of carrying a child herself became increasingly repulsive.
Later, Ms. Elliot said, she was treated poorly by a partner because of her fears, leading to regular panic attacks. She moved on from that partner, but her fear of pregnancy did not. Along the way, she felt her fears were dismissed by doctors and peers alike.
Tokophobia – a severe fear of childbirth – goes beyond the typical anxieties about birth or pregnancy that women often experience. The condition can intrude on everyday life, crippling social interaction and interrupting regular sleep patterns. Although statistics in the United States don’t exist, as many as 14% of women internationally are thought to have tokophobia.
Although psychiatric treatment focusing on past traumas can help, many women resort to managing the condition themselves. Some seek sterilization, whereas others take multiple forms of contraception simultaneously – combining intrauterine devices and oral birth control, for example, experts said. Some women have sought abortions and some even have attempted suicide rather than face giving birth, according to Leila Frodsham, MbChB, a women’s health expert at King’s College London, who has studied tokophobia.
The International Classification of Diseases added tokophobia to its list of diagnostic codes in 2018. But the Diagnostic and Statistical Manual of Mental Disorders, used by clinicians in the United States, has yet to do the same. Without this designation, some doctors are more inclined to diagnose tokophobia than others, Dr. Frodsham said.
“I think some clinicians struggle to understand how much this condition affects women. There isn’t training in it, and I’d like to see it discussed more,” Dr. Frodsham told this news organization.
Dr. Frodsham said she has seen hundreds of patients seeking help with their fear of pregnancy. Many of these women don’t know that they might have a condition that could benefit from psychiatric treatment.
Tokophobia typically takes two forms: primary, which affects women who have never given birth; and secondary, which stems from a previous traumatic birth experience.
“It’s not the pain of childbirth they are afraid of, but rather their fear comes out of a sense that they lack control over themselves and the situation of being pregnant,” Dr. Frodsham said.
Although the phenomenon has been studied internationally, particularly in Europe, fear of childbirth remains almost entirely unexplored in the United States literature.
One of the only scientific examinations of tokophobia in this country was a 2016 survey of 22 women with the condition by researchers at the University of Michigan, Ann Arbor. Published in the Journal of Obstetric, Gynecology & Neonatal Nursing, the survey found that many of the women expressed concern that their race, gender, or level of income might affect the quality of their care. Some women surveyed said they had experienced traumas directly related to systemic inequalities in the health care system.
Lee Roosevelt, PhD, MPH, CNM, a nurse and midwife and a coauthor of the study, said fear of the health care system, coupled with concern over the loss of bodily autonomy, can foster severe aversion to childbirth. In her experience, she said, clinicians often handle these patients poorly.
“If a woman is making the decision not to have children, we want it to be because she has decided for her, and her body, that it is the right thing,” added Lisa Kane Low, PhD, CNM, professor of obstetrics and gynecology at the University of Michigan, who worked with Dr. Roosevelt on the survey. “She shouldn’t feel the decision is made because she can’t access what she needs or the health care system is unable to provide it.”
Access to midwives, doulas, or therapists trained in trauma counseling can allow women to have a voice in their treatment, Dr. Roosevelt said.
No specific medication exists to treat tokophobia; however, drugs for depression or anxiety sometimes help, Dr. Low said. “Women with tokophobia may not need medication but would benefit from other therapies like desensitization or biobehavioral approaches or combinations of those,” she said.
Treating triggers
According to Dr. Frodsham, women with tokophobia often experience guilt and isolation. They may avoid speaking to women who are pregnant or avoid discussing pregnancy and childbirth, afraid that doing so may trigger their fear.
“They can’t see how they can get close to this catastrophic thing they think is going to happen to them,” she said. “Many of them think they will die.”
Many patients avoid thinking about memories of traumatic events so as to not trigger extreme emotional responses.
Dr. Roosevelt said developing ways to assess and treat tokophobia has become more urgent, since the Supreme Court’s recent decision to overturn Roe v. Wade could lead to more instances of women carrying unwanted pregnancies.
Seeking community
The internet has become a place where women with tokophobia and less severe fears about pregnancy can share their experiences. On the online bulletin board Reddit, r/Tokphobia and r/childfree contain thousands of queries and personal stories about the condition, as well as requests for advice.
Jillian Kilcoyne, who lives in New York and attends college in Michigan, said: “Pregnancy has always freaked me out. A part of me believes it’s a biological injustice that women have to go through such pain and be ignored by the medical community just to give birth.” Ms. Kilcoyne said she has not sought counseling or help from a clinician.
“I’m not sure I even want it,” she told this news organization. “Some people want to get over their phobia because they want families, and others don’t want children at all. I think that those individuals should have the help they need.”
Claudia, a South Carolina resident who asked to be identified only by her first name owing to concerns about her privacy, said her tokophobia began when she started having sex. It grew worse when she developed health conditions that could be exacerbated by pregnancy. She said she stocks up on contraceptives and periodically takes a pregnancy test to ease her nerves.
“This started for me when I realized that having children wasn’t a requirement for life. I didn’t even know there was a name for what I was feeling,” Claudia said in an interview. “So, letting women know they have options, and then not making them feel guilty, or ashamed, is the most important thing. We shouldn’t try to convince women that motherhood is the only, or the correct, path.”
Ms. Elliot urged clinicians to have compassion: “Treat tokophobic patients – especially a pregnant one seeking an abortion – like someone with a life-threatening parasite. Don’t belittle or dismiss them. We’re already going to lose so many lives because of unwanted pregnancies and birth. Don’t add to the number.”
A version of this article first appeared on Medscape.com.
Cee Elliot is afraid of pregnancy. The 29-year-old retail manager in Connecticut said she has felt that way since puberty, when she “finally understood” pregnancy and reproduction. Always squeamish around babies and pregnant people, she said, as she learned more about the complications birth can cause, the idea of carrying a child herself became increasingly repulsive.
Later, Ms. Elliot said, she was treated poorly by a partner because of her fears, leading to regular panic attacks. She moved on from that partner, but her fear of pregnancy did not. Along the way, she felt her fears were dismissed by doctors and peers alike.
Tokophobia – a severe fear of childbirth – goes beyond the typical anxieties about birth or pregnancy that women often experience. The condition can intrude on everyday life, crippling social interaction and interrupting regular sleep patterns. Although statistics in the United States don’t exist, as many as 14% of women internationally are thought to have tokophobia.
Although psychiatric treatment focusing on past traumas can help, many women resort to managing the condition themselves. Some seek sterilization, whereas others take multiple forms of contraception simultaneously – combining intrauterine devices and oral birth control, for example, experts said. Some women have sought abortions and some even have attempted suicide rather than face giving birth, according to Leila Frodsham, MbChB, a women’s health expert at King’s College London, who has studied tokophobia.
The International Classification of Diseases added tokophobia to its list of diagnostic codes in 2018. But the Diagnostic and Statistical Manual of Mental Disorders, used by clinicians in the United States, has yet to do the same. Without this designation, some doctors are more inclined to diagnose tokophobia than others, Dr. Frodsham said.
“I think some clinicians struggle to understand how much this condition affects women. There isn’t training in it, and I’d like to see it discussed more,” Dr. Frodsham told this news organization.
Dr. Frodsham said she has seen hundreds of patients seeking help with their fear of pregnancy. Many of these women don’t know that they might have a condition that could benefit from psychiatric treatment.
Tokophobia typically takes two forms: primary, which affects women who have never given birth; and secondary, which stems from a previous traumatic birth experience.
“It’s not the pain of childbirth they are afraid of, but rather their fear comes out of a sense that they lack control over themselves and the situation of being pregnant,” Dr. Frodsham said.
Although the phenomenon has been studied internationally, particularly in Europe, fear of childbirth remains almost entirely unexplored in the United States literature.
One of the only scientific examinations of tokophobia in this country was a 2016 survey of 22 women with the condition by researchers at the University of Michigan, Ann Arbor. Published in the Journal of Obstetric, Gynecology & Neonatal Nursing, the survey found that many of the women expressed concern that their race, gender, or level of income might affect the quality of their care. Some women surveyed said they had experienced traumas directly related to systemic inequalities in the health care system.
Lee Roosevelt, PhD, MPH, CNM, a nurse and midwife and a coauthor of the study, said fear of the health care system, coupled with concern over the loss of bodily autonomy, can foster severe aversion to childbirth. In her experience, she said, clinicians often handle these patients poorly.
“If a woman is making the decision not to have children, we want it to be because she has decided for her, and her body, that it is the right thing,” added Lisa Kane Low, PhD, CNM, professor of obstetrics and gynecology at the University of Michigan, who worked with Dr. Roosevelt on the survey. “She shouldn’t feel the decision is made because she can’t access what she needs or the health care system is unable to provide it.”
Access to midwives, doulas, or therapists trained in trauma counseling can allow women to have a voice in their treatment, Dr. Roosevelt said.
No specific medication exists to treat tokophobia; however, drugs for depression or anxiety sometimes help, Dr. Low said. “Women with tokophobia may not need medication but would benefit from other therapies like desensitization or biobehavioral approaches or combinations of those,” she said.
Treating triggers
According to Dr. Frodsham, women with tokophobia often experience guilt and isolation. They may avoid speaking to women who are pregnant or avoid discussing pregnancy and childbirth, afraid that doing so may trigger their fear.
“They can’t see how they can get close to this catastrophic thing they think is going to happen to them,” she said. “Many of them think they will die.”
Many patients avoid thinking about memories of traumatic events so as to not trigger extreme emotional responses.
Dr. Roosevelt said developing ways to assess and treat tokophobia has become more urgent, since the Supreme Court’s recent decision to overturn Roe v. Wade could lead to more instances of women carrying unwanted pregnancies.
Seeking community
The internet has become a place where women with tokophobia and less severe fears about pregnancy can share their experiences. On the online bulletin board Reddit, r/Tokphobia and r/childfree contain thousands of queries and personal stories about the condition, as well as requests for advice.
Jillian Kilcoyne, who lives in New York and attends college in Michigan, said: “Pregnancy has always freaked me out. A part of me believes it’s a biological injustice that women have to go through such pain and be ignored by the medical community just to give birth.” Ms. Kilcoyne said she has not sought counseling or help from a clinician.
“I’m not sure I even want it,” she told this news organization. “Some people want to get over their phobia because they want families, and others don’t want children at all. I think that those individuals should have the help they need.”
Claudia, a South Carolina resident who asked to be identified only by her first name owing to concerns about her privacy, said her tokophobia began when she started having sex. It grew worse when she developed health conditions that could be exacerbated by pregnancy. She said she stocks up on contraceptives and periodically takes a pregnancy test to ease her nerves.
“This started for me when I realized that having children wasn’t a requirement for life. I didn’t even know there was a name for what I was feeling,” Claudia said in an interview. “So, letting women know they have options, and then not making them feel guilty, or ashamed, is the most important thing. We shouldn’t try to convince women that motherhood is the only, or the correct, path.”
Ms. Elliot urged clinicians to have compassion: “Treat tokophobic patients – especially a pregnant one seeking an abortion – like someone with a life-threatening parasite. Don’t belittle or dismiss them. We’re already going to lose so many lives because of unwanted pregnancies and birth. Don’t add to the number.”
A version of this article first appeared on Medscape.com.