Clinical Psychiatry News

Cluster headache is associated with a significantly increased risk for comorbid conditions, including mental disorders and other neurologic disease, leading to significant disability and absenteeism, new research shows.

Results from a Swedish register-based study also showed that patients with cluster headache had a sixfold increased risk for central nervous system disorders and a twofold increased risk for musculoskeletal disorders.

Although cluster headaches are often more prevalent in men, researchers found that multimorbidity rates were significantly higher in women. In addition, rates of external injuries were significantly higher among individuals with cluster headache than among persons without cluster headache.

“The findings very clearly indicate that cluster headache patients suffer from other health issues as well and that they are at risk of having longer periods of times when they cannot work,” said lead investigator Caroline Ran, PhD, a research specialist in the department of neuroscience at the Karolinska Institutet, Stockholm.

“It’s really important for clinicians to look at cluster headache from a broader perspective and make sure that patients are followed up so that they don’t risk ending up in a situation where they have several comorbidities,” Dr. Ran added.

The findings were published online in Neurology.
 

‘Striking’ finding

Cluster headache is one of the most severe and debilitating types of headache. It causes intense pain behind the eyes, which has been described as being worse than pain associated with childbirth or kidney stones.

Attacks can occur multiple times in a single day and can last up to 3 hours. Cluster headache is rare, occurring in about 1 in 1,000 individuals, and is more common in men. Underdiagnosis is common – especially in women.

The study drew on two Swedish population-based registries and included 3,240 patients with cluster headache aged 16-64 years and 16,200 matched control persons. The analysis covered medical visits from 2001 to 2010.

Results showed that 91.9% of participants with cluster headache had some type of multimorbidity. By comparison, 77.6% of the control group had some type of multimorbidity (odds ratio, 3.26; P < .0001).

Prior studies have shown a higher incidence of mental health and behavioral disorders among patients with cluster headache. However, when the researchers removed those conditions along with external injuries from the dataset, patients with headache were still significantly more likely to have multiple co-occurring illnesses (86.7% vs. 68.8%; OR, 2.95; P < .0001).

The most common comorbid conditions in the overall cluster headache group were diseases of the nervous system (OR, 5.9; 95% CI, 5.46 -6.42); 51.8% of the cluster headache group reported these disorders, compared with just 15.4% of the control group.

Diseases of the eye, the respiratory, gastrointestinal, and musculoskeletal systems, and connective tissue were also significantly more common among patients with cluster headache.

“For each diagnosis that we investigated, we found a higher incidence in the cluster headache group, and we thought this was a very striking finding and worth discussing in the clinical setting that these patients are at risk of general ill health,” Dr. Ran said.
 

Risky behavior?

Another novel finding was the higher rate of external injuries among the cluster headache group, compared with the control group. The finding seems to back up the theory that patients with cluster headache are more likely to engage in risky behaviors, the researchers noted.

In the cluster headache group, external injuries were reported by 47.1% of men and 41% of women, versus 34.9% and 26.0%, respectively, in the control group.

“Now we can also show that cluster headache patients have more injuries and that is totally unrelated to the biological health of the individuals, so that could also indicate higher risk taking,” Dr. Ran said.

Overall multimorbidity rates and diagnoses in each medical category except external injury were higher among women with cluster headache than men with headaches. In addition, the mean number of days on sick leave and disability pension was higher among women with cluster headache than among men with cluster headache (83.71 days vs. 52.56 days).

Overall, the mean number of sickness absence and disability pension net days in 2010 was nearly twice as high in the cluster headache group as in the control group (63.15 days vs. 34.08 days).

Removing mental and behavioral health disorders from the mix did not lower those numbers.

“Our numbers indicate that the mental health issues that are related to cluster headache might not impact their work situation as much as the other comorbidities,” Dr. Ran said.
 

Struggle is real

Commenting on the findings, Heidi Schwarz, MD, professor of clinical neurology at the University of Rochester (N.Y.) Medical Center, called the study a “valuable contribution” to the field and to the treatment of cluster headache.

“It’s a good study that addresses factors that really need to be considered as you take care of these patients,” said Dr. Schwarz, who was not involved with the research.

“The most salient features of this is that cluster headache is quite disabling, and if you add a comorbidity to it, it’s even more disabling,” she said.

Dr. Schwarz noted that cluster headache is often misdiagnosed as migraine or is overlooked altogether, especially in women. These data underscore that, although cluster headache is more common in men, it affects women too and could lead to even greater disability.

“This has a direct impact on patient quality of life, and in the end, that really should be what we’re looking to enhance,” Dr. Schwarz said. “When a patient with cluster comes in and they tell you they’re really struggling, believe them because it’s quite real.”

The findings also fill a gap in the literature and offer the kind of data that could not be collected in the United States, she noted. Sweden provides paid sick time for all workers aged 16 and older and offers a disability pension to all workers whose ability to work is temporarily or permanently inhibited because of illness or injury.

“You will never get this kind of data in the United States because this kind of data comes from two datasets that are extremely inclusive and detailed in a society, Sweden, where they have a social support system,” Dr. Schwarz said.

The study was funded by the Swedish Research Council, the Swedish Brain Foundation, and Mellby Gård, Region Stockholm, Märta Lundkvist stiftelse and Karolinska Institutet research funds. Dr. Ran and Dr. Schwarz report no relevant financial relationships.

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

Cluster headache is associated with a significantly increased risk for comorbid conditions, including mental disorders and other neurologic disease, leading to significant disability and absenteeism, new research shows.

Results from a Swedish register-based study also showed that patients with cluster headache had a sixfold increased risk for central nervous system disorders and a twofold increased risk for musculoskeletal disorders.

Although cluster headaches are often more prevalent in men, researchers found that multimorbidity rates were significantly higher in women. In addition, rates of external injuries were significantly higher among individuals with cluster headache than among persons without cluster headache.

“The findings very clearly indicate that cluster headache patients suffer from other health issues as well and that they are at risk of having longer periods of times when they cannot work,” said lead investigator Caroline Ran, PhD, a research specialist in the department of neuroscience at the Karolinska Institutet, Stockholm.

“It’s really important for clinicians to look at cluster headache from a broader perspective and make sure that patients are followed up so that they don’t risk ending up in a situation where they have several comorbidities,” Dr. Ran added.

The findings were published online in Neurology.
 

‘Striking’ finding

Cluster headache is one of the most severe and debilitating types of headache. It causes intense pain behind the eyes, which has been described as being worse than pain associated with childbirth or kidney stones.

Attacks can occur multiple times in a single day and can last up to 3 hours. Cluster headache is rare, occurring in about 1 in 1,000 individuals, and is more common in men. Underdiagnosis is common – especially in women.

The study drew on two Swedish population-based registries and included 3,240 patients with cluster headache aged 16-64 years and 16,200 matched control persons. The analysis covered medical visits from 2001 to 2010.

Results showed that 91.9% of participants with cluster headache had some type of multimorbidity. By comparison, 77.6% of the control group had some type of multimorbidity (odds ratio, 3.26; P < .0001).

Prior studies have shown a higher incidence of mental health and behavioral disorders among patients with cluster headache. However, when the researchers removed those conditions along with external injuries from the dataset, patients with headache were still significantly more likely to have multiple co-occurring illnesses (86.7% vs. 68.8%; OR, 2.95; P < .0001).

The most common comorbid conditions in the overall cluster headache group were diseases of the nervous system (OR, 5.9; 95% CI, 5.46 -6.42); 51.8% of the cluster headache group reported these disorders, compared with just 15.4% of the control group.

Diseases of the eye, the respiratory, gastrointestinal, and musculoskeletal systems, and connective tissue were also significantly more common among patients with cluster headache.

“For each diagnosis that we investigated, we found a higher incidence in the cluster headache group, and we thought this was a very striking finding and worth discussing in the clinical setting that these patients are at risk of general ill health,” Dr. Ran said.
 

Risky behavior?

Another novel finding was the higher rate of external injuries among the cluster headache group, compared with the control group. The finding seems to back up the theory that patients with cluster headache are more likely to engage in risky behaviors, the researchers noted.

In the cluster headache group, external injuries were reported by 47.1% of men and 41% of women, versus 34.9% and 26.0%, respectively, in the control group.

“Now we can also show that cluster headache patients have more injuries and that is totally unrelated to the biological health of the individuals, so that could also indicate higher risk taking,” Dr. Ran said.

Overall multimorbidity rates and diagnoses in each medical category except external injury were higher among women with cluster headache than men with headaches. In addition, the mean number of days on sick leave and disability pension was higher among women with cluster headache than among men with cluster headache (83.71 days vs. 52.56 days).

Overall, the mean number of sickness absence and disability pension net days in 2010 was nearly twice as high in the cluster headache group as in the control group (63.15 days vs. 34.08 days).

Removing mental and behavioral health disorders from the mix did not lower those numbers.

“Our numbers indicate that the mental health issues that are related to cluster headache might not impact their work situation as much as the other comorbidities,” Dr. Ran said.
 

Struggle is real

Commenting on the findings, Heidi Schwarz, MD, professor of clinical neurology at the University of Rochester (N.Y.) Medical Center, called the study a “valuable contribution” to the field and to the treatment of cluster headache.

“It’s a good study that addresses factors that really need to be considered as you take care of these patients,” said Dr. Schwarz, who was not involved with the research.

“The most salient features of this is that cluster headache is quite disabling, and if you add a comorbidity to it, it’s even more disabling,” she said.

Dr. Schwarz noted that cluster headache is often misdiagnosed as migraine or is overlooked altogether, especially in women. These data underscore that, although cluster headache is more common in men, it affects women too and could lead to even greater disability.

“This has a direct impact on patient quality of life, and in the end, that really should be what we’re looking to enhance,” Dr. Schwarz said. “When a patient with cluster comes in and they tell you they’re really struggling, believe them because it’s quite real.”

The findings also fill a gap in the literature and offer the kind of data that could not be collected in the United States, she noted. Sweden provides paid sick time for all workers aged 16 and older and offers a disability pension to all workers whose ability to work is temporarily or permanently inhibited because of illness or injury.

“You will never get this kind of data in the United States because this kind of data comes from two datasets that are extremely inclusive and detailed in a society, Sweden, where they have a social support system,” Dr. Schwarz said.

The study was funded by the Swedish Research Council, the Swedish Brain Foundation, and Mellby Gård, Region Stockholm, Märta Lundkvist stiftelse and Karolinska Institutet research funds. Dr. Ran and Dr. Schwarz report no relevant financial relationships.

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

Cluster headache is associated with a significantly increased risk for comorbid conditions, including mental disorders and other neurologic disease, leading to significant disability and absenteeism, new research shows.

Results from a Swedish register-based study also showed that patients with cluster headache had a sixfold increased risk for central nervous system disorders and a twofold increased risk for musculoskeletal disorders.

Although cluster headaches are often more prevalent in men, researchers found that multimorbidity rates were significantly higher in women. In addition, rates of external injuries were significantly higher among individuals with cluster headache than among persons without cluster headache.

“The findings very clearly indicate that cluster headache patients suffer from other health issues as well and that they are at risk of having longer periods of times when they cannot work,” said lead investigator Caroline Ran, PhD, a research specialist in the department of neuroscience at the Karolinska Institutet, Stockholm.

“It’s really important for clinicians to look at cluster headache from a broader perspective and make sure that patients are followed up so that they don’t risk ending up in a situation where they have several comorbidities,” Dr. Ran added.

The findings were published online in Neurology.
 

‘Striking’ finding

Cluster headache is one of the most severe and debilitating types of headache. It causes intense pain behind the eyes, which has been described as being worse than pain associated with childbirth or kidney stones.

Attacks can occur multiple times in a single day and can last up to 3 hours. Cluster headache is rare, occurring in about 1 in 1,000 individuals, and is more common in men. Underdiagnosis is common – especially in women.

The study drew on two Swedish population-based registries and included 3,240 patients with cluster headache aged 16-64 years and 16,200 matched control persons. The analysis covered medical visits from 2001 to 2010.

Results showed that 91.9% of participants with cluster headache had some type of multimorbidity. By comparison, 77.6% of the control group had some type of multimorbidity (odds ratio, 3.26; P < .0001).

Prior studies have shown a higher incidence of mental health and behavioral disorders among patients with cluster headache. However, when the researchers removed those conditions along with external injuries from the dataset, patients with headache were still significantly more likely to have multiple co-occurring illnesses (86.7% vs. 68.8%; OR, 2.95; P < .0001).

The most common comorbid conditions in the overall cluster headache group were diseases of the nervous system (OR, 5.9; 95% CI, 5.46 -6.42); 51.8% of the cluster headache group reported these disorders, compared with just 15.4% of the control group.

Diseases of the eye, the respiratory, gastrointestinal, and musculoskeletal systems, and connective tissue were also significantly more common among patients with cluster headache.

“For each diagnosis that we investigated, we found a higher incidence in the cluster headache group, and we thought this was a very striking finding and worth discussing in the clinical setting that these patients are at risk of general ill health,” Dr. Ran said.
 

Risky behavior?

Another novel finding was the higher rate of external injuries among the cluster headache group, compared with the control group. The finding seems to back up the theory that patients with cluster headache are more likely to engage in risky behaviors, the researchers noted.

In the cluster headache group, external injuries were reported by 47.1% of men and 41% of women, versus 34.9% and 26.0%, respectively, in the control group.

“Now we can also show that cluster headache patients have more injuries and that is totally unrelated to the biological health of the individuals, so that could also indicate higher risk taking,” Dr. Ran said.

Overall multimorbidity rates and diagnoses in each medical category except external injury were higher among women with cluster headache than men with headaches. In addition, the mean number of days on sick leave and disability pension was higher among women with cluster headache than among men with cluster headache (83.71 days vs. 52.56 days).

Overall, the mean number of sickness absence and disability pension net days in 2010 was nearly twice as high in the cluster headache group as in the control group (63.15 days vs. 34.08 days).

Removing mental and behavioral health disorders from the mix did not lower those numbers.

“Our numbers indicate that the mental health issues that are related to cluster headache might not impact their work situation as much as the other comorbidities,” Dr. Ran said.
 

Struggle is real

Commenting on the findings, Heidi Schwarz, MD, professor of clinical neurology at the University of Rochester (N.Y.) Medical Center, called the study a “valuable contribution” to the field and to the treatment of cluster headache.

“It’s a good study that addresses factors that really need to be considered as you take care of these patients,” said Dr. Schwarz, who was not involved with the research.

“The most salient features of this is that cluster headache is quite disabling, and if you add a comorbidity to it, it’s even more disabling,” she said.

Dr. Schwarz noted that cluster headache is often misdiagnosed as migraine or is overlooked altogether, especially in women. These data underscore that, although cluster headache is more common in men, it affects women too and could lead to even greater disability.

“This has a direct impact on patient quality of life, and in the end, that really should be what we’re looking to enhance,” Dr. Schwarz said. “When a patient with cluster comes in and they tell you they’re really struggling, believe them because it’s quite real.”

The findings also fill a gap in the literature and offer the kind of data that could not be collected in the United States, she noted. Sweden provides paid sick time for all workers aged 16 and older and offers a disability pension to all workers whose ability to work is temporarily or permanently inhibited because of illness or injury.

“You will never get this kind of data in the United States because this kind of data comes from two datasets that are extremely inclusive and detailed in a society, Sweden, where they have a social support system,” Dr. Schwarz said.

The study was funded by the Swedish Research Council, the Swedish Brain Foundation, and Mellby Gård, Region Stockholm, Märta Lundkvist stiftelse and Karolinska Institutet research funds. Dr. Ran and Dr. Schwarz report no relevant financial relationships.

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

Weak handgrip in older adults is linked to a higher risk for depression – while a stronger handgrip may have protective benefits, new research suggests.
 

In a study of more than 115,000 adults, there was a significant association between stronger handgrip, up to 40 kg in men and 27 kg in women, and lower depression risk.

Investigators add that there was a “dose-response” association between physical strength and risk for depression.

“Being physically strong may serve as a preventive factor for depression in older adults, but this is limited to a maximum specific threshold for men and women,” Ruben Lopez-Bueno, PhD, of the department of physical medicine and nursing, University of Zaragoza, Spain, and colleagues write.

The findings were published online in the British Journal of Psychiatry.
 

Easy, fast, reliable

Depression is a major public health problem, and studies “aimed at examining preventive factors to tackle the increase in depression are required,” the investigators write.

They add that a “growing body of research” is examining the link between depression and muscle strength, with handgrip as an estimator, in healthy middle-aged and older adults.

Handgrip strength is an “easy-to-use, fast and reliable indicator of both sarcopenia (age-related loss of muscle mass) and dynapenia (age-related loss of muscle strength), both of which have been associated with depression,” the researchers note.

It is plausible that there is a “regulatory role of skeletal muscle on brain function affecting this condition,” they add.

They note that exercise seems to play a “key role” because it can improve muscle strength as well as muscle mass, downregulate systemic inflammation, and improve neuroplasticity, neuroendocrine, and oxidative stress responses.

Previous studies have relied either on cross-sectional or prospective cohort models and have focused mostly on a specific country, “not accounting for time-varying changes of both handgrip strength and relevant covariables.”

Moreover, previous evidence has been mixed regarding the “extent to which handgrip strength levels may associate with lower risk of depression, with study results ranging from weak to strong associations,” the investigators write.

So “higher-quality research with representative samples from different countries is required to better clarify the strength of such an association and to confirm directionality,” they add.
 

SHARE data

To fill this gap, the researchers turned to data from waves 1, 2, 4, 5, 6, and 7 of the Survey of Health, Ageing and Retirement in Europe (SHARE). This encompassed 115,601 individuals aged 50 years and older (mean age, 64.3 years; 54.3% women) residing in European countries and Israel (24 countries total).

Data from wave 3 were not used because handgrip measures were not used in that wave. In the other waves, a handheld dynamometer was used to measure handgrip strength.

The participants were divided into tertiles of handgrip strength, with the “first third” being the lowest tertile of strength and the “final third” representing the highest strength.

All participants were followed for a median of 7.3 years (792,459 person-years), during which 26.1% experienced a risk for depression, as reflected by scores on the EURO-D 12-item scale.

The investigators set the time scale as the months from study entry until either a first depression onset or the end of follow-up.

Covariates that the researchers accounted for included gender, age, education, country, body mass index, physical inactivity, smoking, alcohol consumption, whether living with a partner, wave of inclusion, chronic diseases, consumption of prescribed drugs, and fruit and vegetable consumption.

The researchers used two models: the first adjusted for gender and age at time of the interview, and the second adjusted for all confounders.

In the model that was adjusted only for gender and age, greater handgrip strength was associated with a significantly reduced risk for depression among participants in the second, third, and the final third in comparison with the first third (hazard ratio, 0.65; 95% confidence interval, 0.63-0.68; and HR, 0.50; 95% CI, 0.48-0.53, respectively).

The associations remained consistent in the fully adjusted model, although risk for depression was slightly attenuated in the second and final thirds compared with the first third (HR, 0.76; 95% CI, 0.71-0.81; and HR, 0.64; 95% CI, 0.59-0.69, respectively).

When the researchers conducted analyses using restricted cubic spline modeling, they found a significant association for each kilogram increase of handgrip strength and depression, up to 40 kg in men and 27 kg in women (HR, 1.39; 95% CI, 1.08-1.71; and HR, 1.28; 95% CI, 1.05-1.55, respectively).

There was no greater reduction in depression risk in those with handgrip strength above those values.
 

Potential depression screen

The investigators suggest several explanations for their findings. For example, handgrip strength has “been used as an overall indicator of health status, including sarcopenia,” they write.

Adults with sarcopenia have been found to be at greater risk for depression because of reduced muscle strength, since neurotrophins are produced by skeletal muscle, among other tissues, and are associated with improvement in mood.

From a psychological point of view, “being physically strong may lead to a sensation of psychological wellbeing,” the researchers write.

Moreover, being physically active “across the lifespan also promotes structural and functional changes in the brain, benefiting cognitive functioning and reducing the risk of neurodegeneration,” they write.

This can be important because aging adults with cognitive impairments can also experience neuromuscular impairments that “presumably will contribute to becoming weaker,” they note.

Overall, the findings “warrant strength training programmes aimed at older adults to reduce depression risk,” the investigators write. Clinicians “may consider using the observed handgrip strength thresholds to screen for potential depression risk in older adults,” they add.
 

Protective factor?

Commenting for this news organization, Julian Mutz, PhD, postdoctoral research associate at the Social, Genetic and Developmental Psychiatry Centre, King’s College, London, said the study “provides further evidence that physical strength may be a protective factor against depression in older adults.”

This confirms a “plethora of cross-sectional and longitudinal studies,” including one recently conducted by Dr. Mutz’s group.

The design of the current study “allowed the authors to address a number of key limitations of previous studies, for example, by including repeated measurements of grip strength and adjustment for potential confounding factors over time,” said Dr. Mutz, who was not involved with the research.

Additionally, “an important contribution of this study is that the authors show that higher grip strength is only associated with a lower risk of depression up to a specific threshold,” he noted.

“The clinical implication of this finding is that only individuals with grip strength below this threshold are at a higher risk of depression. These individuals especially may benefit from interventions aimed at increasing physical strength,” Dr. Mutz said.

The SHARE data collection has been funded by the European Commission and by DG Employment, Social Affairs and Inclusion. Additional funding was obtained from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, and the U.S. National Institute on Aging. Dr. Lopez-Bueno is supported by the European Union – Next Generation EU. The other investigators and Dr. Mutz have reported no relevant financial relationships.

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

Weak handgrip in older adults is linked to a higher risk for depression – while a stronger handgrip may have protective benefits, new research suggests.
 

In a study of more than 115,000 adults, there was a significant association between stronger handgrip, up to 40 kg in men and 27 kg in women, and lower depression risk.

Investigators add that there was a “dose-response” association between physical strength and risk for depression.

“Being physically strong may serve as a preventive factor for depression in older adults, but this is limited to a maximum specific threshold for men and women,” Ruben Lopez-Bueno, PhD, of the department of physical medicine and nursing, University of Zaragoza, Spain, and colleagues write.

The findings were published online in the British Journal of Psychiatry.
 

Easy, fast, reliable

Depression is a major public health problem, and studies “aimed at examining preventive factors to tackle the increase in depression are required,” the investigators write.

They add that a “growing body of research” is examining the link between depression and muscle strength, with handgrip as an estimator, in healthy middle-aged and older adults.

Handgrip strength is an “easy-to-use, fast and reliable indicator of both sarcopenia (age-related loss of muscle mass) and dynapenia (age-related loss of muscle strength), both of which have been associated with depression,” the researchers note.

It is plausible that there is a “regulatory role of skeletal muscle on brain function affecting this condition,” they add.

They note that exercise seems to play a “key role” because it can improve muscle strength as well as muscle mass, downregulate systemic inflammation, and improve neuroplasticity, neuroendocrine, and oxidative stress responses.

Previous studies have relied either on cross-sectional or prospective cohort models and have focused mostly on a specific country, “not accounting for time-varying changes of both handgrip strength and relevant covariables.”

Moreover, previous evidence has been mixed regarding the “extent to which handgrip strength levels may associate with lower risk of depression, with study results ranging from weak to strong associations,” the investigators write.

So “higher-quality research with representative samples from different countries is required to better clarify the strength of such an association and to confirm directionality,” they add.
 

SHARE data

To fill this gap, the researchers turned to data from waves 1, 2, 4, 5, 6, and 7 of the Survey of Health, Ageing and Retirement in Europe (SHARE). This encompassed 115,601 individuals aged 50 years and older (mean age, 64.3 years; 54.3% women) residing in European countries and Israel (24 countries total).

Data from wave 3 were not used because handgrip measures were not used in that wave. In the other waves, a handheld dynamometer was used to measure handgrip strength.

The participants were divided into tertiles of handgrip strength, with the “first third” being the lowest tertile of strength and the “final third” representing the highest strength.

All participants were followed for a median of 7.3 years (792,459 person-years), during which 26.1% experienced a risk for depression, as reflected by scores on the EURO-D 12-item scale.

The investigators set the time scale as the months from study entry until either a first depression onset or the end of follow-up.

Covariates that the researchers accounted for included gender, age, education, country, body mass index, physical inactivity, smoking, alcohol consumption, whether living with a partner, wave of inclusion, chronic diseases, consumption of prescribed drugs, and fruit and vegetable consumption.

The researchers used two models: the first adjusted for gender and age at time of the interview, and the second adjusted for all confounders.

In the model that was adjusted only for gender and age, greater handgrip strength was associated with a significantly reduced risk for depression among participants in the second, third, and the final third in comparison with the first third (hazard ratio, 0.65; 95% confidence interval, 0.63-0.68; and HR, 0.50; 95% CI, 0.48-0.53, respectively).

The associations remained consistent in the fully adjusted model, although risk for depression was slightly attenuated in the second and final thirds compared with the first third (HR, 0.76; 95% CI, 0.71-0.81; and HR, 0.64; 95% CI, 0.59-0.69, respectively).

When the researchers conducted analyses using restricted cubic spline modeling, they found a significant association for each kilogram increase of handgrip strength and depression, up to 40 kg in men and 27 kg in women (HR, 1.39; 95% CI, 1.08-1.71; and HR, 1.28; 95% CI, 1.05-1.55, respectively).

There was no greater reduction in depression risk in those with handgrip strength above those values.
 

Potential depression screen

The investigators suggest several explanations for their findings. For example, handgrip strength has “been used as an overall indicator of health status, including sarcopenia,” they write.

Adults with sarcopenia have been found to be at greater risk for depression because of reduced muscle strength, since neurotrophins are produced by skeletal muscle, among other tissues, and are associated with improvement in mood.

From a psychological point of view, “being physically strong may lead to a sensation of psychological wellbeing,” the researchers write.

Moreover, being physically active “across the lifespan also promotes structural and functional changes in the brain, benefiting cognitive functioning and reducing the risk of neurodegeneration,” they write.

This can be important because aging adults with cognitive impairments can also experience neuromuscular impairments that “presumably will contribute to becoming weaker,” they note.

Overall, the findings “warrant strength training programmes aimed at older adults to reduce depression risk,” the investigators write. Clinicians “may consider using the observed handgrip strength thresholds to screen for potential depression risk in older adults,” they add.
 

Protective factor?

Commenting for this news organization, Julian Mutz, PhD, postdoctoral research associate at the Social, Genetic and Developmental Psychiatry Centre, King’s College, London, said the study “provides further evidence that physical strength may be a protective factor against depression in older adults.”

This confirms a “plethora of cross-sectional and longitudinal studies,” including one recently conducted by Dr. Mutz’s group.

The design of the current study “allowed the authors to address a number of key limitations of previous studies, for example, by including repeated measurements of grip strength and adjustment for potential confounding factors over time,” said Dr. Mutz, who was not involved with the research.

Additionally, “an important contribution of this study is that the authors show that higher grip strength is only associated with a lower risk of depression up to a specific threshold,” he noted.

“The clinical implication of this finding is that only individuals with grip strength below this threshold are at a higher risk of depression. These individuals especially may benefit from interventions aimed at increasing physical strength,” Dr. Mutz said.

The SHARE data collection has been funded by the European Commission and by DG Employment, Social Affairs and Inclusion. Additional funding was obtained from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, and the U.S. National Institute on Aging. Dr. Lopez-Bueno is supported by the European Union – Next Generation EU. The other investigators and Dr. Mutz have reported no relevant financial relationships.

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

Weak handgrip in older adults is linked to a higher risk for depression – while a stronger handgrip may have protective benefits, new research suggests.
 

In a study of more than 115,000 adults, there was a significant association between stronger handgrip, up to 40 kg in men and 27 kg in women, and lower depression risk.

Investigators add that there was a “dose-response” association between physical strength and risk for depression.

“Being physically strong may serve as a preventive factor for depression in older adults, but this is limited to a maximum specific threshold for men and women,” Ruben Lopez-Bueno, PhD, of the department of physical medicine and nursing, University of Zaragoza, Spain, and colleagues write.

The findings were published online in the British Journal of Psychiatry.
 

Easy, fast, reliable

Depression is a major public health problem, and studies “aimed at examining preventive factors to tackle the increase in depression are required,” the investigators write.

They add that a “growing body of research” is examining the link between depression and muscle strength, with handgrip as an estimator, in healthy middle-aged and older adults.

Handgrip strength is an “easy-to-use, fast and reliable indicator of both sarcopenia (age-related loss of muscle mass) and dynapenia (age-related loss of muscle strength), both of which have been associated with depression,” the researchers note.

It is plausible that there is a “regulatory role of skeletal muscle on brain function affecting this condition,” they add.

They note that exercise seems to play a “key role” because it can improve muscle strength as well as muscle mass, downregulate systemic inflammation, and improve neuroplasticity, neuroendocrine, and oxidative stress responses.

Previous studies have relied either on cross-sectional or prospective cohort models and have focused mostly on a specific country, “not accounting for time-varying changes of both handgrip strength and relevant covariables.”

Moreover, previous evidence has been mixed regarding the “extent to which handgrip strength levels may associate with lower risk of depression, with study results ranging from weak to strong associations,” the investigators write.

So “higher-quality research with representative samples from different countries is required to better clarify the strength of such an association and to confirm directionality,” they add.
 

SHARE data

To fill this gap, the researchers turned to data from waves 1, 2, 4, 5, 6, and 7 of the Survey of Health, Ageing and Retirement in Europe (SHARE). This encompassed 115,601 individuals aged 50 years and older (mean age, 64.3 years; 54.3% women) residing in European countries and Israel (24 countries total).

Data from wave 3 were not used because handgrip measures were not used in that wave. In the other waves, a handheld dynamometer was used to measure handgrip strength.

The participants were divided into tertiles of handgrip strength, with the “first third” being the lowest tertile of strength and the “final third” representing the highest strength.

All participants were followed for a median of 7.3 years (792,459 person-years), during which 26.1% experienced a risk for depression, as reflected by scores on the EURO-D 12-item scale.

The investigators set the time scale as the months from study entry until either a first depression onset or the end of follow-up.

Covariates that the researchers accounted for included gender, age, education, country, body mass index, physical inactivity, smoking, alcohol consumption, whether living with a partner, wave of inclusion, chronic diseases, consumption of prescribed drugs, and fruit and vegetable consumption.

The researchers used two models: the first adjusted for gender and age at time of the interview, and the second adjusted for all confounders.

In the model that was adjusted only for gender and age, greater handgrip strength was associated with a significantly reduced risk for depression among participants in the second, third, and the final third in comparison with the first third (hazard ratio, 0.65; 95% confidence interval, 0.63-0.68; and HR, 0.50; 95% CI, 0.48-0.53, respectively).

The associations remained consistent in the fully adjusted model, although risk for depression was slightly attenuated in the second and final thirds compared with the first third (HR, 0.76; 95% CI, 0.71-0.81; and HR, 0.64; 95% CI, 0.59-0.69, respectively).

When the researchers conducted analyses using restricted cubic spline modeling, they found a significant association for each kilogram increase of handgrip strength and depression, up to 40 kg in men and 27 kg in women (HR, 1.39; 95% CI, 1.08-1.71; and HR, 1.28; 95% CI, 1.05-1.55, respectively).

There was no greater reduction in depression risk in those with handgrip strength above those values.
 

Potential depression screen

The investigators suggest several explanations for their findings. For example, handgrip strength has “been used as an overall indicator of health status, including sarcopenia,” they write.

Adults with sarcopenia have been found to be at greater risk for depression because of reduced muscle strength, since neurotrophins are produced by skeletal muscle, among other tissues, and are associated with improvement in mood.

From a psychological point of view, “being physically strong may lead to a sensation of psychological wellbeing,” the researchers write.

Moreover, being physically active “across the lifespan also promotes structural and functional changes in the brain, benefiting cognitive functioning and reducing the risk of neurodegeneration,” they write.

This can be important because aging adults with cognitive impairments can also experience neuromuscular impairments that “presumably will contribute to becoming weaker,” they note.

Overall, the findings “warrant strength training programmes aimed at older adults to reduce depression risk,” the investigators write. Clinicians “may consider using the observed handgrip strength thresholds to screen for potential depression risk in older adults,” they add.
 

Protective factor?

Commenting for this news organization, Julian Mutz, PhD, postdoctoral research associate at the Social, Genetic and Developmental Psychiatry Centre, King’s College, London, said the study “provides further evidence that physical strength may be a protective factor against depression in older adults.”

This confirms a “plethora of cross-sectional and longitudinal studies,” including one recently conducted by Dr. Mutz’s group.

The design of the current study “allowed the authors to address a number of key limitations of previous studies, for example, by including repeated measurements of grip strength and adjustment for potential confounding factors over time,” said Dr. Mutz, who was not involved with the research.

Additionally, “an important contribution of this study is that the authors show that higher grip strength is only associated with a lower risk of depression up to a specific threshold,” he noted.

“The clinical implication of this finding is that only individuals with grip strength below this threshold are at a higher risk of depression. These individuals especially may benefit from interventions aimed at increasing physical strength,” Dr. Mutz said.

The SHARE data collection has been funded by the European Commission and by DG Employment, Social Affairs and Inclusion. Additional funding was obtained from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, and the U.S. National Institute on Aging. Dr. Lopez-Bueno is supported by the European Union – Next Generation EU. The other investigators and Dr. Mutz have reported no relevant financial relationships.

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

Aspartame, an artificial sweetener commonly found in diet drinks and food, may raise the risk for anxiety, early research suggests.

In a new preclinical study, investigators observed that mice that drank water containing aspartame exhibited pronounced anxiety-like behaviors in a variety of maze tests.

This behavior occurred at aspartame doses equivalent to less than 15% of the maximum daily human intake recommended by the U.S. Food and Drug Administration.

“It was such a robust anxiety-like trait that I don’t think any of us were anticipating we would see. It was completely unexpected. Usually you see subtle changes,” lead author Sara Jones, doctoral candidate at Florida State University, Tallahassee, said in a news release.

The findings were published online in Proceedings of the National Academy of Sciences.


 

Transgenerational transmission

When consumed, aspartame becomes aspartic acid, phenylalanine, and methanol – all of which can have potent effects on the central nervous system, the researchers point out.

Exposing the mice to aspartame also produced changes in the expression of genes regulating excitation-inhibition balance in the amygdala, a brain region that regulates anxiety and fear.

Giving the mice diazepam, which is used to treat generalized anxiety disorder, alleviated the anxiety behavior in the animals.

“The anxiety, its response to diazepam, and the changes in amygdala gene expression are not limited to the aspartame-exposed individuals but also appear in up to two generations descending from the aspartame-exposed males,” the researchers report.

“Extrapolation of the findings to humans suggests that aspartame consumption at doses below the FDA recommended maximum daily intake may produce neurobehavioral changes in aspartame-consuming individuals and their descendants,” they write.

“Thus, human population at risk of aspartame’s potential mental health effects may be larger than current expectations, which only include aspartame-consuming individuals,” they add.
 

Far from harmless?

The investigators plan to publish additional data from the study that focus on how aspartame affected memory in the mice.

In future research, they hope to identify molecular mechanisms that influence the transmission of aspartame’s effect across generations.

The Florida State University study joins several others that discount the long-held notion that aspartame and other nonnutritive sweeteners have no effect on the body.

As reported by this news organization, in a recent study researchers found that these sugar substitutes are not metabolically inert and can alter the gut microbiome in a way that can influence blood glucose levels.

Artificial sweeteners have also been linked to an increased risk for heart disease and stroke and for cancer.

The study was funded by the Jim and Betty Ann Rodgers Chair Fund at Florida State University and by the Bryan Robinson Foundation. The investigators have reported no relevant financial relationships.

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

Aspartame, an artificial sweetener commonly found in diet drinks and food, may raise the risk for anxiety, early research suggests.

In a new preclinical study, investigators observed that mice that drank water containing aspartame exhibited pronounced anxiety-like behaviors in a variety of maze tests.

This behavior occurred at aspartame doses equivalent to less than 15% of the maximum daily human intake recommended by the U.S. Food and Drug Administration.

“It was such a robust anxiety-like trait that I don’t think any of us were anticipating we would see. It was completely unexpected. Usually you see subtle changes,” lead author Sara Jones, doctoral candidate at Florida State University, Tallahassee, said in a news release.

The findings were published online in Proceedings of the National Academy of Sciences.


 

Transgenerational transmission

When consumed, aspartame becomes aspartic acid, phenylalanine, and methanol – all of which can have potent effects on the central nervous system, the researchers point out.

Exposing the mice to aspartame also produced changes in the expression of genes regulating excitation-inhibition balance in the amygdala, a brain region that regulates anxiety and fear.

Giving the mice diazepam, which is used to treat generalized anxiety disorder, alleviated the anxiety behavior in the animals.

“The anxiety, its response to diazepam, and the changes in amygdala gene expression are not limited to the aspartame-exposed individuals but also appear in up to two generations descending from the aspartame-exposed males,” the researchers report.

“Extrapolation of the findings to humans suggests that aspartame consumption at doses below the FDA recommended maximum daily intake may produce neurobehavioral changes in aspartame-consuming individuals and their descendants,” they write.

“Thus, human population at risk of aspartame’s potential mental health effects may be larger than current expectations, which only include aspartame-consuming individuals,” they add.
 

Far from harmless?

The investigators plan to publish additional data from the study that focus on how aspartame affected memory in the mice.

In future research, they hope to identify molecular mechanisms that influence the transmission of aspartame’s effect across generations.

The Florida State University study joins several others that discount the long-held notion that aspartame and other nonnutritive sweeteners have no effect on the body.

As reported by this news organization, in a recent study researchers found that these sugar substitutes are not metabolically inert and can alter the gut microbiome in a way that can influence blood glucose levels.

Artificial sweeteners have also been linked to an increased risk for heart disease and stroke and for cancer.

The study was funded by the Jim and Betty Ann Rodgers Chair Fund at Florida State University and by the Bryan Robinson Foundation. The investigators have reported no relevant financial relationships.

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

Aspartame, an artificial sweetener commonly found in diet drinks and food, may raise the risk for anxiety, early research suggests.

In a new preclinical study, investigators observed that mice that drank water containing aspartame exhibited pronounced anxiety-like behaviors in a variety of maze tests.

This behavior occurred at aspartame doses equivalent to less than 15% of the maximum daily human intake recommended by the U.S. Food and Drug Administration.

“It was such a robust anxiety-like trait that I don’t think any of us were anticipating we would see. It was completely unexpected. Usually you see subtle changes,” lead author Sara Jones, doctoral candidate at Florida State University, Tallahassee, said in a news release.

The findings were published online in Proceedings of the National Academy of Sciences.


 

Transgenerational transmission

When consumed, aspartame becomes aspartic acid, phenylalanine, and methanol – all of which can have potent effects on the central nervous system, the researchers point out.

Exposing the mice to aspartame also produced changes in the expression of genes regulating excitation-inhibition balance in the amygdala, a brain region that regulates anxiety and fear.

Giving the mice diazepam, which is used to treat generalized anxiety disorder, alleviated the anxiety behavior in the animals.

“The anxiety, its response to diazepam, and the changes in amygdala gene expression are not limited to the aspartame-exposed individuals but also appear in up to two generations descending from the aspartame-exposed males,” the researchers report.

“Extrapolation of the findings to humans suggests that aspartame consumption at doses below the FDA recommended maximum daily intake may produce neurobehavioral changes in aspartame-consuming individuals and their descendants,” they write.

“Thus, human population at risk of aspartame’s potential mental health effects may be larger than current expectations, which only include aspartame-consuming individuals,” they add.
 

Far from harmless?

The investigators plan to publish additional data from the study that focus on how aspartame affected memory in the mice.

In future research, they hope to identify molecular mechanisms that influence the transmission of aspartame’s effect across generations.

The Florida State University study joins several others that discount the long-held notion that aspartame and other nonnutritive sweeteners have no effect on the body.

As reported by this news organization, in a recent study researchers found that these sugar substitutes are not metabolically inert and can alter the gut microbiome in a way that can influence blood glucose levels.

Artificial sweeteners have also been linked to an increased risk for heart disease and stroke and for cancer.

The study was funded by the Jim and Betty Ann Rodgers Chair Fund at Florida State University and by the Bryan Robinson Foundation. The investigators have reported no relevant financial relationships.

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

It’s a story perhaps more appropriate for Halloween than for the festive holiday season, given its scary implications. Four Omicron subvariants of the virus that causes COVID-19 will be the most common strains going from person to person in the winter of 2022-2023, new research predicts.

Not too dire so far, until the researchers’ other findings are considered.

The BQ.1, BQ1.1, XBB, and XBB.1 subvariants are the most resistant to neutralizing antibodies, researcher Qian Wang, PhD, and colleagues wrote in a study published online in the journal Cell. This means people have no or “markedly reduced” protection against infection from these four strains, even if they’ve already had COVID-19 or are vaccinated and boosted multiple times, including with a bivalent vaccine.

On top of that, all available monoclonal antibody treatments are mostly or completely ineffective against these subvariants.

What does that mean for the immediate future? The findings are definitely “worrisome,” said Eric Topol, MD, founder and director of the Scripps Translational Research Institute in La Jolla, Calif.

But evidence from other countries, specifically Singapore and France, show that at least two of these variants turned out not to be as damaging as expected, likely because of high numbers of people vaccinated or who survived previous infections, he said.

Still, there is little to celebrate in the new findings, except that COVID-19 vaccinations and prior infections can still reduce the risk for serious outcomes such as hospitalization and death, the researchers wrote.

In fact, Centers for Disease Control and Prevention data released on Dec. 16 shows that people who have received four shots of the original COVID-19 vaccines as well as the bivalent booster were 57% less likely to visit an urgent care clinic or emergency room, regardless of age. 

It comes at a time when BQ.1 and BQ.1.1 account for about 70% of the circulating variants, data show. In addition, hospitalizations are up 18% over the past 2 weeks and COVID-19 deaths are up 50% nationwide, The New York Times reported.

Globally, in many places, an “immunity wall” that has been built, Dr. Topol said. That may not be the case in the United States.  

“The problem in the United States, making it harder to predict, is that we have a very low rate of recent boosters, in the past 6 months, especially in seniors,” he said. For example, only 36% of Americans aged 65 years and older, the group with highest risk, have received an updated bivalent booster.
 

An evolving virus

The subvariants are successfully replacing BA.5, which reigned as one of the most common Omicron variants over the past year. The latest CDC data show that BA.5 now accounts for only about 10% of the circulating virus. The researchers wrote: “This rapid replacement of virus strains is raising the specter of yet another wave of infections in the coming months.”

BQ.1 and BQ.1.1 evolved directly from BA.5 – adding more and some novel mutations to the SARS-CoV-2 virus. XBB and XBB.1 are the “offspring” of a combination of two other strains, known as BJ.1 and BA.2.75.

The story sounds familiar to the researchers. “The rapid rise of these subvariants and their extensive array of spike mutations are reminiscent of the appearance of the first Omicron variant last year, thus raising concerns that they may further compromise the efficacy of current COVID-19 vaccines and monoclonal antibody therapeutics,” they wrote. “We now report findings that indicate that such concerns are, sadly, justified, especially so for the XBB and XBB.1 subvariants.”

To figure out how effective existing antibodies could be against these newer subvariants, Dr. Wang and colleagues used blood samples from five groups of people. They tested serum from people who had three doses of the original COVID-19 vaccine, four doses of the original vaccine, those who received a bivalent booster, people who experienced a breakthrough infection with the BA.2 Omicron variant, and those who had a breakthrough with a BA.4 or BA.5 variant.

Adding the new subvariants to these serum samples revealed that the existing antibodies in the blood were ineffective at wiping out or neutralizing BQ.1, BQ.1.1, XBB, and XBB.1.

The BQ.1 subvariant was six times more resistant to antibodies than BA.5, its parent strain, and XBB.1 was 63 times more resistant compared with its predecessor, BA.2.

This shift in the ability of vaccines to stop the subvariants “is particularly concerning,” the researchers wrote.
 

Wiping out treatments too

Dr. Wang and colleagues also tested how well a panel of 23 different monoclonal antibody drugs might work against the four subvariants. The therapies all worked well against the original Omicron variant and included some approved for use through the Food and Drug Administration emergency use authorization (EUA) program at the time of the study.

They found that 19 of these 23 monoclonal antibodies lost effectiveness “greatly or completely” against XBB and XBB.1, for example.

This is not the first time that monoclonal antibody therapies have gone from effective to ineffective. Previous variants have come out that no longer responded to treatment with bamlanivimab, etesevimab, imdevimab, casirivimab, tixagevimab, cilgavimab, and sotrovimab. Bebtelovimab now joins this list and is no longer available from Eli Lilly under EUA because of this lack of effectiveness.

The lack of an effective monoclonal antibody treatment “poses a serious problem for millions of immunocompromised individuals who do not respond robustly to COVID-19 vaccines,” the researchers wrote, adding that “the urgent need to develop active monoclonal antibodies for clinical use is obvious.”

A limitation of the study is that the work is done in blood samples. The effectiveness of COVID-19 vaccination against the BQ and XBB subvariants should be evaluated in people in clinical studies, the authors noted.

Also, the current study looked at how well antibodies could neutralize the viral strains, but future research, they added, should look at how well “cellular immunity” or other aspects of the immune system might protect people.

Going forward, the challenge remains to develop vaccines and treatments that offer broad protection as the coronavirus continues to evolve.

In an alarming ending, the researchers wrote: “We have collectively chased after SARS-CoV-2 variants for over 2 years, and yet, the virus continues to evolve and evade.”

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

It’s a story perhaps more appropriate for Halloween than for the festive holiday season, given its scary implications. Four Omicron subvariants of the virus that causes COVID-19 will be the most common strains going from person to person in the winter of 2022-2023, new research predicts.

Not too dire so far, until the researchers’ other findings are considered.

The BQ.1, BQ1.1, XBB, and XBB.1 subvariants are the most resistant to neutralizing antibodies, researcher Qian Wang, PhD, and colleagues wrote in a study published online in the journal Cell. This means people have no or “markedly reduced” protection against infection from these four strains, even if they’ve already had COVID-19 or are vaccinated and boosted multiple times, including with a bivalent vaccine.

On top of that, all available monoclonal antibody treatments are mostly or completely ineffective against these subvariants.

What does that mean for the immediate future? The findings are definitely “worrisome,” said Eric Topol, MD, founder and director of the Scripps Translational Research Institute in La Jolla, Calif.

But evidence from other countries, specifically Singapore and France, show that at least two of these variants turned out not to be as damaging as expected, likely because of high numbers of people vaccinated or who survived previous infections, he said.

Still, there is little to celebrate in the new findings, except that COVID-19 vaccinations and prior infections can still reduce the risk for serious outcomes such as hospitalization and death, the researchers wrote.

In fact, Centers for Disease Control and Prevention data released on Dec. 16 shows that people who have received four shots of the original COVID-19 vaccines as well as the bivalent booster were 57% less likely to visit an urgent care clinic or emergency room, regardless of age. 

It comes at a time when BQ.1 and BQ.1.1 account for about 70% of the circulating variants, data show. In addition, hospitalizations are up 18% over the past 2 weeks and COVID-19 deaths are up 50% nationwide, The New York Times reported.

Globally, in many places, an “immunity wall” that has been built, Dr. Topol said. That may not be the case in the United States.  

“The problem in the United States, making it harder to predict, is that we have a very low rate of recent boosters, in the past 6 months, especially in seniors,” he said. For example, only 36% of Americans aged 65 years and older, the group with highest risk, have received an updated bivalent booster.
 

An evolving virus

The subvariants are successfully replacing BA.5, which reigned as one of the most common Omicron variants over the past year. The latest CDC data show that BA.5 now accounts for only about 10% of the circulating virus. The researchers wrote: “This rapid replacement of virus strains is raising the specter of yet another wave of infections in the coming months.”

BQ.1 and BQ.1.1 evolved directly from BA.5 – adding more and some novel mutations to the SARS-CoV-2 virus. XBB and XBB.1 are the “offspring” of a combination of two other strains, known as BJ.1 and BA.2.75.

The story sounds familiar to the researchers. “The rapid rise of these subvariants and their extensive array of spike mutations are reminiscent of the appearance of the first Omicron variant last year, thus raising concerns that they may further compromise the efficacy of current COVID-19 vaccines and monoclonal antibody therapeutics,” they wrote. “We now report findings that indicate that such concerns are, sadly, justified, especially so for the XBB and XBB.1 subvariants.”

To figure out how effective existing antibodies could be against these newer subvariants, Dr. Wang and colleagues used blood samples from five groups of people. They tested serum from people who had three doses of the original COVID-19 vaccine, four doses of the original vaccine, those who received a bivalent booster, people who experienced a breakthrough infection with the BA.2 Omicron variant, and those who had a breakthrough with a BA.4 or BA.5 variant.

Adding the new subvariants to these serum samples revealed that the existing antibodies in the blood were ineffective at wiping out or neutralizing BQ.1, BQ.1.1, XBB, and XBB.1.

The BQ.1 subvariant was six times more resistant to antibodies than BA.5, its parent strain, and XBB.1 was 63 times more resistant compared with its predecessor, BA.2.

This shift in the ability of vaccines to stop the subvariants “is particularly concerning,” the researchers wrote.
 

Wiping out treatments too

Dr. Wang and colleagues also tested how well a panel of 23 different monoclonal antibody drugs might work against the four subvariants. The therapies all worked well against the original Omicron variant and included some approved for use through the Food and Drug Administration emergency use authorization (EUA) program at the time of the study.

They found that 19 of these 23 monoclonal antibodies lost effectiveness “greatly or completely” against XBB and XBB.1, for example.

This is not the first time that monoclonal antibody therapies have gone from effective to ineffective. Previous variants have come out that no longer responded to treatment with bamlanivimab, etesevimab, imdevimab, casirivimab, tixagevimab, cilgavimab, and sotrovimab. Bebtelovimab now joins this list and is no longer available from Eli Lilly under EUA because of this lack of effectiveness.

The lack of an effective monoclonal antibody treatment “poses a serious problem for millions of immunocompromised individuals who do not respond robustly to COVID-19 vaccines,” the researchers wrote, adding that “the urgent need to develop active monoclonal antibodies for clinical use is obvious.”

A limitation of the study is that the work is done in blood samples. The effectiveness of COVID-19 vaccination against the BQ and XBB subvariants should be evaluated in people in clinical studies, the authors noted.

Also, the current study looked at how well antibodies could neutralize the viral strains, but future research, they added, should look at how well “cellular immunity” or other aspects of the immune system might protect people.

Going forward, the challenge remains to develop vaccines and treatments that offer broad protection as the coronavirus continues to evolve.

In an alarming ending, the researchers wrote: “We have collectively chased after SARS-CoV-2 variants for over 2 years, and yet, the virus continues to evolve and evade.”

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

It’s a story perhaps more appropriate for Halloween than for the festive holiday season, given its scary implications. Four Omicron subvariants of the virus that causes COVID-19 will be the most common strains going from person to person in the winter of 2022-2023, new research predicts.

Not too dire so far, until the researchers’ other findings are considered.

The BQ.1, BQ1.1, XBB, and XBB.1 subvariants are the most resistant to neutralizing antibodies, researcher Qian Wang, PhD, and colleagues wrote in a study published online in the journal Cell. This means people have no or “markedly reduced” protection against infection from these four strains, even if they’ve already had COVID-19 or are vaccinated and boosted multiple times, including with a bivalent vaccine.

On top of that, all available monoclonal antibody treatments are mostly or completely ineffective against these subvariants.

What does that mean for the immediate future? The findings are definitely “worrisome,” said Eric Topol, MD, founder and director of the Scripps Translational Research Institute in La Jolla, Calif.

But evidence from other countries, specifically Singapore and France, show that at least two of these variants turned out not to be as damaging as expected, likely because of high numbers of people vaccinated or who survived previous infections, he said.

Still, there is little to celebrate in the new findings, except that COVID-19 vaccinations and prior infections can still reduce the risk for serious outcomes such as hospitalization and death, the researchers wrote.

In fact, Centers for Disease Control and Prevention data released on Dec. 16 shows that people who have received four shots of the original COVID-19 vaccines as well as the bivalent booster were 57% less likely to visit an urgent care clinic or emergency room, regardless of age. 

It comes at a time when BQ.1 and BQ.1.1 account for about 70% of the circulating variants, data show. In addition, hospitalizations are up 18% over the past 2 weeks and COVID-19 deaths are up 50% nationwide, The New York Times reported.

Globally, in many places, an “immunity wall” that has been built, Dr. Topol said. That may not be the case in the United States.  

“The problem in the United States, making it harder to predict, is that we have a very low rate of recent boosters, in the past 6 months, especially in seniors,” he said. For example, only 36% of Americans aged 65 years and older, the group with highest risk, have received an updated bivalent booster.
 

An evolving virus

The subvariants are successfully replacing BA.5, which reigned as one of the most common Omicron variants over the past year. The latest CDC data show that BA.5 now accounts for only about 10% of the circulating virus. The researchers wrote: “This rapid replacement of virus strains is raising the specter of yet another wave of infections in the coming months.”

BQ.1 and BQ.1.1 evolved directly from BA.5 – adding more and some novel mutations to the SARS-CoV-2 virus. XBB and XBB.1 are the “offspring” of a combination of two other strains, known as BJ.1 and BA.2.75.

The story sounds familiar to the researchers. “The rapid rise of these subvariants and their extensive array of spike mutations are reminiscent of the appearance of the first Omicron variant last year, thus raising concerns that they may further compromise the efficacy of current COVID-19 vaccines and monoclonal antibody therapeutics,” they wrote. “We now report findings that indicate that such concerns are, sadly, justified, especially so for the XBB and XBB.1 subvariants.”

To figure out how effective existing antibodies could be against these newer subvariants, Dr. Wang and colleagues used blood samples from five groups of people. They tested serum from people who had three doses of the original COVID-19 vaccine, four doses of the original vaccine, those who received a bivalent booster, people who experienced a breakthrough infection with the BA.2 Omicron variant, and those who had a breakthrough with a BA.4 or BA.5 variant.

Adding the new subvariants to these serum samples revealed that the existing antibodies in the blood were ineffective at wiping out or neutralizing BQ.1, BQ.1.1, XBB, and XBB.1.

The BQ.1 subvariant was six times more resistant to antibodies than BA.5, its parent strain, and XBB.1 was 63 times more resistant compared with its predecessor, BA.2.

This shift in the ability of vaccines to stop the subvariants “is particularly concerning,” the researchers wrote.
 

Wiping out treatments too

Dr. Wang and colleagues also tested how well a panel of 23 different monoclonal antibody drugs might work against the four subvariants. The therapies all worked well against the original Omicron variant and included some approved for use through the Food and Drug Administration emergency use authorization (EUA) program at the time of the study.

They found that 19 of these 23 monoclonal antibodies lost effectiveness “greatly or completely” against XBB and XBB.1, for example.

This is not the first time that monoclonal antibody therapies have gone from effective to ineffective. Previous variants have come out that no longer responded to treatment with bamlanivimab, etesevimab, imdevimab, casirivimab, tixagevimab, cilgavimab, and sotrovimab. Bebtelovimab now joins this list and is no longer available from Eli Lilly under EUA because of this lack of effectiveness.

The lack of an effective monoclonal antibody treatment “poses a serious problem for millions of immunocompromised individuals who do not respond robustly to COVID-19 vaccines,” the researchers wrote, adding that “the urgent need to develop active monoclonal antibodies for clinical use is obvious.”

A limitation of the study is that the work is done in blood samples. The effectiveness of COVID-19 vaccination against the BQ and XBB subvariants should be evaluated in people in clinical studies, the authors noted.

Also, the current study looked at how well antibodies could neutralize the viral strains, but future research, they added, should look at how well “cellular immunity” or other aspects of the immune system might protect people.

Going forward, the challenge remains to develop vaccines and treatments that offer broad protection as the coronavirus continues to evolve.

In an alarming ending, the researchers wrote: “We have collectively chased after SARS-CoV-2 variants for over 2 years, and yet, the virus continues to evolve and evade.”

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

Outpatient behavioral health treatment (OPBHT) for patients newly diagnosed with depression, substance use disorder, or other behavioral health condition (BHC) is cost-effective.

Results of a large retrospective study showed that patients newly diagnosed with a BHC who receive OPBHT following diagnosis incur lower medical and pharmacy costs over roughly the next 1 to 2 years, compared with peers who don’t receive OPBHT.

“Our findings suggest that promoting OPBHT as part of a population health strategy is associated with improved overall medical spending, particularly among adults,” the investigators write.

The study was published online in JAMA Network Open.
 

Common, undertreated

Nearly a quarter of adults in the United States have a BHC, and they incur greater medical costs than those without a BHC. However, diagnosis of a BHC is often delayed, and most affected individuals receive little to no treatment.

In their cost analysis, Johanna Bellon, PhD, and colleagues with Evernorth Health, St. Louis, analyzed commercial insurance claims data for 203,401 U.S. individuals newly diagnosed with one or more BHCs between 2017 and 2018.

About half of participants had depression and/or anxiety, 11% had substance use or alcohol use disorder, and 6% had a higher-acuity diagnosis, such as bipolar disorder, severe depression, eating disorder, psychotic disorder, or autism spectrum disorder.

About 1 in 5 (22%) had at least one chronic medical condition along with their BHC.

The researchers found that having at least one OPBHT visit was associated with lower medical and pharmacy costs during 15- and 27-month follow-up periods.

Over 15 months, the adjusted mean per member per month (PMPM) medical/pharmacy cost was $686 with no OPBHT visit, compared with $571 with one or more OPBHT visits.

Over 27 months, the adjusted mean PMPM was $464 with no OPBHT, versus $391 with one or more OPBHT visits.
 

Dose-response effect

In addition, there was a “dose-response” relationship between OPBHT and medical/pharmacy costs, such that estimated cost savings were significantly lower in the treated versus the untreated groups at almost every level of treatment.

“Our findings were also largely age independent, especially over 15 months, suggesting that OPBHT has favorable effects among children, young adults, and adults,” the researchers report.

“This is promising given that disease etiology and progression, treatment paradigms, presence of comorbid medical conditions, and overall medical and pharmacy costs differ among the three groups,” they say.

Notably, the dataset largely encompassed in-person OPBHT, because the study period preceded the transition into virtual care that occurred in 2020.

However, overall use of OPBHT was low – older adults, adults with lower income, individuals with comorbid medical conditions, and persons of racial and ethnic minorities were less likely to receive OPBHT, they found.

“These findings support the cost-effectiveness of practitioner- and insurance-based interventions to increase OPBHT utilization, which is a critical resource as new BHC diagnoses continue to increase,” the researchers say.

“Future research should validate these findings in other populations, including government-insured individuals, and explore data by chronic disease category, over longer time horizons, by type and quality of OPBHT, by type of medical spending, within subpopulations with BHCs, and including virtual and digital behavioral health services,” they suggest.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

Outpatient behavioral health treatment (OPBHT) for patients newly diagnosed with depression, substance use disorder, or other behavioral health condition (BHC) is cost-effective.

Results of a large retrospective study showed that patients newly diagnosed with a BHC who receive OPBHT following diagnosis incur lower medical and pharmacy costs over roughly the next 1 to 2 years, compared with peers who don’t receive OPBHT.

“Our findings suggest that promoting OPBHT as part of a population health strategy is associated with improved overall medical spending, particularly among adults,” the investigators write.

The study was published online in JAMA Network Open.
 

Common, undertreated

Nearly a quarter of adults in the United States have a BHC, and they incur greater medical costs than those without a BHC. However, diagnosis of a BHC is often delayed, and most affected individuals receive little to no treatment.

In their cost analysis, Johanna Bellon, PhD, and colleagues with Evernorth Health, St. Louis, analyzed commercial insurance claims data for 203,401 U.S. individuals newly diagnosed with one or more BHCs between 2017 and 2018.

About half of participants had depression and/or anxiety, 11% had substance use or alcohol use disorder, and 6% had a higher-acuity diagnosis, such as bipolar disorder, severe depression, eating disorder, psychotic disorder, or autism spectrum disorder.

About 1 in 5 (22%) had at least one chronic medical condition along with their BHC.

The researchers found that having at least one OPBHT visit was associated with lower medical and pharmacy costs during 15- and 27-month follow-up periods.

Over 15 months, the adjusted mean per member per month (PMPM) medical/pharmacy cost was $686 with no OPBHT visit, compared with $571 with one or more OPBHT visits.

Over 27 months, the adjusted mean PMPM was $464 with no OPBHT, versus $391 with one or more OPBHT visits.
 

Dose-response effect

In addition, there was a “dose-response” relationship between OPBHT and medical/pharmacy costs, such that estimated cost savings were significantly lower in the treated versus the untreated groups at almost every level of treatment.

“Our findings were also largely age independent, especially over 15 months, suggesting that OPBHT has favorable effects among children, young adults, and adults,” the researchers report.

“This is promising given that disease etiology and progression, treatment paradigms, presence of comorbid medical conditions, and overall medical and pharmacy costs differ among the three groups,” they say.

Notably, the dataset largely encompassed in-person OPBHT, because the study period preceded the transition into virtual care that occurred in 2020.

However, overall use of OPBHT was low – older adults, adults with lower income, individuals with comorbid medical conditions, and persons of racial and ethnic minorities were less likely to receive OPBHT, they found.

“These findings support the cost-effectiveness of practitioner- and insurance-based interventions to increase OPBHT utilization, which is a critical resource as new BHC diagnoses continue to increase,” the researchers say.

“Future research should validate these findings in other populations, including government-insured individuals, and explore data by chronic disease category, over longer time horizons, by type and quality of OPBHT, by type of medical spending, within subpopulations with BHCs, and including virtual and digital behavioral health services,” they suggest.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

Outpatient behavioral health treatment (OPBHT) for patients newly diagnosed with depression, substance use disorder, or other behavioral health condition (BHC) is cost-effective.

Results of a large retrospective study showed that patients newly diagnosed with a BHC who receive OPBHT following diagnosis incur lower medical and pharmacy costs over roughly the next 1 to 2 years, compared with peers who don’t receive OPBHT.

“Our findings suggest that promoting OPBHT as part of a population health strategy is associated with improved overall medical spending, particularly among adults,” the investigators write.

The study was published online in JAMA Network Open.
 

Common, undertreated

Nearly a quarter of adults in the United States have a BHC, and they incur greater medical costs than those without a BHC. However, diagnosis of a BHC is often delayed, and most affected individuals receive little to no treatment.

In their cost analysis, Johanna Bellon, PhD, and colleagues with Evernorth Health, St. Louis, analyzed commercial insurance claims data for 203,401 U.S. individuals newly diagnosed with one or more BHCs between 2017 and 2018.

About half of participants had depression and/or anxiety, 11% had substance use or alcohol use disorder, and 6% had a higher-acuity diagnosis, such as bipolar disorder, severe depression, eating disorder, psychotic disorder, or autism spectrum disorder.

About 1 in 5 (22%) had at least one chronic medical condition along with their BHC.

The researchers found that having at least one OPBHT visit was associated with lower medical and pharmacy costs during 15- and 27-month follow-up periods.

Over 15 months, the adjusted mean per member per month (PMPM) medical/pharmacy cost was $686 with no OPBHT visit, compared with $571 with one or more OPBHT visits.

Over 27 months, the adjusted mean PMPM was $464 with no OPBHT, versus $391 with one or more OPBHT visits.
 

Dose-response effect

In addition, there was a “dose-response” relationship between OPBHT and medical/pharmacy costs, such that estimated cost savings were significantly lower in the treated versus the untreated groups at almost every level of treatment.

“Our findings were also largely age independent, especially over 15 months, suggesting that OPBHT has favorable effects among children, young adults, and adults,” the researchers report.

“This is promising given that disease etiology and progression, treatment paradigms, presence of comorbid medical conditions, and overall medical and pharmacy costs differ among the three groups,” they say.

Notably, the dataset largely encompassed in-person OPBHT, because the study period preceded the transition into virtual care that occurred in 2020.

However, overall use of OPBHT was low – older adults, adults with lower income, individuals with comorbid medical conditions, and persons of racial and ethnic minorities were less likely to receive OPBHT, they found.

“These findings support the cost-effectiveness of practitioner- and insurance-based interventions to increase OPBHT utilization, which is a critical resource as new BHC diagnoses continue to increase,” the researchers say.

“Future research should validate these findings in other populations, including government-insured individuals, and explore data by chronic disease category, over longer time horizons, by type and quality of OPBHT, by type of medical spending, within subpopulations with BHCs, and including virtual and digital behavioral health services,” they suggest.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

A brief aerobic exercise intervention can augment the benefits of exposure therapy for PTSD, new research suggests.

Investigators randomly assigned individuals with PTSD to receive either exposure therapy with aerobic exercise or exposure therapy with passive stretching for 9 weeks. At 6 months post intervention, participants in the aerobic exercise group showed greater reductions in PTSD severity, compared with those in the stretching group.

“There is a critical need to improve outcomes for treating people with PTSD, and this finding points to one potentially cheap and ready-to-use strategy that all clinicians could employ with most patients,” lead author Richard Bryant, MPsych, PhD, DSc, director of the Traumatic Stress Clinic and Scientia Professor of Psychology at the University of New South Wales, Sydney, told this news organization.

The study was published online in The Lancet Psychiatry.
 

Promoting BDNF

“Trauma-focused psychotherapy is the recommended treatment for PTSD, but up to half of patients do not respond to this treatment,” Dr. Bryant said.

“We know that brain-derived neurotrophic factors [BDNF] are critical for synaptic plasticity, which underpins the learning that occurs in therapy so that reminders of trauma are no longer fear-provoking,” he continued. “Preclinical animal and human research inform us that brief aerobic exercise can promote BDNF and new learning that inhibits fear responses.”

The researchers “hypothesized that brief exercise after exposure therapy to trauma memories – which is the key ingredient of trauma-focused psychotherapy – would lead to greater reductions in PTSD, relative to standard trauma-focused therapy,” he said.

To investigate the question, the researchers randomly assigned 130 adults with PTSD (mean age, 39 years; 61% female; 76% White) to receive nine 90-minute sessions of exposure therapy with either aerobic exercise or passive stretching (n = 65 in each group).

There were no differences at baseline in sociodemographic characteristics or psychopathology measures, although the mean age of the stretching group was slightly older than that of the aerobic group (40 years vs. 37 years, respectively), and there was a slightly higher proportion of women in the stretching group (68% vs. 54%).

Participants did not differ on weekly exercise either at baseline, immediately post treatment, or at 6-week follow-up.

PTSD severity (the primary outcome) was measured using the clinician-administered PTSD scale CAPS-2, with assessments conducted at baseline, 1 week post treatment, and 6 months post treatment.

The aerobic exercise regimen was tailored to each participant, based on an assessment of his/her aerobic target zone.

The exposure therapy sessions were identical for both groups. Following the exposure sessions, participants engaged in their respective exercises: Those in the passive stretching group engaged in 20 minutes of exercise, while those in the aerobic group participated in a total of 20 minutes of exercise, with 10 conducted at their personal aerobic target heart rate.

“This level of exercise was chosen because BDNF concentration in the serum is increased by two 3-minute bouts of aerobic exercise, and 10 minutes of aerobic exercise can facilitate extinction learning,” the authors explained.

The aerobic activity consisted of running on a stepper exercise platform while having cardiac activity recorded. A small portion (10%) of the therapy sessions were recorded and rated for treatment fidelity.

Change in PTSD was the primary outcome, with secondary outcomes consisting of changes in depression, anxiety, alcohol use disorder, and posttraumatic cognitions.
 

Few barriers

The researchers found no significant differences in PTSD severity, as measured by CAPS-2 score, between treatment groups at 10 weeks – that is, immediately post treatment (mean difference, 7.0; 95% confidence interval, –2.3 to 16.4; P = .14).

However, significantly greater reductions in PTSD severity were found in the aerobic versus the stretching group at 6-month follow-up (mean difference, 12.1;95% CI, 2.4-21.8; P = .023), pointing to a “moderate effect size” (d = 0.6; 95% CI, 0.1-1.1]).

Although there were no differences found at 6-month assessment between rates of PTSD diagnosis (25% of the aerobic vs 27% of the stretching group), more participants in the aerobic group reached a “minimal clinically important difference,” compared to those in the stretching group (96% vs. 84%, respectively, x² = 4.4; P = .036). 

There were also superior benefits found in the aerobic versus the stretching group on depression severity at 6 months (a secondary outcome), with a mean difference in Beck Depression Inventory-2 score of 5.7 (95% CI, 0.5-10.9; P = .022), yielding a “moderate effect size” (d = 0.5; 95% CI, 0.1-1.0]).

There were no adverse events associated with the intervention, and almost all the sessions (88%) complied with the treatment protocol.

The researchers noted several limitations. For example, they did not obtain plasma to measure BDNF concentrations, so they could not “infer whether the mechanism of change involved BDNF.”

In addition, they did not perform sex-specific analyses. “Future studies could increase the sample size to investigate sex differences because females display less BDNF change following exercise than do males,” they wrote.

Nevertheless, the study “provides initial evidence of a simple and accessible strategy that clinicians could readily apply in combination with exposure therapy,” they stated. “Whereas many pharmacologic interventions pose barriers, including cost, requirement for prescriptions, and patient resistance to drugs, exercise offers clinicians a strategy that can be implemented with few barriers.”

Dr. Bryant emphasized that one study “does not represent a body of evidence, and so it is essential that this finding be replicated in other trials before it can be recommended for clinical use.” He noted that other trials are “currently underway.”
 

Easy augmentation

In a comment, Barbara Rothbaum, PhD, professor in psychiatry and director of the Trauma and Anxiety Recovery Program at Emory University, Atlanta, called it a “well-controlled trial augmenting exposure therapy for PTSD with brief aerobic exercise and finding some benefits of the augmented condition at 6 months posttreatment but not immediately posttreatment.”

The study’s methodology – that is, using independent standard assessment of PTSD and rating audio recordings of therapy sessions for treatment fidelity and quality – can lead us to “be confident in their [the researchers’] conclusions,” she said.

Dr. Rothbaum, who was not associated with this study, described research into methods to augment exposure therapy for PTSD as “timely and clinically relevant.”

Exercise “would be an easy augmentation for many clinicians if it is helpful,” she noted.

The study was funded by the Australian National Health and Medical Research Council. The authors and Dr. Rothbaum reported no relevant financial relationships.

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

A brief aerobic exercise intervention can augment the benefits of exposure therapy for PTSD, new research suggests.

Investigators randomly assigned individuals with PTSD to receive either exposure therapy with aerobic exercise or exposure therapy with passive stretching for 9 weeks. At 6 months post intervention, participants in the aerobic exercise group showed greater reductions in PTSD severity, compared with those in the stretching group.

“There is a critical need to improve outcomes for treating people with PTSD, and this finding points to one potentially cheap and ready-to-use strategy that all clinicians could employ with most patients,” lead author Richard Bryant, MPsych, PhD, DSc, director of the Traumatic Stress Clinic and Scientia Professor of Psychology at the University of New South Wales, Sydney, told this news organization.

The study was published online in The Lancet Psychiatry.
 

Promoting BDNF

“Trauma-focused psychotherapy is the recommended treatment for PTSD, but up to half of patients do not respond to this treatment,” Dr. Bryant said.

“We know that brain-derived neurotrophic factors [BDNF] are critical for synaptic plasticity, which underpins the learning that occurs in therapy so that reminders of trauma are no longer fear-provoking,” he continued. “Preclinical animal and human research inform us that brief aerobic exercise can promote BDNF and new learning that inhibits fear responses.”

The researchers “hypothesized that brief exercise after exposure therapy to trauma memories – which is the key ingredient of trauma-focused psychotherapy – would lead to greater reductions in PTSD, relative to standard trauma-focused therapy,” he said.

To investigate the question, the researchers randomly assigned 130 adults with PTSD (mean age, 39 years; 61% female; 76% White) to receive nine 90-minute sessions of exposure therapy with either aerobic exercise or passive stretching (n = 65 in each group).

There were no differences at baseline in sociodemographic characteristics or psychopathology measures, although the mean age of the stretching group was slightly older than that of the aerobic group (40 years vs. 37 years, respectively), and there was a slightly higher proportion of women in the stretching group (68% vs. 54%).

Participants did not differ on weekly exercise either at baseline, immediately post treatment, or at 6-week follow-up.

PTSD severity (the primary outcome) was measured using the clinician-administered PTSD scale CAPS-2, with assessments conducted at baseline, 1 week post treatment, and 6 months post treatment.

The aerobic exercise regimen was tailored to each participant, based on an assessment of his/her aerobic target zone.

The exposure therapy sessions were identical for both groups. Following the exposure sessions, participants engaged in their respective exercises: Those in the passive stretching group engaged in 20 minutes of exercise, while those in the aerobic group participated in a total of 20 minutes of exercise, with 10 conducted at their personal aerobic target heart rate.

“This level of exercise was chosen because BDNF concentration in the serum is increased by two 3-minute bouts of aerobic exercise, and 10 minutes of aerobic exercise can facilitate extinction learning,” the authors explained.

The aerobic activity consisted of running on a stepper exercise platform while having cardiac activity recorded. A small portion (10%) of the therapy sessions were recorded and rated for treatment fidelity.

Change in PTSD was the primary outcome, with secondary outcomes consisting of changes in depression, anxiety, alcohol use disorder, and posttraumatic cognitions.
 

Few barriers

The researchers found no significant differences in PTSD severity, as measured by CAPS-2 score, between treatment groups at 10 weeks – that is, immediately post treatment (mean difference, 7.0; 95% confidence interval, –2.3 to 16.4; P = .14).

However, significantly greater reductions in PTSD severity were found in the aerobic versus the stretching group at 6-month follow-up (mean difference, 12.1;95% CI, 2.4-21.8; P = .023), pointing to a “moderate effect size” (d = 0.6; 95% CI, 0.1-1.1]).

Although there were no differences found at 6-month assessment between rates of PTSD diagnosis (25% of the aerobic vs 27% of the stretching group), more participants in the aerobic group reached a “minimal clinically important difference,” compared to those in the stretching group (96% vs. 84%, respectively, x² = 4.4; P = .036). 

There were also superior benefits found in the aerobic versus the stretching group on depression severity at 6 months (a secondary outcome), with a mean difference in Beck Depression Inventory-2 score of 5.7 (95% CI, 0.5-10.9; P = .022), yielding a “moderate effect size” (d = 0.5; 95% CI, 0.1-1.0]).

There were no adverse events associated with the intervention, and almost all the sessions (88%) complied with the treatment protocol.

The researchers noted several limitations. For example, they did not obtain plasma to measure BDNF concentrations, so they could not “infer whether the mechanism of change involved BDNF.”

In addition, they did not perform sex-specific analyses. “Future studies could increase the sample size to investigate sex differences because females display less BDNF change following exercise than do males,” they wrote.

Nevertheless, the study “provides initial evidence of a simple and accessible strategy that clinicians could readily apply in combination with exposure therapy,” they stated. “Whereas many pharmacologic interventions pose barriers, including cost, requirement for prescriptions, and patient resistance to drugs, exercise offers clinicians a strategy that can be implemented with few barriers.”

Dr. Bryant emphasized that one study “does not represent a body of evidence, and so it is essential that this finding be replicated in other trials before it can be recommended for clinical use.” He noted that other trials are “currently underway.”
 

Easy augmentation

In a comment, Barbara Rothbaum, PhD, professor in psychiatry and director of the Trauma and Anxiety Recovery Program at Emory University, Atlanta, called it a “well-controlled trial augmenting exposure therapy for PTSD with brief aerobic exercise and finding some benefits of the augmented condition at 6 months posttreatment but not immediately posttreatment.”

The study’s methodology – that is, using independent standard assessment of PTSD and rating audio recordings of therapy sessions for treatment fidelity and quality – can lead us to “be confident in their [the researchers’] conclusions,” she said.

Dr. Rothbaum, who was not associated with this study, described research into methods to augment exposure therapy for PTSD as “timely and clinically relevant.”

Exercise “would be an easy augmentation for many clinicians if it is helpful,” she noted.

The study was funded by the Australian National Health and Medical Research Council. The authors and Dr. Rothbaum reported no relevant financial relationships.

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

A brief aerobic exercise intervention can augment the benefits of exposure therapy for PTSD, new research suggests.

Investigators randomly assigned individuals with PTSD to receive either exposure therapy with aerobic exercise or exposure therapy with passive stretching for 9 weeks. At 6 months post intervention, participants in the aerobic exercise group showed greater reductions in PTSD severity, compared with those in the stretching group.

“There is a critical need to improve outcomes for treating people with PTSD, and this finding points to one potentially cheap and ready-to-use strategy that all clinicians could employ with most patients,” lead author Richard Bryant, MPsych, PhD, DSc, director of the Traumatic Stress Clinic and Scientia Professor of Psychology at the University of New South Wales, Sydney, told this news organization.

The study was published online in The Lancet Psychiatry.
 

Promoting BDNF

“Trauma-focused psychotherapy is the recommended treatment for PTSD, but up to half of patients do not respond to this treatment,” Dr. Bryant said.

“We know that brain-derived neurotrophic factors [BDNF] are critical for synaptic plasticity, which underpins the learning that occurs in therapy so that reminders of trauma are no longer fear-provoking,” he continued. “Preclinical animal and human research inform us that brief aerobic exercise can promote BDNF and new learning that inhibits fear responses.”

The researchers “hypothesized that brief exercise after exposure therapy to trauma memories – which is the key ingredient of trauma-focused psychotherapy – would lead to greater reductions in PTSD, relative to standard trauma-focused therapy,” he said.

To investigate the question, the researchers randomly assigned 130 adults with PTSD (mean age, 39 years; 61% female; 76% White) to receive nine 90-minute sessions of exposure therapy with either aerobic exercise or passive stretching (n = 65 in each group).

There were no differences at baseline in sociodemographic characteristics or psychopathology measures, although the mean age of the stretching group was slightly older than that of the aerobic group (40 years vs. 37 years, respectively), and there was a slightly higher proportion of women in the stretching group (68% vs. 54%).

Participants did not differ on weekly exercise either at baseline, immediately post treatment, or at 6-week follow-up.

PTSD severity (the primary outcome) was measured using the clinician-administered PTSD scale CAPS-2, with assessments conducted at baseline, 1 week post treatment, and 6 months post treatment.

The aerobic exercise regimen was tailored to each participant, based on an assessment of his/her aerobic target zone.

The exposure therapy sessions were identical for both groups. Following the exposure sessions, participants engaged in their respective exercises: Those in the passive stretching group engaged in 20 minutes of exercise, while those in the aerobic group participated in a total of 20 minutes of exercise, with 10 conducted at their personal aerobic target heart rate.

“This level of exercise was chosen because BDNF concentration in the serum is increased by two 3-minute bouts of aerobic exercise, and 10 minutes of aerobic exercise can facilitate extinction learning,” the authors explained.

The aerobic activity consisted of running on a stepper exercise platform while having cardiac activity recorded. A small portion (10%) of the therapy sessions were recorded and rated for treatment fidelity.

Change in PTSD was the primary outcome, with secondary outcomes consisting of changes in depression, anxiety, alcohol use disorder, and posttraumatic cognitions.
 

Few barriers

The researchers found no significant differences in PTSD severity, as measured by CAPS-2 score, between treatment groups at 10 weeks – that is, immediately post treatment (mean difference, 7.0; 95% confidence interval, –2.3 to 16.4; P = .14).

However, significantly greater reductions in PTSD severity were found in the aerobic versus the stretching group at 6-month follow-up (mean difference, 12.1;95% CI, 2.4-21.8; P = .023), pointing to a “moderate effect size” (d = 0.6; 95% CI, 0.1-1.1]).

Although there were no differences found at 6-month assessment between rates of PTSD diagnosis (25% of the aerobic vs 27% of the stretching group), more participants in the aerobic group reached a “minimal clinically important difference,” compared to those in the stretching group (96% vs. 84%, respectively, x² = 4.4; P = .036). 

There were also superior benefits found in the aerobic versus the stretching group on depression severity at 6 months (a secondary outcome), with a mean difference in Beck Depression Inventory-2 score of 5.7 (95% CI, 0.5-10.9; P = .022), yielding a “moderate effect size” (d = 0.5; 95% CI, 0.1-1.0]).

There were no adverse events associated with the intervention, and almost all the sessions (88%) complied with the treatment protocol.

The researchers noted several limitations. For example, they did not obtain plasma to measure BDNF concentrations, so they could not “infer whether the mechanism of change involved BDNF.”

In addition, they did not perform sex-specific analyses. “Future studies could increase the sample size to investigate sex differences because females display less BDNF change following exercise than do males,” they wrote.

Nevertheless, the study “provides initial evidence of a simple and accessible strategy that clinicians could readily apply in combination with exposure therapy,” they stated. “Whereas many pharmacologic interventions pose barriers, including cost, requirement for prescriptions, and patient resistance to drugs, exercise offers clinicians a strategy that can be implemented with few barriers.”

Dr. Bryant emphasized that one study “does not represent a body of evidence, and so it is essential that this finding be replicated in other trials before it can be recommended for clinical use.” He noted that other trials are “currently underway.”
 

Easy augmentation

In a comment, Barbara Rothbaum, PhD, professor in psychiatry and director of the Trauma and Anxiety Recovery Program at Emory University, Atlanta, called it a “well-controlled trial augmenting exposure therapy for PTSD with brief aerobic exercise and finding some benefits of the augmented condition at 6 months posttreatment but not immediately posttreatment.”

The study’s methodology – that is, using independent standard assessment of PTSD and rating audio recordings of therapy sessions for treatment fidelity and quality – can lead us to “be confident in their [the researchers’] conclusions,” she said.

Dr. Rothbaum, who was not associated with this study, described research into methods to augment exposure therapy for PTSD as “timely and clinically relevant.”

Exercise “would be an easy augmentation for many clinicians if it is helpful,” she noted.

The study was funded by the Australian National Health and Medical Research Council. The authors and Dr. Rothbaum reported no relevant financial relationships.

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

SAN FRANCISCO – In a widely anticipated report, researchers reported that a phase 3 study showed statistically significant improvements in patients with agitation related to Alzheimer’s disease (AD) who took the atypical antipsychotic brexpiprazole (Rexulti).

Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.

“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”

Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.

In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.

Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
 

Three trials

All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.

Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.

The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”

The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).

In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).

In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.

The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.

The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.

Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.

University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”

But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”

What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.

Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
 

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

SAN FRANCISCO – In a widely anticipated report, researchers reported that a phase 3 study showed statistically significant improvements in patients with agitation related to Alzheimer’s disease (AD) who took the atypical antipsychotic brexpiprazole (Rexulti).

Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.

“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”

Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.

In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.

Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
 

Three trials

All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.

Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.

The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”

The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).

In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).

In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.

The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.

The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.

Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.

University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”

But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”

What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.

Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
 

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

SAN FRANCISCO – In a widely anticipated report, researchers reported that a phase 3 study showed statistically significant improvements in patients with agitation related to Alzheimer’s disease (AD) who took the atypical antipsychotic brexpiprazole (Rexulti).

Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.

“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”

Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.

In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.

Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
 

Three trials

All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.

Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.

The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”

The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).

In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).

In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.

The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.

The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.

Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.

University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”

But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”

What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.

Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
 

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

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

We are coming to the end of the year, which always makes me think about getting older. Despite the fact that aging is, definitionally, inexorable, we continue to search for ways to avoid the losses that come with age, whether that is strength, beauty, or our cognitive powers. Much like the search for the fountain of youth, many promising leads have ultimately led to dead ends. And yet, I had high hopes for a trial that focused on two cornerstones of wellness – exercise and mindfulness – to address the subjective loss of memory that comes with aging. Alas, meditation and exercise do not appear to be the fountain of youth.

I’m talking about this study, appearing in JAMA, known as the MEDEX trial.

It’s a clever design: a 2 x 2 factorial randomized trial where participants could be randomized to a mindfulness intervention, an exercise intervention, both, or neither.

Courtesy Dr. F. Perry Wilson

In this manner, you can test multiple hypotheses exploiting a shared control group. Or as a mentor of mine used to say, you get two trials for the price of one and a half.

The participants were older adults, aged 65-84, living in the community. They had to be relatively sedentary at baseline and not engaging in mindfulness practices. They had to subjectively report some memory or concentration issues but had to be cognitively intact, based on a standard dementia screening test. In other words, these are your average older people who are worried that they aren’t as sharp as they used to be.

The interventions themselves were fairly intense. The exercise group had instructor-led sessions for 90 minutes twice a week for the first 6 months of the study, once a week thereafter. And participants were encouraged to exercise at home such that they had a total of 300 minutes of weekly exercise.

The mindfulness program was characterized by eight weekly classes of 2.5 hours each as well as a half-day retreat to teach the tenets of mindfulness and meditation, with monthly refreshers thereafter. Participants were instructed to meditate for 60 minutes a day in addition to the classes.

For the 144 people who were randomized to both meditation and exercise, this trial amounted to something of a part-time job. So you might think that adherence to the interventions was low, but apparently that’s not the case. Attendance to the mindfulness classes was over 90%, and over 80% for the exercise classes. And diary-based reporting of home efforts was also pretty good.

The control group wasn’t left to their own devices. Recognizing that the community aspect of exercise or mindfulness classes might convey a benefit independent of the actual exercise or mindfulness, the control group met on a similar schedule to discuss health education, but no mention of exercise or mindfulness occurred in that setting.

The primary outcome was change in memory and executive function scores across a battery of neuropsychologic testing, but the story is told in just a few pictures.

Memory scores improved in all three groups – mindfulness, exercise, and health education – over time. Cognitive composite score improved in all three groups similarly. There was no synergistic effect of mindfulness and exercise either. Basically, everyone got a bit better.

But the study did way more than look at scores on tests. Researchers used MRI to measure brain anatomic outcomes as well. And the surprising thing is that virtually none of these outcomes were different between the groups either.

Hippocampal volume decreased a bit in all the groups. Dorsolateral prefrontal cortex volume was flat. There was no change in scores measuring tasks of daily living.

When you see negative results like this, right away you worry that the intervention wasn’t properly delivered. Were these people really exercising and meditating? Well, the authors showed that individuals randomized to exercise, at least, had less sleep latency, greater aerobic fitness, and greater strength. So we know something was happening.

They then asked, would the people in the exercise group with the greatest changes in those physiologic parameters show some improvement in cognitive parameters? In other words, we know you were exercising because you got stronger and are sleeping better; is your memory better? The answer? Surprisingly, still no. Even in that honestly somewhat cherry-picked group, the interventions had no effect.

Could it be that the control was inappropriate, that the “health education” intervention was actually so helpful that it obscured the benefits of exercise and meditation? After all, cognitive scores did improve in all groups. The authors doubt it. They say they think the improvement in cognitive scores reflects the fact that patients had learned a bit about how to take the tests. This is pretty common in the neuropsychiatric literature.

So here we are and I just want to say, well, shoot. This is not the result I wanted. And I think the reason I’m so disappointed is because aging and the loss of cognitive faculties that comes with aging are just sort of scary. We are all looking for some control over that fear, and how nice it would be to be able to tell ourselves not to worry – that we won’t have those problems as we get older because we exercise, or meditate, or drink red wine, or don’t drink wine, or whatever. And while I have no doubt that staying healthier physically will keep you healthier mentally, it may take more than one simple thing to move the needle.

Dr. Wilson is associate professor, department of medicine, and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He reported no conflicts of interest.

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

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

We are coming to the end of the year, which always makes me think about getting older. Despite the fact that aging is, definitionally, inexorable, we continue to search for ways to avoid the losses that come with age, whether that is strength, beauty, or our cognitive powers. Much like the search for the fountain of youth, many promising leads have ultimately led to dead ends. And yet, I had high hopes for a trial that focused on two cornerstones of wellness – exercise and mindfulness – to address the subjective loss of memory that comes with aging. Alas, meditation and exercise do not appear to be the fountain of youth.

I’m talking about this study, appearing in JAMA, known as the MEDEX trial.

It’s a clever design: a 2 x 2 factorial randomized trial where participants could be randomized to a mindfulness intervention, an exercise intervention, both, or neither.

Courtesy Dr. F. Perry Wilson

In this manner, you can test multiple hypotheses exploiting a shared control group. Or as a mentor of mine used to say, you get two trials for the price of one and a half.

The participants were older adults, aged 65-84, living in the community. They had to be relatively sedentary at baseline and not engaging in mindfulness practices. They had to subjectively report some memory or concentration issues but had to be cognitively intact, based on a standard dementia screening test. In other words, these are your average older people who are worried that they aren’t as sharp as they used to be.

The interventions themselves were fairly intense. The exercise group had instructor-led sessions for 90 minutes twice a week for the first 6 months of the study, once a week thereafter. And participants were encouraged to exercise at home such that they had a total of 300 minutes of weekly exercise.

The mindfulness program was characterized by eight weekly classes of 2.5 hours each as well as a half-day retreat to teach the tenets of mindfulness and meditation, with monthly refreshers thereafter. Participants were instructed to meditate for 60 minutes a day in addition to the classes.

For the 144 people who were randomized to both meditation and exercise, this trial amounted to something of a part-time job. So you might think that adherence to the interventions was low, but apparently that’s not the case. Attendance to the mindfulness classes was over 90%, and over 80% for the exercise classes. And diary-based reporting of home efforts was also pretty good.

The control group wasn’t left to their own devices. Recognizing that the community aspect of exercise or mindfulness classes might convey a benefit independent of the actual exercise or mindfulness, the control group met on a similar schedule to discuss health education, but no mention of exercise or mindfulness occurred in that setting.

The primary outcome was change in memory and executive function scores across a battery of neuropsychologic testing, but the story is told in just a few pictures.

Memory scores improved in all three groups – mindfulness, exercise, and health education – over time. Cognitive composite score improved in all three groups similarly. There was no synergistic effect of mindfulness and exercise either. Basically, everyone got a bit better.

But the study did way more than look at scores on tests. Researchers used MRI to measure brain anatomic outcomes as well. And the surprising thing is that virtually none of these outcomes were different between the groups either.

Hippocampal volume decreased a bit in all the groups. Dorsolateral prefrontal cortex volume was flat. There was no change in scores measuring tasks of daily living.

When you see negative results like this, right away you worry that the intervention wasn’t properly delivered. Were these people really exercising and meditating? Well, the authors showed that individuals randomized to exercise, at least, had less sleep latency, greater aerobic fitness, and greater strength. So we know something was happening.

They then asked, would the people in the exercise group with the greatest changes in those physiologic parameters show some improvement in cognitive parameters? In other words, we know you were exercising because you got stronger and are sleeping better; is your memory better? The answer? Surprisingly, still no. Even in that honestly somewhat cherry-picked group, the interventions had no effect.

Could it be that the control was inappropriate, that the “health education” intervention was actually so helpful that it obscured the benefits of exercise and meditation? After all, cognitive scores did improve in all groups. The authors doubt it. They say they think the improvement in cognitive scores reflects the fact that patients had learned a bit about how to take the tests. This is pretty common in the neuropsychiatric literature.

So here we are and I just want to say, well, shoot. This is not the result I wanted. And I think the reason I’m so disappointed is because aging and the loss of cognitive faculties that comes with aging are just sort of scary. We are all looking for some control over that fear, and how nice it would be to be able to tell ourselves not to worry – that we won’t have those problems as we get older because we exercise, or meditate, or drink red wine, or don’t drink wine, or whatever. And while I have no doubt that staying healthier physically will keep you healthier mentally, it may take more than one simple thing to move the needle.

Dr. Wilson is associate professor, department of medicine, and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He reported no conflicts of interest.

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

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

We are coming to the end of the year, which always makes me think about getting older. Despite the fact that aging is, definitionally, inexorable, we continue to search for ways to avoid the losses that come with age, whether that is strength, beauty, or our cognitive powers. Much like the search for the fountain of youth, many promising leads have ultimately led to dead ends. And yet, I had high hopes for a trial that focused on two cornerstones of wellness – exercise and mindfulness – to address the subjective loss of memory that comes with aging. Alas, meditation and exercise do not appear to be the fountain of youth.

I’m talking about this study, appearing in JAMA, known as the MEDEX trial.

It’s a clever design: a 2 x 2 factorial randomized trial where participants could be randomized to a mindfulness intervention, an exercise intervention, both, or neither.

Courtesy Dr. F. Perry Wilson

In this manner, you can test multiple hypotheses exploiting a shared control group. Or as a mentor of mine used to say, you get two trials for the price of one and a half.

The participants were older adults, aged 65-84, living in the community. They had to be relatively sedentary at baseline and not engaging in mindfulness practices. They had to subjectively report some memory or concentration issues but had to be cognitively intact, based on a standard dementia screening test. In other words, these are your average older people who are worried that they aren’t as sharp as they used to be.

The interventions themselves were fairly intense. The exercise group had instructor-led sessions for 90 minutes twice a week for the first 6 months of the study, once a week thereafter. And participants were encouraged to exercise at home such that they had a total of 300 minutes of weekly exercise.

The mindfulness program was characterized by eight weekly classes of 2.5 hours each as well as a half-day retreat to teach the tenets of mindfulness and meditation, with monthly refreshers thereafter. Participants were instructed to meditate for 60 minutes a day in addition to the classes.

For the 144 people who were randomized to both meditation and exercise, this trial amounted to something of a part-time job. So you might think that adherence to the interventions was low, but apparently that’s not the case. Attendance to the mindfulness classes was over 90%, and over 80% for the exercise classes. And diary-based reporting of home efforts was also pretty good.

The control group wasn’t left to their own devices. Recognizing that the community aspect of exercise or mindfulness classes might convey a benefit independent of the actual exercise or mindfulness, the control group met on a similar schedule to discuss health education, but no mention of exercise or mindfulness occurred in that setting.

The primary outcome was change in memory and executive function scores across a battery of neuropsychologic testing, but the story is told in just a few pictures.

Memory scores improved in all three groups – mindfulness, exercise, and health education – over time. Cognitive composite score improved in all three groups similarly. There was no synergistic effect of mindfulness and exercise either. Basically, everyone got a bit better.

But the study did way more than look at scores on tests. Researchers used MRI to measure brain anatomic outcomes as well. And the surprising thing is that virtually none of these outcomes were different between the groups either.

Hippocampal volume decreased a bit in all the groups. Dorsolateral prefrontal cortex volume was flat. There was no change in scores measuring tasks of daily living.

When you see negative results like this, right away you worry that the intervention wasn’t properly delivered. Were these people really exercising and meditating? Well, the authors showed that individuals randomized to exercise, at least, had less sleep latency, greater aerobic fitness, and greater strength. So we know something was happening.

They then asked, would the people in the exercise group with the greatest changes in those physiologic parameters show some improvement in cognitive parameters? In other words, we know you were exercising because you got stronger and are sleeping better; is your memory better? The answer? Surprisingly, still no. Even in that honestly somewhat cherry-picked group, the interventions had no effect.

Could it be that the control was inappropriate, that the “health education” intervention was actually so helpful that it obscured the benefits of exercise and meditation? After all, cognitive scores did improve in all groups. The authors doubt it. They say they think the improvement in cognitive scores reflects the fact that patients had learned a bit about how to take the tests. This is pretty common in the neuropsychiatric literature.

So here we are and I just want to say, well, shoot. This is not the result I wanted. And I think the reason I’m so disappointed is because aging and the loss of cognitive faculties that comes with aging are just sort of scary. We are all looking for some control over that fear, and how nice it would be to be able to tell ourselves not to worry – that we won’t have those problems as we get older because we exercise, or meditate, or drink red wine, or don’t drink wine, or whatever. And while I have no doubt that staying healthier physically will keep you healthier mentally, it may take more than one simple thing to move the needle.

Dr. Wilson is associate professor, department of medicine, and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He reported no conflicts of interest.

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

Maybe the cow was late for its appointment

It’s been a long day running the front desk at your doctor’s office. People calling in prescriptions, a million appointments, you’ve been running yourself ragged keeping things together. Finally, it’s almost closing time. The last patient of the day has just checked out and you turn back to the waiting room, expecting to see it blessedly empty.

Instead, a 650-pound cow is staring at you.

“I’m sorry, sir or madam, we’re about to close.”

Moo.
 

tilo/Thinkstock

We can see that decision in your eyes

The cliché that eyes are the windows to the soul doesn’t tell the whole story about how telling eyes really are. It’s all about how they move. In a recent study, researchers determined that a type of eye movement known as a saccade reveals your choice before you even decide.

pxfuel

Saccades involve the eyes jumping from one fixation point to another, senior author Alaa Ahmed of the University of Colorado, Boulder, explained in a statement from the university. Saccade vigor was the key in how aligned the type of decisions were made by the 22 study participants.

In the study, subjects walked on a treadmill at varied inclines for a period of time. Then they sat in front of a monitor and a high-speed camera that tracked their eye movements as the monitor presented them with a series of exercise options. The participants had only 4 seconds to choose between them.

After they made their choices, participants went back on the treadmill to perform the exercises they had chosen. The researchers found that participants’ eyes jumped between the options slowly then faster to the option they eventually picked. The more impulsive decision-makers also tended to move their eyes even more rapidly before slowing down after a decision was made, making it pretty conclusive that the eyes were revealing their choices.

The way your eyes shift gives you away without saying a thing. Might be wise, then, to wear sunglasses to your next poker tournament.
 

Let them eat soap

Okay, we admit it: LOTME spends a lot of time in the bathroom. Today, though, we’re interested in the sinks. Specifically, the P-traps under the sinks. You know, the curvy bit that keeps sewer gas from wafting back into the room?

PxHere

Well, researchers from the University of Reading (England) recently found some fungi while examining a bunch of sinks on the university’s Whiteknights campus. “It isn’t a big surprise to find fungi in a warm, wet environment. But sinks and P-traps have thus far been overlooked as potential reservoirs of these microorganisms,” they said in a written statement.

Samples collected from 289 P-traps contained “a very similar community of yeasts and molds, showing that sinks in use in public environments share a role as reservoirs of fungal organisms,” they noted.

The fungi living in the traps survived conditions with high temperatures, low pH, and little in the way of nutrients. So what were they eating? Some varieties, they said, “use detergents, found in soap, as a source of carbon-rich food.” We’ll repeat that last part: They used the soap as food.

WARNING: Rant Ahead.

There are a lot of cleaning products for sale that say they will make your home safe by killing 99.9% of germs and bacteria. Not fungi, exactly, but we’re still talking microorganisms. Molds, bacteria, and viruses are all stuff that can infect humans and make them sick.

So you kill 99.9% of them. Great, but that leaves 0.1% that you just made angry. And what do they do next? They learn to eat soap. Then University of Reading investigators find out that all the extra hand washing going on during the COVID-19 pandemic was “clogging up sinks with nasty disease-causing bacteria.”

These are microorganisms we’re talking about people. They’ve been at this for a billion years! Rats can’t beat them, cockroaches won’t stop them – Earth’s ultimate survivors are powerless against the invisible horde.

We’re doomed.

Maybe the cow was late for its appointment

It’s been a long day running the front desk at your doctor’s office. People calling in prescriptions, a million appointments, you’ve been running yourself ragged keeping things together. Finally, it’s almost closing time. The last patient of the day has just checked out and you turn back to the waiting room, expecting to see it blessedly empty.

Instead, a 650-pound cow is staring at you.

“I’m sorry, sir or madam, we’re about to close.”

Moo.
 

tilo/Thinkstock

We can see that decision in your eyes

The cliché that eyes are the windows to the soul doesn’t tell the whole story about how telling eyes really are. It’s all about how they move. In a recent study, researchers determined that a type of eye movement known as a saccade reveals your choice before you even decide.

pxfuel

Saccades involve the eyes jumping from one fixation point to another, senior author Alaa Ahmed of the University of Colorado, Boulder, explained in a statement from the university. Saccade vigor was the key in how aligned the type of decisions were made by the 22 study participants.

In the study, subjects walked on a treadmill at varied inclines for a period of time. Then they sat in front of a monitor and a high-speed camera that tracked their eye movements as the monitor presented them with a series of exercise options. The participants had only 4 seconds to choose between them.

After they made their choices, participants went back on the treadmill to perform the exercises they had chosen. The researchers found that participants’ eyes jumped between the options slowly then faster to the option they eventually picked. The more impulsive decision-makers also tended to move their eyes even more rapidly before slowing down after a decision was made, making it pretty conclusive that the eyes were revealing their choices.

The way your eyes shift gives you away without saying a thing. Might be wise, then, to wear sunglasses to your next poker tournament.
 

Let them eat soap

Okay, we admit it: LOTME spends a lot of time in the bathroom. Today, though, we’re interested in the sinks. Specifically, the P-traps under the sinks. You know, the curvy bit that keeps sewer gas from wafting back into the room?

PxHere

Well, researchers from the University of Reading (England) recently found some fungi while examining a bunch of sinks on the university’s Whiteknights campus. “It isn’t a big surprise to find fungi in a warm, wet environment. But sinks and P-traps have thus far been overlooked as potential reservoirs of these microorganisms,” they said in a written statement.

Samples collected from 289 P-traps contained “a very similar community of yeasts and molds, showing that sinks in use in public environments share a role as reservoirs of fungal organisms,” they noted.

The fungi living in the traps survived conditions with high temperatures, low pH, and little in the way of nutrients. So what were they eating? Some varieties, they said, “use detergents, found in soap, as a source of carbon-rich food.” We’ll repeat that last part: They used the soap as food.

WARNING: Rant Ahead.

There are a lot of cleaning products for sale that say they will make your home safe by killing 99.9% of germs and bacteria. Not fungi, exactly, but we’re still talking microorganisms. Molds, bacteria, and viruses are all stuff that can infect humans and make them sick.

So you kill 99.9% of them. Great, but that leaves 0.1% that you just made angry. And what do they do next? They learn to eat soap. Then University of Reading investigators find out that all the extra hand washing going on during the COVID-19 pandemic was “clogging up sinks with nasty disease-causing bacteria.”

These are microorganisms we’re talking about people. They’ve been at this for a billion years! Rats can’t beat them, cockroaches won’t stop them – Earth’s ultimate survivors are powerless against the invisible horde.

We’re doomed.

Maybe the cow was late for its appointment

It’s been a long day running the front desk at your doctor’s office. People calling in prescriptions, a million appointments, you’ve been running yourself ragged keeping things together. Finally, it’s almost closing time. The last patient of the day has just checked out and you turn back to the waiting room, expecting to see it blessedly empty.

Instead, a 650-pound cow is staring at you.

“I’m sorry, sir or madam, we’re about to close.”

Moo.
 

tilo/Thinkstock

We can see that decision in your eyes

The cliché that eyes are the windows to the soul doesn’t tell the whole story about how telling eyes really are. It’s all about how they move. In a recent study, researchers determined that a type of eye movement known as a saccade reveals your choice before you even decide.

pxfuel

Saccades involve the eyes jumping from one fixation point to another, senior author Alaa Ahmed of the University of Colorado, Boulder, explained in a statement from the university. Saccade vigor was the key in how aligned the type of decisions were made by the 22 study participants.

In the study, subjects walked on a treadmill at varied inclines for a period of time. Then they sat in front of a monitor and a high-speed camera that tracked their eye movements as the monitor presented them with a series of exercise options. The participants had only 4 seconds to choose between them.

After they made their choices, participants went back on the treadmill to perform the exercises they had chosen. The researchers found that participants’ eyes jumped between the options slowly then faster to the option they eventually picked. The more impulsive decision-makers also tended to move their eyes even more rapidly before slowing down after a decision was made, making it pretty conclusive that the eyes were revealing their choices.

The way your eyes shift gives you away without saying a thing. Might be wise, then, to wear sunglasses to your next poker tournament.
 

Let them eat soap

Okay, we admit it: LOTME spends a lot of time in the bathroom. Today, though, we’re interested in the sinks. Specifically, the P-traps under the sinks. You know, the curvy bit that keeps sewer gas from wafting back into the room?

PxHere

Well, researchers from the University of Reading (England) recently found some fungi while examining a bunch of sinks on the university’s Whiteknights campus. “It isn’t a big surprise to find fungi in a warm, wet environment. But sinks and P-traps have thus far been overlooked as potential reservoirs of these microorganisms,” they said in a written statement.

Samples collected from 289 P-traps contained “a very similar community of yeasts and molds, showing that sinks in use in public environments share a role as reservoirs of fungal organisms,” they noted.

The fungi living in the traps survived conditions with high temperatures, low pH, and little in the way of nutrients. So what were they eating? Some varieties, they said, “use detergents, found in soap, as a source of carbon-rich food.” We’ll repeat that last part: They used the soap as food.

WARNING: Rant Ahead.

There are a lot of cleaning products for sale that say they will make your home safe by killing 99.9% of germs and bacteria. Not fungi, exactly, but we’re still talking microorganisms. Molds, bacteria, and viruses are all stuff that can infect humans and make them sick.

So you kill 99.9% of them. Great, but that leaves 0.1% that you just made angry. And what do they do next? They learn to eat soap. Then University of Reading investigators find out that all the extra hand washing going on during the COVID-19 pandemic was “clogging up sinks with nasty disease-causing bacteria.”

These are microorganisms we’re talking about people. They’ve been at this for a billion years! Rats can’t beat them, cockroaches won’t stop them – Earth’s ultimate survivors are powerless against the invisible horde.

We’re doomed.

This transcript has been edited for clarity.

Drew Ramsey, MD: Welcome back, everyone. I’m Dr. Drew Ramsey. I’m on the editorial board with Medscape Psychiatry and I’m an assistant clinical professor of psychiatry at Columbia University. We have a special guest today.

I’m here with nutritionist Jessica Bayes, who’s at the University of Technology Sydney, and she’s the lead author of the AMMEND trial. [Editor’s note: Since completing her PhD, Bayes is now at Southern Cross University.] The AMMEND trial is our most recent trial in nutritional psychiatry, finding that giving or helping young men eat a Mediterranean diet can be helpful in the treatment of depression.

Jessica, welcome to Medscape.

Jessica Bayes, PhD: Thank you for having me.

The AMMEND Trial

Dr. Ramsey: Thank you for coming on board and helping all of us as clinicians understand some of your research and some of what is suggested by your research – that young men can change their diet and it helped their depression. Tell us a little bit about the AMMEND trial.

Dr. Bayes: The AMMEND trial was a 12-week randomized controlled trial in young men, 18-25 years old, who had diagnosed moderate to severe clinical depression. They had a poor baseline diet and we got them to eat a healthy Mediterranean diet, which improved their symptoms of depression.

Dr. Ramsey: It was a remarkable trial. Jessica, if I recall, you helped individuals improve the Mediterranean dietary pattern score by 8 points on a 14-point scale. That led to a 20-point reduction in their Beck Depression Inventory. Tell us what that looked like on the ground.

Dr. Bayes: It’s a huge improvement. Obviously, they were feeling much better in the end in terms of their depressive symptoms, but we also measured their energy, sleep, and quality of life. Many of them at the end were at a score cutoff that suggests no depression or in remission.

Dr. Ramsey: There were 72 people in your total trial, so 36% in your intervention arm went into full remission.

Dr. Bayes: Which is just amazing.

Dr. Ramsey: It also follows up the SMILES trial, which was a little bit of a different trial. You had two nutritional counseling sessions and the SMILES trial had seven, but in the SMILES trial, 32.3% of the patients went into full remission when they adopted a Mediterranean-style diet.

Jessica, what is the secret that you and your team know? I think many clinicians, especially clinicians who are parents and have teens, are kind of shaking their heads in disbelief. They’ve been telling their kids to eat healthy. What do you guys know about how to help young men change their diet?

How to Aid Adherence to Mediterranean Diet

Dr. Bayes: Prior to starting this, when I would say this idea to people, everyone would say, “Great idea. There’s no way you’re going to get depressed young men to change their diet. Not going to happen.” We went to them and we asked them. We said, “We’re going to do this study. What do you want from us? What resources would you need? How many appointments would you like? What’s too little or too many?”

We really got their feedback on board when we designed the study, and that obviously paid off. We had a personalized approach and we met them where they were at. We gave them the skills, resources, recipes, meal ideas – all those things – so we could really set them up to succeed.

Dr. Ramsey: You were telling me earlier about a few of the dietary changes that you felt made a big difference for these young men. What were those?

Dr. Bayes: Increasing the vegetables, olive oil, and legumes are probably the big ones that most of them were really not doing beforehand. They were really able to take that on board and make significant improvements in those areas.

Dr. Ramsey: These are really some of the top food categories in nutritional psychiatry as we think about how we help our efforts to improve mental health by thinking about nutrition, nutritional quality, and nutritional density. Certainly, those food categories – nuts and legumes, plants, and olive oil – are really what help get us there.

You also gave the students a food hamper. If you were going to be in charge of mental health in Australia and America and you got to give every college freshman a little box with a note, what would be in that box?

Dr. Bayes: I’d want to put everything in that box! It would be full of brightly colored fruits and vegetables, different nuts and seeds, and legumes. It would be full of recipes and ideas of how to cook things and how to prepare really delicious things. It would be full of different herbs and spices and all of those things to get people really excited about food.

Dr. Ramsey: Did the young men pick up on your enthusiasm and excitement around food? Did they begin to adopt some of that, shifting their view of how they saw the food and how they saw that it is related to their depression?

Dr. Bayes: Hopefully. I do think energy is infectious. I’m sure that played a role somewhat, but trying to get them excited about food can be really quite daunting, thinking, I’ve got to change my entire diet and I’ve got to learn to cook and go out and buy groceries. I don’t even know what to do with a piece of salmon. Trying to get them curious, interested, and just reminding them that it’s not all-or-nothing. Make small changes, give it a go, and have fun.

Dr. Ramsey: You also have a unique aspect of your research that you’re interested in male mental health, and that’s not something that’s been widely researched. Can you tell us a little bit about what these men were like in terms of coming into your trial as depressed young men?

Dr. Bayes: In the context of the COVID-19 pandemic, mental health was at the forefront of many people’s minds. They joined the study saying, “I’ve never seen anything like this before. I’ve never seen myself represented in research. I wanted to contribute. I want to add to that conversation because I feel like we are overlooked.”

Dr. Ramsey: I love hearing this notion that maybe young men aren’t quite who we think they are. They are wanting to be seen around their mental health. They can learn to use olive oil and to cook, and they can engage in mental health interventions that work. We just need to ask, give them some food, encourage them, and it makes a big difference.

Jessica Bayes, thank you so much for joining us and sharing some of your research. Everyone, it’s the AMMEND trial. We will drop a link to the trial below so you can take a peek and tell us what you think.

Please, in the comments, let us know what you think about this notion of helping young men with depression through nutritional interventions. Take a peek at the great work that Jessica and Professor Sibbritt from the University of Technology Sydney have published and put out into the scientific literature for us all.

Thanks so much, Jessica. I look forward to seeing you soon.

Dr. Bayes: Thank you.

Dr. Ramsey is assistant clinical professor, department of psychiatry, Columbia University, New York. He has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for InterContinental Hotels Group; National Kale Day 501(c)3. Received income in an amount equal to or greater than $250 from: Sharecare. Dr. Bayes is a postdoctoral research fellow; clinical nutritionist, Southern Cross University, National Center for Naturopathic Medicine, Lismore, New South Wales, Australia. She has disclosed the following relevant financial relationships: Received research grant from Endeavour College. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Drew Ramsey, MD: Welcome back, everyone. I’m Dr. Drew Ramsey. I’m on the editorial board with Medscape Psychiatry and I’m an assistant clinical professor of psychiatry at Columbia University. We have a special guest today.

I’m here with nutritionist Jessica Bayes, who’s at the University of Technology Sydney, and she’s the lead author of the AMMEND trial. [Editor’s note: Since completing her PhD, Bayes is now at Southern Cross University.] The AMMEND trial is our most recent trial in nutritional psychiatry, finding that giving or helping young men eat a Mediterranean diet can be helpful in the treatment of depression.

Jessica, welcome to Medscape.

Jessica Bayes, PhD: Thank you for having me.

The AMMEND Trial

Dr. Ramsey: Thank you for coming on board and helping all of us as clinicians understand some of your research and some of what is suggested by your research – that young men can change their diet and it helped their depression. Tell us a little bit about the AMMEND trial.

Dr. Bayes: The AMMEND trial was a 12-week randomized controlled trial in young men, 18-25 years old, who had diagnosed moderate to severe clinical depression. They had a poor baseline diet and we got them to eat a healthy Mediterranean diet, which improved their symptoms of depression.

Dr. Ramsey: It was a remarkable trial. Jessica, if I recall, you helped individuals improve the Mediterranean dietary pattern score by 8 points on a 14-point scale. That led to a 20-point reduction in their Beck Depression Inventory. Tell us what that looked like on the ground.

Dr. Bayes: It’s a huge improvement. Obviously, they were feeling much better in the end in terms of their depressive symptoms, but we also measured their energy, sleep, and quality of life. Many of them at the end were at a score cutoff that suggests no depression or in remission.

Dr. Ramsey: There were 72 people in your total trial, so 36% in your intervention arm went into full remission.

Dr. Bayes: Which is just amazing.

Dr. Ramsey: It also follows up the SMILES trial, which was a little bit of a different trial. You had two nutritional counseling sessions and the SMILES trial had seven, but in the SMILES trial, 32.3% of the patients went into full remission when they adopted a Mediterranean-style diet.

Jessica, what is the secret that you and your team know? I think many clinicians, especially clinicians who are parents and have teens, are kind of shaking their heads in disbelief. They’ve been telling their kids to eat healthy. What do you guys know about how to help young men change their diet?

How to Aid Adherence to Mediterranean Diet

Dr. Bayes: Prior to starting this, when I would say this idea to people, everyone would say, “Great idea. There’s no way you’re going to get depressed young men to change their diet. Not going to happen.” We went to them and we asked them. We said, “We’re going to do this study. What do you want from us? What resources would you need? How many appointments would you like? What’s too little or too many?”

We really got their feedback on board when we designed the study, and that obviously paid off. We had a personalized approach and we met them where they were at. We gave them the skills, resources, recipes, meal ideas – all those things – so we could really set them up to succeed.

Dr. Ramsey: You were telling me earlier about a few of the dietary changes that you felt made a big difference for these young men. What were those?

Dr. Bayes: Increasing the vegetables, olive oil, and legumes are probably the big ones that most of them were really not doing beforehand. They were really able to take that on board and make significant improvements in those areas.

Dr. Ramsey: These are really some of the top food categories in nutritional psychiatry as we think about how we help our efforts to improve mental health by thinking about nutrition, nutritional quality, and nutritional density. Certainly, those food categories – nuts and legumes, plants, and olive oil – are really what help get us there.

You also gave the students a food hamper. If you were going to be in charge of mental health in Australia and America and you got to give every college freshman a little box with a note, what would be in that box?

Dr. Bayes: I’d want to put everything in that box! It would be full of brightly colored fruits and vegetables, different nuts and seeds, and legumes. It would be full of recipes and ideas of how to cook things and how to prepare really delicious things. It would be full of different herbs and spices and all of those things to get people really excited about food.

Dr. Ramsey: Did the young men pick up on your enthusiasm and excitement around food? Did they begin to adopt some of that, shifting their view of how they saw the food and how they saw that it is related to their depression?

Dr. Bayes: Hopefully. I do think energy is infectious. I’m sure that played a role somewhat, but trying to get them excited about food can be really quite daunting, thinking, I’ve got to change my entire diet and I’ve got to learn to cook and go out and buy groceries. I don’t even know what to do with a piece of salmon. Trying to get them curious, interested, and just reminding them that it’s not all-or-nothing. Make small changes, give it a go, and have fun.

Dr. Ramsey: You also have a unique aspect of your research that you’re interested in male mental health, and that’s not something that’s been widely researched. Can you tell us a little bit about what these men were like in terms of coming into your trial as depressed young men?

Dr. Bayes: In the context of the COVID-19 pandemic, mental health was at the forefront of many people’s minds. They joined the study saying, “I’ve never seen anything like this before. I’ve never seen myself represented in research. I wanted to contribute. I want to add to that conversation because I feel like we are overlooked.”

Dr. Ramsey: I love hearing this notion that maybe young men aren’t quite who we think they are. They are wanting to be seen around their mental health. They can learn to use olive oil and to cook, and they can engage in mental health interventions that work. We just need to ask, give them some food, encourage them, and it makes a big difference.

Jessica Bayes, thank you so much for joining us and sharing some of your research. Everyone, it’s the AMMEND trial. We will drop a link to the trial below so you can take a peek and tell us what you think.

Please, in the comments, let us know what you think about this notion of helping young men with depression through nutritional interventions. Take a peek at the great work that Jessica and Professor Sibbritt from the University of Technology Sydney have published and put out into the scientific literature for us all.

Thanks so much, Jessica. I look forward to seeing you soon.

Dr. Bayes: Thank you.

Dr. Ramsey is assistant clinical professor, department of psychiatry, Columbia University, New York. He has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for InterContinental Hotels Group; National Kale Day 501(c)3. Received income in an amount equal to or greater than $250 from: Sharecare. Dr. Bayes is a postdoctoral research fellow; clinical nutritionist, Southern Cross University, National Center for Naturopathic Medicine, Lismore, New South Wales, Australia. She has disclosed the following relevant financial relationships: Received research grant from Endeavour College. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Drew Ramsey, MD: Welcome back, everyone. I’m Dr. Drew Ramsey. I’m on the editorial board with Medscape Psychiatry and I’m an assistant clinical professor of psychiatry at Columbia University. We have a special guest today.

I’m here with nutritionist Jessica Bayes, who’s at the University of Technology Sydney, and she’s the lead author of the AMMEND trial. [Editor’s note: Since completing her PhD, Bayes is now at Southern Cross University.] The AMMEND trial is our most recent trial in nutritional psychiatry, finding that giving or helping young men eat a Mediterranean diet can be helpful in the treatment of depression.

Jessica, welcome to Medscape.

Jessica Bayes, PhD: Thank you for having me.

The AMMEND Trial

Dr. Ramsey: Thank you for coming on board and helping all of us as clinicians understand some of your research and some of what is suggested by your research – that young men can change their diet and it helped their depression. Tell us a little bit about the AMMEND trial.

Dr. Bayes: The AMMEND trial was a 12-week randomized controlled trial in young men, 18-25 years old, who had diagnosed moderate to severe clinical depression. They had a poor baseline diet and we got them to eat a healthy Mediterranean diet, which improved their symptoms of depression.

Dr. Ramsey: It was a remarkable trial. Jessica, if I recall, you helped individuals improve the Mediterranean dietary pattern score by 8 points on a 14-point scale. That led to a 20-point reduction in their Beck Depression Inventory. Tell us what that looked like on the ground.

Dr. Bayes: It’s a huge improvement. Obviously, they were feeling much better in the end in terms of their depressive symptoms, but we also measured their energy, sleep, and quality of life. Many of them at the end were at a score cutoff that suggests no depression or in remission.

Dr. Ramsey: There were 72 people in your total trial, so 36% in your intervention arm went into full remission.

Dr. Bayes: Which is just amazing.

Dr. Ramsey: It also follows up the SMILES trial, which was a little bit of a different trial. You had two nutritional counseling sessions and the SMILES trial had seven, but in the SMILES trial, 32.3% of the patients went into full remission when they adopted a Mediterranean-style diet.

Jessica, what is the secret that you and your team know? I think many clinicians, especially clinicians who are parents and have teens, are kind of shaking their heads in disbelief. They’ve been telling their kids to eat healthy. What do you guys know about how to help young men change their diet?

How to Aid Adherence to Mediterranean Diet

Dr. Bayes: Prior to starting this, when I would say this idea to people, everyone would say, “Great idea. There’s no way you’re going to get depressed young men to change their diet. Not going to happen.” We went to them and we asked them. We said, “We’re going to do this study. What do you want from us? What resources would you need? How many appointments would you like? What’s too little or too many?”

We really got their feedback on board when we designed the study, and that obviously paid off. We had a personalized approach and we met them where they were at. We gave them the skills, resources, recipes, meal ideas – all those things – so we could really set them up to succeed.

Dr. Ramsey: You were telling me earlier about a few of the dietary changes that you felt made a big difference for these young men. What were those?

Dr. Bayes: Increasing the vegetables, olive oil, and legumes are probably the big ones that most of them were really not doing beforehand. They were really able to take that on board and make significant improvements in those areas.

Dr. Ramsey: These are really some of the top food categories in nutritional psychiatry as we think about how we help our efforts to improve mental health by thinking about nutrition, nutritional quality, and nutritional density. Certainly, those food categories – nuts and legumes, plants, and olive oil – are really what help get us there.

You also gave the students a food hamper. If you were going to be in charge of mental health in Australia and America and you got to give every college freshman a little box with a note, what would be in that box?

Dr. Bayes: I’d want to put everything in that box! It would be full of brightly colored fruits and vegetables, different nuts and seeds, and legumes. It would be full of recipes and ideas of how to cook things and how to prepare really delicious things. It would be full of different herbs and spices and all of those things to get people really excited about food.

Dr. Ramsey: Did the young men pick up on your enthusiasm and excitement around food? Did they begin to adopt some of that, shifting their view of how they saw the food and how they saw that it is related to their depression?

Dr. Bayes: Hopefully. I do think energy is infectious. I’m sure that played a role somewhat, but trying to get them excited about food can be really quite daunting, thinking, I’ve got to change my entire diet and I’ve got to learn to cook and go out and buy groceries. I don’t even know what to do with a piece of salmon. Trying to get them curious, interested, and just reminding them that it’s not all-or-nothing. Make small changes, give it a go, and have fun.

Dr. Ramsey: You also have a unique aspect of your research that you’re interested in male mental health, and that’s not something that’s been widely researched. Can you tell us a little bit about what these men were like in terms of coming into your trial as depressed young men?

Dr. Bayes: In the context of the COVID-19 pandemic, mental health was at the forefront of many people’s minds. They joined the study saying, “I’ve never seen anything like this before. I’ve never seen myself represented in research. I wanted to contribute. I want to add to that conversation because I feel like we are overlooked.”

Dr. Ramsey: I love hearing this notion that maybe young men aren’t quite who we think they are. They are wanting to be seen around their mental health. They can learn to use olive oil and to cook, and they can engage in mental health interventions that work. We just need to ask, give them some food, encourage them, and it makes a big difference.

Jessica Bayes, thank you so much for joining us and sharing some of your research. Everyone, it’s the AMMEND trial. We will drop a link to the trial below so you can take a peek and tell us what you think.

Please, in the comments, let us know what you think about this notion of helping young men with depression through nutritional interventions. Take a peek at the great work that Jessica and Professor Sibbritt from the University of Technology Sydney have published and put out into the scientific literature for us all.

Thanks so much, Jessica. I look forward to seeing you soon.

Dr. Bayes: Thank you.

Dr. Ramsey is assistant clinical professor, department of psychiatry, Columbia University, New York. He has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for InterContinental Hotels Group; National Kale Day 501(c)3. Received income in an amount equal to or greater than $250 from: Sharecare. Dr. Bayes is a postdoctoral research fellow; clinical nutritionist, Southern Cross University, National Center for Naturopathic Medicine, Lismore, New South Wales, Australia. She has disclosed the following relevant financial relationships: Received research grant from Endeavour College. A version of this article first appeared on Medscape.com.