Mental Health

High plasma concentrations of buprenorphine may reduce fentanyl-induced respiratory depression, new research suggests.

The primary endpoint measure in a small “proof of principal” pharmacology study was effect of escalating fentanyl dosing on respiratory depression by way of decreased isohypercapnic minute ventilation (VE) – or volume of gas inhaled or exhaled per minute from the lungs.

sdominick/iStock/Getty Images

Results showed the maximum decrease in highest-dose fentanyl-induced VE was almost 50% less for opioid-tolerant patients receiving a 2.0 ng/mL concentration of steady-state plasma buprenorphine than when receiving matching placebo.

Risk for apnea requiring stimulation after fentanyl dosing was also significantly lower with buprenorphine.

“Even though the study is small, a lot of data were collected which will allow us to very accurately predict which plasma concentrations, and therefore drug doses, are needed to protect people adequately in practice,” study coinvestigator Geert Jan Groeneveld, MD, PhD, neurologist and clinical pharmacologist at the Centre for Human Drug Research, Leiden, the Netherlands, and professor of clinical neuropharmacology at Leiden University Medical Center, told this news organization.

He added the “beautiful results” were in line with what the researchers expected and although further research is needed, the study provides a lot of useful information for clinicians.

“I think this is an approach that works, and this study makes that clear,” Dr. Groeneveld added.

The findings were published online Jan. 27, 2022, in PLoS One.
 

High death rate from synthetic opioids

A recent report from the Centers for Disease Control and Prevention noted that, between June 2020 and June 2021, there were more than 100,000 drug overdose deaths in the United States. Of these, more than 73,000 were attributed to opioids and more than 60,000 to synthetic opioids such as fentanyl.

Most opioid-related overdose deaths in the United States are attributable to synthetic opioids “that can unexpectedly cause respiratory depression by being ingested as a substitute for heroin or with [other] drugs,” Indivior noted in a press release.

Buprenorphine is a partial agonist that “binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects,” the investigators wrote.

As reported by this news organization, the Food and Drug Administration approved buprenorphine extended release (Sublocade, Indivior) in 2017 as the first once-monthly injection for the treatment of opioid use disorder.

In the current study, which was conducted in Leiden, the Netherlands, the investigators used continuous intravenous buprenorphine in order to “mimic” the sustained plasma concentrations of the drug that can be delivered with the long-acting injectable, noted Christian Heidbreder, PhD, chief scientific officer at Indivior.

“This was an experimental medicine study, whereby we used intravenous buprenorphine to really understand the interaction with escalating doses of fentanyl” on respiratory depression, he told this news organization.
 

Two-part, two-period study

In part A, period one of the two-period crossover study, 14 healthy volunteers were randomly assigned to receive for 360 minutes continuous infusion of 0.02 or 0.05 mg/70 kg per hour of buprenorphine to target plasma concentrations of 0.2 or 0.5 ng/mL, respectively, or matching placebo. In the second period, participants received the alternative infusion – either placebo or the active drug.

In part B, eight opioid-tolerant patients who had used high-dose opioids for at least 3 months prior received a higher infusion rate of 0.1, 0.2, or 0.5 mg/70 kg per hour to target plasma concentrations of 1, 2, or 5 ng/mL, respectively.

The 2 ng/mL “is a very important threshold for us” and the result from several previous experiments, Dr. Heidbreder noted. So the investigators targeted that concentration as well as one below and one “much higher” in the current study.

“Because tolerance to opioid effects is poorly characterized in patients receiving long-term opioids, opioid-tolerant participants in part B had a fixed treatment sequence, receiving placebo infusion plus fentanyl challenges in period 1 to optimize the fentanyl dose escalation before buprenorphine and fentanyl were coadministered in period 2,” the investigators reported.

All participants received up to four escalating doses of intravenous fentanyl after reaching target buprenorphine plasma concentrations.

For healthy volunteers, the planned fentanyl doses were 0.075, 0.15, 0.25, and 0.35 mg/70 kg. For the opioid-tolerant patients, the doses were 0.25, 0.35, 0.5, and 0.7 mg/70 kg.

The infusions began after baseline VE had stabilized at 20 plus or minus 2 L/min, which is about four times above normal resting VE.
 

First clinical evidence?

Results showed fentanyl-induced adverse changes in VE were less at higher concentrations of buprenorphine plasma.

Opioid-tolerant patients receiving the 2.0 ng/mL concentration of buprenorphine had a 33.7% decrease in highest dose fentanyl-induced VE versus an 82.3% decrease when receiving placebo.

In addition, fentanyl reduced VE up to 49% (95% confidence interval, 21%-76%) in opioid-tolerant patients in all buprenorphine concentration groups combined versus reducing VE up to 100% (95% CI, 68%-132%) during placebo infusion (P = .006).

In addition, buprenorphine was associated with a lower risk versus placebo for apnea requiring verbal stimulation after fentanyl dosing (odds ratio, 0.07; P = .001).

For the healthy volunteers, the first fentanyl bolus reduced VE by 26% for those at target buprenorphine concentration of 0.5 ng/mL versus 51% when receiving placebo (P = .001). The second bolus reduced VE by 47% versus 79%, respectively (P < .001).

“Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection,” the investigators reported.

Overall, the findings “provide the first clinical evidence that high sustained plasma concentrations of buprenorphine may protect against respiratory depression induced by potent opioids,” they added.

Additional research is now “warranted to assess the competitive interaction of buprenorphine and fentanyl (as well as other illicitly manufactured fentanyl analogs) as we continue to deepen our understanding of buprenorphine as an evidence-based treatment for patients struggling with opioid use disorder,” Dr. Heidbreder said in a press release.

It’s unclear whether the study’s findings are generalizable to other populations, said Dr. Heidbreder.

“So what we are going to do next is to see what is actually happening in a real world, much broader patient population; and for that we’ll be using [the injectable] Sublocade as the medication of choice,” said Dr. Heidbreder.

“Conceptually, we feel confident about these data, but now we need to demonstrate what is happening in the real world,” he added.

The study was funded by Indivior. Dr. Groeneveld has reported no relevant financial relationships. Dr. Heidbreder is an employee of Indivior.

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

High plasma concentrations of buprenorphine may reduce fentanyl-induced respiratory depression, new research suggests.

The primary endpoint measure in a small “proof of principal” pharmacology study was effect of escalating fentanyl dosing on respiratory depression by way of decreased isohypercapnic minute ventilation (VE) – or volume of gas inhaled or exhaled per minute from the lungs.

sdominick/iStock/Getty Images

Results showed the maximum decrease in highest-dose fentanyl-induced VE was almost 50% less for opioid-tolerant patients receiving a 2.0 ng/mL concentration of steady-state plasma buprenorphine than when receiving matching placebo.

Risk for apnea requiring stimulation after fentanyl dosing was also significantly lower with buprenorphine.

“Even though the study is small, a lot of data were collected which will allow us to very accurately predict which plasma concentrations, and therefore drug doses, are needed to protect people adequately in practice,” study coinvestigator Geert Jan Groeneveld, MD, PhD, neurologist and clinical pharmacologist at the Centre for Human Drug Research, Leiden, the Netherlands, and professor of clinical neuropharmacology at Leiden University Medical Center, told this news organization.

He added the “beautiful results” were in line with what the researchers expected and although further research is needed, the study provides a lot of useful information for clinicians.

“I think this is an approach that works, and this study makes that clear,” Dr. Groeneveld added.

The findings were published online Jan. 27, 2022, in PLoS One.
 

High death rate from synthetic opioids

A recent report from the Centers for Disease Control and Prevention noted that, between June 2020 and June 2021, there were more than 100,000 drug overdose deaths in the United States. Of these, more than 73,000 were attributed to opioids and more than 60,000 to synthetic opioids such as fentanyl.

Most opioid-related overdose deaths in the United States are attributable to synthetic opioids “that can unexpectedly cause respiratory depression by being ingested as a substitute for heroin or with [other] drugs,” Indivior noted in a press release.

Buprenorphine is a partial agonist that “binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects,” the investigators wrote.

As reported by this news organization, the Food and Drug Administration approved buprenorphine extended release (Sublocade, Indivior) in 2017 as the first once-monthly injection for the treatment of opioid use disorder.

In the current study, which was conducted in Leiden, the Netherlands, the investigators used continuous intravenous buprenorphine in order to “mimic” the sustained plasma concentrations of the drug that can be delivered with the long-acting injectable, noted Christian Heidbreder, PhD, chief scientific officer at Indivior.

“This was an experimental medicine study, whereby we used intravenous buprenorphine to really understand the interaction with escalating doses of fentanyl” on respiratory depression, he told this news organization.
 

Two-part, two-period study

In part A, period one of the two-period crossover study, 14 healthy volunteers were randomly assigned to receive for 360 minutes continuous infusion of 0.02 or 0.05 mg/70 kg per hour of buprenorphine to target plasma concentrations of 0.2 or 0.5 ng/mL, respectively, or matching placebo. In the second period, participants received the alternative infusion – either placebo or the active drug.

In part B, eight opioid-tolerant patients who had used high-dose opioids for at least 3 months prior received a higher infusion rate of 0.1, 0.2, or 0.5 mg/70 kg per hour to target plasma concentrations of 1, 2, or 5 ng/mL, respectively.

The 2 ng/mL “is a very important threshold for us” and the result from several previous experiments, Dr. Heidbreder noted. So the investigators targeted that concentration as well as one below and one “much higher” in the current study.

“Because tolerance to opioid effects is poorly characterized in patients receiving long-term opioids, opioid-tolerant participants in part B had a fixed treatment sequence, receiving placebo infusion plus fentanyl challenges in period 1 to optimize the fentanyl dose escalation before buprenorphine and fentanyl were coadministered in period 2,” the investigators reported.

All participants received up to four escalating doses of intravenous fentanyl after reaching target buprenorphine plasma concentrations.

For healthy volunteers, the planned fentanyl doses were 0.075, 0.15, 0.25, and 0.35 mg/70 kg. For the opioid-tolerant patients, the doses were 0.25, 0.35, 0.5, and 0.7 mg/70 kg.

The infusions began after baseline VE had stabilized at 20 plus or minus 2 L/min, which is about four times above normal resting VE.
 

First clinical evidence?

Results showed fentanyl-induced adverse changes in VE were less at higher concentrations of buprenorphine plasma.

Opioid-tolerant patients receiving the 2.0 ng/mL concentration of buprenorphine had a 33.7% decrease in highest dose fentanyl-induced VE versus an 82.3% decrease when receiving placebo.

In addition, fentanyl reduced VE up to 49% (95% confidence interval, 21%-76%) in opioid-tolerant patients in all buprenorphine concentration groups combined versus reducing VE up to 100% (95% CI, 68%-132%) during placebo infusion (P = .006).

In addition, buprenorphine was associated with a lower risk versus placebo for apnea requiring verbal stimulation after fentanyl dosing (odds ratio, 0.07; P = .001).

For the healthy volunteers, the first fentanyl bolus reduced VE by 26% for those at target buprenorphine concentration of 0.5 ng/mL versus 51% when receiving placebo (P = .001). The second bolus reduced VE by 47% versus 79%, respectively (P < .001).

“Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection,” the investigators reported.

Overall, the findings “provide the first clinical evidence that high sustained plasma concentrations of buprenorphine may protect against respiratory depression induced by potent opioids,” they added.

Additional research is now “warranted to assess the competitive interaction of buprenorphine and fentanyl (as well as other illicitly manufactured fentanyl analogs) as we continue to deepen our understanding of buprenorphine as an evidence-based treatment for patients struggling with opioid use disorder,” Dr. Heidbreder said in a press release.

It’s unclear whether the study’s findings are generalizable to other populations, said Dr. Heidbreder.

“So what we are going to do next is to see what is actually happening in a real world, much broader patient population; and for that we’ll be using [the injectable] Sublocade as the medication of choice,” said Dr. Heidbreder.

“Conceptually, we feel confident about these data, but now we need to demonstrate what is happening in the real world,” he added.

The study was funded by Indivior. Dr. Groeneveld has reported no relevant financial relationships. Dr. Heidbreder is an employee of Indivior.

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

High plasma concentrations of buprenorphine may reduce fentanyl-induced respiratory depression, new research suggests.

The primary endpoint measure in a small “proof of principal” pharmacology study was effect of escalating fentanyl dosing on respiratory depression by way of decreased isohypercapnic minute ventilation (VE) – or volume of gas inhaled or exhaled per minute from the lungs.

sdominick/iStock/Getty Images

Results showed the maximum decrease in highest-dose fentanyl-induced VE was almost 50% less for opioid-tolerant patients receiving a 2.0 ng/mL concentration of steady-state plasma buprenorphine than when receiving matching placebo.

Risk for apnea requiring stimulation after fentanyl dosing was also significantly lower with buprenorphine.

“Even though the study is small, a lot of data were collected which will allow us to very accurately predict which plasma concentrations, and therefore drug doses, are needed to protect people adequately in practice,” study coinvestigator Geert Jan Groeneveld, MD, PhD, neurologist and clinical pharmacologist at the Centre for Human Drug Research, Leiden, the Netherlands, and professor of clinical neuropharmacology at Leiden University Medical Center, told this news organization.

He added the “beautiful results” were in line with what the researchers expected and although further research is needed, the study provides a lot of useful information for clinicians.

“I think this is an approach that works, and this study makes that clear,” Dr. Groeneveld added.

The findings were published online Jan. 27, 2022, in PLoS One.
 

High death rate from synthetic opioids

A recent report from the Centers for Disease Control and Prevention noted that, between June 2020 and June 2021, there were more than 100,000 drug overdose deaths in the United States. Of these, more than 73,000 were attributed to opioids and more than 60,000 to synthetic opioids such as fentanyl.

Most opioid-related overdose deaths in the United States are attributable to synthetic opioids “that can unexpectedly cause respiratory depression by being ingested as a substitute for heroin or with [other] drugs,” Indivior noted in a press release.

Buprenorphine is a partial agonist that “binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects,” the investigators wrote.

As reported by this news organization, the Food and Drug Administration approved buprenorphine extended release (Sublocade, Indivior) in 2017 as the first once-monthly injection for the treatment of opioid use disorder.

In the current study, which was conducted in Leiden, the Netherlands, the investigators used continuous intravenous buprenorphine in order to “mimic” the sustained plasma concentrations of the drug that can be delivered with the long-acting injectable, noted Christian Heidbreder, PhD, chief scientific officer at Indivior.

“This was an experimental medicine study, whereby we used intravenous buprenorphine to really understand the interaction with escalating doses of fentanyl” on respiratory depression, he told this news organization.
 

Two-part, two-period study

In part A, period one of the two-period crossover study, 14 healthy volunteers were randomly assigned to receive for 360 minutes continuous infusion of 0.02 or 0.05 mg/70 kg per hour of buprenorphine to target plasma concentrations of 0.2 or 0.5 ng/mL, respectively, or matching placebo. In the second period, participants received the alternative infusion – either placebo or the active drug.

In part B, eight opioid-tolerant patients who had used high-dose opioids for at least 3 months prior received a higher infusion rate of 0.1, 0.2, or 0.5 mg/70 kg per hour to target plasma concentrations of 1, 2, or 5 ng/mL, respectively.

The 2 ng/mL “is a very important threshold for us” and the result from several previous experiments, Dr. Heidbreder noted. So the investigators targeted that concentration as well as one below and one “much higher” in the current study.

“Because tolerance to opioid effects is poorly characterized in patients receiving long-term opioids, opioid-tolerant participants in part B had a fixed treatment sequence, receiving placebo infusion plus fentanyl challenges in period 1 to optimize the fentanyl dose escalation before buprenorphine and fentanyl were coadministered in period 2,” the investigators reported.

All participants received up to four escalating doses of intravenous fentanyl after reaching target buprenorphine plasma concentrations.

For healthy volunteers, the planned fentanyl doses were 0.075, 0.15, 0.25, and 0.35 mg/70 kg. For the opioid-tolerant patients, the doses were 0.25, 0.35, 0.5, and 0.7 mg/70 kg.

The infusions began after baseline VE had stabilized at 20 plus or minus 2 L/min, which is about four times above normal resting VE.
 

First clinical evidence?

Results showed fentanyl-induced adverse changes in VE were less at higher concentrations of buprenorphine plasma.

Opioid-tolerant patients receiving the 2.0 ng/mL concentration of buprenorphine had a 33.7% decrease in highest dose fentanyl-induced VE versus an 82.3% decrease when receiving placebo.

In addition, fentanyl reduced VE up to 49% (95% confidence interval, 21%-76%) in opioid-tolerant patients in all buprenorphine concentration groups combined versus reducing VE up to 100% (95% CI, 68%-132%) during placebo infusion (P = .006).

In addition, buprenorphine was associated with a lower risk versus placebo for apnea requiring verbal stimulation after fentanyl dosing (odds ratio, 0.07; P = .001).

For the healthy volunteers, the first fentanyl bolus reduced VE by 26% for those at target buprenorphine concentration of 0.5 ng/mL versus 51% when receiving placebo (P = .001). The second bolus reduced VE by 47% versus 79%, respectively (P < .001).

“Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection,” the investigators reported.

Overall, the findings “provide the first clinical evidence that high sustained plasma concentrations of buprenorphine may protect against respiratory depression induced by potent opioids,” they added.

Additional research is now “warranted to assess the competitive interaction of buprenorphine and fentanyl (as well as other illicitly manufactured fentanyl analogs) as we continue to deepen our understanding of buprenorphine as an evidence-based treatment for patients struggling with opioid use disorder,” Dr. Heidbreder said in a press release.

It’s unclear whether the study’s findings are generalizable to other populations, said Dr. Heidbreder.

“So what we are going to do next is to see what is actually happening in a real world, much broader patient population; and for that we’ll be using [the injectable] Sublocade as the medication of choice,” said Dr. Heidbreder.

“Conceptually, we feel confident about these data, but now we need to demonstrate what is happening in the real world,” he added.

The study was funded by Indivior. Dr. Groeneveld has reported no relevant financial relationships. Dr. Heidbreder is an employee of Indivior.

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

I’m in a crowded commercial kitchen, and everywhere I look I see bottles of colorful drinks and jars holding faded vegetables suspended in brine. The smell of fermented cabbage permeates the room. I open a mason jar, which lets out a loud hiss. I’d spent months researching the gut-brain axis during my PhD, hoping to understand the role that fermented food may play in our mental health. So I enrolled in a class on how to make fermented foods.

The teacher is praising these ancient foods as a magical cure for every ailment you can imagine. I’m uncomfortable – not because of the smell, but because I’ve never found a scientific article that definitively supported this idea. I’m subconsciously applying a fact filter and wondering what the other unsuspecting students must think. I let this slide, since I’m here to learn the art of fermentation. I bravely take a spoonful of sauerkraut. The salty brine overwhelms my senses. Gulp!

If you’ve ever eaten sauerkraut, kimchi, tempeh, kombucha, or kefir, then you’ve had a fermented food (or drink). The first time I gave them a proper go (with a mind open to enjoying them), I noticed the sour, vinegar-like taste and the noticeable absence of sugar. It didn’t take me long to get used to the taste. After a while of drinking my bubbly kombucha, I noticed that my palate had adapted and sweet flavors felt overpowering.

Fermentation is a natural process of curdling or culturing that has been used for thousands of years to preserve foods. Fermented foods and drinks are made through “desired microbial growth and enzymatic conversions of food components” (as opposed to undesirable microbial growth, which happens when your food spoils). Fermented foods are made either by the bacteria and yeast already present in the environment/food material or by introducing bacteria or yeast to help start the fermentation process.

For example, when I made sauerkraut, I shredded the cabbage, added salt, then pummeled and squeezed the cabbage until it released its own juices, which also allowed the “probiotic” lactic acid bacteria in the cabbage to kickstart the fermentation process. Probiotic bacteria like Lactobacillus and Bifidobacterium are considered probiotic good bugs, and are also present in many yogurts and cheeses.

We can’t necessarily call our sauerkraut a “probiotic food” because we don’t know the exact probiotic strains that are in our sauerkraut and whether they are present in the correct “probiotic” dose. It’s also worth noting that foods and drinks that are produced by fermentation don’t necessarily need to have live bacteria in them when you eat them to still be considered a fermented food. For example, sourdough is born from a bubbly live starter culture that contains yeast and bacteria, but once cooked it might no longer have any live bacteria in it.

So, what about the health claims?

Microbial fermentation may interact with health through multiple different biological pathways. It can enhance the nutritional composition of the final food, create bioactive compounds, and change the composition of the gut microbiota (potentially outcompeting harmful pathogens). The lactic acid bacteria in fermented food might also help to influence your immune system and strengthen your intestinal barrier. Some fermented foods, like tempeh, also contain prebiotics; these are fibers that escape your digestion and are broken down by your gut bacteria, including your lactic acid bacteria, which feed off prebiotic fiber to help grow their colonies. In a recent diet experiment, a high-fiber diet was compared with a diet high in fermented foods (eg, yogurt, fermented vegetables, kefir, fermented cheese); those who ate higher fermented food had lower markers of inflammation and an increased diversity of gut microbiota (which is thought to be a good thing in adults). So, in theory, fermented foods sound good.

Still wanting to understand more, and dispel a few myths, a team of researchers and I investigated what’s known about the link between fermented foods and mental health. We looked at the pathways by which fermented foods might affect mental health, such as by reducing inflammation and strengthening the intestinal barrier. These pathways are relevant because they might reduce your brain’s exposure to certain inflammatory molecules that can impact brain function and mental health.

Fermented foods also contain neurotransmitters that are important to mental health. Research about fermented food and mental health is still in its early infancy. Animal studies provide experimental evidence that fermented foods can help with symptoms of depression and anxiety – but that’s in animals. The problem is in knowing how the animal findings relate to our human experience.

We found eight studies in humans that experimented with fermented foods (for example, fermented milk products) to measure their impact on depression, anxiety, and stress in adults, but the studies were all so different that we were unable to make firm conclusions. It is still difficult to know what the active ingredient in fermented foods is. Is it the microbes? Is it the byproducts? Is it the nutrition? And how much of each is needed, and what are safe levels of each? We really need more studies, with detailed descriptions of exactly what is in each food being tested. At this stage, there is not enough human evidence to make firm clinical recommendations for eating fermented food to improve mental health symptoms.

I’ve since moved on from sauerkraut to making sourdough bread as a COVID lockdown project (as this involves a fermented starter culture). When my delicious fresh bread comes out of the oven, my world is paused for a few minutes, and my family mill around to enjoy the warm, fresh bread. While it may be too soon to tell whether fermented foods help our mental health, my sourdough itself has sure helped us.

Dr. Dawson is a nutritionist and bioinformatician research fellow at the Food & Mood Centre at Deakin University, Geelong, Australia. She disclosed no relevant financial relationships.

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

I’m in a crowded commercial kitchen, and everywhere I look I see bottles of colorful drinks and jars holding faded vegetables suspended in brine. The smell of fermented cabbage permeates the room. I open a mason jar, which lets out a loud hiss. I’d spent months researching the gut-brain axis during my PhD, hoping to understand the role that fermented food may play in our mental health. So I enrolled in a class on how to make fermented foods.

The teacher is praising these ancient foods as a magical cure for every ailment you can imagine. I’m uncomfortable – not because of the smell, but because I’ve never found a scientific article that definitively supported this idea. I’m subconsciously applying a fact filter and wondering what the other unsuspecting students must think. I let this slide, since I’m here to learn the art of fermentation. I bravely take a spoonful of sauerkraut. The salty brine overwhelms my senses. Gulp!

If you’ve ever eaten sauerkraut, kimchi, tempeh, kombucha, or kefir, then you’ve had a fermented food (or drink). The first time I gave them a proper go (with a mind open to enjoying them), I noticed the sour, vinegar-like taste and the noticeable absence of sugar. It didn’t take me long to get used to the taste. After a while of drinking my bubbly kombucha, I noticed that my palate had adapted and sweet flavors felt overpowering.

Fermentation is a natural process of curdling or culturing that has been used for thousands of years to preserve foods. Fermented foods and drinks are made through “desired microbial growth and enzymatic conversions of food components” (as opposed to undesirable microbial growth, which happens when your food spoils). Fermented foods are made either by the bacteria and yeast already present in the environment/food material or by introducing bacteria or yeast to help start the fermentation process.

For example, when I made sauerkraut, I shredded the cabbage, added salt, then pummeled and squeezed the cabbage until it released its own juices, which also allowed the “probiotic” lactic acid bacteria in the cabbage to kickstart the fermentation process. Probiotic bacteria like Lactobacillus and Bifidobacterium are considered probiotic good bugs, and are also present in many yogurts and cheeses.

We can’t necessarily call our sauerkraut a “probiotic food” because we don’t know the exact probiotic strains that are in our sauerkraut and whether they are present in the correct “probiotic” dose. It’s also worth noting that foods and drinks that are produced by fermentation don’t necessarily need to have live bacteria in them when you eat them to still be considered a fermented food. For example, sourdough is born from a bubbly live starter culture that contains yeast and bacteria, but once cooked it might no longer have any live bacteria in it.

So, what about the health claims?

Microbial fermentation may interact with health through multiple different biological pathways. It can enhance the nutritional composition of the final food, create bioactive compounds, and change the composition of the gut microbiota (potentially outcompeting harmful pathogens). The lactic acid bacteria in fermented food might also help to influence your immune system and strengthen your intestinal barrier. Some fermented foods, like tempeh, also contain prebiotics; these are fibers that escape your digestion and are broken down by your gut bacteria, including your lactic acid bacteria, which feed off prebiotic fiber to help grow their colonies. In a recent diet experiment, a high-fiber diet was compared with a diet high in fermented foods (eg, yogurt, fermented vegetables, kefir, fermented cheese); those who ate higher fermented food had lower markers of inflammation and an increased diversity of gut microbiota (which is thought to be a good thing in adults). So, in theory, fermented foods sound good.

Still wanting to understand more, and dispel a few myths, a team of researchers and I investigated what’s known about the link between fermented foods and mental health. We looked at the pathways by which fermented foods might affect mental health, such as by reducing inflammation and strengthening the intestinal barrier. These pathways are relevant because they might reduce your brain’s exposure to certain inflammatory molecules that can impact brain function and mental health.

Fermented foods also contain neurotransmitters that are important to mental health. Research about fermented food and mental health is still in its early infancy. Animal studies provide experimental evidence that fermented foods can help with symptoms of depression and anxiety – but that’s in animals. The problem is in knowing how the animal findings relate to our human experience.

We found eight studies in humans that experimented with fermented foods (for example, fermented milk products) to measure their impact on depression, anxiety, and stress in adults, but the studies were all so different that we were unable to make firm conclusions. It is still difficult to know what the active ingredient in fermented foods is. Is it the microbes? Is it the byproducts? Is it the nutrition? And how much of each is needed, and what are safe levels of each? We really need more studies, with detailed descriptions of exactly what is in each food being tested. At this stage, there is not enough human evidence to make firm clinical recommendations for eating fermented food to improve mental health symptoms.

I’ve since moved on from sauerkraut to making sourdough bread as a COVID lockdown project (as this involves a fermented starter culture). When my delicious fresh bread comes out of the oven, my world is paused for a few minutes, and my family mill around to enjoy the warm, fresh bread. While it may be too soon to tell whether fermented foods help our mental health, my sourdough itself has sure helped us.

Dr. Dawson is a nutritionist and bioinformatician research fellow at the Food & Mood Centre at Deakin University, Geelong, Australia. She disclosed no relevant financial relationships.

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

I’m in a crowded commercial kitchen, and everywhere I look I see bottles of colorful drinks and jars holding faded vegetables suspended in brine. The smell of fermented cabbage permeates the room. I open a mason jar, which lets out a loud hiss. I’d spent months researching the gut-brain axis during my PhD, hoping to understand the role that fermented food may play in our mental health. So I enrolled in a class on how to make fermented foods.

The teacher is praising these ancient foods as a magical cure for every ailment you can imagine. I’m uncomfortable – not because of the smell, but because I’ve never found a scientific article that definitively supported this idea. I’m subconsciously applying a fact filter and wondering what the other unsuspecting students must think. I let this slide, since I’m here to learn the art of fermentation. I bravely take a spoonful of sauerkraut. The salty brine overwhelms my senses. Gulp!

If you’ve ever eaten sauerkraut, kimchi, tempeh, kombucha, or kefir, then you’ve had a fermented food (or drink). The first time I gave them a proper go (with a mind open to enjoying them), I noticed the sour, vinegar-like taste and the noticeable absence of sugar. It didn’t take me long to get used to the taste. After a while of drinking my bubbly kombucha, I noticed that my palate had adapted and sweet flavors felt overpowering.

Fermentation is a natural process of curdling or culturing that has been used for thousands of years to preserve foods. Fermented foods and drinks are made through “desired microbial growth and enzymatic conversions of food components” (as opposed to undesirable microbial growth, which happens when your food spoils). Fermented foods are made either by the bacteria and yeast already present in the environment/food material or by introducing bacteria or yeast to help start the fermentation process.

For example, when I made sauerkraut, I shredded the cabbage, added salt, then pummeled and squeezed the cabbage until it released its own juices, which also allowed the “probiotic” lactic acid bacteria in the cabbage to kickstart the fermentation process. Probiotic bacteria like Lactobacillus and Bifidobacterium are considered probiotic good bugs, and are also present in many yogurts and cheeses.

We can’t necessarily call our sauerkraut a “probiotic food” because we don’t know the exact probiotic strains that are in our sauerkraut and whether they are present in the correct “probiotic” dose. It’s also worth noting that foods and drinks that are produced by fermentation don’t necessarily need to have live bacteria in them when you eat them to still be considered a fermented food. For example, sourdough is born from a bubbly live starter culture that contains yeast and bacteria, but once cooked it might no longer have any live bacteria in it.

So, what about the health claims?

Microbial fermentation may interact with health through multiple different biological pathways. It can enhance the nutritional composition of the final food, create bioactive compounds, and change the composition of the gut microbiota (potentially outcompeting harmful pathogens). The lactic acid bacteria in fermented food might also help to influence your immune system and strengthen your intestinal barrier. Some fermented foods, like tempeh, also contain prebiotics; these are fibers that escape your digestion and are broken down by your gut bacteria, including your lactic acid bacteria, which feed off prebiotic fiber to help grow their colonies. In a recent diet experiment, a high-fiber diet was compared with a diet high in fermented foods (eg, yogurt, fermented vegetables, kefir, fermented cheese); those who ate higher fermented food had lower markers of inflammation and an increased diversity of gut microbiota (which is thought to be a good thing in adults). So, in theory, fermented foods sound good.

Still wanting to understand more, and dispel a few myths, a team of researchers and I investigated what’s known about the link between fermented foods and mental health. We looked at the pathways by which fermented foods might affect mental health, such as by reducing inflammation and strengthening the intestinal barrier. These pathways are relevant because they might reduce your brain’s exposure to certain inflammatory molecules that can impact brain function and mental health.

Fermented foods also contain neurotransmitters that are important to mental health. Research about fermented food and mental health is still in its early infancy. Animal studies provide experimental evidence that fermented foods can help with symptoms of depression and anxiety – but that’s in animals. The problem is in knowing how the animal findings relate to our human experience.

We found eight studies in humans that experimented with fermented foods (for example, fermented milk products) to measure their impact on depression, anxiety, and stress in adults, but the studies were all so different that we were unable to make firm conclusions. It is still difficult to know what the active ingredient in fermented foods is. Is it the microbes? Is it the byproducts? Is it the nutrition? And how much of each is needed, and what are safe levels of each? We really need more studies, with detailed descriptions of exactly what is in each food being tested. At this stage, there is not enough human evidence to make firm clinical recommendations for eating fermented food to improve mental health symptoms.

I’ve since moved on from sauerkraut to making sourdough bread as a COVID lockdown project (as this involves a fermented starter culture). When my delicious fresh bread comes out of the oven, my world is paused for a few minutes, and my family mill around to enjoy the warm, fresh bread. While it may be too soon to tell whether fermented foods help our mental health, my sourdough itself has sure helped us.

Dr. Dawson is a nutritionist and bioinformatician research fellow at the Food & Mood Centre at Deakin University, Geelong, Australia. She disclosed no relevant financial relationships.

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

Intravenous ketamine is effective for treating depression but is inferior to electroconvulsive therapy (ECT), new research suggests.

In the first head-to-head trial, ECT was more effective than intravenous ketamine in hospitalized patients with severe depression, with higher remission rates and a greater reduction in symptoms.

However, ketamine led to remission in nearly half of participants and is a “valuable” option for treating severe depression, particularly in younger patients, the investigators noted.

The high rate of remission for ketamine infusion “indicates that it definitely can be used in a clinical setting, but it is more probable that a patient will achieve remission with ECT compared to ketamine,” principal investigator Pouya Movahed Rad, MD, PhD (pharmacology), senior consultant and researcher in psychiatry, Lund (Sweden) University, said in an interview.

Results of the KetECT study were recently published online in the International Journal of Neuropsychopharmacology.
 

Primary focus on remission

The parallel, open-label, noninferiority study included 186 patients aged 18-85 years who were hospitalized with severe unipolar depression and had a score of at least 20 on the Montgomery-Åsberg Depression Rating Scale (MADRS).

Participants were randomly allocated (1:1) to thrice-weekly infusions of racemic ketamine (0.5 mg/kg over 40 minutes) or ECT. All patients continued to take their antidepressant medication during the study. The primary outcome was remission, defined as a MADRS score of 10 or less.  

Results showed the remission rate was significantly higher in the ECT group than in the ketamine group (63% vs. 46%, respectively; P = .026). The 95% confidence interval of the difference in remission rates was estimated between 2% and 30%. 

Both ketamine and ECT required a median of six treatment sessions to induce remission.

Post-hoc analysis indicated that age was a factor in the findings. In the ECT group, remission was significantly more likely in older patients (51-85 years), compared with younger patients (18-50 years), with remission rates of 77% and 50%, respectively.

But the opposite was true in the ketamine group, with significantly higher remission rates in younger versus older patients (61% vs. 37%).

The study results also support the safety and efficacy of ketamine in patients with psychotic depression, which was present in 15% of patients in the ECT group and 18% of those in the ketamine group.

In this subgroup, half of patients with psychotic depression remitted after ketamine, with no indications of adverse reactions particular for these patients. The remission rate with ECT was 79%.

During the 12-month follow-up period, rate of relapse among remitters was similar at 64% in the ECT group and 70% in the ketamine group (log rank P = .44).
 

Let the patient decide

As expected, ECT and ketamine had distinct side effect profiles. Subjectively reported prolonged amnesia was more common with ECT and reports of dissociative side effects, anxiety, blurred vision, euphoria, vertigo, and diplopia (double vision) were more common with ketamine. 

“Dissociative symptoms were, as expected, observed during treatment with ketamine, but they were brief and in the majority of cases mild and tolerable,” Dr. Movahed Rad said.

The investigators noted that participating study sites all had long-time experience with ECT but no experience administering ketamine.

“Staffs, and some patients, were familiar with side effects common to ECT but were less prepared for the adverse psychological effects of ketamine. This, and knowing ECT was available after the study, probably contributed to the higher dropout rate in the ketamine group,” they wrote.

If both ECT and ketamine are available, “the patient’s preference should, of course, be taken in account when choosing treatment,” said Dr. Movahed Rad.

“Ketamine should be offered if ECT is not available, or cannot be given due to excessive risks with anesthesia or other somatic risk factor. Patients who have not responded to ECT or have had unacceptable side effects should be offered ketamine infusion and vice versa,” he added.

A good alternative

Commenting on the findings, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said the data confirm ECT is highly effective for treatment-resistant depression and show that “newcomer” intravenous ketamine also performs “exceptionally well.”

“This is an extremely important study that really establishes the efficacy of ketamine in a very difficult to treat population,” added Dr. McIntyre, who was not involved in the research.

He added that this “rigorous, well-designed study addresses a critical question” about the comparative efficacy of ECT and intravenous ketamine. It also makes “quite a strong statement about the efficacy of ketamine in younger people.”

He cautioned, however, that this study represents the “first data point and, of course, is not the final word on the topic. There are other studies currently still ongoing that are also comparing ECT to IV ketamine and we’ll look forward to seeing the results.”

The fact that 15%-20% of the study patients had psychotic depression is also noteworthy, said Dr. McIntyre.

“We’ve been hesitant to use ketamine in these patients, I think for obvious reasons, but we recently published a paper showing that it is safe and very effective in these patients,” he said.

Having ketamine as a treatment option is important because the majority of patients who could benefit from ECT decline it, often because of the stigma associated with the procedure, which is often portrayed negatively in films and other media.

“I have been recommending ECT almost every day of my professional life and 98 times out of 100 people say: ‘Thanks but no thanks.’ That’s a problem because ECT is so effective,” Dr. McIntyre said.

The study was funded by the Swedish Research Council, Crafoord Foundation, Skåne Regional Council, Königska Foundation, Lions Forskningsfond Skåne, and the OM Perssons donation foundation. Dr. Movahed Rad has received lecturer honoraria from Lundbeck. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, and other companies. McIntyre is also CEO of AltMed.

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

Intravenous ketamine is effective for treating depression but is inferior to electroconvulsive therapy (ECT), new research suggests.

In the first head-to-head trial, ECT was more effective than intravenous ketamine in hospitalized patients with severe depression, with higher remission rates and a greater reduction in symptoms.

However, ketamine led to remission in nearly half of participants and is a “valuable” option for treating severe depression, particularly in younger patients, the investigators noted.

The high rate of remission for ketamine infusion “indicates that it definitely can be used in a clinical setting, but it is more probable that a patient will achieve remission with ECT compared to ketamine,” principal investigator Pouya Movahed Rad, MD, PhD (pharmacology), senior consultant and researcher in psychiatry, Lund (Sweden) University, said in an interview.

Results of the KetECT study were recently published online in the International Journal of Neuropsychopharmacology.
 

Primary focus on remission

The parallel, open-label, noninferiority study included 186 patients aged 18-85 years who were hospitalized with severe unipolar depression and had a score of at least 20 on the Montgomery-Åsberg Depression Rating Scale (MADRS).

Participants were randomly allocated (1:1) to thrice-weekly infusions of racemic ketamine (0.5 mg/kg over 40 minutes) or ECT. All patients continued to take their antidepressant medication during the study. The primary outcome was remission, defined as a MADRS score of 10 or less.  

Results showed the remission rate was significantly higher in the ECT group than in the ketamine group (63% vs. 46%, respectively; P = .026). The 95% confidence interval of the difference in remission rates was estimated between 2% and 30%. 

Both ketamine and ECT required a median of six treatment sessions to induce remission.

Post-hoc analysis indicated that age was a factor in the findings. In the ECT group, remission was significantly more likely in older patients (51-85 years), compared with younger patients (18-50 years), with remission rates of 77% and 50%, respectively.

But the opposite was true in the ketamine group, with significantly higher remission rates in younger versus older patients (61% vs. 37%).

The study results also support the safety and efficacy of ketamine in patients with psychotic depression, which was present in 15% of patients in the ECT group and 18% of those in the ketamine group.

In this subgroup, half of patients with psychotic depression remitted after ketamine, with no indications of adverse reactions particular for these patients. The remission rate with ECT was 79%.

During the 12-month follow-up period, rate of relapse among remitters was similar at 64% in the ECT group and 70% in the ketamine group (log rank P = .44).
 

Let the patient decide

As expected, ECT and ketamine had distinct side effect profiles. Subjectively reported prolonged amnesia was more common with ECT and reports of dissociative side effects, anxiety, blurred vision, euphoria, vertigo, and diplopia (double vision) were more common with ketamine. 

“Dissociative symptoms were, as expected, observed during treatment with ketamine, but they were brief and in the majority of cases mild and tolerable,” Dr. Movahed Rad said.

The investigators noted that participating study sites all had long-time experience with ECT but no experience administering ketamine.

“Staffs, and some patients, were familiar with side effects common to ECT but were less prepared for the adverse psychological effects of ketamine. This, and knowing ECT was available after the study, probably contributed to the higher dropout rate in the ketamine group,” they wrote.

If both ECT and ketamine are available, “the patient’s preference should, of course, be taken in account when choosing treatment,” said Dr. Movahed Rad.

“Ketamine should be offered if ECT is not available, or cannot be given due to excessive risks with anesthesia or other somatic risk factor. Patients who have not responded to ECT or have had unacceptable side effects should be offered ketamine infusion and vice versa,” he added.

A good alternative

Commenting on the findings, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said the data confirm ECT is highly effective for treatment-resistant depression and show that “newcomer” intravenous ketamine also performs “exceptionally well.”

“This is an extremely important study that really establishes the efficacy of ketamine in a very difficult to treat population,” added Dr. McIntyre, who was not involved in the research.

He added that this “rigorous, well-designed study addresses a critical question” about the comparative efficacy of ECT and intravenous ketamine. It also makes “quite a strong statement about the efficacy of ketamine in younger people.”

He cautioned, however, that this study represents the “first data point and, of course, is not the final word on the topic. There are other studies currently still ongoing that are also comparing ECT to IV ketamine and we’ll look forward to seeing the results.”

The fact that 15%-20% of the study patients had psychotic depression is also noteworthy, said Dr. McIntyre.

“We’ve been hesitant to use ketamine in these patients, I think for obvious reasons, but we recently published a paper showing that it is safe and very effective in these patients,” he said.

Having ketamine as a treatment option is important because the majority of patients who could benefit from ECT decline it, often because of the stigma associated with the procedure, which is often portrayed negatively in films and other media.

“I have been recommending ECT almost every day of my professional life and 98 times out of 100 people say: ‘Thanks but no thanks.’ That’s a problem because ECT is so effective,” Dr. McIntyre said.

The study was funded by the Swedish Research Council, Crafoord Foundation, Skåne Regional Council, Königska Foundation, Lions Forskningsfond Skåne, and the OM Perssons donation foundation. Dr. Movahed Rad has received lecturer honoraria from Lundbeck. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, and other companies. McIntyre is also CEO of AltMed.

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

Intravenous ketamine is effective for treating depression but is inferior to electroconvulsive therapy (ECT), new research suggests.

In the first head-to-head trial, ECT was more effective than intravenous ketamine in hospitalized patients with severe depression, with higher remission rates and a greater reduction in symptoms.

However, ketamine led to remission in nearly half of participants and is a “valuable” option for treating severe depression, particularly in younger patients, the investigators noted.

The high rate of remission for ketamine infusion “indicates that it definitely can be used in a clinical setting, but it is more probable that a patient will achieve remission with ECT compared to ketamine,” principal investigator Pouya Movahed Rad, MD, PhD (pharmacology), senior consultant and researcher in psychiatry, Lund (Sweden) University, said in an interview.

Results of the KetECT study were recently published online in the International Journal of Neuropsychopharmacology.
 

Primary focus on remission

The parallel, open-label, noninferiority study included 186 patients aged 18-85 years who were hospitalized with severe unipolar depression and had a score of at least 20 on the Montgomery-Åsberg Depression Rating Scale (MADRS).

Participants were randomly allocated (1:1) to thrice-weekly infusions of racemic ketamine (0.5 mg/kg over 40 minutes) or ECT. All patients continued to take their antidepressant medication during the study. The primary outcome was remission, defined as a MADRS score of 10 or less.  

Results showed the remission rate was significantly higher in the ECT group than in the ketamine group (63% vs. 46%, respectively; P = .026). The 95% confidence interval of the difference in remission rates was estimated between 2% and 30%. 

Both ketamine and ECT required a median of six treatment sessions to induce remission.

Post-hoc analysis indicated that age was a factor in the findings. In the ECT group, remission was significantly more likely in older patients (51-85 years), compared with younger patients (18-50 years), with remission rates of 77% and 50%, respectively.

But the opposite was true in the ketamine group, with significantly higher remission rates in younger versus older patients (61% vs. 37%).

The study results also support the safety and efficacy of ketamine in patients with psychotic depression, which was present in 15% of patients in the ECT group and 18% of those in the ketamine group.

In this subgroup, half of patients with psychotic depression remitted after ketamine, with no indications of adverse reactions particular for these patients. The remission rate with ECT was 79%.

During the 12-month follow-up period, rate of relapse among remitters was similar at 64% in the ECT group and 70% in the ketamine group (log rank P = .44).
 

Let the patient decide

As expected, ECT and ketamine had distinct side effect profiles. Subjectively reported prolonged amnesia was more common with ECT and reports of dissociative side effects, anxiety, blurred vision, euphoria, vertigo, and diplopia (double vision) were more common with ketamine. 

“Dissociative symptoms were, as expected, observed during treatment with ketamine, but they were brief and in the majority of cases mild and tolerable,” Dr. Movahed Rad said.

The investigators noted that participating study sites all had long-time experience with ECT but no experience administering ketamine.

“Staffs, and some patients, were familiar with side effects common to ECT but were less prepared for the adverse psychological effects of ketamine. This, and knowing ECT was available after the study, probably contributed to the higher dropout rate in the ketamine group,” they wrote.

If both ECT and ketamine are available, “the patient’s preference should, of course, be taken in account when choosing treatment,” said Dr. Movahed Rad.

“Ketamine should be offered if ECT is not available, or cannot be given due to excessive risks with anesthesia or other somatic risk factor. Patients who have not responded to ECT or have had unacceptable side effects should be offered ketamine infusion and vice versa,” he added.

A good alternative

Commenting on the findings, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said the data confirm ECT is highly effective for treatment-resistant depression and show that “newcomer” intravenous ketamine also performs “exceptionally well.”

“This is an extremely important study that really establishes the efficacy of ketamine in a very difficult to treat population,” added Dr. McIntyre, who was not involved in the research.

He added that this “rigorous, well-designed study addresses a critical question” about the comparative efficacy of ECT and intravenous ketamine. It also makes “quite a strong statement about the efficacy of ketamine in younger people.”

He cautioned, however, that this study represents the “first data point and, of course, is not the final word on the topic. There are other studies currently still ongoing that are also comparing ECT to IV ketamine and we’ll look forward to seeing the results.”

The fact that 15%-20% of the study patients had psychotic depression is also noteworthy, said Dr. McIntyre.

“We’ve been hesitant to use ketamine in these patients, I think for obvious reasons, but we recently published a paper showing that it is safe and very effective in these patients,” he said.

Having ketamine as a treatment option is important because the majority of patients who could benefit from ECT decline it, often because of the stigma associated with the procedure, which is often portrayed negatively in films and other media.

“I have been recommending ECT almost every day of my professional life and 98 times out of 100 people say: ‘Thanks but no thanks.’ That’s a problem because ECT is so effective,” Dr. McIntyre said.

The study was funded by the Swedish Research Council, Crafoord Foundation, Skåne Regional Council, Königska Foundation, Lions Forskningsfond Skåne, and the OM Perssons donation foundation. Dr. Movahed Rad has received lecturer honoraria from Lundbeck. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, and other companies. McIntyre is also CEO of AltMed.

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

Long story short, we still have a lot to learn about long COVID-19.

But it is a real phenomenon with real long-term health effects for people recovering from coronavirus infections. And diagnosing and managing it can get tricky, as some symptoms of long COVID-19 overlap with those of other conditions – and what many people have as they recover from any challenging stay in the ICU.

Risk factors remain largely unknown as well: What makes one person more likely to have symptoms like fatigue, “brain fog,” or headaches versus someone else? Researchers are just starting to offer some intriguing answers, but the evidence is preliminary at this point, experts said at a media briefing sponsored by the Infectious Diseases Society of America.

Unanswered questions include: Does an autoimmune reaction drive long COVID? Does the coronavirus linger in reservoirs within the body and reactivate later? What protection against long COVID do vaccines and treatments offer, if any?

To get a handle on these and other questions, nailing down a standard definition of long COVID would be a good start.

“Studies so far have used different definitions of long COVID,” Nahid Bhadelia, MD, founding director of the Boston University Center for Emerging Infectious Diseases Policy and Research, said during the briefing.

Fatigue is the most commonly symptom of long COVID in research so far, said Dr. Bhadelia, who is also an associate professor of medicine at Boston University.

“What’s difficult in this situation is it’s been 2 years in a global pandemic. We’re all fatigued. How do you tease this apart?” she asked.

Other common symptoms are a hard time thinking quickly – also known as “brain fog” – and the feeling that, despite normal oxygen levels, breathing is difficult, said Kathleen Bell, MD.

Headache, joint and muscle pain, and persistent loss of smell and taste are also widely reported, said Dr. Bell, a professor and chair of the department of physical medicine and rehabilitation at the University of Texas Southwestern Medical Center in Dallas.

Not all the symptoms are physical either.

“Pretty prominent things that we’re seeing are very high levels of anxiety, depression, and insomnia,” Dr. Bell said. These “actually seem to be associated independently with the virus as opposed to just being a completely reactive component.”

More research will be needed to distinguish the causes of these conditions.
 

A difficult diagnosis

Without a standard definition, the wide range of symptoms, and the lack of specific guidance on how to manage them, contribute to making it more challenging to distinguish long COVID from other conditions, the experts said.

“We are starting to see some interesting features of inaccurate attributions to COVID, both on the part of perhaps the person with long COVID symptoms and health care providers,” Dr. Bell said.“It’s sometimes a little difficult to sort it out.”

Dr. Bell said she was not suggesting misdiagnoses are common, “but it is difficult for physicians that don’t see a lot of people with long COVID.”

The advice is to consider other conditions. “You can have both a long COVID syndrome and other syndromes as well,” she said. “As one of my teachers used to say: ‘You can have both ticks and fleas.’ ”
 

Predicting long COVID

In a study getting attention, researchers identified four early things linked to greater chances that someone with COVID-19 will have long-term effects: type 2 diabetes at the time of diagnosis, the presence of specific autoantibodies, unusual levels of SARS-CoV-2 RNA in the blood, and signs of the Epstein-Barr virus in the blood.

The study, published in Cell, followed 309 people 2-3 months after COVID-19.

“That’s important work, but it’s early work,” Dr. Bhadelia said. “I think we still have a while to go in terms of understanding the mechanism of long COVID.”
 

Unexpected patients getting long COVID care

“We are seeing different populations than we all expected to see when this pandemic first started,” Dr. Bell said.

Instead of seeing primarily patients who had severe COVID-19, “the preponderance of people that we’re seeing in long COVID clinics are people who are enabled, were never hospitalized, and have what people might call mild to moderate cases of coronavirus infection,” she said.

Also, instead of just older patients, people of all ages are seeking long COVID care.

One thing that appears more certain is a lack of diversity in people seeking care at long COVID clinics nationwide.

“Many of us who have long COVID specialty clinics will tell you that we are tending to see fairly educated, socioeconomically stable population in these clinics,” Dr. Bell said. “We know that based on the early statistics of who’s getting COVID and having significant COVID that we may not be seeing those populations for follow-up.”
 

Is an autoinflammatory process to blame?

It remains unclear if a hyperinflammatory response is driving persistent post–COVID-19 symptoms. Children and some adults have developed multisystem inflammatory conditions associated with COVID-19, for example.

There is a signal, and “I think there is enough data now to show something does happen,” Dr. Bhadelia said. “The question is, how often does it happen?”

Spending time in critical care, even without COVID-19, can result in persistent symptoms after a hospital stay, such as acute respiratory distress syndrome. Recovery can take time because being in an ICU is “basically the physiologically equivalent of a car crash,” Dr. Bhadelia said. “So you’re recovering from that, too.”

Dr. Bell agreed. “You’re not only recovering from the virus itself, you’re recovering from intubation, secondary infections, secondary lung conditions, perhaps other organ failure, and prolonged bed rest. There are so many things that go into that, that it’s a little bit hard to sort that out from what long COVID is and what the direct effects of the virus are.”
 

Also a research opportunity

“I hate to call it this, but we’ve never had an opportunity [where] we have so many people in such a short amount of time with the same viral disorder,” Dr. Bell said. “We also have the technology to investigate it. This has never happened.

“SARS-CoV-2 is not the only virus. This is just the only one we’ve gotten whacked with in such a huge quantity at one time,” she said.

What researchers learn now about COVID-19 and long COVID “is a model that’s going to be able to be applied in the future to infectious diseases in general,” Dr. Bell predicted.
 

How long will long COVID last?

The vast majority of people with long COVID will get better over time, given enough support and relief of their symptoms, Dr. Bell said.

Type 2 diabetes, preexisting pulmonary disease, and other things could affect how long it takes to recover from long COVID, she said, although more evidence is needed.

“I don’t think at this point that anyone can say how long this long COVID will last because there are a variety of factors,” Dr. Bell said.

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

Long story short, we still have a lot to learn about long COVID-19.

But it is a real phenomenon with real long-term health effects for people recovering from coronavirus infections. And diagnosing and managing it can get tricky, as some symptoms of long COVID-19 overlap with those of other conditions – and what many people have as they recover from any challenging stay in the ICU.

Risk factors remain largely unknown as well: What makes one person more likely to have symptoms like fatigue, “brain fog,” or headaches versus someone else? Researchers are just starting to offer some intriguing answers, but the evidence is preliminary at this point, experts said at a media briefing sponsored by the Infectious Diseases Society of America.

Unanswered questions include: Does an autoimmune reaction drive long COVID? Does the coronavirus linger in reservoirs within the body and reactivate later? What protection against long COVID do vaccines and treatments offer, if any?

To get a handle on these and other questions, nailing down a standard definition of long COVID would be a good start.

“Studies so far have used different definitions of long COVID,” Nahid Bhadelia, MD, founding director of the Boston University Center for Emerging Infectious Diseases Policy and Research, said during the briefing.

Fatigue is the most commonly symptom of long COVID in research so far, said Dr. Bhadelia, who is also an associate professor of medicine at Boston University.

“What’s difficult in this situation is it’s been 2 years in a global pandemic. We’re all fatigued. How do you tease this apart?” she asked.

Other common symptoms are a hard time thinking quickly – also known as “brain fog” – and the feeling that, despite normal oxygen levels, breathing is difficult, said Kathleen Bell, MD.

Headache, joint and muscle pain, and persistent loss of smell and taste are also widely reported, said Dr. Bell, a professor and chair of the department of physical medicine and rehabilitation at the University of Texas Southwestern Medical Center in Dallas.

Not all the symptoms are physical either.

“Pretty prominent things that we’re seeing are very high levels of anxiety, depression, and insomnia,” Dr. Bell said. These “actually seem to be associated independently with the virus as opposed to just being a completely reactive component.”

More research will be needed to distinguish the causes of these conditions.
 

A difficult diagnosis

Without a standard definition, the wide range of symptoms, and the lack of specific guidance on how to manage them, contribute to making it more challenging to distinguish long COVID from other conditions, the experts said.

“We are starting to see some interesting features of inaccurate attributions to COVID, both on the part of perhaps the person with long COVID symptoms and health care providers,” Dr. Bell said.“It’s sometimes a little difficult to sort it out.”

Dr. Bell said she was not suggesting misdiagnoses are common, “but it is difficult for physicians that don’t see a lot of people with long COVID.”

The advice is to consider other conditions. “You can have both a long COVID syndrome and other syndromes as well,” she said. “As one of my teachers used to say: ‘You can have both ticks and fleas.’ ”
 

Predicting long COVID

In a study getting attention, researchers identified four early things linked to greater chances that someone with COVID-19 will have long-term effects: type 2 diabetes at the time of diagnosis, the presence of specific autoantibodies, unusual levels of SARS-CoV-2 RNA in the blood, and signs of the Epstein-Barr virus in the blood.

The study, published in Cell, followed 309 people 2-3 months after COVID-19.

“That’s important work, but it’s early work,” Dr. Bhadelia said. “I think we still have a while to go in terms of understanding the mechanism of long COVID.”
 

Unexpected patients getting long COVID care

“We are seeing different populations than we all expected to see when this pandemic first started,” Dr. Bell said.

Instead of seeing primarily patients who had severe COVID-19, “the preponderance of people that we’re seeing in long COVID clinics are people who are enabled, were never hospitalized, and have what people might call mild to moderate cases of coronavirus infection,” she said.

Also, instead of just older patients, people of all ages are seeking long COVID care.

One thing that appears more certain is a lack of diversity in people seeking care at long COVID clinics nationwide.

“Many of us who have long COVID specialty clinics will tell you that we are tending to see fairly educated, socioeconomically stable population in these clinics,” Dr. Bell said. “We know that based on the early statistics of who’s getting COVID and having significant COVID that we may not be seeing those populations for follow-up.”
 

Is an autoinflammatory process to blame?

It remains unclear if a hyperinflammatory response is driving persistent post–COVID-19 symptoms. Children and some adults have developed multisystem inflammatory conditions associated with COVID-19, for example.

There is a signal, and “I think there is enough data now to show something does happen,” Dr. Bhadelia said. “The question is, how often does it happen?”

Spending time in critical care, even without COVID-19, can result in persistent symptoms after a hospital stay, such as acute respiratory distress syndrome. Recovery can take time because being in an ICU is “basically the physiologically equivalent of a car crash,” Dr. Bhadelia said. “So you’re recovering from that, too.”

Dr. Bell agreed. “You’re not only recovering from the virus itself, you’re recovering from intubation, secondary infections, secondary lung conditions, perhaps other organ failure, and prolonged bed rest. There are so many things that go into that, that it’s a little bit hard to sort that out from what long COVID is and what the direct effects of the virus are.”
 

Also a research opportunity

“I hate to call it this, but we’ve never had an opportunity [where] we have so many people in such a short amount of time with the same viral disorder,” Dr. Bell said. “We also have the technology to investigate it. This has never happened.

“SARS-CoV-2 is not the only virus. This is just the only one we’ve gotten whacked with in such a huge quantity at one time,” she said.

What researchers learn now about COVID-19 and long COVID “is a model that’s going to be able to be applied in the future to infectious diseases in general,” Dr. Bell predicted.
 

How long will long COVID last?

The vast majority of people with long COVID will get better over time, given enough support and relief of their symptoms, Dr. Bell said.

Type 2 diabetes, preexisting pulmonary disease, and other things could affect how long it takes to recover from long COVID, she said, although more evidence is needed.

“I don’t think at this point that anyone can say how long this long COVID will last because there are a variety of factors,” Dr. Bell said.

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

Long story short, we still have a lot to learn about long COVID-19.

But it is a real phenomenon with real long-term health effects for people recovering from coronavirus infections. And diagnosing and managing it can get tricky, as some symptoms of long COVID-19 overlap with those of other conditions – and what many people have as they recover from any challenging stay in the ICU.

Risk factors remain largely unknown as well: What makes one person more likely to have symptoms like fatigue, “brain fog,” or headaches versus someone else? Researchers are just starting to offer some intriguing answers, but the evidence is preliminary at this point, experts said at a media briefing sponsored by the Infectious Diseases Society of America.

Unanswered questions include: Does an autoimmune reaction drive long COVID? Does the coronavirus linger in reservoirs within the body and reactivate later? What protection against long COVID do vaccines and treatments offer, if any?

To get a handle on these and other questions, nailing down a standard definition of long COVID would be a good start.

“Studies so far have used different definitions of long COVID,” Nahid Bhadelia, MD, founding director of the Boston University Center for Emerging Infectious Diseases Policy and Research, said during the briefing.

Fatigue is the most commonly symptom of long COVID in research so far, said Dr. Bhadelia, who is also an associate professor of medicine at Boston University.

“What’s difficult in this situation is it’s been 2 years in a global pandemic. We’re all fatigued. How do you tease this apart?” she asked.

Other common symptoms are a hard time thinking quickly – also known as “brain fog” – and the feeling that, despite normal oxygen levels, breathing is difficult, said Kathleen Bell, MD.

Headache, joint and muscle pain, and persistent loss of smell and taste are also widely reported, said Dr. Bell, a professor and chair of the department of physical medicine and rehabilitation at the University of Texas Southwestern Medical Center in Dallas.

Not all the symptoms are physical either.

“Pretty prominent things that we’re seeing are very high levels of anxiety, depression, and insomnia,” Dr. Bell said. These “actually seem to be associated independently with the virus as opposed to just being a completely reactive component.”

More research will be needed to distinguish the causes of these conditions.
 

A difficult diagnosis

Without a standard definition, the wide range of symptoms, and the lack of specific guidance on how to manage them, contribute to making it more challenging to distinguish long COVID from other conditions, the experts said.

“We are starting to see some interesting features of inaccurate attributions to COVID, both on the part of perhaps the person with long COVID symptoms and health care providers,” Dr. Bell said.“It’s sometimes a little difficult to sort it out.”

Dr. Bell said she was not suggesting misdiagnoses are common, “but it is difficult for physicians that don’t see a lot of people with long COVID.”

The advice is to consider other conditions. “You can have both a long COVID syndrome and other syndromes as well,” she said. “As one of my teachers used to say: ‘You can have both ticks and fleas.’ ”
 

Predicting long COVID

In a study getting attention, researchers identified four early things linked to greater chances that someone with COVID-19 will have long-term effects: type 2 diabetes at the time of diagnosis, the presence of specific autoantibodies, unusual levels of SARS-CoV-2 RNA in the blood, and signs of the Epstein-Barr virus in the blood.

The study, published in Cell, followed 309 people 2-3 months after COVID-19.

“That’s important work, but it’s early work,” Dr. Bhadelia said. “I think we still have a while to go in terms of understanding the mechanism of long COVID.”
 

Unexpected patients getting long COVID care

“We are seeing different populations than we all expected to see when this pandemic first started,” Dr. Bell said.

Instead of seeing primarily patients who had severe COVID-19, “the preponderance of people that we’re seeing in long COVID clinics are people who are enabled, were never hospitalized, and have what people might call mild to moderate cases of coronavirus infection,” she said.

Also, instead of just older patients, people of all ages are seeking long COVID care.

One thing that appears more certain is a lack of diversity in people seeking care at long COVID clinics nationwide.

“Many of us who have long COVID specialty clinics will tell you that we are tending to see fairly educated, socioeconomically stable population in these clinics,” Dr. Bell said. “We know that based on the early statistics of who’s getting COVID and having significant COVID that we may not be seeing those populations for follow-up.”
 

Is an autoinflammatory process to blame?

It remains unclear if a hyperinflammatory response is driving persistent post–COVID-19 symptoms. Children and some adults have developed multisystem inflammatory conditions associated with COVID-19, for example.

There is a signal, and “I think there is enough data now to show something does happen,” Dr. Bhadelia said. “The question is, how often does it happen?”

Spending time in critical care, even without COVID-19, can result in persistent symptoms after a hospital stay, such as acute respiratory distress syndrome. Recovery can take time because being in an ICU is “basically the physiologically equivalent of a car crash,” Dr. Bhadelia said. “So you’re recovering from that, too.”

Dr. Bell agreed. “You’re not only recovering from the virus itself, you’re recovering from intubation, secondary infections, secondary lung conditions, perhaps other organ failure, and prolonged bed rest. There are so many things that go into that, that it’s a little bit hard to sort that out from what long COVID is and what the direct effects of the virus are.”
 

Also a research opportunity

“I hate to call it this, but we’ve never had an opportunity [where] we have so many people in such a short amount of time with the same viral disorder,” Dr. Bell said. “We also have the technology to investigate it. This has never happened.

“SARS-CoV-2 is not the only virus. This is just the only one we’ve gotten whacked with in such a huge quantity at one time,” she said.

What researchers learn now about COVID-19 and long COVID “is a model that’s going to be able to be applied in the future to infectious diseases in general,” Dr. Bell predicted.
 

How long will long COVID last?

The vast majority of people with long COVID will get better over time, given enough support and relief of their symptoms, Dr. Bell said.

Type 2 diabetes, preexisting pulmonary disease, and other things could affect how long it takes to recover from long COVID, she said, although more evidence is needed.

“I don’t think at this point that anyone can say how long this long COVID will last because there are a variety of factors,” Dr. Bell said.

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

Subclinical changes in cardiac structure and diastolic function in early adulthood may serve as risk markers for cognitive decline in midlife, new research suggests.

Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.

“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.

“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.

The findings were published online Jan. 26, 2022, in Neurology.
 

Heart/brain connection

The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.

Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m² in year 5 to 86.0 g/m² in year 30.

Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m² in year 5 to 26 mL/m² in year 30.

Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.

After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).

An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.

“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.

“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.

Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.

They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
 

First structural biomarker

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.

“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.

As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.

Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”

The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.

Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.

How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.

“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.

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

Subclinical changes in cardiac structure and diastolic function in early adulthood may serve as risk markers for cognitive decline in midlife, new research suggests.

Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.

“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.

“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.

The findings were published online Jan. 26, 2022, in Neurology.
 

Heart/brain connection

The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.

Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m² in year 5 to 86.0 g/m² in year 30.

Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m² in year 5 to 26 mL/m² in year 30.

Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.

After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).

An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.

“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.

“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.

Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.

They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
 

First structural biomarker

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.

“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.

As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.

Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”

The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.

Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.

How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.

“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.

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

Subclinical changes in cardiac structure and diastolic function in early adulthood may serve as risk markers for cognitive decline in midlife, new research suggests.

Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.

“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.

“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.

The findings were published online Jan. 26, 2022, in Neurology.
 

Heart/brain connection

The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.

Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m² in year 5 to 86.0 g/m² in year 30.

Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m² in year 5 to 26 mL/m² in year 30.

Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.

After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).

An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.

“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.

“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.

Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.

They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
 

First structural biomarker

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.

“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.

As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.

Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”

The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.

Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.

How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.

“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.

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

Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.

Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.

The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.

The study was published online Jan. 11 in the American Journal of Psychiatry.
 

Target depression

Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.

“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.

Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.

To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.

All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.

Participants were randomly allocated to one of four groups:

1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy

2. three saline infusions plus psychological therapy

3. three ketamine infusions plus alcohol education

4. three saline infusions plus alcohol education

The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.

At 6-month follow-up, ketamine was associated with a significantly greater number of days abstinent from alcohol (mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.

The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).

There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
 

Growing evidence

These findings support some other studies that have also suggested a benefit of ketamine in AUD.

As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.

A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.

“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.

“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.

Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
 

An ‘Intriguing new therapy’

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”

“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.

“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.

The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.

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

Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.

Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.

The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.

The study was published online Jan. 11 in the American Journal of Psychiatry.
 

Target depression

Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.

“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.

Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.

To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.

All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.

Participants were randomly allocated to one of four groups:

1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy

2. three saline infusions plus psychological therapy

3. three ketamine infusions plus alcohol education

4. three saline infusions plus alcohol education

The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.

At 6-month follow-up, ketamine was associated with a significantly greater number of days abstinent from alcohol (mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.

The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).

There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
 

Growing evidence

These findings support some other studies that have also suggested a benefit of ketamine in AUD.

As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.

A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.

“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.

“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.

Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
 

An ‘Intriguing new therapy’

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”

“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.

“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.

The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.

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

Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.

Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.

The results suggest ketamine plus psychological therapy may be a “new, relatively brief treatment that has long lasting effects in AUD,” Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, United Kingdom, told this news organization.

The study was published online Jan. 11 in the American Journal of Psychiatry.
 

Target depression

Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.

“Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” the investigators note.

Ketamine may also provide a “temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily,” they add.

To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.

All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.

Participants were randomly allocated to one of four groups:

1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy

2. three saline infusions plus psychological therapy

3. three ketamine infusions plus alcohol education

4. three saline infusions plus alcohol education

The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.

At 6-month follow-up, ketamine was associated with a significantly greater number of days abstinent from alcohol (mean difference, 10.1%; 95% confidence interval, 1.1-19.0), “although confidence intervals were wide, consistent with a proof-of-concept study,” the authors note.

The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8-28.1).

There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.
 

Growing evidence

These findings support some other studies that have also suggested a benefit of ketamine in AUD.

As reported by this news organization, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.

A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone.

“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” the researchers write.

“While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity,” they add.

Dr. Morgan said in an interview that adjunctive ketamine with relapse-prevention therapy is “currently being delivered in Awakn Clinics in the U.K. and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible.”
 

An ‘Intriguing new therapy’

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai, New York, said ketamine “continues to be an intriguing new therapy for a variety of mental health conditions.”

“Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy,” Dr. Brennan said in an interview.

“Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder,” he cautioned.

The study was supported by the Medical Research Council. Dr. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Dr. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other coauthors have disclosed relationships with industry; the full list can be found with the original article. Dr. Brennan has disclosed no relevant financial relationships.

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

Violence against women remains a global dilemma in need of attention. Physical violence in particular, is the most prevalent type of violence across all genders, races, and nationalities.

The Centers for Disease Control and Prevention says more than 43 million women and 38 million men report experiencing psychological aggression by an intimate partner in their lifetime. Meanwhile, 11 million women and 5 million men report enduring sexual or physical violence and intimate partner violence (IPV), and/or stalking by an intimate partner during their lifetimes, according to the CDC.1

COVID pandemic’s influence

Isolation tied to the COVID-19 pandemic has been linked to increased IPV. A study conducted by researchers at the University of California, Davis, suggested that extra stress experienced during the COVID-19 pandemic caused by income loss, and the inability to pay for housing and food exacerbated the prevalence of IPV early during the pandemic.⁶

That study, where researchers collected in surveys of nearly 400 adults in the beginning in April 2020 for 10 weeks, showed that more services and communication are needed so that frontline health care and food bank workers, for example, in addition to social workers, doctors, and therapists, can spot the signs and ask clients questions about potential IPV. They could then link survivors to pertinent assistance and resources.

Furthermore, multiple factors probably have played a pivotal role in increasing the prevalence of IPV during the COVID-19 pandemic. For instance, disruption to usual health and social services as well as diminished access to support systems, such as shelters, and charity helplines negatively affected the reporting of domestic violence.

Long before the pandemic, over the past decade, international and national bodies have played a crucial role in terms of improving the awareness and response to domestic violence.^7,8 In addition, several policies have been introduced in countries around the globe emphasizing the need to inquire routinely about domestic violence. Nevertheless, mental health services often fail to adequately address domestic violence in clinical encounters. A systematic review of domestic violence assessment screening performed in a variety of health care settings found that evidence was insufficient to conclude that routine inquiry improved morbidity and mortality among victims of IPV.⁹ So the question becomes: How can we get our patients to tell us about these experiences so we can intervene?
 

Gender differences in perpetuating IPV

Several studies have found that abuse can result in various mental illnesses, such as depression, PTSD, anxiety, and suicidal ideation. Again, men have a disproportionately higher rate of perpetrating IPV, compared with women. This theory has been a source of debate in the academic community for years, but recent research has confirmed that women do perpetuate violence against their partners to some extent.^10,11

Some members of the LGBTQ+ community also report experiencing violence from partners, so as clinicians, we also need to raise our awareness about the existence of violence among same-sex couples. In fact, a team of Italian researchers report more than 50% of gay men and almost 75% of lesbian women reported that they had been psychologically abused by a partner.¹² More research into this area is needed.
 

Our role as health care professionals

The U.S. Preventive Services Task Force advises that all clinic visits include regular IPV screening.¹³ But these screenings are all too rare. In fact, a meta-analysis of 19 trials of more than 1,600 participants showed only 9%-40% of doctors routinely test for IPV.¹⁴ That research clearly shows how important it is for all clinicians to execute IPV screening. However, numerous challenges toward screening exist, including personal discomfort, limited time during appointments, insufficient resources, and inadequate training.

One ongoing debate revolves around which clinician should screen for IPV. Should the psychiatrist carry out this role – or perhaps the primary care physician, nurse, or social worker? These issues become even more fraught when clinicians worry about offending the patient – especially if the clinician is a male.¹⁵

The bottom line is that physicians should inquire about intimate partner violence, because research indicates that women are more likely to reveal abuse when prompted. In addition, during physician appointments, they can use the physician-patient therapeutic connection to conduct a domestic violence evaluation, give resources to victims, and provide ongoing care. Patients who exhibit treatment resistance, persistent pain, depression, sleeplessness, and headaches should prompt psychiatrists to conduct additional investigations into the likelihood of intimate partner violence and domestic abuse.

W also should be attentive when counseling patients about domestic violence when suggesting life-changing events such as pregnancy, employment loss, separation, or divorce. Similar to the recommendations of the USPSTF that all women and men should be screened for IPV, it is suggested that physicians be conscious of facilitating a conversation and not being overtly judgmental while observing body cues. Using the statements such as “we have been hearing a lot of violence in our community lately” could be a segue to introduce the subject.

Asking the question of whether you are being hit rather than being abused has allowed more women to open up more about domestic violence. While physicians are aware that most victims might recant and often go back to their abusers, victims need to be counseled that the abuse might intensify and lead to death.

For women who perpetuate IPV and survivors of IPV, safety is the priority. Physicians should provide safety options and be the facilitators. Studies have shown that fewer victims get the referral to the supporting agencies when IPV is indicated, which puts their safety at risk. In women who commit IPV, clinicians should assess the role of the individual in an IPV disclosure. There are various treatment modalities, whether the violence is performed through self-defense, bidirectionally, or because of aggression.

With the advancement of technology, web-based training on how to ask for IPV, documentation, acknowledgment, and structured referral increase physicians’ confidence when faced with an IPV disclosure than none.¹⁶ Treatment modalities should include medication reconciliation and cognitive-behavioral therapy – focusing on emotion regulation.

Using instruments such as the danger assessment tool can help physicians intervene early, reducing the risk of domestic violence and IPV recurrence instead of using clinical assessment alone.¹⁷ Physicians should convey empathy, validate victims, and help, especially when abuse is reported.

Also, it is important to evaluate survivors’ safety. Counseling can help people rebuild their self-esteem. Structured referrals for psychiatric help and support services are needed to help survivors on the long road to recovery.

Training all physicians, regardless of specialty, is essential to improve prompt IPV identification and bring awareness to resources available to survivors when IPV is disclosed. Although we described an association between IPV victims becoming possible perpetrators of IPV, more long-term studies are required to show the various processes that influence IPV perpetration rates, especially by survivors.

We would also like international and national regulatory bodies to increase the awareness of IPV and adequately address IPV with special emphasis on how mental health services should assess, identify, and respond to services for people who are survivors and perpetrators of IPV.

Dr. Kumari, Dr. Otite, Dr. Afzal, Dr. Alcera, and Dr. Doumas are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. They have no conflicts of interest.

References

1. Centers for Disease Control and Prevention. Preventing intimate partner violence. 2020 Oct 9.

2. Yu R et al. PLOS Med. 16(12):e1002995. doi: 10.1371/journal.pmed.1002995.

3. Oram S et al. Epidemiol Psychiatr Sci. 2014 Dec;23(4):361-76.

4. Munro OE and Sellbom M. Pers Ment Health. 2020 Mar 11. doi: 10.1002/pmh.1480.

5. Sahraian A et al. Asian J Psychiatry. 2020 Jun. doi: 10.1016/j.ajp.2020.102062.

6. Nikos-Rose K. “COVID-19 Isolation Linked to Increased Domestic Violence, Researchers Suggest.” 2021 Feb 24. University of California, Davis.

7. World Health Organization. “Responding to intimate partner violence and sexual violence against women.” WHO clinical policy guidelines. 2013.

8. National Institute for Health and Care Excellence. “Domestic violence and abuse: Multi-agency working.” PH50. 2014 Feb 26.

9. Feder GS et al. Arch Intern Med. 2006;166(1):22-37.

10. Gondolf EW. Violence Against Women. 2014 Dec;20(12)1539-46.

11. Hamberger LK and Larsen SE. J Fam Violence. 2015;30(6):699-717.

12. Rollè L et al. Front Psychol. 21 Aug 2018. doi: 10.3389/fpsyg.2018.01506.

13. Paterno MT and Draughon JE. J Midwif Women Health. 2016;61(31):370-5.

14. Kalra N et al. Cochrane Database Syst Rev. 2021 May 31;5(5)CD012423.

15. Larsen SE and Hamberger LK. J Fam Viol. 2015;30:1007-30.

16. Kalra N et al. Cochrane Database Syst Rev. 2017 Feb;2017(2):CD012423.

17. Campbell JC et al. J Interpers Violence. 2009;24(4):653-74.

Violence against women remains a global dilemma in need of attention. Physical violence in particular, is the most prevalent type of violence across all genders, races, and nationalities.

The Centers for Disease Control and Prevention says more than 43 million women and 38 million men report experiencing psychological aggression by an intimate partner in their lifetime. Meanwhile, 11 million women and 5 million men report enduring sexual or physical violence and intimate partner violence (IPV), and/or stalking by an intimate partner during their lifetimes, according to the CDC.1

COVID pandemic’s influence

Isolation tied to the COVID-19 pandemic has been linked to increased IPV. A study conducted by researchers at the University of California, Davis, suggested that extra stress experienced during the COVID-19 pandemic caused by income loss, and the inability to pay for housing and food exacerbated the prevalence of IPV early during the pandemic.⁶

That study, where researchers collected in surveys of nearly 400 adults in the beginning in April 2020 for 10 weeks, showed that more services and communication are needed so that frontline health care and food bank workers, for example, in addition to social workers, doctors, and therapists, can spot the signs and ask clients questions about potential IPV. They could then link survivors to pertinent assistance and resources.

Furthermore, multiple factors probably have played a pivotal role in increasing the prevalence of IPV during the COVID-19 pandemic. For instance, disruption to usual health and social services as well as diminished access to support systems, such as shelters, and charity helplines negatively affected the reporting of domestic violence.

Long before the pandemic, over the past decade, international and national bodies have played a crucial role in terms of improving the awareness and response to domestic violence.^7,8 In addition, several policies have been introduced in countries around the globe emphasizing the need to inquire routinely about domestic violence. Nevertheless, mental health services often fail to adequately address domestic violence in clinical encounters. A systematic review of domestic violence assessment screening performed in a variety of health care settings found that evidence was insufficient to conclude that routine inquiry improved morbidity and mortality among victims of IPV.⁹ So the question becomes: How can we get our patients to tell us about these experiences so we can intervene?
 

Gender differences in perpetuating IPV

Several studies have found that abuse can result in various mental illnesses, such as depression, PTSD, anxiety, and suicidal ideation. Again, men have a disproportionately higher rate of perpetrating IPV, compared with women. This theory has been a source of debate in the academic community for years, but recent research has confirmed that women do perpetuate violence against their partners to some extent.^10,11

Some members of the LGBTQ+ community also report experiencing violence from partners, so as clinicians, we also need to raise our awareness about the existence of violence among same-sex couples. In fact, a team of Italian researchers report more than 50% of gay men and almost 75% of lesbian women reported that they had been psychologically abused by a partner.¹² More research into this area is needed.
 

Our role as health care professionals

The U.S. Preventive Services Task Force advises that all clinic visits include regular IPV screening.¹³ But these screenings are all too rare. In fact, a meta-analysis of 19 trials of more than 1,600 participants showed only 9%-40% of doctors routinely test for IPV.¹⁴ That research clearly shows how important it is for all clinicians to execute IPV screening. However, numerous challenges toward screening exist, including personal discomfort, limited time during appointments, insufficient resources, and inadequate training.

One ongoing debate revolves around which clinician should screen for IPV. Should the psychiatrist carry out this role – or perhaps the primary care physician, nurse, or social worker? These issues become even more fraught when clinicians worry about offending the patient – especially if the clinician is a male.¹⁵

The bottom line is that physicians should inquire about intimate partner violence, because research indicates that women are more likely to reveal abuse when prompted. In addition, during physician appointments, they can use the physician-patient therapeutic connection to conduct a domestic violence evaluation, give resources to victims, and provide ongoing care. Patients who exhibit treatment resistance, persistent pain, depression, sleeplessness, and headaches should prompt psychiatrists to conduct additional investigations into the likelihood of intimate partner violence and domestic abuse.

W also should be attentive when counseling patients about domestic violence when suggesting life-changing events such as pregnancy, employment loss, separation, or divorce. Similar to the recommendations of the USPSTF that all women and men should be screened for IPV, it is suggested that physicians be conscious of facilitating a conversation and not being overtly judgmental while observing body cues. Using the statements such as “we have been hearing a lot of violence in our community lately” could be a segue to introduce the subject.

Asking the question of whether you are being hit rather than being abused has allowed more women to open up more about domestic violence. While physicians are aware that most victims might recant and often go back to their abusers, victims need to be counseled that the abuse might intensify and lead to death.

For women who perpetuate IPV and survivors of IPV, safety is the priority. Physicians should provide safety options and be the facilitators. Studies have shown that fewer victims get the referral to the supporting agencies when IPV is indicated, which puts their safety at risk. In women who commit IPV, clinicians should assess the role of the individual in an IPV disclosure. There are various treatment modalities, whether the violence is performed through self-defense, bidirectionally, or because of aggression.

With the advancement of technology, web-based training on how to ask for IPV, documentation, acknowledgment, and structured referral increase physicians’ confidence when faced with an IPV disclosure than none.¹⁶ Treatment modalities should include medication reconciliation and cognitive-behavioral therapy – focusing on emotion regulation.

Using instruments such as the danger assessment tool can help physicians intervene early, reducing the risk of domestic violence and IPV recurrence instead of using clinical assessment alone.¹⁷ Physicians should convey empathy, validate victims, and help, especially when abuse is reported.

Also, it is important to evaluate survivors’ safety. Counseling can help people rebuild their self-esteem. Structured referrals for psychiatric help and support services are needed to help survivors on the long road to recovery.

Training all physicians, regardless of specialty, is essential to improve prompt IPV identification and bring awareness to resources available to survivors when IPV is disclosed. Although we described an association between IPV victims becoming possible perpetrators of IPV, more long-term studies are required to show the various processes that influence IPV perpetration rates, especially by survivors.

We would also like international and national regulatory bodies to increase the awareness of IPV and adequately address IPV with special emphasis on how mental health services should assess, identify, and respond to services for people who are survivors and perpetrators of IPV.

Dr. Kumari, Dr. Otite, Dr. Afzal, Dr. Alcera, and Dr. Doumas are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. They have no conflicts of interest.

References

1. Centers for Disease Control and Prevention. Preventing intimate partner violence. 2020 Oct 9.

2. Yu R et al. PLOS Med. 16(12):e1002995. doi: 10.1371/journal.pmed.1002995.

3. Oram S et al. Epidemiol Psychiatr Sci. 2014 Dec;23(4):361-76.

4. Munro OE and Sellbom M. Pers Ment Health. 2020 Mar 11. doi: 10.1002/pmh.1480.

5. Sahraian A et al. Asian J Psychiatry. 2020 Jun. doi: 10.1016/j.ajp.2020.102062.

6. Nikos-Rose K. “COVID-19 Isolation Linked to Increased Domestic Violence, Researchers Suggest.” 2021 Feb 24. University of California, Davis.

7. World Health Organization. “Responding to intimate partner violence and sexual violence against women.” WHO clinical policy guidelines. 2013.

8. National Institute for Health and Care Excellence. “Domestic violence and abuse: Multi-agency working.” PH50. 2014 Feb 26.

9. Feder GS et al. Arch Intern Med. 2006;166(1):22-37.

10. Gondolf EW. Violence Against Women. 2014 Dec;20(12)1539-46.

11. Hamberger LK and Larsen SE. J Fam Violence. 2015;30(6):699-717.

12. Rollè L et al. Front Psychol. 21 Aug 2018. doi: 10.3389/fpsyg.2018.01506.

13. Paterno MT and Draughon JE. J Midwif Women Health. 2016;61(31):370-5.

14. Kalra N et al. Cochrane Database Syst Rev. 2021 May 31;5(5)CD012423.

15. Larsen SE and Hamberger LK. J Fam Viol. 2015;30:1007-30.

16. Kalra N et al. Cochrane Database Syst Rev. 2017 Feb;2017(2):CD012423.

17. Campbell JC et al. J Interpers Violence. 2009;24(4):653-74.

Violence against women remains a global dilemma in need of attention. Physical violence in particular, is the most prevalent type of violence across all genders, races, and nationalities.

The Centers for Disease Control and Prevention says more than 43 million women and 38 million men report experiencing psychological aggression by an intimate partner in their lifetime. Meanwhile, 11 million women and 5 million men report enduring sexual or physical violence and intimate partner violence (IPV), and/or stalking by an intimate partner during their lifetimes, according to the CDC.1

COVID pandemic’s influence

Isolation tied to the COVID-19 pandemic has been linked to increased IPV. A study conducted by researchers at the University of California, Davis, suggested that extra stress experienced during the COVID-19 pandemic caused by income loss, and the inability to pay for housing and food exacerbated the prevalence of IPV early during the pandemic.⁶

That study, where researchers collected in surveys of nearly 400 adults in the beginning in April 2020 for 10 weeks, showed that more services and communication are needed so that frontline health care and food bank workers, for example, in addition to social workers, doctors, and therapists, can spot the signs and ask clients questions about potential IPV. They could then link survivors to pertinent assistance and resources.

Furthermore, multiple factors probably have played a pivotal role in increasing the prevalence of IPV during the COVID-19 pandemic. For instance, disruption to usual health and social services as well as diminished access to support systems, such as shelters, and charity helplines negatively affected the reporting of domestic violence.

Long before the pandemic, over the past decade, international and national bodies have played a crucial role in terms of improving the awareness and response to domestic violence.^7,8 In addition, several policies have been introduced in countries around the globe emphasizing the need to inquire routinely about domestic violence. Nevertheless, mental health services often fail to adequately address domestic violence in clinical encounters. A systematic review of domestic violence assessment screening performed in a variety of health care settings found that evidence was insufficient to conclude that routine inquiry improved morbidity and mortality among victims of IPV.⁹ So the question becomes: How can we get our patients to tell us about these experiences so we can intervene?
 

Gender differences in perpetuating IPV

Several studies have found that abuse can result in various mental illnesses, such as depression, PTSD, anxiety, and suicidal ideation. Again, men have a disproportionately higher rate of perpetrating IPV, compared with women. This theory has been a source of debate in the academic community for years, but recent research has confirmed that women do perpetuate violence against their partners to some extent.^10,11

Some members of the LGBTQ+ community also report experiencing violence from partners, so as clinicians, we also need to raise our awareness about the existence of violence among same-sex couples. In fact, a team of Italian researchers report more than 50% of gay men and almost 75% of lesbian women reported that they had been psychologically abused by a partner.¹² More research into this area is needed.
 

Our role as health care professionals

The U.S. Preventive Services Task Force advises that all clinic visits include regular IPV screening.¹³ But these screenings are all too rare. In fact, a meta-analysis of 19 trials of more than 1,600 participants showed only 9%-40% of doctors routinely test for IPV.¹⁴ That research clearly shows how important it is for all clinicians to execute IPV screening. However, numerous challenges toward screening exist, including personal discomfort, limited time during appointments, insufficient resources, and inadequate training.

One ongoing debate revolves around which clinician should screen for IPV. Should the psychiatrist carry out this role – or perhaps the primary care physician, nurse, or social worker? These issues become even more fraught when clinicians worry about offending the patient – especially if the clinician is a male.¹⁵

The bottom line is that physicians should inquire about intimate partner violence, because research indicates that women are more likely to reveal abuse when prompted. In addition, during physician appointments, they can use the physician-patient therapeutic connection to conduct a domestic violence evaluation, give resources to victims, and provide ongoing care. Patients who exhibit treatment resistance, persistent pain, depression, sleeplessness, and headaches should prompt psychiatrists to conduct additional investigations into the likelihood of intimate partner violence and domestic abuse.

W also should be attentive when counseling patients about domestic violence when suggesting life-changing events such as pregnancy, employment loss, separation, or divorce. Similar to the recommendations of the USPSTF that all women and men should be screened for IPV, it is suggested that physicians be conscious of facilitating a conversation and not being overtly judgmental while observing body cues. Using the statements such as “we have been hearing a lot of violence in our community lately” could be a segue to introduce the subject.

Asking the question of whether you are being hit rather than being abused has allowed more women to open up more about domestic violence. While physicians are aware that most victims might recant and often go back to their abusers, victims need to be counseled that the abuse might intensify and lead to death.

For women who perpetuate IPV and survivors of IPV, safety is the priority. Physicians should provide safety options and be the facilitators. Studies have shown that fewer victims get the referral to the supporting agencies when IPV is indicated, which puts their safety at risk. In women who commit IPV, clinicians should assess the role of the individual in an IPV disclosure. There are various treatment modalities, whether the violence is performed through self-defense, bidirectionally, or because of aggression.

With the advancement of technology, web-based training on how to ask for IPV, documentation, acknowledgment, and structured referral increase physicians’ confidence when faced with an IPV disclosure than none.¹⁶ Treatment modalities should include medication reconciliation and cognitive-behavioral therapy – focusing on emotion regulation.

Using instruments such as the danger assessment tool can help physicians intervene early, reducing the risk of domestic violence and IPV recurrence instead of using clinical assessment alone.¹⁷ Physicians should convey empathy, validate victims, and help, especially when abuse is reported.

Also, it is important to evaluate survivors’ safety. Counseling can help people rebuild their self-esteem. Structured referrals for psychiatric help and support services are needed to help survivors on the long road to recovery.

Training all physicians, regardless of specialty, is essential to improve prompt IPV identification and bring awareness to resources available to survivors when IPV is disclosed. Although we described an association between IPV victims becoming possible perpetrators of IPV, more long-term studies are required to show the various processes that influence IPV perpetration rates, especially by survivors.

We would also like international and national regulatory bodies to increase the awareness of IPV and adequately address IPV with special emphasis on how mental health services should assess, identify, and respond to services for people who are survivors and perpetrators of IPV.

Dr. Kumari, Dr. Otite, Dr. Afzal, Dr. Alcera, and Dr. Doumas are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. They have no conflicts of interest.

References

1. Centers for Disease Control and Prevention. Preventing intimate partner violence. 2020 Oct 9.

2. Yu R et al. PLOS Med. 16(12):e1002995. doi: 10.1371/journal.pmed.1002995.

3. Oram S et al. Epidemiol Psychiatr Sci. 2014 Dec;23(4):361-76.

4. Munro OE and Sellbom M. Pers Ment Health. 2020 Mar 11. doi: 10.1002/pmh.1480.

5. Sahraian A et al. Asian J Psychiatry. 2020 Jun. doi: 10.1016/j.ajp.2020.102062.

6. Nikos-Rose K. “COVID-19 Isolation Linked to Increased Domestic Violence, Researchers Suggest.” 2021 Feb 24. University of California, Davis.

7. World Health Organization. “Responding to intimate partner violence and sexual violence against women.” WHO clinical policy guidelines. 2013.

8. National Institute for Health and Care Excellence. “Domestic violence and abuse: Multi-agency working.” PH50. 2014 Feb 26.

9. Feder GS et al. Arch Intern Med. 2006;166(1):22-37.

10. Gondolf EW. Violence Against Women. 2014 Dec;20(12)1539-46.

11. Hamberger LK and Larsen SE. J Fam Violence. 2015;30(6):699-717.

12. Rollè L et al. Front Psychol. 21 Aug 2018. doi: 10.3389/fpsyg.2018.01506.

13. Paterno MT and Draughon JE. J Midwif Women Health. 2016;61(31):370-5.

14. Kalra N et al. Cochrane Database Syst Rev. 2021 May 31;5(5)CD012423.

15. Larsen SE and Hamberger LK. J Fam Viol. 2015;30:1007-30.

16. Kalra N et al. Cochrane Database Syst Rev. 2017 Feb;2017(2):CD012423.

17. Campbell JC et al. J Interpers Violence. 2009;24(4):653-74.

Depending on the data you’re looking at, 40%-60% of physicians are burned out.

Research studies and the eye test reveal the painfully obvious: Colleagues are tired, winded, spent, and at times way past burned out. People aren’t asking me if they’re burned out. They know they’re burned out; heck, they can even recite the Maslach burnout inventory, forward and backward, in a mask, or while completing a COVID quarantine. A fair share of people know the key steps to prevent burnout and promote recovery.

What I’m starting to see more of is, “Why should I even bother to recover from this? Why pick myself up again just to get another occupational stress injury (burnout, demoralization, moral injury, etc.)?” In other words, it’s not just simply about negating burnout; it’s about supporting and facilitating the motivation to work.

We’ve been through so much with COVID that it might be challenging to remember when you saw a truly engaged work environment. No doubt, we have outstanding professionals across medicine who answer the bell every day. However, if you’ve been looking closely, many teams/units have lost a bit of the zip and pep. The synergy and trust aren’t as smooth, and at noon, everyone counts the hours to the end of the shift.

You may be thinking, Well, of course, they are; we’re still amid a pandemic, and people have been through hell. Your observation would be correct, except I’ve personally seen some teams weather the pandemic storm and still remain engaged (some even more involved).

The No. 1 consult result for the GW Resiliency and Well-Being Center, where I work, has been on lectures for burnout. The R&WC has given so many of these lectures that my dreams take the form of a PowerPoint presentation. Overall the talks have gone very well. We’ve added skills sections on practices of whole-person care. We’ve blitzed the daylights out of restorative sleep, yet I know we are still searching for the correct narrative.

Motivated staff, faculty, and students will genuinely take in the information and follow the recommendations; however, they still struggle to find that drive and zest for work. Yes, moving from burnout to neutral is reasonable but likely won’t move the needle of your professional or personal life. We need to have the emotional energy and the clear desire to utilize that energy for a meaningful purpose.

Talking about burnout in specific ways is straightforward and, in my opinion, much easier than talking about engagement. Part of the challenge when trying to discuss engagement is that people can feel invalidated or that you’re telling them to be stoic. Or worse yet, that the problem of burnout primarily lies with them. It’s essential to recognize the role of an organizational factor in burnout (approximately 80%, depending on the study); still, even if you address burnout, people may not be miserable, but it doesn’t mean they will stay at their current job (please cue intro music for the Great Resignation).

Engagement models have existed for some time and certainly have gained much more attention in health care settings over the past 2 decades. Engagement can be described as having three components: dedication, vigor, and absorption. When a person is filling all three of these components over time, presto – you get the much-sought-after state of the supremely engaged professional.

These models definitely give us excellent starting points to approach engagement from a pre-COVID era. In COVID and beyond, I’m not sure how these models will stand up in a hybrid work environment, where autonomy and flexibility could be more valued than ever. Personally, COVID revealed some things I was missing in my work pre-COVID:

• Time to think and process. This was one of the great things about being a consultation-liaison psychiatrist; it was literally feast or famine.
• Doing what I’m talented at and really enjoy.
• Time is short, and I want to be more present in the life of my family.
• Growth and curiosity are vitally important to me. These have to be part of my daily ritual and practice.

The list above isn’t exhaustive, but I’ve found them to be my own personal recipe for being engaged. Over the next series of articles, I’m going to focus on engagement and factors related to key resilience. These articles will be informed by a front-line view from my colleagues, and hopefully start to separate the myth from reality on the subject of health professional engagement and resilience.

Everyone be safe and well!

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

Depending on the data you’re looking at, 40%-60% of physicians are burned out.

Research studies and the eye test reveal the painfully obvious: Colleagues are tired, winded, spent, and at times way past burned out. People aren’t asking me if they’re burned out. They know they’re burned out; heck, they can even recite the Maslach burnout inventory, forward and backward, in a mask, or while completing a COVID quarantine. A fair share of people know the key steps to prevent burnout and promote recovery.

What I’m starting to see more of is, “Why should I even bother to recover from this? Why pick myself up again just to get another occupational stress injury (burnout, demoralization, moral injury, etc.)?” In other words, it’s not just simply about negating burnout; it’s about supporting and facilitating the motivation to work.

We’ve been through so much with COVID that it might be challenging to remember when you saw a truly engaged work environment. No doubt, we have outstanding professionals across medicine who answer the bell every day. However, if you’ve been looking closely, many teams/units have lost a bit of the zip and pep. The synergy and trust aren’t as smooth, and at noon, everyone counts the hours to the end of the shift.

You may be thinking, Well, of course, they are; we’re still amid a pandemic, and people have been through hell. Your observation would be correct, except I’ve personally seen some teams weather the pandemic storm and still remain engaged (some even more involved).

The No. 1 consult result for the GW Resiliency and Well-Being Center, where I work, has been on lectures for burnout. The R&WC has given so many of these lectures that my dreams take the form of a PowerPoint presentation. Overall the talks have gone very well. We’ve added skills sections on practices of whole-person care. We’ve blitzed the daylights out of restorative sleep, yet I know we are still searching for the correct narrative.

Motivated staff, faculty, and students will genuinely take in the information and follow the recommendations; however, they still struggle to find that drive and zest for work. Yes, moving from burnout to neutral is reasonable but likely won’t move the needle of your professional or personal life. We need to have the emotional energy and the clear desire to utilize that energy for a meaningful purpose.

Talking about burnout in specific ways is straightforward and, in my opinion, much easier than talking about engagement. Part of the challenge when trying to discuss engagement is that people can feel invalidated or that you’re telling them to be stoic. Or worse yet, that the problem of burnout primarily lies with them. It’s essential to recognize the role of an organizational factor in burnout (approximately 80%, depending on the study); still, even if you address burnout, people may not be miserable, but it doesn’t mean they will stay at their current job (please cue intro music for the Great Resignation).

Engagement models have existed for some time and certainly have gained much more attention in health care settings over the past 2 decades. Engagement can be described as having three components: dedication, vigor, and absorption. When a person is filling all three of these components over time, presto – you get the much-sought-after state of the supremely engaged professional.

These models definitely give us excellent starting points to approach engagement from a pre-COVID era. In COVID and beyond, I’m not sure how these models will stand up in a hybrid work environment, where autonomy and flexibility could be more valued than ever. Personally, COVID revealed some things I was missing in my work pre-COVID:

• Time to think and process. This was one of the great things about being a consultation-liaison psychiatrist; it was literally feast or famine.
• Doing what I’m talented at and really enjoy.
• Time is short, and I want to be more present in the life of my family.
• Growth and curiosity are vitally important to me. These have to be part of my daily ritual and practice.

The list above isn’t exhaustive, but I’ve found them to be my own personal recipe for being engaged. Over the next series of articles, I’m going to focus on engagement and factors related to key resilience. These articles will be informed by a front-line view from my colleagues, and hopefully start to separate the myth from reality on the subject of health professional engagement and resilience.

Everyone be safe and well!

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

Depending on the data you’re looking at, 40%-60% of physicians are burned out.

Research studies and the eye test reveal the painfully obvious: Colleagues are tired, winded, spent, and at times way past burned out. People aren’t asking me if they’re burned out. They know they’re burned out; heck, they can even recite the Maslach burnout inventory, forward and backward, in a mask, or while completing a COVID quarantine. A fair share of people know the key steps to prevent burnout and promote recovery.

What I’m starting to see more of is, “Why should I even bother to recover from this? Why pick myself up again just to get another occupational stress injury (burnout, demoralization, moral injury, etc.)?” In other words, it’s not just simply about negating burnout; it’s about supporting and facilitating the motivation to work.

We’ve been through so much with COVID that it might be challenging to remember when you saw a truly engaged work environment. No doubt, we have outstanding professionals across medicine who answer the bell every day. However, if you’ve been looking closely, many teams/units have lost a bit of the zip and pep. The synergy and trust aren’t as smooth, and at noon, everyone counts the hours to the end of the shift.

You may be thinking, Well, of course, they are; we’re still amid a pandemic, and people have been through hell. Your observation would be correct, except I’ve personally seen some teams weather the pandemic storm and still remain engaged (some even more involved).

The No. 1 consult result for the GW Resiliency and Well-Being Center, where I work, has been on lectures for burnout. The R&WC has given so many of these lectures that my dreams take the form of a PowerPoint presentation. Overall the talks have gone very well. We’ve added skills sections on practices of whole-person care. We’ve blitzed the daylights out of restorative sleep, yet I know we are still searching for the correct narrative.

Motivated staff, faculty, and students will genuinely take in the information and follow the recommendations; however, they still struggle to find that drive and zest for work. Yes, moving from burnout to neutral is reasonable but likely won’t move the needle of your professional or personal life. We need to have the emotional energy and the clear desire to utilize that energy for a meaningful purpose.

Talking about burnout in specific ways is straightforward and, in my opinion, much easier than talking about engagement. Part of the challenge when trying to discuss engagement is that people can feel invalidated or that you’re telling them to be stoic. Or worse yet, that the problem of burnout primarily lies with them. It’s essential to recognize the role of an organizational factor in burnout (approximately 80%, depending on the study); still, even if you address burnout, people may not be miserable, but it doesn’t mean they will stay at their current job (please cue intro music for the Great Resignation).

Engagement models have existed for some time and certainly have gained much more attention in health care settings over the past 2 decades. Engagement can be described as having three components: dedication, vigor, and absorption. When a person is filling all three of these components over time, presto – you get the much-sought-after state of the supremely engaged professional.

These models definitely give us excellent starting points to approach engagement from a pre-COVID era. In COVID and beyond, I’m not sure how these models will stand up in a hybrid work environment, where autonomy and flexibility could be more valued than ever. Personally, COVID revealed some things I was missing in my work pre-COVID:

• Time to think and process. This was one of the great things about being a consultation-liaison psychiatrist; it was literally feast or famine.
• Doing what I’m talented at and really enjoy.
• Time is short, and I want to be more present in the life of my family.
• Growth and curiosity are vitally important to me. These have to be part of my daily ritual and practice.

The list above isn’t exhaustive, but I’ve found them to be my own personal recipe for being engaged. Over the next series of articles, I’m going to focus on engagement and factors related to key resilience. These articles will be informed by a front-line view from my colleagues, and hopefully start to separate the myth from reality on the subject of health professional engagement and resilience.

Everyone be safe and well!

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

In another salvo in the heated debate over treatment for kids who believe they’re transgender, a study published in PLoS One suggests that transgender adults who received hormone therapy as teenagers are mentally healthier in a pair of ways than those who didn’t.

The study, which only looks at transgender adults, doesn’t confirm that hormone therapy in childhood is a beneficial treatment. Still, “we found that for all age groups, access to [adolescent] gender-affirming hormone initiation was associated with lower odds of past-year suicidal ideation and past-month severe psychological distress measured in adulthood,” said lead author Jack Turban, MD, chief fellow in child and adolescent psychiatry at Stanford (Calif.) University, in an interview. “We also found better mental-health outcomes for those who started gender-affirming hormones as adolescents when compared to those who didn’t start them until they were adults.”

The use of hormone treatment and puberty blockers by transgender teens is extremely controversial. Critics say the treatments are harmful and unnecessary, and Republican politicians are trying to ban their use in some states. Last spring, Arkansas became the first state to ban the treatments. The law is on hold amid a legal challenge.

The researchers launched the study to gain more insight into the impact of hormone therapy on children. “There have been several longitudinal studies showing that mental health improves following gender-affirming medical care for transgender youth, but there has been less research looking at the relationship between when these medications are started and adult mental health outcomes,” Dr. Turban said. “This is the first study to look at various ages of initiation of gender-affirming hormones and compare outcomes between those who started gender-affirming hormones during adolescence and those who did not start them until adulthood.”

For the new study, the authors analyzed the findings of the 2015 U.S. Transgender Survey of 27,715 adults and focused on 21,598 who said they’d wanted hormone therapy (40% aged 18-24, 83% White, 35% transgender male, 41% transgender female, with the rest using other terms such as “queer” or “nonbinary” to describe themselves).

Of these subjects, 41.0% never received hormone therapy, 0.6% underwent therapy in early adolescence, 1.7% received it in late adolescence, and 56.8% got it as adults.

The researchers made various adjustments for confounders – age, partnership status, employment status, K-12 harassment, and experience of gender identity conversion efforts. Those who received hormone therapy had lower odds of past-year suicidal ideation vs. those who didn’t: adjusted odds ratio, 0.4; 95% confidence interval, 0.2-0.6; P < .0001 for therapy that occurred from age 14 to 15, aOR, 0.5; 95% CI, 0.4-0.7; P < .0001, for therapy that occurred from age 16 to 17, and aOR, 0.8; 95% CI, 0.7-0.8; P < .0001 for therapy that occurred in adulthood.

However, there was no statistically significant link between hormone therapy and past-year suicidal ideation with a plan or past-year suicide attempt.

The study also found lower rates of past-month severe psychological distress: aOR. 0.3; 95% CI, 0.2-0.4; P < .0001 for therapy from age 14 to 15, aOR, 0.3; 95% CI, 0.3-0.4; P < .0001 for therapy from age 16 to 17, and aOR, 0.6 (95% CI, 0.5-0.6; P < .0001) for therapy in adulthood.

There was no statistically significant link between hormone therapy and past-month binge drinking or lifetime illicit drug use.

“The findings indicate that clinicians caring for adolescents need to be properly trained in gender-affirming medical care, including hormone therapy, in order to help promote good mental health outcomes for transgender people. Comprehensive training in gender-affirming care is currently not part of standard medical education curricula,” said study coauthor Alex Keuroghlian, MD, MPH, director of the National LGBTQIA+ Health Education Center at the Fenway Institute and associate professor of psychiatry at Harvard Medical School, Boston, in an interview.

The study has limitations. The survey population doesn’t include anyone who committed suicide, nor does it include people who had gender dysphoria as children but didn’t go on to identify as transgender as adults. It is also retrospective. “There is a general consensus that, given the data we have so far, it would be unethical to conduct a randomized controlled trial in this space,” said study lead author Dr. Turban.

Several critics of hormone therapy in teens support a psychotherapy-based approach to gender dysphoria that considers whether other factors are at play than transgender orientation. They’ve united to attack research based on the 2015 transgender survey. In a 2021 report in Archives of Sexual Behavior, they called it “a highly skewed sample” and objected to “a conflation of ethical nonaffirmative psychotherapy with conversion therapy.”

In an interview, one of the critics – developmental psychologist and retired University of Sydney professor Dianna Kenny, PhD – said the new study’s “serious problem of recall bias” about hormone therapy in the survey is “insurmountable.” The survey, she said, also fails to explore why participants who wanted hormone therapy didn’t get it.

Dr. Kenny, who believes all hormone therapy in teens with gender dysphoria outside of clinical trials is inappropriate, also pointed out that hormone therapy has many side effects. She added that young people with gender dysphoria often “realize through a process of cognitive and psychosocial maturation that they were not ‘genuinely’ trans but suffering from other conditions that needed treatment – e.g., internalized homophobia, trauma, including sexual abuse, attention-deficit/hyperactivity disorder, autism spectrum disorder, etc.”

No specific funding is reported, although two of the authors report receiving various grants, fellowship and research funding. Dr. Turban discloses textbook royalties from Springer Nature and expert witness payments from the ACLU. Dr. Keuroghlian discloses textbook royalties from McGraw Hill. Dr. Kenny reports no disclosures.

In another salvo in the heated debate over treatment for kids who believe they’re transgender, a study published in PLoS One suggests that transgender adults who received hormone therapy as teenagers are mentally healthier in a pair of ways than those who didn’t.

The study, which only looks at transgender adults, doesn’t confirm that hormone therapy in childhood is a beneficial treatment. Still, “we found that for all age groups, access to [adolescent] gender-affirming hormone initiation was associated with lower odds of past-year suicidal ideation and past-month severe psychological distress measured in adulthood,” said lead author Jack Turban, MD, chief fellow in child and adolescent psychiatry at Stanford (Calif.) University, in an interview. “We also found better mental-health outcomes for those who started gender-affirming hormones as adolescents when compared to those who didn’t start them until they were adults.”

The use of hormone treatment and puberty blockers by transgender teens is extremely controversial. Critics say the treatments are harmful and unnecessary, and Republican politicians are trying to ban their use in some states. Last spring, Arkansas became the first state to ban the treatments. The law is on hold amid a legal challenge.

The researchers launched the study to gain more insight into the impact of hormone therapy on children. “There have been several longitudinal studies showing that mental health improves following gender-affirming medical care for transgender youth, but there has been less research looking at the relationship between when these medications are started and adult mental health outcomes,” Dr. Turban said. “This is the first study to look at various ages of initiation of gender-affirming hormones and compare outcomes between those who started gender-affirming hormones during adolescence and those who did not start them until adulthood.”

For the new study, the authors analyzed the findings of the 2015 U.S. Transgender Survey of 27,715 adults and focused on 21,598 who said they’d wanted hormone therapy (40% aged 18-24, 83% White, 35% transgender male, 41% transgender female, with the rest using other terms such as “queer” or “nonbinary” to describe themselves).

Of these subjects, 41.0% never received hormone therapy, 0.6% underwent therapy in early adolescence, 1.7% received it in late adolescence, and 56.8% got it as adults.

The researchers made various adjustments for confounders – age, partnership status, employment status, K-12 harassment, and experience of gender identity conversion efforts. Those who received hormone therapy had lower odds of past-year suicidal ideation vs. those who didn’t: adjusted odds ratio, 0.4; 95% confidence interval, 0.2-0.6; P < .0001 for therapy that occurred from age 14 to 15, aOR, 0.5; 95% CI, 0.4-0.7; P < .0001, for therapy that occurred from age 16 to 17, and aOR, 0.8; 95% CI, 0.7-0.8; P < .0001 for therapy that occurred in adulthood.

However, there was no statistically significant link between hormone therapy and past-year suicidal ideation with a plan or past-year suicide attempt.

The study also found lower rates of past-month severe psychological distress: aOR. 0.3; 95% CI, 0.2-0.4; P < .0001 for therapy from age 14 to 15, aOR, 0.3; 95% CI, 0.3-0.4; P < .0001 for therapy from age 16 to 17, and aOR, 0.6 (95% CI, 0.5-0.6; P < .0001) for therapy in adulthood.

There was no statistically significant link between hormone therapy and past-month binge drinking or lifetime illicit drug use.

“The findings indicate that clinicians caring for adolescents need to be properly trained in gender-affirming medical care, including hormone therapy, in order to help promote good mental health outcomes for transgender people. Comprehensive training in gender-affirming care is currently not part of standard medical education curricula,” said study coauthor Alex Keuroghlian, MD, MPH, director of the National LGBTQIA+ Health Education Center at the Fenway Institute and associate professor of psychiatry at Harvard Medical School, Boston, in an interview.

The study has limitations. The survey population doesn’t include anyone who committed suicide, nor does it include people who had gender dysphoria as children but didn’t go on to identify as transgender as adults. It is also retrospective. “There is a general consensus that, given the data we have so far, it would be unethical to conduct a randomized controlled trial in this space,” said study lead author Dr. Turban.

Several critics of hormone therapy in teens support a psychotherapy-based approach to gender dysphoria that considers whether other factors are at play than transgender orientation. They’ve united to attack research based on the 2015 transgender survey. In a 2021 report in Archives of Sexual Behavior, they called it “a highly skewed sample” and objected to “a conflation of ethical nonaffirmative psychotherapy with conversion therapy.”

In an interview, one of the critics – developmental psychologist and retired University of Sydney professor Dianna Kenny, PhD – said the new study’s “serious problem of recall bias” about hormone therapy in the survey is “insurmountable.” The survey, she said, also fails to explore why participants who wanted hormone therapy didn’t get it.

Dr. Kenny, who believes all hormone therapy in teens with gender dysphoria outside of clinical trials is inappropriate, also pointed out that hormone therapy has many side effects. She added that young people with gender dysphoria often “realize through a process of cognitive and psychosocial maturation that they were not ‘genuinely’ trans but suffering from other conditions that needed treatment – e.g., internalized homophobia, trauma, including sexual abuse, attention-deficit/hyperactivity disorder, autism spectrum disorder, etc.”

No specific funding is reported, although two of the authors report receiving various grants, fellowship and research funding. Dr. Turban discloses textbook royalties from Springer Nature and expert witness payments from the ACLU. Dr. Keuroghlian discloses textbook royalties from McGraw Hill. Dr. Kenny reports no disclosures.

In another salvo in the heated debate over treatment for kids who believe they’re transgender, a study published in PLoS One suggests that transgender adults who received hormone therapy as teenagers are mentally healthier in a pair of ways than those who didn’t.

The study, which only looks at transgender adults, doesn’t confirm that hormone therapy in childhood is a beneficial treatment. Still, “we found that for all age groups, access to [adolescent] gender-affirming hormone initiation was associated with lower odds of past-year suicidal ideation and past-month severe psychological distress measured in adulthood,” said lead author Jack Turban, MD, chief fellow in child and adolescent psychiatry at Stanford (Calif.) University, in an interview. “We also found better mental-health outcomes for those who started gender-affirming hormones as adolescents when compared to those who didn’t start them until they were adults.”

The use of hormone treatment and puberty blockers by transgender teens is extremely controversial. Critics say the treatments are harmful and unnecessary, and Republican politicians are trying to ban their use in some states. Last spring, Arkansas became the first state to ban the treatments. The law is on hold amid a legal challenge.

The researchers launched the study to gain more insight into the impact of hormone therapy on children. “There have been several longitudinal studies showing that mental health improves following gender-affirming medical care for transgender youth, but there has been less research looking at the relationship between when these medications are started and adult mental health outcomes,” Dr. Turban said. “This is the first study to look at various ages of initiation of gender-affirming hormones and compare outcomes between those who started gender-affirming hormones during adolescence and those who did not start them until adulthood.”

For the new study, the authors analyzed the findings of the 2015 U.S. Transgender Survey of 27,715 adults and focused on 21,598 who said they’d wanted hormone therapy (40% aged 18-24, 83% White, 35% transgender male, 41% transgender female, with the rest using other terms such as “queer” or “nonbinary” to describe themselves).

Of these subjects, 41.0% never received hormone therapy, 0.6% underwent therapy in early adolescence, 1.7% received it in late adolescence, and 56.8% got it as adults.

The researchers made various adjustments for confounders – age, partnership status, employment status, K-12 harassment, and experience of gender identity conversion efforts. Those who received hormone therapy had lower odds of past-year suicidal ideation vs. those who didn’t: adjusted odds ratio, 0.4; 95% confidence interval, 0.2-0.6; P < .0001 for therapy that occurred from age 14 to 15, aOR, 0.5; 95% CI, 0.4-0.7; P < .0001, for therapy that occurred from age 16 to 17, and aOR, 0.8; 95% CI, 0.7-0.8; P < .0001 for therapy that occurred in adulthood.

However, there was no statistically significant link between hormone therapy and past-year suicidal ideation with a plan or past-year suicide attempt.

The study also found lower rates of past-month severe psychological distress: aOR. 0.3; 95% CI, 0.2-0.4; P < .0001 for therapy from age 14 to 15, aOR, 0.3; 95% CI, 0.3-0.4; P < .0001 for therapy from age 16 to 17, and aOR, 0.6 (95% CI, 0.5-0.6; P < .0001) for therapy in adulthood.

There was no statistically significant link between hormone therapy and past-month binge drinking or lifetime illicit drug use.

“The findings indicate that clinicians caring for adolescents need to be properly trained in gender-affirming medical care, including hormone therapy, in order to help promote good mental health outcomes for transgender people. Comprehensive training in gender-affirming care is currently not part of standard medical education curricula,” said study coauthor Alex Keuroghlian, MD, MPH, director of the National LGBTQIA+ Health Education Center at the Fenway Institute and associate professor of psychiatry at Harvard Medical School, Boston, in an interview.

The study has limitations. The survey population doesn’t include anyone who committed suicide, nor does it include people who had gender dysphoria as children but didn’t go on to identify as transgender as adults. It is also retrospective. “There is a general consensus that, given the data we have so far, it would be unethical to conduct a randomized controlled trial in this space,” said study lead author Dr. Turban.

Several critics of hormone therapy in teens support a psychotherapy-based approach to gender dysphoria that considers whether other factors are at play than transgender orientation. They’ve united to attack research based on the 2015 transgender survey. In a 2021 report in Archives of Sexual Behavior, they called it “a highly skewed sample” and objected to “a conflation of ethical nonaffirmative psychotherapy with conversion therapy.”

In an interview, one of the critics – developmental psychologist and retired University of Sydney professor Dianna Kenny, PhD – said the new study’s “serious problem of recall bias” about hormone therapy in the survey is “insurmountable.” The survey, she said, also fails to explore why participants who wanted hormone therapy didn’t get it.

Dr. Kenny, who believes all hormone therapy in teens with gender dysphoria outside of clinical trials is inappropriate, also pointed out that hormone therapy has many side effects. She added that young people with gender dysphoria often “realize through a process of cognitive and psychosocial maturation that they were not ‘genuinely’ trans but suffering from other conditions that needed treatment – e.g., internalized homophobia, trauma, including sexual abuse, attention-deficit/hyperactivity disorder, autism spectrum disorder, etc.”

No specific funding is reported, although two of the authors report receiving various grants, fellowship and research funding. Dr. Turban discloses textbook royalties from Springer Nature and expert witness payments from the ACLU. Dr. Keuroghlian discloses textbook royalties from McGraw Hill. Dr. Kenny reports no disclosures.

Over-the-counter cannabidiol (CBD) products appear to improve pain, sleep, and anxiety disorders, preliminary research suggests.

Interim findings from Advancing CBD Education and Science, a 100% virtual, open label, randomized, controlled trial, show study participants experienced various degrees of “clinically meaningful” improvements in sleep quality, anxiety, and pain.

“ACES is the largest clinical trial ever conducted on commercially available CBD products and provides first-of-its-kind real world evidence into what conditions users may experience benefit from CBD usage, whether these benefits are clinically meaningful, what attributes of CBD products may impact health outcomes, and what side effects may occur,” study coinvestigator Jessica Saleska, PhD, MPH, director of research at Radicle Science, the company that conducted the study, told this news organization.
 

Scant evidence

Despite the growing market size of commercially available CBD products “there is still scant data on the effectiveness of over-the-counter cannabinoid products due to the cost, speed, and scale limitations of the current approach to scientific research,” Jeff Chen, MD, MBA, cofounder and CEO of Radicle Science, told this news organization.

One of the study’s goals, said Ethan Russo, MD, a neurologist, founder/CEO of CReDO Science, and scientific adviser for Radicle, is to help consumers make informed decisions before purchasing and using commercially available oral CBD products. 

Designed to eliminate all physical infrastructure, which minimizes costs and facilitates faster execution, ACES was conducted much like a phase 4 clinical trial, collating real-world data gathered over 4 weeks.

“The process that Radicle scientists [have] advanced is sort of a crowdsourcing approach to doing clinical science,” Dr. Russo said. “Hopefully, there is going to be a considerable amount of data generated that [will] affect people’s buying options.”

The study also aimed to evaluate product attributes, including composition, mode of use, dosage, dosage timing and frequency, and their correlation to degrees of outcomes.

Dr. Russo explained why product composition is an important factor, especially when dealing with CBD. “What happens with any given [CBD] preparation is going to be totally a function of other components, if any. 

“For example, there’s this mistaken notion that cannabidiol is sedating; it is not. Pure cannabidiol is stimulating in low and moderate amounts. Where the confusion has arisen is that the early chemovars containing cannabidiol were also predominant in myrcene, the sedating terpene, [thereby] creating this misimpression that it is good for sleep,” he added.

However, CBD might also affect sleep by reducing anxiety that interferes with it. “What’s clear is that cannabidiol is an antianxiety agent, if you have a sufficient dose,” Dr. Russo said.

The 4-week study included 2,704 participants aged 21 years and older, self-reporting anxiety, chronic pain, or sleep disturbances as a primary reason for taking CBD. Study participants were randomly assigned to receive 1 of 13 commercially available oral CBD extracts.

Participants were allocated to 1 of 14 cohorts, comprising 13 treatment groups with 208 participants each who received a single CBD product, or a wait-list control group of 296 participants who received product at the study’s end.

The primary outcome focused on “clinically meaningful” changes, which were defined as “distinct and palpable improvements in quality of life through improvements in respective health outcomes.”

Secondary outcomes included changes in sleep, anxiety, and pain based on several validated indices, including the PROMIS (Patient-Reported Outcome Measurement Information System) Sleep Short Form; the PROMIS Anxiety Scale; the Patient Global Impression of Change; the Pain, Enjoyment, General Activity scale; and the General Anxiety Disorder–7 scale.

The interim study results are promising, with participants reporting, on average, a 71% improvement in well-being. Additionally, 63% reported clinically meaningful improvements in anxiety, and 61% in sleep quality. The CBD products provided smaller benefits in pain management, with less than half (47%) experiencing meaningful improvements.

In addition to improvement in sleep, pain, and anxiety, these data highlight how rapidly benefits occurred; most were realized during the first week of the study, with up to 61% of treatment group participants reporting a therapeutic effect within 1-4 hours of taking their assigned product.
 

Overcoming the placebo effect

Commenting on the research, Justin Strickland, PhD, an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, who was not involved in the research, said without knowing a lot about the pharmacology of the products being tested, early dramatic improvements in these measures, such as sleep impairment, are common.

“There are some data to suggest that there is an expectancy effect when we talk about the therapeutic benefit of cannabinoid products, (i.e., when someone has the expectation that they are going to experience a stronger effect) but this is true of any drug in an open label trial,” Dr. Strickland added.

Dr. Russo took the point a step further. “It’s getting near impossible to look at cannabinoid compounds, even with randomized, controlled trials because of the burgeoning placebo responses. When you couple it with the fact that consumers have the mistaken notion that cannabis-based drugs are miraculous, the expectations are so high that everyone thinks that they’re on the real stuff, even if it’s a placebo group.”

Still, both Dr. Strickland and Dr. Russo highlighted the fact that ACES mirrors real-world experience, which will they hope will inform the use of CBD and CBD-based preparations moving forward. By removing certain barriers like institutional bureaucracy or federal funding restrictions inherent to more traditional randomized controlled trial design, ACES might provide data that bridge the gap between efficacy and effectiveness.

ACES was funded by Radicle Science. Dr. Chen is cofounder and CEO of Radicle Science. Dr. Russo and Dr. Strickland disclosed no relevant financial relationships.

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

Over-the-counter cannabidiol (CBD) products appear to improve pain, sleep, and anxiety disorders, preliminary research suggests.

Interim findings from Advancing CBD Education and Science, a 100% virtual, open label, randomized, controlled trial, show study participants experienced various degrees of “clinically meaningful” improvements in sleep quality, anxiety, and pain.

“ACES is the largest clinical trial ever conducted on commercially available CBD products and provides first-of-its-kind real world evidence into what conditions users may experience benefit from CBD usage, whether these benefits are clinically meaningful, what attributes of CBD products may impact health outcomes, and what side effects may occur,” study coinvestigator Jessica Saleska, PhD, MPH, director of research at Radicle Science, the company that conducted the study, told this news organization.
 

Scant evidence

Despite the growing market size of commercially available CBD products “there is still scant data on the effectiveness of over-the-counter cannabinoid products due to the cost, speed, and scale limitations of the current approach to scientific research,” Jeff Chen, MD, MBA, cofounder and CEO of Radicle Science, told this news organization.

One of the study’s goals, said Ethan Russo, MD, a neurologist, founder/CEO of CReDO Science, and scientific adviser for Radicle, is to help consumers make informed decisions before purchasing and using commercially available oral CBD products. 

Designed to eliminate all physical infrastructure, which minimizes costs and facilitates faster execution, ACES was conducted much like a phase 4 clinical trial, collating real-world data gathered over 4 weeks.

“The process that Radicle scientists [have] advanced is sort of a crowdsourcing approach to doing clinical science,” Dr. Russo said. “Hopefully, there is going to be a considerable amount of data generated that [will] affect people’s buying options.”

The study also aimed to evaluate product attributes, including composition, mode of use, dosage, dosage timing and frequency, and their correlation to degrees of outcomes.

Dr. Russo explained why product composition is an important factor, especially when dealing with CBD. “What happens with any given [CBD] preparation is going to be totally a function of other components, if any. 

“For example, there’s this mistaken notion that cannabidiol is sedating; it is not. Pure cannabidiol is stimulating in low and moderate amounts. Where the confusion has arisen is that the early chemovars containing cannabidiol were also predominant in myrcene, the sedating terpene, [thereby] creating this misimpression that it is good for sleep,” he added.

However, CBD might also affect sleep by reducing anxiety that interferes with it. “What’s clear is that cannabidiol is an antianxiety agent, if you have a sufficient dose,” Dr. Russo said.

The 4-week study included 2,704 participants aged 21 years and older, self-reporting anxiety, chronic pain, or sleep disturbances as a primary reason for taking CBD. Study participants were randomly assigned to receive 1 of 13 commercially available oral CBD extracts.

Participants were allocated to 1 of 14 cohorts, comprising 13 treatment groups with 208 participants each who received a single CBD product, or a wait-list control group of 296 participants who received product at the study’s end.

The primary outcome focused on “clinically meaningful” changes, which were defined as “distinct and palpable improvements in quality of life through improvements in respective health outcomes.”

Secondary outcomes included changes in sleep, anxiety, and pain based on several validated indices, including the PROMIS (Patient-Reported Outcome Measurement Information System) Sleep Short Form; the PROMIS Anxiety Scale; the Patient Global Impression of Change; the Pain, Enjoyment, General Activity scale; and the General Anxiety Disorder–7 scale.

The interim study results are promising, with participants reporting, on average, a 71% improvement in well-being. Additionally, 63% reported clinically meaningful improvements in anxiety, and 61% in sleep quality. The CBD products provided smaller benefits in pain management, with less than half (47%) experiencing meaningful improvements.

In addition to improvement in sleep, pain, and anxiety, these data highlight how rapidly benefits occurred; most were realized during the first week of the study, with up to 61% of treatment group participants reporting a therapeutic effect within 1-4 hours of taking their assigned product.
 

Overcoming the placebo effect

Commenting on the research, Justin Strickland, PhD, an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, who was not involved in the research, said without knowing a lot about the pharmacology of the products being tested, early dramatic improvements in these measures, such as sleep impairment, are common.

“There are some data to suggest that there is an expectancy effect when we talk about the therapeutic benefit of cannabinoid products, (i.e., when someone has the expectation that they are going to experience a stronger effect) but this is true of any drug in an open label trial,” Dr. Strickland added.

Dr. Russo took the point a step further. “It’s getting near impossible to look at cannabinoid compounds, even with randomized, controlled trials because of the burgeoning placebo responses. When you couple it with the fact that consumers have the mistaken notion that cannabis-based drugs are miraculous, the expectations are so high that everyone thinks that they’re on the real stuff, even if it’s a placebo group.”

Still, both Dr. Strickland and Dr. Russo highlighted the fact that ACES mirrors real-world experience, which will they hope will inform the use of CBD and CBD-based preparations moving forward. By removing certain barriers like institutional bureaucracy or federal funding restrictions inherent to more traditional randomized controlled trial design, ACES might provide data that bridge the gap between efficacy and effectiveness.

ACES was funded by Radicle Science. Dr. Chen is cofounder and CEO of Radicle Science. Dr. Russo and Dr. Strickland disclosed no relevant financial relationships.

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

Over-the-counter cannabidiol (CBD) products appear to improve pain, sleep, and anxiety disorders, preliminary research suggests.

Interim findings from Advancing CBD Education and Science, a 100% virtual, open label, randomized, controlled trial, show study participants experienced various degrees of “clinically meaningful” improvements in sleep quality, anxiety, and pain.

“ACES is the largest clinical trial ever conducted on commercially available CBD products and provides first-of-its-kind real world evidence into what conditions users may experience benefit from CBD usage, whether these benefits are clinically meaningful, what attributes of CBD products may impact health outcomes, and what side effects may occur,” study coinvestigator Jessica Saleska, PhD, MPH, director of research at Radicle Science, the company that conducted the study, told this news organization.
 

Scant evidence

Despite the growing market size of commercially available CBD products “there is still scant data on the effectiveness of over-the-counter cannabinoid products due to the cost, speed, and scale limitations of the current approach to scientific research,” Jeff Chen, MD, MBA, cofounder and CEO of Radicle Science, told this news organization.

One of the study’s goals, said Ethan Russo, MD, a neurologist, founder/CEO of CReDO Science, and scientific adviser for Radicle, is to help consumers make informed decisions before purchasing and using commercially available oral CBD products. 

Designed to eliminate all physical infrastructure, which minimizes costs and facilitates faster execution, ACES was conducted much like a phase 4 clinical trial, collating real-world data gathered over 4 weeks.

“The process that Radicle scientists [have] advanced is sort of a crowdsourcing approach to doing clinical science,” Dr. Russo said. “Hopefully, there is going to be a considerable amount of data generated that [will] affect people’s buying options.”

The study also aimed to evaluate product attributes, including composition, mode of use, dosage, dosage timing and frequency, and their correlation to degrees of outcomes.

Dr. Russo explained why product composition is an important factor, especially when dealing with CBD. “What happens with any given [CBD] preparation is going to be totally a function of other components, if any. 

“For example, there’s this mistaken notion that cannabidiol is sedating; it is not. Pure cannabidiol is stimulating in low and moderate amounts. Where the confusion has arisen is that the early chemovars containing cannabidiol were also predominant in myrcene, the sedating terpene, [thereby] creating this misimpression that it is good for sleep,” he added.

However, CBD might also affect sleep by reducing anxiety that interferes with it. “What’s clear is that cannabidiol is an antianxiety agent, if you have a sufficient dose,” Dr. Russo said.

The 4-week study included 2,704 participants aged 21 years and older, self-reporting anxiety, chronic pain, or sleep disturbances as a primary reason for taking CBD. Study participants were randomly assigned to receive 1 of 13 commercially available oral CBD extracts.

Participants were allocated to 1 of 14 cohorts, comprising 13 treatment groups with 208 participants each who received a single CBD product, or a wait-list control group of 296 participants who received product at the study’s end.

The primary outcome focused on “clinically meaningful” changes, which were defined as “distinct and palpable improvements in quality of life through improvements in respective health outcomes.”

Secondary outcomes included changes in sleep, anxiety, and pain based on several validated indices, including the PROMIS (Patient-Reported Outcome Measurement Information System) Sleep Short Form; the PROMIS Anxiety Scale; the Patient Global Impression of Change; the Pain, Enjoyment, General Activity scale; and the General Anxiety Disorder–7 scale.

The interim study results are promising, with participants reporting, on average, a 71% improvement in well-being. Additionally, 63% reported clinically meaningful improvements in anxiety, and 61% in sleep quality. The CBD products provided smaller benefits in pain management, with less than half (47%) experiencing meaningful improvements.

In addition to improvement in sleep, pain, and anxiety, these data highlight how rapidly benefits occurred; most were realized during the first week of the study, with up to 61% of treatment group participants reporting a therapeutic effect within 1-4 hours of taking their assigned product.
 

Overcoming the placebo effect

Commenting on the research, Justin Strickland, PhD, an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, who was not involved in the research, said without knowing a lot about the pharmacology of the products being tested, early dramatic improvements in these measures, such as sleep impairment, are common.

“There are some data to suggest that there is an expectancy effect when we talk about the therapeutic benefit of cannabinoid products, (i.e., when someone has the expectation that they are going to experience a stronger effect) but this is true of any drug in an open label trial,” Dr. Strickland added.

Dr. Russo took the point a step further. “It’s getting near impossible to look at cannabinoid compounds, even with randomized, controlled trials because of the burgeoning placebo responses. When you couple it with the fact that consumers have the mistaken notion that cannabis-based drugs are miraculous, the expectations are so high that everyone thinks that they’re on the real stuff, even if it’s a placebo group.”

Still, both Dr. Strickland and Dr. Russo highlighted the fact that ACES mirrors real-world experience, which will they hope will inform the use of CBD and CBD-based preparations moving forward. By removing certain barriers like institutional bureaucracy or federal funding restrictions inherent to more traditional randomized controlled trial design, ACES might provide data that bridge the gap between efficacy and effectiveness.

ACES was funded by Radicle Science. Dr. Chen is cofounder and CEO of Radicle Science. Dr. Russo and Dr. Strickland disclosed no relevant financial relationships.

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