Compared with placebo, sporebiotics significantly reduced postprandial distress, epigastric pain, and several other symptoms of functional dyspepsia, reported lead author Lucas Wauters, MD, PhD, of University Hospitals Leuven (Belgium), and colleagues.

“Acid suppressive or first-line therapy with PPIs [proton pump inhibitors] for functional dyspepsia has limited efficacy and potential long-term side effects,” the investigators reported at the annual Digestive Disease Week® (DDW). “Spore-forming bacteria or sporebiotics may be effective for postprandial distress and epigastric pain or burning symptoms, offering benefits which may differ in relation to PPI intake.”
 

Sporebiotics improve variety of symptoms

To test this hypothesis, the investigators recruited 68 patients with functional dyspepsia who had similar characteristics at baseline. Half of the participants (n = 34) were taking PPIs.

Patients were randomized in a 1:1 ratio to receive 2.5 x 10⁹ CFU of Bacillus coagulans MY01 and B. subtilis MY02 twice daily for 8 weeks, or matching placebo. Following this period, an additional 8-week open-label regimen was instituted, during which time all patients received sporebiotics. Throughout the study, a daily diary was used to self-report symptoms.

The primary outcome, measured at 8 weeks, was clinical response, defined by a decrease in weekly postprandial distress symptoms greater than 0.7 among patients who had a baseline score greater than 1.0. Secondary outcomes included change in postprandial distress symptoms greater than 0.5 (minimal clinical response), as well as changes in cardinal epigastric pain, cardinal postprandial distress, and other symptoms. At baseline and 8 weeks, patients taking PPIs underwent a ¹⁴C-glycocolic acid breath test to detect changes in small intestinal bacterial overgrowth.

At 8 weeks, a clinical response was observed in 48% of patients taking sporebiotics, compared with 20% of those in the placebo group (P = .03). At the same time point, 56% of patients in the treatment group had a minimal clinical response versus 27% in the control group (P = .03).

Spore-forming probiotics were also associated with significantly greater improvements in cardinal postprandial distress, cardinal epigastric pain, postprandial fullness, and upper abdominal pain. A trend toward improvement in upper abdominal bloating was also seen (P = .07).

Among patients taking PPIs, baseline rates of positivity for bile acid breath testing were similar between those in the sporebiotic and placebo group, at 18% and 25%, respectively (P = .29). After 8 weeks, however, patients taking spore-forming probiotics had a significantly lower rate of bile acid breath test positivity (7% vs. 36%; P = .04), suggesting improvements in small intestinal bacterial overgrowth.

In the open-label portion of the trial, patients in the treatment group maintained improvements in postprandial distress. Patients who switched from placebo to sporebiotics had a significant reduction in postprandial distress symptoms.

At 8 weeks, sporebiotics were associated with a trend toward fewer side effects of any kind (16% vs. 33%; P = .09), while rates of GI-specific side effects were comparable between groups, at 3% and 15% for sporebiotics and placebo, respectively (P = .2).“Spore-forming probiotics are effective and safe in patients with functional dyspepsia, decreasing both postprandial distress and epigastric pain symptoms,” the investigators concluded. “In patients [taking PPIs], sporebiotics decrease the percentage of positive bile acid breath tests, suggesting a reduction of small intestinal bacterial overgrowth.”

Results are promising, but big questions remain

Pankaj Jay Pasricha, MBBS, MD, vice chair of medicine innovation and commercialization at Johns Hopkins and director of the Johns Hopkins Center for Neurogastroenterology, Baltimore, called the results “very encouraging.”

“This [study] is the first of its kind for this condition,” Dr. Pasricha said in an interview. “It will be very interesting to see whether others can reproduce these findings, and whether [these improvements] are sustained beyond the first few weeks or months.”

He noted that determining associated mechanisms of action could potentially open up new lines of therapy, and provide greater understanding of pathophysiology, which is currently lacking.

“We don’t fully understand the pathophysiology [of functional dyspepsia],” Dr. Pasricha said. “If you don’t understand the pathophysiology, then it’s difficult to identify the right molecular target to address the root cause. Instead, we use a variety of symptomatic treatments that aren’t actually addressing the root cause, but studies like this may help us gain some insight into the cause of the problem, and if it is in fact a fundamental imbalance in the intestinal microbiota, then this would be a rational approach.”

It’s unclear how sporebiotics may improve functional dyspepsia, Dr. Pasricha noted. He proposed three possible mechanisms: the bacteria could be colonizing the intestine, they could be releasing products as they pass through the intestine that have a therapeutic effect, or they may be altering bile acid metabolism in the colon or having some other effect there.

“It’s speculative on my part to say how it works,” Dr. Pasricha said. “All the dots remain to be connected. But it’s a good start, and an outstanding group of investigators.”Dr. Wauters and colleagues reported no conflicts of interest. Dr. Pasricha disclosed a relationship with Pendulum Therapeutics.

Compared with placebo, sporebiotics significantly reduced postprandial distress, epigastric pain, and several other symptoms of functional dyspepsia, reported lead author Lucas Wauters, MD, PhD, of University Hospitals Leuven (Belgium), and colleagues.

“Acid suppressive or first-line therapy with PPIs [proton pump inhibitors] for functional dyspepsia has limited efficacy and potential long-term side effects,” the investigators reported at the annual Digestive Disease Week® (DDW). “Spore-forming bacteria or sporebiotics may be effective for postprandial distress and epigastric pain or burning symptoms, offering benefits which may differ in relation to PPI intake.”
 

Sporebiotics improve variety of symptoms

To test this hypothesis, the investigators recruited 68 patients with functional dyspepsia who had similar characteristics at baseline. Half of the participants (n = 34) were taking PPIs.

Patients were randomized in a 1:1 ratio to receive 2.5 x 10⁹ CFU of Bacillus coagulans MY01 and B. subtilis MY02 twice daily for 8 weeks, or matching placebo. Following this period, an additional 8-week open-label regimen was instituted, during which time all patients received sporebiotics. Throughout the study, a daily diary was used to self-report symptoms.

The primary outcome, measured at 8 weeks, was clinical response, defined by a decrease in weekly postprandial distress symptoms greater than 0.7 among patients who had a baseline score greater than 1.0. Secondary outcomes included change in postprandial distress symptoms greater than 0.5 (minimal clinical response), as well as changes in cardinal epigastric pain, cardinal postprandial distress, and other symptoms. At baseline and 8 weeks, patients taking PPIs underwent a ¹⁴C-glycocolic acid breath test to detect changes in small intestinal bacterial overgrowth.

At 8 weeks, a clinical response was observed in 48% of patients taking sporebiotics, compared with 20% of those in the placebo group (P = .03). At the same time point, 56% of patients in the treatment group had a minimal clinical response versus 27% in the control group (P = .03).

Spore-forming probiotics were also associated with significantly greater improvements in cardinal postprandial distress, cardinal epigastric pain, postprandial fullness, and upper abdominal pain. A trend toward improvement in upper abdominal bloating was also seen (P = .07).

Among patients taking PPIs, baseline rates of positivity for bile acid breath testing were similar between those in the sporebiotic and placebo group, at 18% and 25%, respectively (P = .29). After 8 weeks, however, patients taking spore-forming probiotics had a significantly lower rate of bile acid breath test positivity (7% vs. 36%; P = .04), suggesting improvements in small intestinal bacterial overgrowth.

In the open-label portion of the trial, patients in the treatment group maintained improvements in postprandial distress. Patients who switched from placebo to sporebiotics had a significant reduction in postprandial distress symptoms.

At 8 weeks, sporebiotics were associated with a trend toward fewer side effects of any kind (16% vs. 33%; P = .09), while rates of GI-specific side effects were comparable between groups, at 3% and 15% for sporebiotics and placebo, respectively (P = .2).“Spore-forming probiotics are effective and safe in patients with functional dyspepsia, decreasing both postprandial distress and epigastric pain symptoms,” the investigators concluded. “In patients [taking PPIs], sporebiotics decrease the percentage of positive bile acid breath tests, suggesting a reduction of small intestinal bacterial overgrowth.”

Results are promising, but big questions remain

Pankaj Jay Pasricha, MBBS, MD, vice chair of medicine innovation and commercialization at Johns Hopkins and director of the Johns Hopkins Center for Neurogastroenterology, Baltimore, called the results “very encouraging.”

“This [study] is the first of its kind for this condition,” Dr. Pasricha said in an interview. “It will be very interesting to see whether others can reproduce these findings, and whether [these improvements] are sustained beyond the first few weeks or months.”

He noted that determining associated mechanisms of action could potentially open up new lines of therapy, and provide greater understanding of pathophysiology, which is currently lacking.

“We don’t fully understand the pathophysiology [of functional dyspepsia],” Dr. Pasricha said. “If you don’t understand the pathophysiology, then it’s difficult to identify the right molecular target to address the root cause. Instead, we use a variety of symptomatic treatments that aren’t actually addressing the root cause, but studies like this may help us gain some insight into the cause of the problem, and if it is in fact a fundamental imbalance in the intestinal microbiota, then this would be a rational approach.”

It’s unclear how sporebiotics may improve functional dyspepsia, Dr. Pasricha noted. He proposed three possible mechanisms: the bacteria could be colonizing the intestine, they could be releasing products as they pass through the intestine that have a therapeutic effect, or they may be altering bile acid metabolism in the colon or having some other effect there.

“It’s speculative on my part to say how it works,” Dr. Pasricha said. “All the dots remain to be connected. But it’s a good start, and an outstanding group of investigators.”Dr. Wauters and colleagues reported no conflicts of interest. Dr. Pasricha disclosed a relationship with Pendulum Therapeutics.

Compared with placebo, sporebiotics significantly reduced postprandial distress, epigastric pain, and several other symptoms of functional dyspepsia, reported lead author Lucas Wauters, MD, PhD, of University Hospitals Leuven (Belgium), and colleagues.

“Acid suppressive or first-line therapy with PPIs [proton pump inhibitors] for functional dyspepsia has limited efficacy and potential long-term side effects,” the investigators reported at the annual Digestive Disease Week® (DDW). “Spore-forming bacteria or sporebiotics may be effective for postprandial distress and epigastric pain or burning symptoms, offering benefits which may differ in relation to PPI intake.”
 

Sporebiotics improve variety of symptoms

To test this hypothesis, the investigators recruited 68 patients with functional dyspepsia who had similar characteristics at baseline. Half of the participants (n = 34) were taking PPIs.

Patients were randomized in a 1:1 ratio to receive 2.5 x 10⁹ CFU of Bacillus coagulans MY01 and B. subtilis MY02 twice daily for 8 weeks, or matching placebo. Following this period, an additional 8-week open-label regimen was instituted, during which time all patients received sporebiotics. Throughout the study, a daily diary was used to self-report symptoms.

The primary outcome, measured at 8 weeks, was clinical response, defined by a decrease in weekly postprandial distress symptoms greater than 0.7 among patients who had a baseline score greater than 1.0. Secondary outcomes included change in postprandial distress symptoms greater than 0.5 (minimal clinical response), as well as changes in cardinal epigastric pain, cardinal postprandial distress, and other symptoms. At baseline and 8 weeks, patients taking PPIs underwent a ¹⁴C-glycocolic acid breath test to detect changes in small intestinal bacterial overgrowth.

At 8 weeks, a clinical response was observed in 48% of patients taking sporebiotics, compared with 20% of those in the placebo group (P = .03). At the same time point, 56% of patients in the treatment group had a minimal clinical response versus 27% in the control group (P = .03).

Spore-forming probiotics were also associated with significantly greater improvements in cardinal postprandial distress, cardinal epigastric pain, postprandial fullness, and upper abdominal pain. A trend toward improvement in upper abdominal bloating was also seen (P = .07).

Among patients taking PPIs, baseline rates of positivity for bile acid breath testing were similar between those in the sporebiotic and placebo group, at 18% and 25%, respectively (P = .29). After 8 weeks, however, patients taking spore-forming probiotics had a significantly lower rate of bile acid breath test positivity (7% vs. 36%; P = .04), suggesting improvements in small intestinal bacterial overgrowth.

In the open-label portion of the trial, patients in the treatment group maintained improvements in postprandial distress. Patients who switched from placebo to sporebiotics had a significant reduction in postprandial distress symptoms.

At 8 weeks, sporebiotics were associated with a trend toward fewer side effects of any kind (16% vs. 33%; P = .09), while rates of GI-specific side effects were comparable between groups, at 3% and 15% for sporebiotics and placebo, respectively (P = .2).“Spore-forming probiotics are effective and safe in patients with functional dyspepsia, decreasing both postprandial distress and epigastric pain symptoms,” the investigators concluded. “In patients [taking PPIs], sporebiotics decrease the percentage of positive bile acid breath tests, suggesting a reduction of small intestinal bacterial overgrowth.”

Results are promising, but big questions remain

Pankaj Jay Pasricha, MBBS, MD, vice chair of medicine innovation and commercialization at Johns Hopkins and director of the Johns Hopkins Center for Neurogastroenterology, Baltimore, called the results “very encouraging.”

“This [study] is the first of its kind for this condition,” Dr. Pasricha said in an interview. “It will be very interesting to see whether others can reproduce these findings, and whether [these improvements] are sustained beyond the first few weeks or months.”

He noted that determining associated mechanisms of action could potentially open up new lines of therapy, and provide greater understanding of pathophysiology, which is currently lacking.

“We don’t fully understand the pathophysiology [of functional dyspepsia],” Dr. Pasricha said. “If you don’t understand the pathophysiology, then it’s difficult to identify the right molecular target to address the root cause. Instead, we use a variety of symptomatic treatments that aren’t actually addressing the root cause, but studies like this may help us gain some insight into the cause of the problem, and if it is in fact a fundamental imbalance in the intestinal microbiota, then this would be a rational approach.”

It’s unclear how sporebiotics may improve functional dyspepsia, Dr. Pasricha noted. He proposed three possible mechanisms: the bacteria could be colonizing the intestine, they could be releasing products as they pass through the intestine that have a therapeutic effect, or they may be altering bile acid metabolism in the colon or having some other effect there.

“It’s speculative on my part to say how it works,” Dr. Pasricha said. “All the dots remain to be connected. But it’s a good start, and an outstanding group of investigators.”Dr. Wauters and colleagues reported no conflicts of interest. Dr. Pasricha disclosed a relationship with Pendulum Therapeutics.

Nasogastric intubation for esophageal manometry or impedance monitoring does not generate significant aerosol particles and is associated with minimal droplet spread, according to a Belgian study presented at the annual Digestive Disease Week® (DDW). These findings suggest that standard personal protective equipment and appropriate patient positioning are likely sufficient to protect health care workers from increased risk of coronavirus transmission during tube placement and removal, reported lead author Wout Verbeure, PhD, of Leuven University Hospital, Belgium, and colleagues.

“Subsequent to the COVID-19 peak, [nasogastric tube insertion and extraction] were scaled back based on the assumption that they generate respiratory aerosol particles and droplet spread,” the investigators reported. “However, there is no scientific evidence for this theory.”

To address this knowledge gap, the investigators conducted an observational trial involving SARS-CoV-2-negative patients and including 21 insertions and removals for high-resolution manometry (HRM), plus 12 insertions and 10 removals for 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH). During the study, a Camfil City M Air Purifier was added to the examination room. This was present during 13 of the 21 HRM insertions and removals, allowing for comparison of aerosol particle measurements before and after introduction of the device.
 

The mechanics of the study

Aerosol particles (0.3-10 mcm) were measured with a Particle Measuring Systems LASAIR II Particle Counter positioned 1 cm away from the patient’s face. For both procedures, measurements were taken before, during, and up to 5 minutes after each nasogastric tube placement and removal. Additional measurements were taken while the HRM examination was being conducted.

To measure droplet spread, 1% medical fluorescein in saline was applied to each patient’s nasal cavity; droplets were visualized on a white sheet covering the patient and a white apron worn by the health care worker. The patients’ masks were kept below their noses but were covering their mouths.

“During the placement and removal of the catheter, the health care worker was always standing sideways or even behind the patient, and they always stood higher relative to the patient to ensure that when there was aerosol or droplet spread, it was not in their direction,” Dr. Verbeure said during his virtual presentation.

During placement for HRM and removal for MII-pH, aerosol particles (excluding those that were 0.3 mcm), decreased significantly. Otherwise, particle counts remained stable. “This shows that these investigations do not generate additional aerosol [particles], which is good news,” Dr. Verbeure said.

When the air purifier was present, placement and examination for HRM were associated with significant reductions in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm), whereas removal caused a slight uptick in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm) that did not decline after 5 minutes. “This was actually a surprise to us,” Dr. Verbeure said. “Because we now had an air purifier present, and we expected an even lower number of particles.”

He suggested that the purifier may have been reducing particle counts during HRM examination, thereby lowering baseline values before removal, making small changes more noticeable; or the purifier may have been causing turbulence that spread particles during removal. Whether either of these hypotheses is true, Dr. Verbeure noted that particle counts were never higher than at the start of the examination. Fluorescein visualization showed “surprisingly little droplet spread,” Dr. Verbeure said, apart from some contamination around the patient’s neck.

“Esophageal investigations do not seem to generate additional [aerosol] particles,” Dr. Verbeure concluded. “So wearing the recommended protective gear and also considering the right positioning of the health care worker relative to the patient is important to keep performing this daily clinical routine.” To avoid droplet spread, health care workers should “be aware of the [patient’s] neck region and the direction of the catheter,” Dr. Verbeure added.
 

SORTing the results

According to Mahdi Najafi, MD, associate professor in the department of anesthesiology at Tehran University of Medical Sciences, Iran, and adjunct professor at Schulich School of Medicine & Dentistry, Western University, London, Ontario, the findings offer valuable insights. “[This study] is very important for at least two reasons: The extent of using this procedure in patient care, especially in the critical care setting, and the paucity of information for COVID-19 transmission and route of transmission as well,” Dr. Najafi said in an interview.

Yet he cautioned against generalizing the results. “We cannot extend the results to all nasogastric tube intubations,” Dr. Najafi said. “There are reasons for that. The tube for manometry is delicate and flexible, while the nasogastric tube used for drainage and GI pressure release – which is used commonly in intensive care and the operating room – is larger and rather rigid. Moreover, the patient is awake and conscious for manometry while the other procedures are done in sedated or unconscious patients.”

He noted that nasogastric intubation is more challenging in unconscious patients, and often requires a laryngoscope and/or Magill forceps. “The result [of using these instruments] is coughing, which is undoubtedly the most important cause of aerosol generation,” Dr. Najafi said. “It can be regarded as a drawback to this study as well. The authors would be better to report the number and/or severity of the airway reactions during the procedures, which are the main source of droplets and aerosols.”

To reduce risk of coronavirus transmission during nasogastric intubation of unconscious patients, Dr. Najafi recommended the SORT (Sniffing position, nasogastric tube Orientation, contralateral Rotation, and Twisting movement) maneuver, which he introduced in 2016 for use in critical care and operating room settings.

“The employment of anatomical approach and avoiding equipment for intubation were devised to increase the level of safety and decrease hazards and adverse effects,” Dr. Najafi said of the SORT maneuver. “The procedure needs to be done step-by-step and as smooth as possible.”

In a recent study, the SORT maneuver was compared with nasogastric intubation using neck flexion lateral pressure in critically ill patients. The investigators concluded that the SORT maneuver is “a promising method” notable for its simple technique, and suggested that more trials are needed.

The investigators and Dr. Najafi reported no conflicts of interest.

Nasogastric intubation for esophageal manometry or impedance monitoring does not generate significant aerosol particles and is associated with minimal droplet spread, according to a Belgian study presented at the annual Digestive Disease Week® (DDW). These findings suggest that standard personal protective equipment and appropriate patient positioning are likely sufficient to protect health care workers from increased risk of coronavirus transmission during tube placement and removal, reported lead author Wout Verbeure, PhD, of Leuven University Hospital, Belgium, and colleagues.

“Subsequent to the COVID-19 peak, [nasogastric tube insertion and extraction] were scaled back based on the assumption that they generate respiratory aerosol particles and droplet spread,” the investigators reported. “However, there is no scientific evidence for this theory.”

To address this knowledge gap, the investigators conducted an observational trial involving SARS-CoV-2-negative patients and including 21 insertions and removals for high-resolution manometry (HRM), plus 12 insertions and 10 removals for 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH). During the study, a Camfil City M Air Purifier was added to the examination room. This was present during 13 of the 21 HRM insertions and removals, allowing for comparison of aerosol particle measurements before and after introduction of the device.
 

The mechanics of the study

Aerosol particles (0.3-10 mcm) were measured with a Particle Measuring Systems LASAIR II Particle Counter positioned 1 cm away from the patient’s face. For both procedures, measurements were taken before, during, and up to 5 minutes after each nasogastric tube placement and removal. Additional measurements were taken while the HRM examination was being conducted.

To measure droplet spread, 1% medical fluorescein in saline was applied to each patient’s nasal cavity; droplets were visualized on a white sheet covering the patient and a white apron worn by the health care worker. The patients’ masks were kept below their noses but were covering their mouths.

“During the placement and removal of the catheter, the health care worker was always standing sideways or even behind the patient, and they always stood higher relative to the patient to ensure that when there was aerosol or droplet spread, it was not in their direction,” Dr. Verbeure said during his virtual presentation.

During placement for HRM and removal for MII-pH, aerosol particles (excluding those that were 0.3 mcm), decreased significantly. Otherwise, particle counts remained stable. “This shows that these investigations do not generate additional aerosol [particles], which is good news,” Dr. Verbeure said.

When the air purifier was present, placement and examination for HRM were associated with significant reductions in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm), whereas removal caused a slight uptick in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm) that did not decline after 5 minutes. “This was actually a surprise to us,” Dr. Verbeure said. “Because we now had an air purifier present, and we expected an even lower number of particles.”

He suggested that the purifier may have been reducing particle counts during HRM examination, thereby lowering baseline values before removal, making small changes more noticeable; or the purifier may have been causing turbulence that spread particles during removal. Whether either of these hypotheses is true, Dr. Verbeure noted that particle counts were never higher than at the start of the examination. Fluorescein visualization showed “surprisingly little droplet spread,” Dr. Verbeure said, apart from some contamination around the patient’s neck.

“Esophageal investigations do not seem to generate additional [aerosol] particles,” Dr. Verbeure concluded. “So wearing the recommended protective gear and also considering the right positioning of the health care worker relative to the patient is important to keep performing this daily clinical routine.” To avoid droplet spread, health care workers should “be aware of the [patient’s] neck region and the direction of the catheter,” Dr. Verbeure added.
 

SORTing the results

According to Mahdi Najafi, MD, associate professor in the department of anesthesiology at Tehran University of Medical Sciences, Iran, and adjunct professor at Schulich School of Medicine & Dentistry, Western University, London, Ontario, the findings offer valuable insights. “[This study] is very important for at least two reasons: The extent of using this procedure in patient care, especially in the critical care setting, and the paucity of information for COVID-19 transmission and route of transmission as well,” Dr. Najafi said in an interview.

Yet he cautioned against generalizing the results. “We cannot extend the results to all nasogastric tube intubations,” Dr. Najafi said. “There are reasons for that. The tube for manometry is delicate and flexible, while the nasogastric tube used for drainage and GI pressure release – which is used commonly in intensive care and the operating room – is larger and rather rigid. Moreover, the patient is awake and conscious for manometry while the other procedures are done in sedated or unconscious patients.”

He noted that nasogastric intubation is more challenging in unconscious patients, and often requires a laryngoscope and/or Magill forceps. “The result [of using these instruments] is coughing, which is undoubtedly the most important cause of aerosol generation,” Dr. Najafi said. “It can be regarded as a drawback to this study as well. The authors would be better to report the number and/or severity of the airway reactions during the procedures, which are the main source of droplets and aerosols.”

To reduce risk of coronavirus transmission during nasogastric intubation of unconscious patients, Dr. Najafi recommended the SORT (Sniffing position, nasogastric tube Orientation, contralateral Rotation, and Twisting movement) maneuver, which he introduced in 2016 for use in critical care and operating room settings.

“The employment of anatomical approach and avoiding equipment for intubation were devised to increase the level of safety and decrease hazards and adverse effects,” Dr. Najafi said of the SORT maneuver. “The procedure needs to be done step-by-step and as smooth as possible.”

In a recent study, the SORT maneuver was compared with nasogastric intubation using neck flexion lateral pressure in critically ill patients. The investigators concluded that the SORT maneuver is “a promising method” notable for its simple technique, and suggested that more trials are needed.

The investigators and Dr. Najafi reported no conflicts of interest.

Nasogastric intubation for esophageal manometry or impedance monitoring does not generate significant aerosol particles and is associated with minimal droplet spread, according to a Belgian study presented at the annual Digestive Disease Week® (DDW). These findings suggest that standard personal protective equipment and appropriate patient positioning are likely sufficient to protect health care workers from increased risk of coronavirus transmission during tube placement and removal, reported lead author Wout Verbeure, PhD, of Leuven University Hospital, Belgium, and colleagues.

“Subsequent to the COVID-19 peak, [nasogastric tube insertion and extraction] were scaled back based on the assumption that they generate respiratory aerosol particles and droplet spread,” the investigators reported. “However, there is no scientific evidence for this theory.”

To address this knowledge gap, the investigators conducted an observational trial involving SARS-CoV-2-negative patients and including 21 insertions and removals for high-resolution manometry (HRM), plus 12 insertions and 10 removals for 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH). During the study, a Camfil City M Air Purifier was added to the examination room. This was present during 13 of the 21 HRM insertions and removals, allowing for comparison of aerosol particle measurements before and after introduction of the device.
 

The mechanics of the study

Aerosol particles (0.3-10 mcm) were measured with a Particle Measuring Systems LASAIR II Particle Counter positioned 1 cm away from the patient’s face. For both procedures, measurements were taken before, during, and up to 5 minutes after each nasogastric tube placement and removal. Additional measurements were taken while the HRM examination was being conducted.

To measure droplet spread, 1% medical fluorescein in saline was applied to each patient’s nasal cavity; droplets were visualized on a white sheet covering the patient and a white apron worn by the health care worker. The patients’ masks were kept below their noses but were covering their mouths.

“During the placement and removal of the catheter, the health care worker was always standing sideways or even behind the patient, and they always stood higher relative to the patient to ensure that when there was aerosol or droplet spread, it was not in their direction,” Dr. Verbeure said during his virtual presentation.

During placement for HRM and removal for MII-pH, aerosol particles (excluding those that were 0.3 mcm), decreased significantly. Otherwise, particle counts remained stable. “This shows that these investigations do not generate additional aerosol [particles], which is good news,” Dr. Verbeure said.

When the air purifier was present, placement and examination for HRM were associated with significant reductions in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm), whereas removal caused a slight uptick in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm) that did not decline after 5 minutes. “This was actually a surprise to us,” Dr. Verbeure said. “Because we now had an air purifier present, and we expected an even lower number of particles.”

He suggested that the purifier may have been reducing particle counts during HRM examination, thereby lowering baseline values before removal, making small changes more noticeable; or the purifier may have been causing turbulence that spread particles during removal. Whether either of these hypotheses is true, Dr. Verbeure noted that particle counts were never higher than at the start of the examination. Fluorescein visualization showed “surprisingly little droplet spread,” Dr. Verbeure said, apart from some contamination around the patient’s neck.

“Esophageal investigations do not seem to generate additional [aerosol] particles,” Dr. Verbeure concluded. “So wearing the recommended protective gear and also considering the right positioning of the health care worker relative to the patient is important to keep performing this daily clinical routine.” To avoid droplet spread, health care workers should “be aware of the [patient’s] neck region and the direction of the catheter,” Dr. Verbeure added.
 

SORTing the results

According to Mahdi Najafi, MD, associate professor in the department of anesthesiology at Tehran University of Medical Sciences, Iran, and adjunct professor at Schulich School of Medicine & Dentistry, Western University, London, Ontario, the findings offer valuable insights. “[This study] is very important for at least two reasons: The extent of using this procedure in patient care, especially in the critical care setting, and the paucity of information for COVID-19 transmission and route of transmission as well,” Dr. Najafi said in an interview.

Yet he cautioned against generalizing the results. “We cannot extend the results to all nasogastric tube intubations,” Dr. Najafi said. “There are reasons for that. The tube for manometry is delicate and flexible, while the nasogastric tube used for drainage and GI pressure release – which is used commonly in intensive care and the operating room – is larger and rather rigid. Moreover, the patient is awake and conscious for manometry while the other procedures are done in sedated or unconscious patients.”

He noted that nasogastric intubation is more challenging in unconscious patients, and often requires a laryngoscope and/or Magill forceps. “The result [of using these instruments] is coughing, which is undoubtedly the most important cause of aerosol generation,” Dr. Najafi said. “It can be regarded as a drawback to this study as well. The authors would be better to report the number and/or severity of the airway reactions during the procedures, which are the main source of droplets and aerosols.”

To reduce risk of coronavirus transmission during nasogastric intubation of unconscious patients, Dr. Najafi recommended the SORT (Sniffing position, nasogastric tube Orientation, contralateral Rotation, and Twisting movement) maneuver, which he introduced in 2016 for use in critical care and operating room settings.

“The employment of anatomical approach and avoiding equipment for intubation were devised to increase the level of safety and decrease hazards and adverse effects,” Dr. Najafi said of the SORT maneuver. “The procedure needs to be done step-by-step and as smooth as possible.”

In a recent study, the SORT maneuver was compared with nasogastric intubation using neck flexion lateral pressure in critically ill patients. The investigators concluded that the SORT maneuver is “a promising method” notable for its simple technique, and suggested that more trials are needed.

The investigators and Dr. Najafi reported no conflicts of interest.

Adding bevacizumab (Avastin) to second-line osimertinib (Tagrisso) provided no overall benefit versus osimertinib alone for advanced non–small cell lung cancer with epidermal growth factor receptor (EGFR) and T790M mutations in the randomized, open-label, phase 2 European Thoracic Oncology Platform (ETOP) BOOSTER trial.

The combination treatment did, however, show superiority over osimertinib alone in current and former smokers in the study, say the investigators.

“The use of osimertinib and bevacizumab was associated with longer progression-free survival in the subgroup of patients who were former or current smokers [hazard ratio, 0.57],” Ross Soo, MD, reported during a European Society of Medical Oncology virtual plenary session.

The findings were also published May 12, 2021, in Annals of Oncology.

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) with selective activity toward EGFR-sensitizing and T790M resistance mutations, is the standard treatment in this patient population, but progression inevitably occurs.

Based on preclinical studies suggesting that the angiogenic pathway is implicated in EGFR TKI resistance, the current study was designed to assess the efficacy and safety of combined osimertinib and the antiangiogenic agent bevacizumab versus osimertinib alone in patients who progressed on prior EGFR TKI therapy, explained Dr. Soo, a senior consultant in the department of hematology-oncology at the National University Cancer Institute, Singapore.

Median overall progression-free survival (PFS) at a median follow-up of 34 months was 15.4 months versus 12.3 months in 78 patients in the bevacizumab/osimertinib combination therapy group and 77 patients in the osimertinib monotherapy group, respectively – which translated into a nonstatistically significant difference (HR, 0.96).

In the current and former smoker subgroup, median PFS was 16.5 months and 8.4 months with combination versus monotherapy, respectively (HR, .57), Dr. Soo said.

An exploratory analysis showed that the effect of the combination therapy was statistically different in current/former smokers versus never-smokers (HR, 0.52 and 1.47, respectively), he noted.

For the secondary study endpoint of overall survival (OS), no significant difference was seen overall with the combination versus monotherapy (24.0 vs. 24.3 months; HR, 1.03) or the current or former smoker subgroup (HR, 0.54).

However, in the current and former smoker subgroup, the effect of the treatment combination “was in the same direction and similar in magnitude to progression-free survival, but did not reach statistical significance,” Dr. Soo noted.

The exploratory analysis showed OS HRs of 0.59 and 1.54 in the current/former smokers versus never-smokers, respectively.
 

Smoking data may be important

Study participants were adults with a median age of 67 years who had exon 19 del or L858R and T790M mutation at progression on prior EGFR TKI therapy. Most (62%) were women and 40% were current or former smokers. They were enrolled between 2017 and 2019 from 22 centers in six countries and randomly assigned to receive bevacizumab at a dose of 15 mg/kg intravenously on day 1 every 3 weeks plus osimertinib at 80 mg daily or osimertinib alone.

The median time to treatment failure was 8.2 months in the combination therapy, (with TTF of 8.2 months for bevacizumab and 12.4 for osimertinib), compared with 10.8 months for osimertinib monotherapy.

Overall response was 55% in both groups, and disease control rates were 90% and 82% in the groups, respectively. Median duration of response was 14.5 months versus 16.6 months, Dr. Soo said.

Grade 3 or greater treatment-related adverse events occurred in 47% and 18% of patients in the combination and monotherapy groups. The most frequent adverse event in both groups was diarrhea. Proteinuria and hypertension occurred more often in the combination-therapy group.

Based on these findings, osimertinib remains the standard of care in patients with advanced NSCLC with acquired EGFR TKI resistance harboring EGFR T790M mutations, he concluded.

The findings are in line with those from prior smaller studies, and are “hypothesis generating,” said invited discussant Edward B. Garon, MD, professor and director of the thoracic oncology program at the University of California, Los Angeles.

The new data are hypothesis generating and will help in analyzing other studies to determine whether there is a difference based on smoking history, he said. 

Dr. Garon also noted that there has been increasing interest in similar combination approaches in the frontline setting, but to date there is little to support frontline use.

“It is certainly a situation where there is room for studies exploring other approaches in the frontline setting,” he concluded.

This study was supported by Astra Zeneca and Roche. Dr. Soo reported financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Lilly, Merck, Novartis, Otsuka, Pfizer, Roche, Synthorx, Taiho, Takeda, and Yuhan. Dr. Garon reported relationships with ABL-Bio, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dracen Pharmaceuticals, Dynavax Technologies, Eli Lilly, EMD Serono, Eisai, Genentech, GlaxoSmithKline, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Natera, Neon, Novartis, Regeneron, Sanofi, Shionogi, and Xilio.

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

Adding bevacizumab (Avastin) to second-line osimertinib (Tagrisso) provided no overall benefit versus osimertinib alone for advanced non–small cell lung cancer with epidermal growth factor receptor (EGFR) and T790M mutations in the randomized, open-label, phase 2 European Thoracic Oncology Platform (ETOP) BOOSTER trial.

The combination treatment did, however, show superiority over osimertinib alone in current and former smokers in the study, say the investigators.

“The use of osimertinib and bevacizumab was associated with longer progression-free survival in the subgroup of patients who were former or current smokers [hazard ratio, 0.57],” Ross Soo, MD, reported during a European Society of Medical Oncology virtual plenary session.

The findings were also published May 12, 2021, in Annals of Oncology.

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) with selective activity toward EGFR-sensitizing and T790M resistance mutations, is the standard treatment in this patient population, but progression inevitably occurs.

Based on preclinical studies suggesting that the angiogenic pathway is implicated in EGFR TKI resistance, the current study was designed to assess the efficacy and safety of combined osimertinib and the antiangiogenic agent bevacizumab versus osimertinib alone in patients who progressed on prior EGFR TKI therapy, explained Dr. Soo, a senior consultant in the department of hematology-oncology at the National University Cancer Institute, Singapore.

Median overall progression-free survival (PFS) at a median follow-up of 34 months was 15.4 months versus 12.3 months in 78 patients in the bevacizumab/osimertinib combination therapy group and 77 patients in the osimertinib monotherapy group, respectively – which translated into a nonstatistically significant difference (HR, 0.96).

In the current and former smoker subgroup, median PFS was 16.5 months and 8.4 months with combination versus monotherapy, respectively (HR, .57), Dr. Soo said.

An exploratory analysis showed that the effect of the combination therapy was statistically different in current/former smokers versus never-smokers (HR, 0.52 and 1.47, respectively), he noted.

For the secondary study endpoint of overall survival (OS), no significant difference was seen overall with the combination versus monotherapy (24.0 vs. 24.3 months; HR, 1.03) or the current or former smoker subgroup (HR, 0.54).

However, in the current and former smoker subgroup, the effect of the treatment combination “was in the same direction and similar in magnitude to progression-free survival, but did not reach statistical significance,” Dr. Soo noted.

The exploratory analysis showed OS HRs of 0.59 and 1.54 in the current/former smokers versus never-smokers, respectively.
 

Smoking data may be important

Study participants were adults with a median age of 67 years who had exon 19 del or L858R and T790M mutation at progression on prior EGFR TKI therapy. Most (62%) were women and 40% were current or former smokers. They were enrolled between 2017 and 2019 from 22 centers in six countries and randomly assigned to receive bevacizumab at a dose of 15 mg/kg intravenously on day 1 every 3 weeks plus osimertinib at 80 mg daily or osimertinib alone.

The median time to treatment failure was 8.2 months in the combination therapy, (with TTF of 8.2 months for bevacizumab and 12.4 for osimertinib), compared with 10.8 months for osimertinib monotherapy.

Overall response was 55% in both groups, and disease control rates were 90% and 82% in the groups, respectively. Median duration of response was 14.5 months versus 16.6 months, Dr. Soo said.

Grade 3 or greater treatment-related adverse events occurred in 47% and 18% of patients in the combination and monotherapy groups. The most frequent adverse event in both groups was diarrhea. Proteinuria and hypertension occurred more often in the combination-therapy group.

Based on these findings, osimertinib remains the standard of care in patients with advanced NSCLC with acquired EGFR TKI resistance harboring EGFR T790M mutations, he concluded.

The findings are in line with those from prior smaller studies, and are “hypothesis generating,” said invited discussant Edward B. Garon, MD, professor and director of the thoracic oncology program at the University of California, Los Angeles.

The new data are hypothesis generating and will help in analyzing other studies to determine whether there is a difference based on smoking history, he said. 

Dr. Garon also noted that there has been increasing interest in similar combination approaches in the frontline setting, but to date there is little to support frontline use.

“It is certainly a situation where there is room for studies exploring other approaches in the frontline setting,” he concluded.

This study was supported by Astra Zeneca and Roche. Dr. Soo reported financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Lilly, Merck, Novartis, Otsuka, Pfizer, Roche, Synthorx, Taiho, Takeda, and Yuhan. Dr. Garon reported relationships with ABL-Bio, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dracen Pharmaceuticals, Dynavax Technologies, Eli Lilly, EMD Serono, Eisai, Genentech, GlaxoSmithKline, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Natera, Neon, Novartis, Regeneron, Sanofi, Shionogi, and Xilio.

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

Adding bevacizumab (Avastin) to second-line osimertinib (Tagrisso) provided no overall benefit versus osimertinib alone for advanced non–small cell lung cancer with epidermal growth factor receptor (EGFR) and T790M mutations in the randomized, open-label, phase 2 European Thoracic Oncology Platform (ETOP) BOOSTER trial.

The combination treatment did, however, show superiority over osimertinib alone in current and former smokers in the study, say the investigators.

“The use of osimertinib and bevacizumab was associated with longer progression-free survival in the subgroup of patients who were former or current smokers [hazard ratio, 0.57],” Ross Soo, MD, reported during a European Society of Medical Oncology virtual plenary session.

The findings were also published May 12, 2021, in Annals of Oncology.

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) with selective activity toward EGFR-sensitizing and T790M resistance mutations, is the standard treatment in this patient population, but progression inevitably occurs.

Based on preclinical studies suggesting that the angiogenic pathway is implicated in EGFR TKI resistance, the current study was designed to assess the efficacy and safety of combined osimertinib and the antiangiogenic agent bevacizumab versus osimertinib alone in patients who progressed on prior EGFR TKI therapy, explained Dr. Soo, a senior consultant in the department of hematology-oncology at the National University Cancer Institute, Singapore.

Median overall progression-free survival (PFS) at a median follow-up of 34 months was 15.4 months versus 12.3 months in 78 patients in the bevacizumab/osimertinib combination therapy group and 77 patients in the osimertinib monotherapy group, respectively – which translated into a nonstatistically significant difference (HR, 0.96).

In the current and former smoker subgroup, median PFS was 16.5 months and 8.4 months with combination versus monotherapy, respectively (HR, .57), Dr. Soo said.

An exploratory analysis showed that the effect of the combination therapy was statistically different in current/former smokers versus never-smokers (HR, 0.52 and 1.47, respectively), he noted.

For the secondary study endpoint of overall survival (OS), no significant difference was seen overall with the combination versus monotherapy (24.0 vs. 24.3 months; HR, 1.03) or the current or former smoker subgroup (HR, 0.54).

However, in the current and former smoker subgroup, the effect of the treatment combination “was in the same direction and similar in magnitude to progression-free survival, but did not reach statistical significance,” Dr. Soo noted.

The exploratory analysis showed OS HRs of 0.59 and 1.54 in the current/former smokers versus never-smokers, respectively.
 

Smoking data may be important

Study participants were adults with a median age of 67 years who had exon 19 del or L858R and T790M mutation at progression on prior EGFR TKI therapy. Most (62%) were women and 40% were current or former smokers. They were enrolled between 2017 and 2019 from 22 centers in six countries and randomly assigned to receive bevacizumab at a dose of 15 mg/kg intravenously on day 1 every 3 weeks plus osimertinib at 80 mg daily or osimertinib alone.

The median time to treatment failure was 8.2 months in the combination therapy, (with TTF of 8.2 months for bevacizumab and 12.4 for osimertinib), compared with 10.8 months for osimertinib monotherapy.

Overall response was 55% in both groups, and disease control rates were 90% and 82% in the groups, respectively. Median duration of response was 14.5 months versus 16.6 months, Dr. Soo said.

Grade 3 or greater treatment-related adverse events occurred in 47% and 18% of patients in the combination and monotherapy groups. The most frequent adverse event in both groups was diarrhea. Proteinuria and hypertension occurred more often in the combination-therapy group.

Based on these findings, osimertinib remains the standard of care in patients with advanced NSCLC with acquired EGFR TKI resistance harboring EGFR T790M mutations, he concluded.

The findings are in line with those from prior smaller studies, and are “hypothesis generating,” said invited discussant Edward B. Garon, MD, professor and director of the thoracic oncology program at the University of California, Los Angeles.

The new data are hypothesis generating and will help in analyzing other studies to determine whether there is a difference based on smoking history, he said. 

Dr. Garon also noted that there has been increasing interest in similar combination approaches in the frontline setting, but to date there is little to support frontline use.

“It is certainly a situation where there is room for studies exploring other approaches in the frontline setting,” he concluded.

This study was supported by Astra Zeneca and Roche. Dr. Soo reported financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Lilly, Merck, Novartis, Otsuka, Pfizer, Roche, Synthorx, Taiho, Takeda, and Yuhan. Dr. Garon reported relationships with ABL-Bio, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dracen Pharmaceuticals, Dynavax Technologies, Eli Lilly, EMD Serono, Eisai, Genentech, GlaxoSmithKline, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Natera, Neon, Novartis, Regeneron, Sanofi, Shionogi, and Xilio.

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

The first drug to target KRAS mutations in non–small cell lung cancer (NSCLC) has been approved by the Food and Drug Administration.

KRAS mutations are the most common mutations to occur in NSCLC tumors, accounting for about 25% of them, but for a long time they appeared to be resistant to drug therapy.  

The new drug, sotorasib (Lumakras), specifically targets the KRAS G12C mutation, which accounts for about 13% of NSCLC mutations.

It is considered to be something of a breakthrough in cancer research. When clinical data on the new drug (from 126 patients) were presented last year at the World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically, as reported by Medscape Medical News at the time.

“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the time.

Now, in a press release from the manufacturer, Amgen, he said: “Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non–small cell lung cancer.

“Patients with non–small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly four decades of research,” he added.
 

Details of clinical data

This is an accelerated approval based on response rate data.

The FDA notes that the clinical data come from a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.

The major outcome measured was overall response rate (ORR), which was 36%. Of the patients who responded, 58% had a duration of response of 6 months or longer.

Sotorasib was approved at a dose of 960 mg, and this dose was based on available clinical data as well as pharmacokinetic and pharmacodynamic modeling, the FDA noted. As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.

The most common side effects include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Sotorasib should not be used if patients develop symptoms of interstitial lung disease, and should be permanently discontinued if interstitial lung disease is confirmed.

Patients on sotorasib should have liver function tests prior to starting and while taking the drug; if liver damage develops, the drug should be stopped or the dose reduced. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver, and drugs that are substrates of P-glycoprotein (P-gp).
 

Companion diagnostic tests also approved

Along with the new drug, the FDA approved two companion diagnostic tests – the QIAGEN therascreen KRAS RGQ PCR kit (approval granted to QIAGEN GmbH) for analyzing tumor tissue and the Guardant360 CDx (approval granted to Guardant Health) for analyzing plasma specimens to determine if the KRAS G12C mutation is present. The agency notes that if the plasma test comes back negative, the patient’s tumor tissue should be tested.

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

The first drug to target KRAS mutations in non–small cell lung cancer (NSCLC) has been approved by the Food and Drug Administration.

KRAS mutations are the most common mutations to occur in NSCLC tumors, accounting for about 25% of them, but for a long time they appeared to be resistant to drug therapy.  

The new drug, sotorasib (Lumakras), specifically targets the KRAS G12C mutation, which accounts for about 13% of NSCLC mutations.

It is considered to be something of a breakthrough in cancer research. When clinical data on the new drug (from 126 patients) were presented last year at the World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically, as reported by Medscape Medical News at the time.

“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the time.

Now, in a press release from the manufacturer, Amgen, he said: “Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non–small cell lung cancer.

“Patients with non–small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly four decades of research,” he added.
 

Details of clinical data

This is an accelerated approval based on response rate data.

The FDA notes that the clinical data come from a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.

The major outcome measured was overall response rate (ORR), which was 36%. Of the patients who responded, 58% had a duration of response of 6 months or longer.

Sotorasib was approved at a dose of 960 mg, and this dose was based on available clinical data as well as pharmacokinetic and pharmacodynamic modeling, the FDA noted. As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.

The most common side effects include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Sotorasib should not be used if patients develop symptoms of interstitial lung disease, and should be permanently discontinued if interstitial lung disease is confirmed.

Patients on sotorasib should have liver function tests prior to starting and while taking the drug; if liver damage develops, the drug should be stopped or the dose reduced. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver, and drugs that are substrates of P-glycoprotein (P-gp).
 

Companion diagnostic tests also approved

Along with the new drug, the FDA approved two companion diagnostic tests – the QIAGEN therascreen KRAS RGQ PCR kit (approval granted to QIAGEN GmbH) for analyzing tumor tissue and the Guardant360 CDx (approval granted to Guardant Health) for analyzing plasma specimens to determine if the KRAS G12C mutation is present. The agency notes that if the plasma test comes back negative, the patient’s tumor tissue should be tested.

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

The first drug to target KRAS mutations in non–small cell lung cancer (NSCLC) has been approved by the Food and Drug Administration.

KRAS mutations are the most common mutations to occur in NSCLC tumors, accounting for about 25% of them, but for a long time they appeared to be resistant to drug therapy.  

The new drug, sotorasib (Lumakras), specifically targets the KRAS G12C mutation, which accounts for about 13% of NSCLC mutations.

It is considered to be something of a breakthrough in cancer research. When clinical data on the new drug (from 126 patients) were presented last year at the World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically, as reported by Medscape Medical News at the time.

“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the time.

Now, in a press release from the manufacturer, Amgen, he said: “Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non–small cell lung cancer.

“Patients with non–small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly four decades of research,” he added.
 

Details of clinical data

This is an accelerated approval based on response rate data.

The FDA notes that the clinical data come from a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.

The major outcome measured was overall response rate (ORR), which was 36%. Of the patients who responded, 58% had a duration of response of 6 months or longer.

Sotorasib was approved at a dose of 960 mg, and this dose was based on available clinical data as well as pharmacokinetic and pharmacodynamic modeling, the FDA noted. As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.

The most common side effects include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Sotorasib should not be used if patients develop symptoms of interstitial lung disease, and should be permanently discontinued if interstitial lung disease is confirmed.

Patients on sotorasib should have liver function tests prior to starting and while taking the drug; if liver damage develops, the drug should be stopped or the dose reduced. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver, and drugs that are substrates of P-glycoprotein (P-gp).
 

Companion diagnostic tests also approved

Along with the new drug, the FDA approved two companion diagnostic tests – the QIAGEN therascreen KRAS RGQ PCR kit (approval granted to QIAGEN GmbH) for analyzing tumor tissue and the Guardant360 CDx (approval granted to Guardant Health) for analyzing plasma specimens to determine if the KRAS G12C mutation is present. The agency notes that if the plasma test comes back negative, the patient’s tumor tissue should be tested.

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

As mounting evidence points to a significant psychiatric component of COVID-19, experts are concerned about an influx of survivors presenting with persistent mental health problems and how best to prepare.

Clinicians should be aware that patients who have had COVID frequently develop psychiatric symptoms, Silvia S. Martins, MD, PhD, associate professor of epidemiology, Columbia University, New York, said in an interview.

“There should be more screening of all patients recovering from a COVID infection for anxiety, posttraumatic stress disorder, and depression, as well as referral to services, including psychotherapy, and medication as needed,” said Dr. Martins, who, along with colleagues, uncovered a high rate of these symptoms in patients who had the disease.

The COVID-19 pandemic has taken an enormous social, emotional, and public health toll. It has disrupted lives and caused stress, fear, and uncertainty about loss of health and income, not to mention forced isolation.

In addition, a significant number of patients who contract COVID-19 continue to have symptoms after the acute phase of the illness. This post-COVID, or “long-haul,” syndrome isn’t well defined; experts cite a range of symptoms that persist for weeks or months.

These ongoing symptoms can include cough, fatigue, and chronic pain, as well as psychiatric complaints. As reported by this news organization, an observational study of more than 230,000 U.S. patient health records revealed that one in three COVID-19 survivors received a psychiatric or neurologic diagnosis within 6 months of contracting the virus.

The most common psychiatric diagnoses were anxiety disorders, mood disorders, substance misuse disorders, and insomnia.
 

Significant symptoms even in mild cases

Another study showed that even those with mild COVID-19 may experience psychiatric symptoms independently of previous psychiatric diagnoses. Results revealed that 26% of the sample of almost 900 patients reported depression, 22% reported anxiety, and 17% reported symptoms of posttraumatic stress 2 months after testing positive for the virus. This finding is important because the majority of individuals who contract COVID-19 have a mild case.

“We saw very high levels of clinically significant depression, anxiety, and posttraumatic stress symptoms in people who had mild disease,” study investigator João Mauricio Castaldelli-Maia, MD, PhD, postdoctoral fellow, department of epidemiology, Columbia University, said in an interview.

He attributed these symptoms in part to long periods of isolation, even from relatives in the same household, in cramped spaces typical of large cities such as São Paulo.

Social isolation can have a huge impact on persons who depend on social connections and relationships, Vivian Pender, MD, president of the American Psychiatric Association and clinical professor of psychiatry, Weill Cornell Medical Center, New York, said in an interview.

“The fact that we have not been able to see our colleagues, our friends, our family, and in the case of psychiatrists, even our patients has taken a toll on everyone, and that leads to more stress, more anxiety,” she said.

National surveys show that psychiatric symptoms occur after acute COVID. One survey revealed that over 50% of 3,900 respondents who had COVID reported having at least moderate symptoms of major depression.
 

Unique depression subtype?

Another survey, slated for publication later this year, shows that among patients who have had COVID, risk factors for depression as well as certain symptoms of depression differ somewhat from those typical of major depressive disorder, lead investigator Roy Perlis, MD, professor of psychiatry, Harvard Medical School, Boston, said in an interview.

This might suggest a neurobiological element. Researchers are speculating as to whether lingering psychiatric problems that occur after having COVID are linked to the psychosocial impact of the disease or to pathological processes, such as inflammation, that affect the brain.

Although rates of post-COVID psychiatric symptoms vary from study to study, “they seem to be pretty enduring,” noted Faith Gunning, PhD, vice chair of research, department of psychology, Weill Cornell Medicine, who specializes in clinical neuropsychology.

“So they’re not just a brief response” to getting sick, a fact that points to the possible need for treatment, she told this news organization. “In some of the work that’s starting to emerge, it does appear that the symptoms persist, at least for a relatively large subset of individuals.”

Although depression typically affects twice as many women as men, these new surveys show that, after COVID, “that difference is not so distinct,” said Dr. Gunning.

It’s unclear why this is, but it could be cause by financial stresses that may affect men to a greater extent, she added. “There is so much we’re still learning.”
 

Increased suicide risk?

Other researchers, including Leo Sher, MD, professor of psychiatry, Icahn School of Medicine at Mount Sinai, and director of inpatient psychiatry, James J. Peters Veterans Affairs Medical Center, both in New York, are concerned that higher rates of psychiatric symptoms among patients with long-haul COVID raise the risk for suicidal ideation and behavior.

Studies of suicidality in COVID-19 survivors “are urgently needed,” said Dr. Sher in an article published in the Monthly Journal of the Association of Physicians.

“We need to study what factors may increase suicide risk among the COVID-19 survivors during and after the recovery. We also need to investigate whether there is a long-term increased suicide risk among COVID-19 survivors,” Dr. Sher said.

COVID-19 is not unique among viral respiratory diseases in being associated with long-term mental health problems. Research shows that survivors of the 2003 outbreak of severe acute respiratory syndrome experienced increased psychological distress that persisted for at least a year, as did patients who in 2015 had Middle East respiratory syndrome coronavirus (MERS-CoV).

Some experts believe clinicians should screen patients for mental health symptoms after the acute phase of COVID and offer early and prolonged care.

“Early mental health intervention such as psychotherapy and supportive groups could play an important role in preventing incident mental health problems for post-COVID sufferers,” said Dr. Castaldelli-Maia.

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

As mounting evidence points to a significant psychiatric component of COVID-19, experts are concerned about an influx of survivors presenting with persistent mental health problems and how best to prepare.

Clinicians should be aware that patients who have had COVID frequently develop psychiatric symptoms, Silvia S. Martins, MD, PhD, associate professor of epidemiology, Columbia University, New York, said in an interview.

“There should be more screening of all patients recovering from a COVID infection for anxiety, posttraumatic stress disorder, and depression, as well as referral to services, including psychotherapy, and medication as needed,” said Dr. Martins, who, along with colleagues, uncovered a high rate of these symptoms in patients who had the disease.

The COVID-19 pandemic has taken an enormous social, emotional, and public health toll. It has disrupted lives and caused stress, fear, and uncertainty about loss of health and income, not to mention forced isolation.

In addition, a significant number of patients who contract COVID-19 continue to have symptoms after the acute phase of the illness. This post-COVID, or “long-haul,” syndrome isn’t well defined; experts cite a range of symptoms that persist for weeks or months.

These ongoing symptoms can include cough, fatigue, and chronic pain, as well as psychiatric complaints. As reported by this news organization, an observational study of more than 230,000 U.S. patient health records revealed that one in three COVID-19 survivors received a psychiatric or neurologic diagnosis within 6 months of contracting the virus.

The most common psychiatric diagnoses were anxiety disorders, mood disorders, substance misuse disorders, and insomnia.
 

Significant symptoms even in mild cases

Another study showed that even those with mild COVID-19 may experience psychiatric symptoms independently of previous psychiatric diagnoses. Results revealed that 26% of the sample of almost 900 patients reported depression, 22% reported anxiety, and 17% reported symptoms of posttraumatic stress 2 months after testing positive for the virus. This finding is important because the majority of individuals who contract COVID-19 have a mild case.

“We saw very high levels of clinically significant depression, anxiety, and posttraumatic stress symptoms in people who had mild disease,” study investigator João Mauricio Castaldelli-Maia, MD, PhD, postdoctoral fellow, department of epidemiology, Columbia University, said in an interview.

He attributed these symptoms in part to long periods of isolation, even from relatives in the same household, in cramped spaces typical of large cities such as São Paulo.

Social isolation can have a huge impact on persons who depend on social connections and relationships, Vivian Pender, MD, president of the American Psychiatric Association and clinical professor of psychiatry, Weill Cornell Medical Center, New York, said in an interview.

“The fact that we have not been able to see our colleagues, our friends, our family, and in the case of psychiatrists, even our patients has taken a toll on everyone, and that leads to more stress, more anxiety,” she said.

National surveys show that psychiatric symptoms occur after acute COVID. One survey revealed that over 50% of 3,900 respondents who had COVID reported having at least moderate symptoms of major depression.
 

Unique depression subtype?

Another survey, slated for publication later this year, shows that among patients who have had COVID, risk factors for depression as well as certain symptoms of depression differ somewhat from those typical of major depressive disorder, lead investigator Roy Perlis, MD, professor of psychiatry, Harvard Medical School, Boston, said in an interview.

This might suggest a neurobiological element. Researchers are speculating as to whether lingering psychiatric problems that occur after having COVID are linked to the psychosocial impact of the disease or to pathological processes, such as inflammation, that affect the brain.

Although rates of post-COVID psychiatric symptoms vary from study to study, “they seem to be pretty enduring,” noted Faith Gunning, PhD, vice chair of research, department of psychology, Weill Cornell Medicine, who specializes in clinical neuropsychology.

“So they’re not just a brief response” to getting sick, a fact that points to the possible need for treatment, she told this news organization. “In some of the work that’s starting to emerge, it does appear that the symptoms persist, at least for a relatively large subset of individuals.”

Although depression typically affects twice as many women as men, these new surveys show that, after COVID, “that difference is not so distinct,” said Dr. Gunning.

It’s unclear why this is, but it could be cause by financial stresses that may affect men to a greater extent, she added. “There is so much we’re still learning.”
 

Increased suicide risk?

Other researchers, including Leo Sher, MD, professor of psychiatry, Icahn School of Medicine at Mount Sinai, and director of inpatient psychiatry, James J. Peters Veterans Affairs Medical Center, both in New York, are concerned that higher rates of psychiatric symptoms among patients with long-haul COVID raise the risk for suicidal ideation and behavior.

Studies of suicidality in COVID-19 survivors “are urgently needed,” said Dr. Sher in an article published in the Monthly Journal of the Association of Physicians.

“We need to study what factors may increase suicide risk among the COVID-19 survivors during and after the recovery. We also need to investigate whether there is a long-term increased suicide risk among COVID-19 survivors,” Dr. Sher said.

COVID-19 is not unique among viral respiratory diseases in being associated with long-term mental health problems. Research shows that survivors of the 2003 outbreak of severe acute respiratory syndrome experienced increased psychological distress that persisted for at least a year, as did patients who in 2015 had Middle East respiratory syndrome coronavirus (MERS-CoV).

Some experts believe clinicians should screen patients for mental health symptoms after the acute phase of COVID and offer early and prolonged care.

“Early mental health intervention such as psychotherapy and supportive groups could play an important role in preventing incident mental health problems for post-COVID sufferers,” said Dr. Castaldelli-Maia.

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

As mounting evidence points to a significant psychiatric component of COVID-19, experts are concerned about an influx of survivors presenting with persistent mental health problems and how best to prepare.

Clinicians should be aware that patients who have had COVID frequently develop psychiatric symptoms, Silvia S. Martins, MD, PhD, associate professor of epidemiology, Columbia University, New York, said in an interview.

“There should be more screening of all patients recovering from a COVID infection for anxiety, posttraumatic stress disorder, and depression, as well as referral to services, including psychotherapy, and medication as needed,” said Dr. Martins, who, along with colleagues, uncovered a high rate of these symptoms in patients who had the disease.

The COVID-19 pandemic has taken an enormous social, emotional, and public health toll. It has disrupted lives and caused stress, fear, and uncertainty about loss of health and income, not to mention forced isolation.

In addition, a significant number of patients who contract COVID-19 continue to have symptoms after the acute phase of the illness. This post-COVID, or “long-haul,” syndrome isn’t well defined; experts cite a range of symptoms that persist for weeks or months.

These ongoing symptoms can include cough, fatigue, and chronic pain, as well as psychiatric complaints. As reported by this news organization, an observational study of more than 230,000 U.S. patient health records revealed that one in three COVID-19 survivors received a psychiatric or neurologic diagnosis within 6 months of contracting the virus.

The most common psychiatric diagnoses were anxiety disorders, mood disorders, substance misuse disorders, and insomnia.
 

Significant symptoms even in mild cases

Another study showed that even those with mild COVID-19 may experience psychiatric symptoms independently of previous psychiatric diagnoses. Results revealed that 26% of the sample of almost 900 patients reported depression, 22% reported anxiety, and 17% reported symptoms of posttraumatic stress 2 months after testing positive for the virus. This finding is important because the majority of individuals who contract COVID-19 have a mild case.

“We saw very high levels of clinically significant depression, anxiety, and posttraumatic stress symptoms in people who had mild disease,” study investigator João Mauricio Castaldelli-Maia, MD, PhD, postdoctoral fellow, department of epidemiology, Columbia University, said in an interview.

He attributed these symptoms in part to long periods of isolation, even from relatives in the same household, in cramped spaces typical of large cities such as São Paulo.

Social isolation can have a huge impact on persons who depend on social connections and relationships, Vivian Pender, MD, president of the American Psychiatric Association and clinical professor of psychiatry, Weill Cornell Medical Center, New York, said in an interview.

“The fact that we have not been able to see our colleagues, our friends, our family, and in the case of psychiatrists, even our patients has taken a toll on everyone, and that leads to more stress, more anxiety,” she said.

National surveys show that psychiatric symptoms occur after acute COVID. One survey revealed that over 50% of 3,900 respondents who had COVID reported having at least moderate symptoms of major depression.
 

Unique depression subtype?

Another survey, slated for publication later this year, shows that among patients who have had COVID, risk factors for depression as well as certain symptoms of depression differ somewhat from those typical of major depressive disorder, lead investigator Roy Perlis, MD, professor of psychiatry, Harvard Medical School, Boston, said in an interview.

This might suggest a neurobiological element. Researchers are speculating as to whether lingering psychiatric problems that occur after having COVID are linked to the psychosocial impact of the disease or to pathological processes, such as inflammation, that affect the brain.

Although rates of post-COVID psychiatric symptoms vary from study to study, “they seem to be pretty enduring,” noted Faith Gunning, PhD, vice chair of research, department of psychology, Weill Cornell Medicine, who specializes in clinical neuropsychology.

“So they’re not just a brief response” to getting sick, a fact that points to the possible need for treatment, she told this news organization. “In some of the work that’s starting to emerge, it does appear that the symptoms persist, at least for a relatively large subset of individuals.”

Although depression typically affects twice as many women as men, these new surveys show that, after COVID, “that difference is not so distinct,” said Dr. Gunning.

It’s unclear why this is, but it could be cause by financial stresses that may affect men to a greater extent, she added. “There is so much we’re still learning.”
 

Increased suicide risk?

Other researchers, including Leo Sher, MD, professor of psychiatry, Icahn School of Medicine at Mount Sinai, and director of inpatient psychiatry, James J. Peters Veterans Affairs Medical Center, both in New York, are concerned that higher rates of psychiatric symptoms among patients with long-haul COVID raise the risk for suicidal ideation and behavior.

Studies of suicidality in COVID-19 survivors “are urgently needed,” said Dr. Sher in an article published in the Monthly Journal of the Association of Physicians.

“We need to study what factors may increase suicide risk among the COVID-19 survivors during and after the recovery. We also need to investigate whether there is a long-term increased suicide risk among COVID-19 survivors,” Dr. Sher said.

COVID-19 is not unique among viral respiratory diseases in being associated with long-term mental health problems. Research shows that survivors of the 2003 outbreak of severe acute respiratory syndrome experienced increased psychological distress that persisted for at least a year, as did patients who in 2015 had Middle East respiratory syndrome coronavirus (MERS-CoV).

Some experts believe clinicians should screen patients for mental health symptoms after the acute phase of COVID and offer early and prolonged care.

“Early mental health intervention such as psychotherapy and supportive groups could play an important role in preventing incident mental health problems for post-COVID sufferers,” said Dr. Castaldelli-Maia.

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

Somatic symptom and related disorders—physical complaints that may or may not be medically explained that are associated with significant distress and impairment—are common in children and adolescents, and are often accompanied by anxiety and depression.¹ Clinicians are likely to see children with these disorders in emergency departments, consultation services, or outpatient clinics. Common presenting symptoms include abdominal pain, headache, nausea, vomiting, dizziness, and seizures.¹ Talking to the caregivers of these children can be challenging due to the subjective nature of the illness. In this article, I offer 4 tips for mental health practitioners to consider when working with caregivers of children with somatic disorders.

1. Support. Talk to the child and caregiver individually, and then together. Try to understand the caregiver’s concerns and express empathy to establish rapport. Being dismissive of their concerns is not going to help the child. Acknowledge the caregiver’s complaints and ask how seriously they feel other clinicians regard their concerns. Ask the caregiver about their perception of their child’s health, how frequently they worry about their child’s health, and the impact their worries have on their lives and their child’s life. Often the caregiver and child must miss out on obligations (eg, work, school, extracurricular activities) due to the child’s care and medical appointments.

2. Educate. This may be difficult, particularly when interacting with a caregiver who is convinced that their child is seriously physically sick. The caregiver may feel that involving psychiatry services is discrediting their concerns. Your initial interaction may be to allow the caregiver to express their frustrations toward the primary service. When talking with caregivers, avoid using medical jargon; in some instances, however, it may be necessary to use medical terminology to reassure the caregiver that you know what you are talking about. Be direct, and do not give false hope. These children often undergo extensive medical workup before psychiatry services are involved. To minimize conflicting messages from multiple clinicians who are caring for the same child, review the patient’s chart in advance, and maintain constant communication with other clinicians involved in the patient’s care.

3. Reassure. When the caregiver finally begins to acknowledge the psychological nature of their child’s illness, provide them with reassurance, but avoid emphasizing that the child is medically healthy because any relief caregivers gain from this can quickly fade and worsen their anxiety. Discuss the importance of treating underlying anxiety or depression with medication and psychotherapy where necessary. Assess the child for substance use disorders, personality disorders, and psychosocial stressors, and if present, target treatment accordingly. Discuss the potential long-term outcomes with and without treatment. Share examples of success stories from your past experiences. Emphasize the importance of noticing even slight improvements. Encourage the child to focus on goals such as attending school or passing online tests, etc.

4. Refer. Connecting the child with a therapist can significantly improve long-term outcomes, especially if coordinated well.² This becomes more crucial in cases where caregivers are opposed to pharmacotherapy for their child. Whenever possible, communicate with the therapist before the child’s initial appointment to formulate a plan of action. The best approach is integrated care characterized by close collaboration of primary care, a somatic specialist, and mental health care professionals operating on a biopsychosocial model of distress and therapeutic factors.³

The ultimate goal is to help the child and caregiver achieve some level of relief by acknowledgment and support. Utilizing some of these tips can make our work even more meaningful for ourselves and our patients.

Somatic symptom and related disorders—physical complaints that may or may not be medically explained that are associated with significant distress and impairment—are common in children and adolescents, and are often accompanied by anxiety and depression.¹ Clinicians are likely to see children with these disorders in emergency departments, consultation services, or outpatient clinics. Common presenting symptoms include abdominal pain, headache, nausea, vomiting, dizziness, and seizures.¹ Talking to the caregivers of these children can be challenging due to the subjective nature of the illness. In this article, I offer 4 tips for mental health practitioners to consider when working with caregivers of children with somatic disorders.

1. Support. Talk to the child and caregiver individually, and then together. Try to understand the caregiver’s concerns and express empathy to establish rapport. Being dismissive of their concerns is not going to help the child. Acknowledge the caregiver’s complaints and ask how seriously they feel other clinicians regard their concerns. Ask the caregiver about their perception of their child’s health, how frequently they worry about their child’s health, and the impact their worries have on their lives and their child’s life. Often the caregiver and child must miss out on obligations (eg, work, school, extracurricular activities) due to the child’s care and medical appointments.

2. Educate. This may be difficult, particularly when interacting with a caregiver who is convinced that their child is seriously physically sick. The caregiver may feel that involving psychiatry services is discrediting their concerns. Your initial interaction may be to allow the caregiver to express their frustrations toward the primary service. When talking with caregivers, avoid using medical jargon; in some instances, however, it may be necessary to use medical terminology to reassure the caregiver that you know what you are talking about. Be direct, and do not give false hope. These children often undergo extensive medical workup before psychiatry services are involved. To minimize conflicting messages from multiple clinicians who are caring for the same child, review the patient’s chart in advance, and maintain constant communication with other clinicians involved in the patient’s care.

3. Reassure. When the caregiver finally begins to acknowledge the psychological nature of their child’s illness, provide them with reassurance, but avoid emphasizing that the child is medically healthy because any relief caregivers gain from this can quickly fade and worsen their anxiety. Discuss the importance of treating underlying anxiety or depression with medication and psychotherapy where necessary. Assess the child for substance use disorders, personality disorders, and psychosocial stressors, and if present, target treatment accordingly. Discuss the potential long-term outcomes with and without treatment. Share examples of success stories from your past experiences. Emphasize the importance of noticing even slight improvements. Encourage the child to focus on goals such as attending school or passing online tests, etc.

4. Refer. Connecting the child with a therapist can significantly improve long-term outcomes, especially if coordinated well.² This becomes more crucial in cases where caregivers are opposed to pharmacotherapy for their child. Whenever possible, communicate with the therapist before the child’s initial appointment to formulate a plan of action. The best approach is integrated care characterized by close collaboration of primary care, a somatic specialist, and mental health care professionals operating on a biopsychosocial model of distress and therapeutic factors.³

The ultimate goal is to help the child and caregiver achieve some level of relief by acknowledgment and support. Utilizing some of these tips can make our work even more meaningful for ourselves and our patients.

Somatic symptom and related disorders—physical complaints that may or may not be medically explained that are associated with significant distress and impairment—are common in children and adolescents, and are often accompanied by anxiety and depression.¹ Clinicians are likely to see children with these disorders in emergency departments, consultation services, or outpatient clinics. Common presenting symptoms include abdominal pain, headache, nausea, vomiting, dizziness, and seizures.¹ Talking to the caregivers of these children can be challenging due to the subjective nature of the illness. In this article, I offer 4 tips for mental health practitioners to consider when working with caregivers of children with somatic disorders.

1. Support. Talk to the child and caregiver individually, and then together. Try to understand the caregiver’s concerns and express empathy to establish rapport. Being dismissive of their concerns is not going to help the child. Acknowledge the caregiver’s complaints and ask how seriously they feel other clinicians regard their concerns. Ask the caregiver about their perception of their child’s health, how frequently they worry about their child’s health, and the impact their worries have on their lives and their child’s life. Often the caregiver and child must miss out on obligations (eg, work, school, extracurricular activities) due to the child’s care and medical appointments.

2. Educate. This may be difficult, particularly when interacting with a caregiver who is convinced that their child is seriously physically sick. The caregiver may feel that involving psychiatry services is discrediting their concerns. Your initial interaction may be to allow the caregiver to express their frustrations toward the primary service. When talking with caregivers, avoid using medical jargon; in some instances, however, it may be necessary to use medical terminology to reassure the caregiver that you know what you are talking about. Be direct, and do not give false hope. These children often undergo extensive medical workup before psychiatry services are involved. To minimize conflicting messages from multiple clinicians who are caring for the same child, review the patient’s chart in advance, and maintain constant communication with other clinicians involved in the patient’s care.

3. Reassure. When the caregiver finally begins to acknowledge the psychological nature of their child’s illness, provide them with reassurance, but avoid emphasizing that the child is medically healthy because any relief caregivers gain from this can quickly fade and worsen their anxiety. Discuss the importance of treating underlying anxiety or depression with medication and psychotherapy where necessary. Assess the child for substance use disorders, personality disorders, and psychosocial stressors, and if present, target treatment accordingly. Discuss the potential long-term outcomes with and without treatment. Share examples of success stories from your past experiences. Emphasize the importance of noticing even slight improvements. Encourage the child to focus on goals such as attending school or passing online tests, etc.

4. Refer. Connecting the child with a therapist can significantly improve long-term outcomes, especially if coordinated well.² This becomes more crucial in cases where caregivers are opposed to pharmacotherapy for their child. Whenever possible, communicate with the therapist before the child’s initial appointment to formulate a plan of action. The best approach is integrated care characterized by close collaboration of primary care, a somatic specialist, and mental health care professionals operating on a biopsychosocial model of distress and therapeutic factors.³

The ultimate goal is to help the child and caregiver achieve some level of relief by acknowledgment and support. Utilizing some of these tips can make our work even more meaningful for ourselves and our patients.

Mr. J, age 30, a Black man with major depressive disorder (MDD), has been your patient for the past year. At the time of his diagnosis, Mr. J received sertraline, 100 mg/d, but had little to no improvement. During the past year, he received trials of citalopram and paroxetine, but they were not effective for his recurrent depressive symptoms and/or resulted in significant adverse effects.

During a recent visit, Mr. J asks you about “the genetic tests that help determine which medications will work.” He mentions that his brother had this testing done and that it had “worked for him,” but offers no other details. You research the different testing panels to see which test you might use. After a brief online review, you identify at least 4 different products, and are not sure which test—if any—you should consider.

During the last few years, there has been a rise in commercial pharmacogenetic testing options, including tests available to clinicians at academic medical centers as well as direct-to-consumer testing (Table). Clinician and patient interest regarding pharmacogenetic testing in practice is often followed by the question, “Which test is best?” Although this is a logical question, providing an answer is multifactorial.^1-3 Because none of the currently available tests have been compared in head-to-head clinical trials, it is nearly impossible to identify the “best” test.

In this article, we focus on the evidence-based principles that clinicians should consider when adopting pharmacogenetic testing in their practice. We discuss which genes are of most interest when prescribing psychotropic medications, the value of decision support tools, cost considerations, and patient education regarding this type of testing.

Which genes and variants should be tested?

The genes relevant to medication treatment outcomes can be broadly classified into those with pharmacokinetic vs pharmacodynamic effects. Pharmacogenes, such as those coding for the drug-metabolizing enzymes cytochrome P450 (CYP) 1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4, and UDP-glucuronosyltransferase (UGT)2B1, may alter the rate at which medications are metabolized, thus varying the serum drug concentration across patients. Variants that impact the function of these enzymes are considered pharmacokinetic. Up to 40% of the variance in patients’ response to antidepressants may be due to variations in the pharmacokinetic genes.⁴ Alternatively, pharmacodynamic pharmacogenes impact drug action and therefore may affect the degree of receptor activation at a given drug concentration, overall drug efficacy, and/or the occurrence of medication sensitivity. These pharmacogenes may include:

• brain-derived neurotrophic factor (BDNF)
• catechol-O-methyltransferase (COMT)
• human leukocyte antigens A (HLA-A)
• serotonin receptor subtype 2 (HTR2)
• serotonin receptor subtype 2C (HTR2C)
• opioid receptor mu 1 (OPRM1)
• solute carrier family 6 member 4 (SLC6A4).

In articles previously published in Current Psychiatry, we outlined some of the evidence regarding these pharmacogenes, and resources available to clinicians to support their use of these tests.^1,2

Currently, there is no standardization among commercial pharmacogenetic tests on:

• which genes to test
• which variants specific to a gene need to be included
• how the genetic data is translated to phenotype
• how the phenotype is translated to a treatment recommendation.

Continue to: Due to these factors...

Due to these factors, the FDA has advised clinicians to consult the dosing recommendations provided in a medication’s package insert for information regarding how genetic information should be used in making treatment decisions.²

The value of decision support tools

Researchers have assessed how various manufacturers’ decision support tools (DSTs) (ie, the reports the commercial testing companies send to the clinician who orders the test) agree on genotypes, predicted phenotypes, and medication recommendations.⁴ Overall, this research found varying levels of disagreement in the medication recommendations of the testing panels they studied, which indicates that not all tests are equivalent or interchangeable.⁴ Of the actionable recommendations for antidepressants, 16% were conflicting; the recommendations for fluoxetine and imipramine were most frequently in disagreement.⁴ Similarly, 20% of the actionable antipsychotic advice was conflicting, with the recommendations for aripiprazole and clozapine most frequently in disagreement.⁴ Researchers also reported a situation in which 4 testing panels agreed on the patient’s phenotyping status for CYP2C19, but the dosing recommendations provided for the CYP2C19 substrate, amitriptyline, differed.⁴ Thus, it is understandable why DSTs can result in confusion, and why clinicians should use testing panels with recommendations that best align with their individual practices, their patient’s needs, and FDA information.

Additionally, while the genes included on these panels vary, these testing panels also may not evaluate the same variants within a specific gene. These differences may impact the patient’s reported phenotypes and medication recommendations across DSTs. For example, the FDA has recommended HLA gene testing prior to prescribing carbamazepine. However, few of the available tests may include the HLA-B*15:02 variant, which has been associated with carbamazepine-induced severe cutaneous reactions in patients of Asian descent, and fewer may include the HLA-A*31:01 variant, for which testing is recommended prior to prescribing carbamazepine in patients of Caucasian descent.⁴ Additionally, some of the CYP enzymes—such as CYP2D6*17 and CYP2C19*3 variants, which may be more common in certain populations of patients who are members of ethnic or racial minority groups—may not be consistently included in the various panels. Thus, before deciding on a specific test, clinicians should understand which gene variants are relevant to their patients with regard to race and ethnicity, and key variants for specific medications. Clinicians should refer to FDA guidance and the Clinical Pharmacogenomics Implementation Consortium (CPIC) guidelines to determine the appropriate interpretations of genetic test results.^1,2

Despite the disagreement in recommendations from the various testing companies, DSTs are useful and have been shown to facilitate implementation of relevant psycho­pharmacology dosing guidelines, assist in identifying optimal medication therapy, and improve patient outcomes. A recently published meta-analysis of randomized controlled trials (RCTs) of pharmacogenetic testing found that DSTs improved symptom remission among individuals with MDD by 70%.⁵ This suggests that pharmacogenetic-guided DSTs may provide superior treatment compared with treatment for DSTs were not used. However, the RCTs in this meta-analysis only included patients who had previously failed an antidepressant trial.⁵ Therefore, it is currently unknown at what point in care DSTs should be used, and whether they would be more beneficial if they are used when starting a new therapy, or after several trials have failed.

Consider the cost

The cost and availability of pharmacogenetic testing can be an issue when making treatment decisions, and such testing may not be covered by a patient’s insurance plan. Recently, the Centers for Medicare & Medicaid Services announced that Medicare would cover FDA-approved genomic tests that encompass broad gene panels if the evidence supports their use. Similarly, commercial insurers such as UnitedHealthcare have begun to cover some pharmacogenetic tests.⁶ Medicare or Medicaid plans cover some testing panels’ costs and patients do not incur any out-of-pocket costs; however, some private insurance companies require patients to pay at least a portion of the cost, and many companies offer financial assistance for patients based on income and other factors. Although financial coverage for testing has improved, patients may still face out-of-pocket costs; therefore, clinicians may need to weigh the benefits of pharmacogenetic testing vs its cost.⁷ Clinicians should also determine what timeline best suits their patient’s financial and clinical needs, and test accordingly.

Continue to: Patient education is critical

 

 

Patient education is critical

Although the benefits of using pharmacogenetic testing information when making certain treatment decisions is promising, it is important for both patients and clinicians to understand that test results do not always change therapy. A study on the impact of pharmacogenetic testing on clinical outcomes of patients with MDD found that 79% of patients were already prescribed medications that aligned with recommendations.⁸ Therefore, switching medications based on the test results of a patient who is doing well clinically is not recommended. However, DSTs may help with clinical decisions for ambiguous cases. For example, if a patient has a genotype and/or phenotype that aligns with medication recommendations, the DST might not be able to identify a better medication to use, but may be able to recommend dosing guidance to improve the tolerability of the patient’s current therapy.⁶ It is also important to understand that the results of such testing may have a broader use beyond the initial reason for obtaining testing, such as when prescribing a common blood thinner such as warfarin or clopidogrel. However, for many of the pharmacodynamic genes that are included in these panels, their use beyond the treatment of depression may be limited because outcome studies for pharmacodynamic pharmacogenes may vary based on psychiatric diagnosis. Regardless, it may be beneficial to securely save and store patient test results in a standardized place within the medical record for future use.

CASE CONTINUED

You work with Mr. J to help him understand the benefits and limitations associated with pharmacogenetic testing. Assuming Mr. J is comfortable with the costs of obtaining testing, you contact the testing companies you identified to determine the specific pharmacogene variants included on each of these panels, and which would be the most appropriate given his race. If the decision is made to order the testing, provide Mr. J with a copy of his testing report so that he can use this information should he need any additional pharmacotherapy in the future, and also maintain a copy in his patient records using a standardized location for easy future access. If Mr. J is not comfortable with the costs associated with the testing, find out which medication his brother is currently receiving for treatment; this information may help identify a treatment plan for Mr. J.

Impact on practice

As psychiatry continues to gain experience in using pharmacogenetic testing and DSTs to help guide treatments for depression and other disorders, clinicians need to learn about these tools and how to use an evidence-based approach to best implement them in their practice. Many academic medical centers have developed continuing education programs or consult services to help with this.^9,10 Just as the choice of which medication to use may be based partly on clinician experience, so too may be which pharmacogenetic test to use.

Bottom Line

Pharmacogenetic tests have not been examined in head-to-head clinical trials, which makes it nearly impossible to identify which test is best to use. Although the testing companies’ decision support tools (DSTs) often disagree in their recommendations, research has shown that using DSTs can facilitate implementation of relevant psychopharmacology dosing guidelines, assist in identifying optimal medication therapy, and improve patient outcomes. Clinicians should use testing panels with recommendations that best align with their individual practices, their patient’s needs, and FDA information.

Related Resources

• PGx Gene-specific information tables. www.pharmgkb.org/page/pgxGeneRef
• Clinical Pharmacogenetics Implementation Consortium. https://cpicpgx.org/guidelines/

Drug Brand Names

Aripiprazole • Abilify
Carbamazepine • Tegretol
Citalopram • Celexa
Clopidogrel • Plavix
Clozapine • Clozaril
Fluoxetine • Prozac
Imipramine • Tofranil
Paroxetine • Paxil
Sertraline • Zoloft
Warfarin • Coumadin, Jantoven

Mr. J, age 30, a Black man with major depressive disorder (MDD), has been your patient for the past year. At the time of his diagnosis, Mr. J received sertraline, 100 mg/d, but had little to no improvement. During the past year, he received trials of citalopram and paroxetine, but they were not effective for his recurrent depressive symptoms and/or resulted in significant adverse effects.

During a recent visit, Mr. J asks you about “the genetic tests that help determine which medications will work.” He mentions that his brother had this testing done and that it had “worked for him,” but offers no other details. You research the different testing panels to see which test you might use. After a brief online review, you identify at least 4 different products, and are not sure which test—if any—you should consider.

During the last few years, there has been a rise in commercial pharmacogenetic testing options, including tests available to clinicians at academic medical centers as well as direct-to-consumer testing (Table). Clinician and patient interest regarding pharmacogenetic testing in practice is often followed by the question, “Which test is best?” Although this is a logical question, providing an answer is multifactorial.^1-3 Because none of the currently available tests have been compared in head-to-head clinical trials, it is nearly impossible to identify the “best” test.

In this article, we focus on the evidence-based principles that clinicians should consider when adopting pharmacogenetic testing in their practice. We discuss which genes are of most interest when prescribing psychotropic medications, the value of decision support tools, cost considerations, and patient education regarding this type of testing.

Which genes and variants should be tested?

The genes relevant to medication treatment outcomes can be broadly classified into those with pharmacokinetic vs pharmacodynamic effects. Pharmacogenes, such as those coding for the drug-metabolizing enzymes cytochrome P450 (CYP) 1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4, and UDP-glucuronosyltransferase (UGT)2B1, may alter the rate at which medications are metabolized, thus varying the serum drug concentration across patients. Variants that impact the function of these enzymes are considered pharmacokinetic. Up to 40% of the variance in patients’ response to antidepressants may be due to variations in the pharmacokinetic genes.⁴ Alternatively, pharmacodynamic pharmacogenes impact drug action and therefore may affect the degree of receptor activation at a given drug concentration, overall drug efficacy, and/or the occurrence of medication sensitivity. These pharmacogenes may include:

• brain-derived neurotrophic factor (BDNF)
• catechol-O-methyltransferase (COMT)
• human leukocyte antigens A (HLA-A)
• serotonin receptor subtype 2 (HTR2)
• serotonin receptor subtype 2C (HTR2C)
• opioid receptor mu 1 (OPRM1)
• solute carrier family 6 member 4 (SLC6A4).

In articles previously published in Current Psychiatry, we outlined some of the evidence regarding these pharmacogenes, and resources available to clinicians to support their use of these tests.^1,2

Currently, there is no standardization among commercial pharmacogenetic tests on:

• which genes to test
• which variants specific to a gene need to be included
• how the genetic data is translated to phenotype
• how the phenotype is translated to a treatment recommendation.

Continue to: Due to these factors...

Due to these factors, the FDA has advised clinicians to consult the dosing recommendations provided in a medication’s package insert for information regarding how genetic information should be used in making treatment decisions.²

The value of decision support tools

Researchers have assessed how various manufacturers’ decision support tools (DSTs) (ie, the reports the commercial testing companies send to the clinician who orders the test) agree on genotypes, predicted phenotypes, and medication recommendations.⁴ Overall, this research found varying levels of disagreement in the medication recommendations of the testing panels they studied, which indicates that not all tests are equivalent or interchangeable.⁴ Of the actionable recommendations for antidepressants, 16% were conflicting; the recommendations for fluoxetine and imipramine were most frequently in disagreement.⁴ Similarly, 20% of the actionable antipsychotic advice was conflicting, with the recommendations for aripiprazole and clozapine most frequently in disagreement.⁴ Researchers also reported a situation in which 4 testing panels agreed on the patient’s phenotyping status for CYP2C19, but the dosing recommendations provided for the CYP2C19 substrate, amitriptyline, differed.⁴ Thus, it is understandable why DSTs can result in confusion, and why clinicians should use testing panels with recommendations that best align with their individual practices, their patient’s needs, and FDA information.

Additionally, while the genes included on these panels vary, these testing panels also may not evaluate the same variants within a specific gene. These differences may impact the patient’s reported phenotypes and medication recommendations across DSTs. For example, the FDA has recommended HLA gene testing prior to prescribing carbamazepine. However, few of the available tests may include the HLA-B*15:02 variant, which has been associated with carbamazepine-induced severe cutaneous reactions in patients of Asian descent, and fewer may include the HLA-A*31:01 variant, for which testing is recommended prior to prescribing carbamazepine in patients of Caucasian descent.⁴ Additionally, some of the CYP enzymes—such as CYP2D6*17 and CYP2C19*3 variants, which may be more common in certain populations of patients who are members of ethnic or racial minority groups—may not be consistently included in the various panels. Thus, before deciding on a specific test, clinicians should understand which gene variants are relevant to their patients with regard to race and ethnicity, and key variants for specific medications. Clinicians should refer to FDA guidance and the Clinical Pharmacogenomics Implementation Consortium (CPIC) guidelines to determine the appropriate interpretations of genetic test results.^1,2

Despite the disagreement in recommendations from the various testing companies, DSTs are useful and have been shown to facilitate implementation of relevant psycho­pharmacology dosing guidelines, assist in identifying optimal medication therapy, and improve patient outcomes. A recently published meta-analysis of randomized controlled trials (RCTs) of pharmacogenetic testing found that DSTs improved symptom remission among individuals with MDD by 70%.⁵ This suggests that pharmacogenetic-guided DSTs may provide superior treatment compared with treatment for DSTs were not used. However, the RCTs in this meta-analysis only included patients who had previously failed an antidepressant trial.⁵ Therefore, it is currently unknown at what point in care DSTs should be used, and whether they would be more beneficial if they are used when starting a new therapy, or after several trials have failed.

Consider the cost

The cost and availability of pharmacogenetic testing can be an issue when making treatment decisions, and such testing may not be covered by a patient’s insurance plan. Recently, the Centers for Medicare & Medicaid Services announced that Medicare would cover FDA-approved genomic tests that encompass broad gene panels if the evidence supports their use. Similarly, commercial insurers such as UnitedHealthcare have begun to cover some pharmacogenetic tests.⁶ Medicare or Medicaid plans cover some testing panels’ costs and patients do not incur any out-of-pocket costs; however, some private insurance companies require patients to pay at least a portion of the cost, and many companies offer financial assistance for patients based on income and other factors. Although financial coverage for testing has improved, patients may still face out-of-pocket costs; therefore, clinicians may need to weigh the benefits of pharmacogenetic testing vs its cost.⁷ Clinicians should also determine what timeline best suits their patient’s financial and clinical needs, and test accordingly.

Continue to: Patient education is critical

 

 

Patient education is critical

Although the benefits of using pharmacogenetic testing information when making certain treatment decisions is promising, it is important for both patients and clinicians to understand that test results do not always change therapy. A study on the impact of pharmacogenetic testing on clinical outcomes of patients with MDD found that 79% of patients were already prescribed medications that aligned with recommendations.⁸ Therefore, switching medications based on the test results of a patient who is doing well clinically is not recommended. However, DSTs may help with clinical decisions for ambiguous cases. For example, if a patient has a genotype and/or phenotype that aligns with medication recommendations, the DST might not be able to identify a better medication to use, but may be able to recommend dosing guidance to improve the tolerability of the patient’s current therapy.⁶ It is also important to understand that the results of such testing may have a broader use beyond the initial reason for obtaining testing, such as when prescribing a common blood thinner such as warfarin or clopidogrel. However, for many of the pharmacodynamic genes that are included in these panels, their use beyond the treatment of depression may be limited because outcome studies for pharmacodynamic pharmacogenes may vary based on psychiatric diagnosis. Regardless, it may be beneficial to securely save and store patient test results in a standardized place within the medical record for future use.

CASE CONTINUED

You work with Mr. J to help him understand the benefits and limitations associated with pharmacogenetic testing. Assuming Mr. J is comfortable with the costs of obtaining testing, you contact the testing companies you identified to determine the specific pharmacogene variants included on each of these panels, and which would be the most appropriate given his race. If the decision is made to order the testing, provide Mr. J with a copy of his testing report so that he can use this information should he need any additional pharmacotherapy in the future, and also maintain a copy in his patient records using a standardized location for easy future access. If Mr. J is not comfortable with the costs associated with the testing, find out which medication his brother is currently receiving for treatment; this information may help identify a treatment plan for Mr. J.

Impact on practice

As psychiatry continues to gain experience in using pharmacogenetic testing and DSTs to help guide treatments for depression and other disorders, clinicians need to learn about these tools and how to use an evidence-based approach to best implement them in their practice. Many academic medical centers have developed continuing education programs or consult services to help with this.^9,10 Just as the choice of which medication to use may be based partly on clinician experience, so too may be which pharmacogenetic test to use.

Bottom Line

Pharmacogenetic tests have not been examined in head-to-head clinical trials, which makes it nearly impossible to identify which test is best to use. Although the testing companies’ decision support tools (DSTs) often disagree in their recommendations, research has shown that using DSTs can facilitate implementation of relevant psychopharmacology dosing guidelines, assist in identifying optimal medication therapy, and improve patient outcomes. Clinicians should use testing panels with recommendations that best align with their individual practices, their patient’s needs, and FDA information.

Related Resources

• PGx Gene-specific information tables. www.pharmgkb.org/page/pgxGeneRef
• Clinical Pharmacogenetics Implementation Consortium. https://cpicpgx.org/guidelines/

Drug Brand Names

Aripiprazole • Abilify
Carbamazepine • Tegretol
Citalopram • Celexa
Clopidogrel • Plavix
Clozapine • Clozaril
Fluoxetine • Prozac
Imipramine • Tofranil
Paroxetine • Paxil
Sertraline • Zoloft
Warfarin • Coumadin, Jantoven

Mr. J, age 30, a Black man with major depressive disorder (MDD), has been your patient for the past year. At the time of his diagnosis, Mr. J received sertraline, 100 mg/d, but had little to no improvement. During the past year, he received trials of citalopram and paroxetine, but they were not effective for his recurrent depressive symptoms and/or resulted in significant adverse effects.

During a recent visit, Mr. J asks you about “the genetic tests that help determine which medications will work.” He mentions that his brother had this testing done and that it had “worked for him,” but offers no other details. You research the different testing panels to see which test you might use. After a brief online review, you identify at least 4 different products, and are not sure which test—if any—you should consider.

During the last few years, there has been a rise in commercial pharmacogenetic testing options, including tests available to clinicians at academic medical centers as well as direct-to-consumer testing (Table). Clinician and patient interest regarding pharmacogenetic testing in practice is often followed by the question, “Which test is best?” Although this is a logical question, providing an answer is multifactorial.^1-3 Because none of the currently available tests have been compared in head-to-head clinical trials, it is nearly impossible to identify the “best” test.

In this article, we focus on the evidence-based principles that clinicians should consider when adopting pharmacogenetic testing in their practice. We discuss which genes are of most interest when prescribing psychotropic medications, the value of decision support tools, cost considerations, and patient education regarding this type of testing.

Which genes and variants should be tested?

The genes relevant to medication treatment outcomes can be broadly classified into those with pharmacokinetic vs pharmacodynamic effects. Pharmacogenes, such as those coding for the drug-metabolizing enzymes cytochrome P450 (CYP) 1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4, and UDP-glucuronosyltransferase (UGT)2B1, may alter the rate at which medications are metabolized, thus varying the serum drug concentration across patients. Variants that impact the function of these enzymes are considered pharmacokinetic. Up to 40% of the variance in patients’ response to antidepressants may be due to variations in the pharmacokinetic genes.⁴ Alternatively, pharmacodynamic pharmacogenes impact drug action and therefore may affect the degree of receptor activation at a given drug concentration, overall drug efficacy, and/or the occurrence of medication sensitivity. These pharmacogenes may include:

• brain-derived neurotrophic factor (BDNF)
• catechol-O-methyltransferase (COMT)
• human leukocyte antigens A (HLA-A)
• serotonin receptor subtype 2 (HTR2)
• serotonin receptor subtype 2C (HTR2C)
• opioid receptor mu 1 (OPRM1)
• solute carrier family 6 member 4 (SLC6A4).

In articles previously published in Current Psychiatry, we outlined some of the evidence regarding these pharmacogenes, and resources available to clinicians to support their use of these tests.^1,2

Currently, there is no standardization among commercial pharmacogenetic tests on:

• which genes to test
• which variants specific to a gene need to be included
• how the genetic data is translated to phenotype
• how the phenotype is translated to a treatment recommendation.

Continue to: Due to these factors...

Due to these factors, the FDA has advised clinicians to consult the dosing recommendations provided in a medication’s package insert for information regarding how genetic information should be used in making treatment decisions.²

The value of decision support tools

Researchers have assessed how various manufacturers’ decision support tools (DSTs) (ie, the reports the commercial testing companies send to the clinician who orders the test) agree on genotypes, predicted phenotypes, and medication recommendations.⁴ Overall, this research found varying levels of disagreement in the medication recommendations of the testing panels they studied, which indicates that not all tests are equivalent or interchangeable.⁴ Of the actionable recommendations for antidepressants, 16% were conflicting; the recommendations for fluoxetine and imipramine were most frequently in disagreement.⁴ Similarly, 20% of the actionable antipsychotic advice was conflicting, with the recommendations for aripiprazole and clozapine most frequently in disagreement.⁴ Researchers also reported a situation in which 4 testing panels agreed on the patient’s phenotyping status for CYP2C19, but the dosing recommendations provided for the CYP2C19 substrate, amitriptyline, differed.⁴ Thus, it is understandable why DSTs can result in confusion, and why clinicians should use testing panels with recommendations that best align with their individual practices, their patient’s needs, and FDA information.

Additionally, while the genes included on these panels vary, these testing panels also may not evaluate the same variants within a specific gene. These differences may impact the patient’s reported phenotypes and medication recommendations across DSTs. For example, the FDA has recommended HLA gene testing prior to prescribing carbamazepine. However, few of the available tests may include the HLA-B*15:02 variant, which has been associated with carbamazepine-induced severe cutaneous reactions in patients of Asian descent, and fewer may include the HLA-A*31:01 variant, for which testing is recommended prior to prescribing carbamazepine in patients of Caucasian descent.⁴ Additionally, some of the CYP enzymes—such as CYP2D6*17 and CYP2C19*3 variants, which may be more common in certain populations of patients who are members of ethnic or racial minority groups—may not be consistently included in the various panels. Thus, before deciding on a specific test, clinicians should understand which gene variants are relevant to their patients with regard to race and ethnicity, and key variants for specific medications. Clinicians should refer to FDA guidance and the Clinical Pharmacogenomics Implementation Consortium (CPIC) guidelines to determine the appropriate interpretations of genetic test results.^1,2

Despite the disagreement in recommendations from the various testing companies, DSTs are useful and have been shown to facilitate implementation of relevant psycho­pharmacology dosing guidelines, assist in identifying optimal medication therapy, and improve patient outcomes. A recently published meta-analysis of randomized controlled trials (RCTs) of pharmacogenetic testing found that DSTs improved symptom remission among individuals with MDD by 70%.⁵ This suggests that pharmacogenetic-guided DSTs may provide superior treatment compared with treatment for DSTs were not used. However, the RCTs in this meta-analysis only included patients who had previously failed an antidepressant trial.⁵ Therefore, it is currently unknown at what point in care DSTs should be used, and whether they would be more beneficial if they are used when starting a new therapy, or after several trials have failed.

Consider the cost

The cost and availability of pharmacogenetic testing can be an issue when making treatment decisions, and such testing may not be covered by a patient’s insurance plan. Recently, the Centers for Medicare & Medicaid Services announced that Medicare would cover FDA-approved genomic tests that encompass broad gene panels if the evidence supports their use. Similarly, commercial insurers such as UnitedHealthcare have begun to cover some pharmacogenetic tests.⁶ Medicare or Medicaid plans cover some testing panels’ costs and patients do not incur any out-of-pocket costs; however, some private insurance companies require patients to pay at least a portion of the cost, and many companies offer financial assistance for patients based on income and other factors. Although financial coverage for testing has improved, patients may still face out-of-pocket costs; therefore, clinicians may need to weigh the benefits of pharmacogenetic testing vs its cost.⁷ Clinicians should also determine what timeline best suits their patient’s financial and clinical needs, and test accordingly.

Continue to: Patient education is critical

 

 

Patient education is critical

Although the benefits of using pharmacogenetic testing information when making certain treatment decisions is promising, it is important for both patients and clinicians to understand that test results do not always change therapy. A study on the impact of pharmacogenetic testing on clinical outcomes of patients with MDD found that 79% of patients were already prescribed medications that aligned with recommendations.⁸ Therefore, switching medications based on the test results of a patient who is doing well clinically is not recommended. However, DSTs may help with clinical decisions for ambiguous cases. For example, if a patient has a genotype and/or phenotype that aligns with medication recommendations, the DST might not be able to identify a better medication to use, but may be able to recommend dosing guidance to improve the tolerability of the patient’s current therapy.⁶ It is also important to understand that the results of such testing may have a broader use beyond the initial reason for obtaining testing, such as when prescribing a common blood thinner such as warfarin or clopidogrel. However, for many of the pharmacodynamic genes that are included in these panels, their use beyond the treatment of depression may be limited because outcome studies for pharmacodynamic pharmacogenes may vary based on psychiatric diagnosis. Regardless, it may be beneficial to securely save and store patient test results in a standardized place within the medical record for future use.

CASE CONTINUED

You work with Mr. J to help him understand the benefits and limitations associated with pharmacogenetic testing. Assuming Mr. J is comfortable with the costs of obtaining testing, you contact the testing companies you identified to determine the specific pharmacogene variants included on each of these panels, and which would be the most appropriate given his race. If the decision is made to order the testing, provide Mr. J with a copy of his testing report so that he can use this information should he need any additional pharmacotherapy in the future, and also maintain a copy in his patient records using a standardized location for easy future access. If Mr. J is not comfortable with the costs associated with the testing, find out which medication his brother is currently receiving for treatment; this information may help identify a treatment plan for Mr. J.

Impact on practice

As psychiatry continues to gain experience in using pharmacogenetic testing and DSTs to help guide treatments for depression and other disorders, clinicians need to learn about these tools and how to use an evidence-based approach to best implement them in their practice. Many academic medical centers have developed continuing education programs or consult services to help with this.^9,10 Just as the choice of which medication to use may be based partly on clinician experience, so too may be which pharmacogenetic test to use.

Bottom Line

Pharmacogenetic tests have not been examined in head-to-head clinical trials, which makes it nearly impossible to identify which test is best to use. Although the testing companies’ decision support tools (DSTs) often disagree in their recommendations, research has shown that using DSTs can facilitate implementation of relevant psychopharmacology dosing guidelines, assist in identifying optimal medication therapy, and improve patient outcomes. Clinicians should use testing panels with recommendations that best align with their individual practices, their patient’s needs, and FDA information.

Related Resources

• PGx Gene-specific information tables. www.pharmgkb.org/page/pgxGeneRef
• Clinical Pharmacogenetics Implementation Consortium. https://cpicpgx.org/guidelines/

Drug Brand Names

Aripiprazole • Abilify
Carbamazepine • Tegretol
Citalopram • Celexa
Clopidogrel • Plavix
Clozapine • Clozaril
Fluoxetine • Prozac
Imipramine • Tofranil
Paroxetine • Paxil
Sertraline • Zoloft
Warfarin • Coumadin, Jantoven

The COVID-19 pandemic has had a negative impact on the mental health of people worldwide, and a disproportionate effect on peripartum women. In this article, we discuss the reasons for this disparity, review the limited literature on this topic, and suggest strategies to safeguard the mental health of peripartum women during the COVID-19 pandemic.

Catastrophic events and women’s mental health

During the peripartum period, women have increased psychosocial and physical health needs.¹ In addition, women are disproportionately affected by natural disasters and catastrophic events,² which are predictors of psychiatric symptoms during the peripartum period.³ Mass tragedies previously associated with maternal stress include wildfires, hurricanes, migrations, earthquakes, and tsunamis.^4,5 For example, pregnant women who survived severe exposure during Hurricane Katrina (ie, feeling that one’s life was in danger, experiencing illness or injury to self or a family member, walking through floodwaters) in 2005 had a significantly increased risk of developing posttraumatic stress disorder (PTSD) and depression compared with pregnant women who did not have such exposure.⁶ After the 2011 Tōhoku earthquake and tsunami in Japan, the prevalence of psychological distress in pregnant women increased, especially among those living in the area directly affected by the tsunami.⁵

Epidemics and pandemics also can adversely affect peripartum women’s mental health. Studies conducted before the COVID-19 pandemic found that previous infectious disease outbreaks such as severe acute respiratory syndrome (SARS), the 2009 influenza A (H1N1) pandemic, and Zika had negative emotional impacts on pregnant women.⁷ Our review of the limited literature published to date suggests that COVID-19 is having similar adverse effects.

COVID-19 poses both medical and psychiatric threats

COVID-19 infection is a physical threat to pregnant women who are already vulnerable due to the hormonal and immunological changes inherent to pregnancy. A meta-analysis of 39 studies with a total of 1,316 pregnant women indicated that the most frequently reported symptoms of COVID-19 infection were cough, fever, and myalgias.⁸ However, COVID-19 infection during pregnancy is also associated with an increase in pregnancy complications and adverse birth outcomes.⁹ According to the CDC, compared with their nonpregnant counterparts, pregnant women are at greater risk for severe COVID-19 infection and adverse birth outcomes such as preterm birth.¹⁰ Pregnant women who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; the virus responsible for COVID-19) risk ICU admission, caesarean section, and perinatal death.⁸ A Swedish study of 2,682 pregnant women found an increase in preeclampsia among women who tested positive for SARS-CoV-2, a finding attributed to COVID-19’s pattern of systemic effects.¹¹ Vertical transmission of the novel coronavirus from mother to fetus appears to be rare but possible.¹²

In addition to the physical dangers of becoming infected with COVID-19, the perceived threat of infection is an added source of anxiety for some peripartum women. In addition to the concerns involved in any pregnancy, COVID-19–related sources of distress for pregnant women include worrying about harm to the fetus during pregnancy, the possibility of vertical transmission, and exposures during antenatal appointments, during employment, or from a partner.^8,13

The death toll from factors associated with COVID-19 adds to the mental health burden. For every person who dies of COVID-19, an estimated 9 others may develop prolonged grief or PTSD due to the loss of someone they loved.^14,15 A systematic review found that PTSD in the perinatal period is associated with negative birth and child outcomes, including low birth weight and decreased rates of breastfeeding.¹⁶ The COVID-19 pandemic has disrupted human interactions, from social distancing rules and lockdowns of businesses and social activities to panic buying of grocery staples and increased economic insecurity.¹ These changes have been accompanied by a rise in mental health challenges. For example, according to an August 2020 CDC survey, 40.9% of US adults reported at least 1 adverse mental or behavioral health condition, including symptoms of anxiety or depression (30.9%), symptoms of a trauma- and stressor-related disorder related to the pandemic (26.3%), and having started or increased substance use to cope with stress or emotions related to COVID-19 (13.3%).¹⁷

COVID-19–related traumas and stressors appear to affect women more than men. A study from China found that compared with men, women had significantly higher levels of self-reported pandemic-related anxiety, depression, and posttraumatic stress symptoms (PTSS).¹⁸ This trend has been observed in other parts of the world. A study conducted by the UK Office of National Statistics reported anxiety levels were 24% higher in women vs men as reflected by scores on a self-rated anxiety scale.¹⁹

Continue to: Many factors influence...

Many factors influence the disproportionate impact of COVID-19 on women in general, and peripartum women in particular (Box^20-26).

Box

Psychiatric diagnoses in peripartum women

Multiple studies and meta-analyses have begun to assess the impact of the COVID-19 pandemic on maternal mental health. One meta-analysis of 8 studies conducted in 5 countries determined that COVID-19 significantly increases the risk of anxiety in women during the peripartum period.²⁷ Results of another meta-analysis of 23 studies with >24,000 participants indicated that the prevalence of anxiety, depression, and insomnia in peripartum women was significantly higher during the pandemic than in pre-pandemic times.²⁸

In an online survey of 4,451 pregnant women in the United States, nearly one-third of respondents reported elevated levels of pandemic-related stress as measured by the newly-developed Pandemic-Related Pregnancy Stress Scale.³ The rates were even higher among women who were already at risk for elevated stress levels, such as those who had survived abuse, those giving birth for the first time, or those experiencing high-risk pregnancies.³ Living in a pandemic “hot spot” also appeared to impact peripartum stress levels.

COVID-19 has adverse effects on women’s mental health specifically during the postpartum period. One study from a center in Italy found a high prevalence of depressive symptoms and PTSS in the postpartum period, with COVID-19–related factors playing an “indirect role” compared with prenatal experiences and other individual factors.² A British study of mothers of infants age ≤12 months found that traveling for work, the impact of lockdown on food affordability, and having an income of less than £30,000 per year (approximately $41,000) predicted poorer mental health during the pandemic.²⁹ Results of a study from China indicated that more than one-quarter of pregnant and postpartum women experienced depression during the pandemic, and women who worried about infection risk or missing pediatric visits were at increased risk.³⁰

How to mitigate these risks

The increase in pandemic-related mental health concerns in the general population and specifically in peripartum women is a global health care challenge. Investing in mitigation strategies is necessary not only to address the current pandemic, but also to help prepare for the possibility of future traumatic events, such as another global pandemic.

Continue to: For pregnant women...

For pregnant women, ensuring access to outdoor space, increasing participation in healthy activities, and minimizing disruptions to prenatal care can protect against pandemic-related stress.³ Physical activity is an effective treatment for mild to moderate depressive symptoms. Because of the significant decrease in exercise among pregnant women during the pandemic, encouraging safe forms of physical activity such as online fitness classes could improve mental health outcomes for these patients.²⁷ When counseling peripartum women, psychiatrists need to be creative in recommending fitness interventions to target mood symptoms, such as by suggesting virtual or at-home programs.

In an online survey, 118 obstetricians called for increased mental health resources for peripartum women, such as easier access to a helpline, educational videos, and mental health professionals.¹³ Increased screening for psychiatric disorders throughout the peripartum period can help identify women at greater risk, and advancements in telepsychiatry could help meet the increased need for psychiatric care during COVID-19. Psychiatrists and other mental health clinicians should consider reaching out to their colleagues who specialize in women’s health to establish new partnerships and create teams of multidisciplinary professionals.

Similarly, psychiatrists should familiarize themselves with telehealth services available to peripartum patients who could benefit from such services. Telehealth options can increase women’s access to peripartum care for both medical and psychiatric illnesses. Online options such as women’s support groups, parenting classes, and labor coaching seminars also represent valuable virtual tools to strengthen women’s social supports.

Women who need inpatient treatment for severe peripartum depression or anxiety might be particularly reluctant to receive this care during COVID-19 due to fears of becoming infected and of being separated from their infant and family while hospitalized. Clinicians should remain vigilant in screening peripartum women for mood disorders that might represent a danger to mothers and infants, and not allow concerns about COVID-19 to interfere with recommendations for psychiatric hospitalizations, when necessary. The creation of small, women-only inpatient behavioral units can help address this situation, especially given the possibility of frequent visits with infants and other peripartum support. Investment into such units is critical for supporting peripartum mental health, even in nonpandemic times.

What about vaccination? As of mid-May 2021, no large clinical trials of any COVID-19 vaccine that included pregnant women had been completed. However, 2 small preliminary studies suggested that the mRNA vaccines are safe and effective during pregnancy.^31,32 When counseling peripartum patients on the risks and benefits, clinicians need to rely on this evidence, animal trials, and limited data from inadvertent exposures during pregnancy. While every woman will weigh the risks and benefits for her own circumstances, the CDC, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine have all stated that the mRNA vaccines should be offered to pregnant and breastfeeding individuals who are eligible for vaccination.³³ Rasmussen et al³³ have published a useful resource for clinicians regarding COVID-19 vaccination and pregnant women.

Continue to: Bottom Line

 

 

Bottom Line

During the COVID-19 pandemic, peripartum women have experienced increased rates of anxiety, depression, and stress. Psychiatric clinicians can help these patients by remaining vigilant in screening for psychiatric disorders, encouraging them to engage in activities to mitigate COVID-19’s adverse psychological effects, and referring them to care via telehealth and other resources as appropriate.

Related Resources

• Hu YJ, Wake M, Saffery R. Clarifying the sweeping consequences of COVID-19 in pregnant women, newborns, and children with existing cohorts. JAMA Pediatr. 2021; 75(2):117-118. doi: 10.1001/jamapediatrics.2020.2395
• Tomfohr-Madsen LM, Racine N, Giesbrecht GF, et al. Depression and anxiety in pregnancy during COVID-19: a rapid review and meta-analysis. Psychiatry Res. 2021; 300:113912. doi: 10.1016/j.psychres.2021.113912

The COVID-19 pandemic has had a negative impact on the mental health of people worldwide, and a disproportionate effect on peripartum women. In this article, we discuss the reasons for this disparity, review the limited literature on this topic, and suggest strategies to safeguard the mental health of peripartum women during the COVID-19 pandemic.

Catastrophic events and women’s mental health

During the peripartum period, women have increased psychosocial and physical health needs.¹ In addition, women are disproportionately affected by natural disasters and catastrophic events,² which are predictors of psychiatric symptoms during the peripartum period.³ Mass tragedies previously associated with maternal stress include wildfires, hurricanes, migrations, earthquakes, and tsunamis.^4,5 For example, pregnant women who survived severe exposure during Hurricane Katrina (ie, feeling that one’s life was in danger, experiencing illness or injury to self or a family member, walking through floodwaters) in 2005 had a significantly increased risk of developing posttraumatic stress disorder (PTSD) and depression compared with pregnant women who did not have such exposure.⁶ After the 2011 Tōhoku earthquake and tsunami in Japan, the prevalence of psychological distress in pregnant women increased, especially among those living in the area directly affected by the tsunami.⁵

Epidemics and pandemics also can adversely affect peripartum women’s mental health. Studies conducted before the COVID-19 pandemic found that previous infectious disease outbreaks such as severe acute respiratory syndrome (SARS), the 2009 influenza A (H1N1) pandemic, and Zika had negative emotional impacts on pregnant women.⁷ Our review of the limited literature published to date suggests that COVID-19 is having similar adverse effects.

COVID-19 poses both medical and psychiatric threats

COVID-19 infection is a physical threat to pregnant women who are already vulnerable due to the hormonal and immunological changes inherent to pregnancy. A meta-analysis of 39 studies with a total of 1,316 pregnant women indicated that the most frequently reported symptoms of COVID-19 infection were cough, fever, and myalgias.⁸ However, COVID-19 infection during pregnancy is also associated with an increase in pregnancy complications and adverse birth outcomes.⁹ According to the CDC, compared with their nonpregnant counterparts, pregnant women are at greater risk for severe COVID-19 infection and adverse birth outcomes such as preterm birth.¹⁰ Pregnant women who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; the virus responsible for COVID-19) risk ICU admission, caesarean section, and perinatal death.⁸ A Swedish study of 2,682 pregnant women found an increase in preeclampsia among women who tested positive for SARS-CoV-2, a finding attributed to COVID-19’s pattern of systemic effects.¹¹ Vertical transmission of the novel coronavirus from mother to fetus appears to be rare but possible.¹²

In addition to the physical dangers of becoming infected with COVID-19, the perceived threat of infection is an added source of anxiety for some peripartum women. In addition to the concerns involved in any pregnancy, COVID-19–related sources of distress for pregnant women include worrying about harm to the fetus during pregnancy, the possibility of vertical transmission, and exposures during antenatal appointments, during employment, or from a partner.^8,13

The death toll from factors associated with COVID-19 adds to the mental health burden. For every person who dies of COVID-19, an estimated 9 others may develop prolonged grief or PTSD due to the loss of someone they loved.^14,15 A systematic review found that PTSD in the perinatal period is associated with negative birth and child outcomes, including low birth weight and decreased rates of breastfeeding.¹⁶ The COVID-19 pandemic has disrupted human interactions, from social distancing rules and lockdowns of businesses and social activities to panic buying of grocery staples and increased economic insecurity.¹ These changes have been accompanied by a rise in mental health challenges. For example, according to an August 2020 CDC survey, 40.9% of US adults reported at least 1 adverse mental or behavioral health condition, including symptoms of anxiety or depression (30.9%), symptoms of a trauma- and stressor-related disorder related to the pandemic (26.3%), and having started or increased substance use to cope with stress or emotions related to COVID-19 (13.3%).¹⁷

COVID-19–related traumas and stressors appear to affect women more than men. A study from China found that compared with men, women had significantly higher levels of self-reported pandemic-related anxiety, depression, and posttraumatic stress symptoms (PTSS).¹⁸ This trend has been observed in other parts of the world. A study conducted by the UK Office of National Statistics reported anxiety levels were 24% higher in women vs men as reflected by scores on a self-rated anxiety scale.¹⁹

Continue to: Many factors influence...

Many factors influence the disproportionate impact of COVID-19 on women in general, and peripartum women in particular (Box^20-26).

Box

Psychiatric diagnoses in peripartum women

Multiple studies and meta-analyses have begun to assess the impact of the COVID-19 pandemic on maternal mental health. One meta-analysis of 8 studies conducted in 5 countries determined that COVID-19 significantly increases the risk of anxiety in women during the peripartum period.²⁷ Results of another meta-analysis of 23 studies with >24,000 participants indicated that the prevalence of anxiety, depression, and insomnia in peripartum women was significantly higher during the pandemic than in pre-pandemic times.²⁸

In an online survey of 4,451 pregnant women in the United States, nearly one-third of respondents reported elevated levels of pandemic-related stress as measured by the newly-developed Pandemic-Related Pregnancy Stress Scale.³ The rates were even higher among women who were already at risk for elevated stress levels, such as those who had survived abuse, those giving birth for the first time, or those experiencing high-risk pregnancies.³ Living in a pandemic “hot spot” also appeared to impact peripartum stress levels.

COVID-19 has adverse effects on women’s mental health specifically during the postpartum period. One study from a center in Italy found a high prevalence of depressive symptoms and PTSS in the postpartum period, with COVID-19–related factors playing an “indirect role” compared with prenatal experiences and other individual factors.² A British study of mothers of infants age ≤12 months found that traveling for work, the impact of lockdown on food affordability, and having an income of less than £30,000 per year (approximately $41,000) predicted poorer mental health during the pandemic.²⁹ Results of a study from China indicated that more than one-quarter of pregnant and postpartum women experienced depression during the pandemic, and women who worried about infection risk or missing pediatric visits were at increased risk.³⁰

How to mitigate these risks

The increase in pandemic-related mental health concerns in the general population and specifically in peripartum women is a global health care challenge. Investing in mitigation strategies is necessary not only to address the current pandemic, but also to help prepare for the possibility of future traumatic events, such as another global pandemic.

Continue to: For pregnant women...

For pregnant women, ensuring access to outdoor space, increasing participation in healthy activities, and minimizing disruptions to prenatal care can protect against pandemic-related stress.³ Physical activity is an effective treatment for mild to moderate depressive symptoms. Because of the significant decrease in exercise among pregnant women during the pandemic, encouraging safe forms of physical activity such as online fitness classes could improve mental health outcomes for these patients.²⁷ When counseling peripartum women, psychiatrists need to be creative in recommending fitness interventions to target mood symptoms, such as by suggesting virtual or at-home programs.

In an online survey, 118 obstetricians called for increased mental health resources for peripartum women, such as easier access to a helpline, educational videos, and mental health professionals.¹³ Increased screening for psychiatric disorders throughout the peripartum period can help identify women at greater risk, and advancements in telepsychiatry could help meet the increased need for psychiatric care during COVID-19. Psychiatrists and other mental health clinicians should consider reaching out to their colleagues who specialize in women’s health to establish new partnerships and create teams of multidisciplinary professionals.

Similarly, psychiatrists should familiarize themselves with telehealth services available to peripartum patients who could benefit from such services. Telehealth options can increase women’s access to peripartum care for both medical and psychiatric illnesses. Online options such as women’s support groups, parenting classes, and labor coaching seminars also represent valuable virtual tools to strengthen women’s social supports.

Women who need inpatient treatment for severe peripartum depression or anxiety might be particularly reluctant to receive this care during COVID-19 due to fears of becoming infected and of being separated from their infant and family while hospitalized. Clinicians should remain vigilant in screening peripartum women for mood disorders that might represent a danger to mothers and infants, and not allow concerns about COVID-19 to interfere with recommendations for psychiatric hospitalizations, when necessary. The creation of small, women-only inpatient behavioral units can help address this situation, especially given the possibility of frequent visits with infants and other peripartum support. Investment into such units is critical for supporting peripartum mental health, even in nonpandemic times.

What about vaccination? As of mid-May 2021, no large clinical trials of any COVID-19 vaccine that included pregnant women had been completed. However, 2 small preliminary studies suggested that the mRNA vaccines are safe and effective during pregnancy.^31,32 When counseling peripartum patients on the risks and benefits, clinicians need to rely on this evidence, animal trials, and limited data from inadvertent exposures during pregnancy. While every woman will weigh the risks and benefits for her own circumstances, the CDC, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine have all stated that the mRNA vaccines should be offered to pregnant and breastfeeding individuals who are eligible for vaccination.³³ Rasmussen et al³³ have published a useful resource for clinicians regarding COVID-19 vaccination and pregnant women.

Continue to: Bottom Line

 

 

Bottom Line

During the COVID-19 pandemic, peripartum women have experienced increased rates of anxiety, depression, and stress. Psychiatric clinicians can help these patients by remaining vigilant in screening for psychiatric disorders, encouraging them to engage in activities to mitigate COVID-19’s adverse psychological effects, and referring them to care via telehealth and other resources as appropriate.

Related Resources

• Hu YJ, Wake M, Saffery R. Clarifying the sweeping consequences of COVID-19 in pregnant women, newborns, and children with existing cohorts. JAMA Pediatr. 2021; 75(2):117-118. doi: 10.1001/jamapediatrics.2020.2395
• Tomfohr-Madsen LM, Racine N, Giesbrecht GF, et al. Depression and anxiety in pregnancy during COVID-19: a rapid review and meta-analysis. Psychiatry Res. 2021; 300:113912. doi: 10.1016/j.psychres.2021.113912

The COVID-19 pandemic has had a negative impact on the mental health of people worldwide, and a disproportionate effect on peripartum women. In this article, we discuss the reasons for this disparity, review the limited literature on this topic, and suggest strategies to safeguard the mental health of peripartum women during the COVID-19 pandemic.

Catastrophic events and women’s mental health

During the peripartum period, women have increased psychosocial and physical health needs.¹ In addition, women are disproportionately affected by natural disasters and catastrophic events,² which are predictors of psychiatric symptoms during the peripartum period.³ Mass tragedies previously associated with maternal stress include wildfires, hurricanes, migrations, earthquakes, and tsunamis.^4,5 For example, pregnant women who survived severe exposure during Hurricane Katrina (ie, feeling that one’s life was in danger, experiencing illness or injury to self or a family member, walking through floodwaters) in 2005 had a significantly increased risk of developing posttraumatic stress disorder (PTSD) and depression compared with pregnant women who did not have such exposure.⁶ After the 2011 Tōhoku earthquake and tsunami in Japan, the prevalence of psychological distress in pregnant women increased, especially among those living in the area directly affected by the tsunami.⁵

Epidemics and pandemics also can adversely affect peripartum women’s mental health. Studies conducted before the COVID-19 pandemic found that previous infectious disease outbreaks such as severe acute respiratory syndrome (SARS), the 2009 influenza A (H1N1) pandemic, and Zika had negative emotional impacts on pregnant women.⁷ Our review of the limited literature published to date suggests that COVID-19 is having similar adverse effects.

COVID-19 poses both medical and psychiatric threats

COVID-19 infection is a physical threat to pregnant women who are already vulnerable due to the hormonal and immunological changes inherent to pregnancy. A meta-analysis of 39 studies with a total of 1,316 pregnant women indicated that the most frequently reported symptoms of COVID-19 infection were cough, fever, and myalgias.⁸ However, COVID-19 infection during pregnancy is also associated with an increase in pregnancy complications and adverse birth outcomes.⁹ According to the CDC, compared with their nonpregnant counterparts, pregnant women are at greater risk for severe COVID-19 infection and adverse birth outcomes such as preterm birth.¹⁰ Pregnant women who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; the virus responsible for COVID-19) risk ICU admission, caesarean section, and perinatal death.⁸ A Swedish study of 2,682 pregnant women found an increase in preeclampsia among women who tested positive for SARS-CoV-2, a finding attributed to COVID-19’s pattern of systemic effects.¹¹ Vertical transmission of the novel coronavirus from mother to fetus appears to be rare but possible.¹²

In addition to the physical dangers of becoming infected with COVID-19, the perceived threat of infection is an added source of anxiety for some peripartum women. In addition to the concerns involved in any pregnancy, COVID-19–related sources of distress for pregnant women include worrying about harm to the fetus during pregnancy, the possibility of vertical transmission, and exposures during antenatal appointments, during employment, or from a partner.^8,13

The death toll from factors associated with COVID-19 adds to the mental health burden. For every person who dies of COVID-19, an estimated 9 others may develop prolonged grief or PTSD due to the loss of someone they loved.^14,15 A systematic review found that PTSD in the perinatal period is associated with negative birth and child outcomes, including low birth weight and decreased rates of breastfeeding.¹⁶ The COVID-19 pandemic has disrupted human interactions, from social distancing rules and lockdowns of businesses and social activities to panic buying of grocery staples and increased economic insecurity.¹ These changes have been accompanied by a rise in mental health challenges. For example, according to an August 2020 CDC survey, 40.9% of US adults reported at least 1 adverse mental or behavioral health condition, including symptoms of anxiety or depression (30.9%), symptoms of a trauma- and stressor-related disorder related to the pandemic (26.3%), and having started or increased substance use to cope with stress or emotions related to COVID-19 (13.3%).¹⁷

COVID-19–related traumas and stressors appear to affect women more than men. A study from China found that compared with men, women had significantly higher levels of self-reported pandemic-related anxiety, depression, and posttraumatic stress symptoms (PTSS).¹⁸ This trend has been observed in other parts of the world. A study conducted by the UK Office of National Statistics reported anxiety levels were 24% higher in women vs men as reflected by scores on a self-rated anxiety scale.¹⁹

Continue to: Many factors influence...

Many factors influence the disproportionate impact of COVID-19 on women in general, and peripartum women in particular (Box^20-26).

Box

Psychiatric diagnoses in peripartum women

Multiple studies and meta-analyses have begun to assess the impact of the COVID-19 pandemic on maternal mental health. One meta-analysis of 8 studies conducted in 5 countries determined that COVID-19 significantly increases the risk of anxiety in women during the peripartum period.²⁷ Results of another meta-analysis of 23 studies with >24,000 participants indicated that the prevalence of anxiety, depression, and insomnia in peripartum women was significantly higher during the pandemic than in pre-pandemic times.²⁸

In an online survey of 4,451 pregnant women in the United States, nearly one-third of respondents reported elevated levels of pandemic-related stress as measured by the newly-developed Pandemic-Related Pregnancy Stress Scale.³ The rates were even higher among women who were already at risk for elevated stress levels, such as those who had survived abuse, those giving birth for the first time, or those experiencing high-risk pregnancies.³ Living in a pandemic “hot spot” also appeared to impact peripartum stress levels.

COVID-19 has adverse effects on women’s mental health specifically during the postpartum period. One study from a center in Italy found a high prevalence of depressive symptoms and PTSS in the postpartum period, with COVID-19–related factors playing an “indirect role” compared with prenatal experiences and other individual factors.² A British study of mothers of infants age ≤12 months found that traveling for work, the impact of lockdown on food affordability, and having an income of less than £30,000 per year (approximately $41,000) predicted poorer mental health during the pandemic.²⁹ Results of a study from China indicated that more than one-quarter of pregnant and postpartum women experienced depression during the pandemic, and women who worried about infection risk or missing pediatric visits were at increased risk.³⁰

How to mitigate these risks

The increase in pandemic-related mental health concerns in the general population and specifically in peripartum women is a global health care challenge. Investing in mitigation strategies is necessary not only to address the current pandemic, but also to help prepare for the possibility of future traumatic events, such as another global pandemic.

Continue to: For pregnant women...

For pregnant women, ensuring access to outdoor space, increasing participation in healthy activities, and minimizing disruptions to prenatal care can protect against pandemic-related stress.³ Physical activity is an effective treatment for mild to moderate depressive symptoms. Because of the significant decrease in exercise among pregnant women during the pandemic, encouraging safe forms of physical activity such as online fitness classes could improve mental health outcomes for these patients.²⁷ When counseling peripartum women, psychiatrists need to be creative in recommending fitness interventions to target mood symptoms, such as by suggesting virtual or at-home programs.

In an online survey, 118 obstetricians called for increased mental health resources for peripartum women, such as easier access to a helpline, educational videos, and mental health professionals.¹³ Increased screening for psychiatric disorders throughout the peripartum period can help identify women at greater risk, and advancements in telepsychiatry could help meet the increased need for psychiatric care during COVID-19. Psychiatrists and other mental health clinicians should consider reaching out to their colleagues who specialize in women’s health to establish new partnerships and create teams of multidisciplinary professionals.

Similarly, psychiatrists should familiarize themselves with telehealth services available to peripartum patients who could benefit from such services. Telehealth options can increase women’s access to peripartum care for both medical and psychiatric illnesses. Online options such as women’s support groups, parenting classes, and labor coaching seminars also represent valuable virtual tools to strengthen women’s social supports.

Women who need inpatient treatment for severe peripartum depression or anxiety might be particularly reluctant to receive this care during COVID-19 due to fears of becoming infected and of being separated from their infant and family while hospitalized. Clinicians should remain vigilant in screening peripartum women for mood disorders that might represent a danger to mothers and infants, and not allow concerns about COVID-19 to interfere with recommendations for psychiatric hospitalizations, when necessary. The creation of small, women-only inpatient behavioral units can help address this situation, especially given the possibility of frequent visits with infants and other peripartum support. Investment into such units is critical for supporting peripartum mental health, even in nonpandemic times.

What about vaccination? As of mid-May 2021, no large clinical trials of any COVID-19 vaccine that included pregnant women had been completed. However, 2 small preliminary studies suggested that the mRNA vaccines are safe and effective during pregnancy.^31,32 When counseling peripartum patients on the risks and benefits, clinicians need to rely on this evidence, animal trials, and limited data from inadvertent exposures during pregnancy. While every woman will weigh the risks and benefits for her own circumstances, the CDC, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine have all stated that the mRNA vaccines should be offered to pregnant and breastfeeding individuals who are eligible for vaccination.³³ Rasmussen et al³³ have published a useful resource for clinicians regarding COVID-19 vaccination and pregnant women.

Continue to: Bottom Line

 

 

Bottom Line

During the COVID-19 pandemic, peripartum women have experienced increased rates of anxiety, depression, and stress. Psychiatric clinicians can help these patients by remaining vigilant in screening for psychiatric disorders, encouraging them to engage in activities to mitigate COVID-19’s adverse psychological effects, and referring them to care via telehealth and other resources as appropriate.

Related Resources

• Hu YJ, Wake M, Saffery R. Clarifying the sweeping consequences of COVID-19 in pregnant women, newborns, and children with existing cohorts. JAMA Pediatr. 2021; 75(2):117-118. doi: 10.1001/jamapediatrics.2020.2395
• Tomfohr-Madsen LM, Racine N, Giesbrecht GF, et al. Depression and anxiety in pregnancy during COVID-19: a rapid review and meta-analysis. Psychiatry Res. 2021; 300:113912. doi: 10.1016/j.psychres.2021.113912