Negative home COVID test no ‘free pass’ for kids, study finds

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Changed
Thu, 12/15/2022 - 14:34

With the country looking increasingly to rapid testing as an off-ramp from the COVID-19 pandemic, a new study shows that the performance of the tests in children falls below standards set by regulatory agencies in the United States and elsewhere for diagnostic accuracy.

Experts said the findings, from a meta-analysis by researchers in the United Kingdom and Germany, underscore that, while a positive result on a rapid test is almost certainly an indicator of infection, negative results often are unreliable and can lead to a false sense of security.

“Real-life performance of current antigen tests for professional use in pediatric populations is below the minimum performance criteria set by WHO, the United States Food and Drug Administration, or the Medicines and Healthcare products Regulatory Agency (U.K.),” according to Naomi Fujita-Rohwerder, PhD, a research associate at the Cologne-based German Institute for Quality and Efficiency in Health Care (IQWiG), and her colleagues, whose study appears in BMJ Evidence-Based Medicine.

The researchers said that the study suggests that performance of rapid testing in a pediatric population is comparable to that in adults. However, they said they could not identify any studies investigating self-testing in children, which also could affect test performance.

Egon Ozer, MD, PhD, director of the center for pathogen genomics and microbial evolution at Northwestern University in Chicago, said the finding that specificity was high but sensitivity was middling “suggests that we should be very careful about interpreting negative antigen test results in children and recognize that there is a fair amount of uncertainty in the tests in this situation.”

Researchers from IQWiG, which examines the advantages and disadvantages of medical interventions, and the University of Manchester (England), conducted the systematic review and meta-analysis, which they described as the first of its kind to evaluate the diagnostic accuracy of rapid point-of-care tests for current SARS-CoV-2 infections in children.

They compiled information from 17 studies with a total 6,355 participants. They compared all antigen tests to reverse-transcription polymerase chain reaction (PCR). The studies compared eight antigen tests from six different brands. The rapid antigen tests, available from pharmacies and online stores, are widely used for self-testing in schools and testing toddlers before kindergarten.

The pooled diagnostic sensitivity of antigen tests was 64.2% and specificity was 99.1%.

Dr. Ozer noted that the analysis “was not able to address important outstanding questions such as the likelihood of transmitting infection with a false-negative antigen test versus a true-negative antigen test or how much repeated testing can increase the sensitivity.”

“In Europe, we don’t know how most tests perform in real life,” Dr. Fujita-Rohwerder said. “And even in countries like the United States, where market access is more stringent, we don’t know whether self-testing performed by children or sample collection in toddlers by laypersons has a significant impact on the diagnostic accuracy. Also, diagnostic accuracy estimates reported in our study may not apply to the current omicron or future variants of SARS-CoV-2 or vaccinated children. Hopefully, these essential gaps in the evidence will get addressed soon.”

Dr. Ozer said one takeaway from this study is negative antigen tests should not be considered a “free pass” in children, especially if the child is symptomatic, has been recently exposed to COVID-19, or is planning to spend time with individuals with conditions that place them at high risk for complications of COVID-19 infection. “In such cases, consider getting PCR testing or at least performing a repeat antigen test 36-48 hours after the first negative,” he said.

Dr. Fujita-Rohwerder said the low diagnostic sensitivity may affect the use of the tests. The gaps in evidence her group found in their study point to research needed to support evidence-based decision-making. “In particular, evidence is needed on real-life performance of tests in schools, self-testing performed by children, and kindergarten, [particularly] sample collection in toddlers by laypersons,” she said.

However, she stressed, testing is only a single measure. “Effectively reducing the spread of SARS-CoV-2 during the current pandemic requires multilayered mitigation measures,” she said. “Rapid testing represents one single layer. It can have its use at the population level, even though the sensitivity of antigen tests is lower than expected. However, antigen-based rapid testing is not a magic bullet: If your kid tests negative, do not disregard other mitigation measures.”

Edward Campbell, PhD, a virologist at Loyola University of Chicago, who serves on the board of LaGrange Elementary School District 102 outside Chicago, said the findings were unsurprising.

“This study generally looks consistent with what is known for adults. These rapid antigen tests are less sensitive than other tests,” said Dr. Campbell, who also runs a testing company for private schools in the Chicago area using reverse transcription-loop-mediated isothermal amplification technology. Even so, he said, “These tests are still effective at identifying people who are infectious to some degree. Never miss an opportunity to test.”

Dr. Fujita-Rohwerder disclosed no relevant financial conflicts of interest. Dr. Campbell owns Safeguard Surveillance.

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With the country looking increasingly to rapid testing as an off-ramp from the COVID-19 pandemic, a new study shows that the performance of the tests in children falls below standards set by regulatory agencies in the United States and elsewhere for diagnostic accuracy.

Experts said the findings, from a meta-analysis by researchers in the United Kingdom and Germany, underscore that, while a positive result on a rapid test is almost certainly an indicator of infection, negative results often are unreliable and can lead to a false sense of security.

“Real-life performance of current antigen tests for professional use in pediatric populations is below the minimum performance criteria set by WHO, the United States Food and Drug Administration, or the Medicines and Healthcare products Regulatory Agency (U.K.),” according to Naomi Fujita-Rohwerder, PhD, a research associate at the Cologne-based German Institute for Quality and Efficiency in Health Care (IQWiG), and her colleagues, whose study appears in BMJ Evidence-Based Medicine.

The researchers said that the study suggests that performance of rapid testing in a pediatric population is comparable to that in adults. However, they said they could not identify any studies investigating self-testing in children, which also could affect test performance.

Egon Ozer, MD, PhD, director of the center for pathogen genomics and microbial evolution at Northwestern University in Chicago, said the finding that specificity was high but sensitivity was middling “suggests that we should be very careful about interpreting negative antigen test results in children and recognize that there is a fair amount of uncertainty in the tests in this situation.”

Researchers from IQWiG, which examines the advantages and disadvantages of medical interventions, and the University of Manchester (England), conducted the systematic review and meta-analysis, which they described as the first of its kind to evaluate the diagnostic accuracy of rapid point-of-care tests for current SARS-CoV-2 infections in children.

They compiled information from 17 studies with a total 6,355 participants. They compared all antigen tests to reverse-transcription polymerase chain reaction (PCR). The studies compared eight antigen tests from six different brands. The rapid antigen tests, available from pharmacies and online stores, are widely used for self-testing in schools and testing toddlers before kindergarten.

The pooled diagnostic sensitivity of antigen tests was 64.2% and specificity was 99.1%.

Dr. Ozer noted that the analysis “was not able to address important outstanding questions such as the likelihood of transmitting infection with a false-negative antigen test versus a true-negative antigen test or how much repeated testing can increase the sensitivity.”

“In Europe, we don’t know how most tests perform in real life,” Dr. Fujita-Rohwerder said. “And even in countries like the United States, where market access is more stringent, we don’t know whether self-testing performed by children or sample collection in toddlers by laypersons has a significant impact on the diagnostic accuracy. Also, diagnostic accuracy estimates reported in our study may not apply to the current omicron or future variants of SARS-CoV-2 or vaccinated children. Hopefully, these essential gaps in the evidence will get addressed soon.”

Dr. Ozer said one takeaway from this study is negative antigen tests should not be considered a “free pass” in children, especially if the child is symptomatic, has been recently exposed to COVID-19, or is planning to spend time with individuals with conditions that place them at high risk for complications of COVID-19 infection. “In such cases, consider getting PCR testing or at least performing a repeat antigen test 36-48 hours after the first negative,” he said.

Dr. Fujita-Rohwerder said the low diagnostic sensitivity may affect the use of the tests. The gaps in evidence her group found in their study point to research needed to support evidence-based decision-making. “In particular, evidence is needed on real-life performance of tests in schools, self-testing performed by children, and kindergarten, [particularly] sample collection in toddlers by laypersons,” she said.

However, she stressed, testing is only a single measure. “Effectively reducing the spread of SARS-CoV-2 during the current pandemic requires multilayered mitigation measures,” she said. “Rapid testing represents one single layer. It can have its use at the population level, even though the sensitivity of antigen tests is lower than expected. However, antigen-based rapid testing is not a magic bullet: If your kid tests negative, do not disregard other mitigation measures.”

Edward Campbell, PhD, a virologist at Loyola University of Chicago, who serves on the board of LaGrange Elementary School District 102 outside Chicago, said the findings were unsurprising.

“This study generally looks consistent with what is known for adults. These rapid antigen tests are less sensitive than other tests,” said Dr. Campbell, who also runs a testing company for private schools in the Chicago area using reverse transcription-loop-mediated isothermal amplification technology. Even so, he said, “These tests are still effective at identifying people who are infectious to some degree. Never miss an opportunity to test.”

Dr. Fujita-Rohwerder disclosed no relevant financial conflicts of interest. Dr. Campbell owns Safeguard Surveillance.

With the country looking increasingly to rapid testing as an off-ramp from the COVID-19 pandemic, a new study shows that the performance of the tests in children falls below standards set by regulatory agencies in the United States and elsewhere for diagnostic accuracy.

Experts said the findings, from a meta-analysis by researchers in the United Kingdom and Germany, underscore that, while a positive result on a rapid test is almost certainly an indicator of infection, negative results often are unreliable and can lead to a false sense of security.

“Real-life performance of current antigen tests for professional use in pediatric populations is below the minimum performance criteria set by WHO, the United States Food and Drug Administration, or the Medicines and Healthcare products Regulatory Agency (U.K.),” according to Naomi Fujita-Rohwerder, PhD, a research associate at the Cologne-based German Institute for Quality and Efficiency in Health Care (IQWiG), and her colleagues, whose study appears in BMJ Evidence-Based Medicine.

The researchers said that the study suggests that performance of rapid testing in a pediatric population is comparable to that in adults. However, they said they could not identify any studies investigating self-testing in children, which also could affect test performance.

Egon Ozer, MD, PhD, director of the center for pathogen genomics and microbial evolution at Northwestern University in Chicago, said the finding that specificity was high but sensitivity was middling “suggests that we should be very careful about interpreting negative antigen test results in children and recognize that there is a fair amount of uncertainty in the tests in this situation.”

Researchers from IQWiG, which examines the advantages and disadvantages of medical interventions, and the University of Manchester (England), conducted the systematic review and meta-analysis, which they described as the first of its kind to evaluate the diagnostic accuracy of rapid point-of-care tests for current SARS-CoV-2 infections in children.

They compiled information from 17 studies with a total 6,355 participants. They compared all antigen tests to reverse-transcription polymerase chain reaction (PCR). The studies compared eight antigen tests from six different brands. The rapid antigen tests, available from pharmacies and online stores, are widely used for self-testing in schools and testing toddlers before kindergarten.

The pooled diagnostic sensitivity of antigen tests was 64.2% and specificity was 99.1%.

Dr. Ozer noted that the analysis “was not able to address important outstanding questions such as the likelihood of transmitting infection with a false-negative antigen test versus a true-negative antigen test or how much repeated testing can increase the sensitivity.”

“In Europe, we don’t know how most tests perform in real life,” Dr. Fujita-Rohwerder said. “And even in countries like the United States, where market access is more stringent, we don’t know whether self-testing performed by children or sample collection in toddlers by laypersons has a significant impact on the diagnostic accuracy. Also, diagnostic accuracy estimates reported in our study may not apply to the current omicron or future variants of SARS-CoV-2 or vaccinated children. Hopefully, these essential gaps in the evidence will get addressed soon.”

Dr. Ozer said one takeaway from this study is negative antigen tests should not be considered a “free pass” in children, especially if the child is symptomatic, has been recently exposed to COVID-19, or is planning to spend time with individuals with conditions that place them at high risk for complications of COVID-19 infection. “In such cases, consider getting PCR testing or at least performing a repeat antigen test 36-48 hours after the first negative,” he said.

Dr. Fujita-Rohwerder said the low diagnostic sensitivity may affect the use of the tests. The gaps in evidence her group found in their study point to research needed to support evidence-based decision-making. “In particular, evidence is needed on real-life performance of tests in schools, self-testing performed by children, and kindergarten, [particularly] sample collection in toddlers by laypersons,” she said.

However, she stressed, testing is only a single measure. “Effectively reducing the spread of SARS-CoV-2 during the current pandemic requires multilayered mitigation measures,” she said. “Rapid testing represents one single layer. It can have its use at the population level, even though the sensitivity of antigen tests is lower than expected. However, antigen-based rapid testing is not a magic bullet: If your kid tests negative, do not disregard other mitigation measures.”

Edward Campbell, PhD, a virologist at Loyola University of Chicago, who serves on the board of LaGrange Elementary School District 102 outside Chicago, said the findings were unsurprising.

“This study generally looks consistent with what is known for adults. These rapid antigen tests are less sensitive than other tests,” said Dr. Campbell, who also runs a testing company for private schools in the Chicago area using reverse transcription-loop-mediated isothermal amplification technology. Even so, he said, “These tests are still effective at identifying people who are infectious to some degree. Never miss an opportunity to test.”

Dr. Fujita-Rohwerder disclosed no relevant financial conflicts of interest. Dr. Campbell owns Safeguard Surveillance.

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Feds’ website for free at-home COVID tests launches day early

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Changed
Tue, 01/18/2022 - 16:13

Americans can now have free COVID-19 rapid tests delivered directly to their homes.

The Biden administration’s new no-cost, at-home testing program launched Jan. 18, a day ahead of schedule.


The administration said 500 million tests are available to be delivered to homes across the country. This accounts for half of the president’s recent pledge to purchase 1 billion free at-home COVID-19 tests to distribute to the American public.

On a Jan. 14 call with reporters, senior White House officials offered some details about the new program.

Here’s what we know so far.

How do I order my free tests?

Americans can visit COVIDtests.gov to order their rapid at-home tests. You can also order directly from the U.S. Postal Service website. After you order, you’ll receive a confirmation email that promises to send tracking information once your order ships.

What information do I need to order the tests?

You only need your name and home mailing address.

There is also an option to provide your email address to get updates on the status of your order.

What if someone needs help ordering the tests?

There will be a free call-in line for people needing more help, including those having trouble accessing the internet, according to White House officials.

What tests will be available?

There are nine at-home tests available through FDA emergency use authorization. According to the Frequently Asked Questions section of COVIDtests.gov, "You will not be able to choose the  brand  you order as part of this program.”

 

 

How long will it take to get the tests once I order them?

Tests are expected to ship 7 to 12 days after you order them.

But White House officials say that the time frame will likely shorten as the program gains steam.

How many can I order?

There’s a limit of four tests per residential mailing address.

For larger families, White House officials suggest trying other free testing options, like visiting COVID-19 testing sites or your local health center.

Is this a one-time opportunity?

The White House doesn’t say, but officials did mention that if you run out of your four free tests, there are many other ways to access free at-home tests, such as COVID-19 testing sites, pharmacies, and community health centers.

The free tests available through COVIDtests.gov are in addition to an estimated 375 million at-home rapid tests on the market in the U.S. this month.

When should people use a rapid at-home test?

The CDC and experts with other public health groups agree that Americans should consider using at-home rapid tests in the following situations:

  • If they begin to have symptoms consistent with COVID-19;
  • At least 5 days after close contact with someone who has COVID;
  • If someone is indoors with a group of people who are at risk of severe disease or are unvaccinated.

Are at-home rapid tests accurate?

The U.S. Department of Health and Human Services and other federal officials confirmed through studies that all tests distributed through this program can detect the Omicron variant. These agencies also confirmed that their performance is consistent with the FDA’s emergency use authorization.

Is the website designed to handle high demand?

After the original website to sign up for health insurance under the Affordable Care Act crashed repeatedly at launch, the government says it has prepared for high demand for ordering at-home rapid tests.

The U.S. Digital Service (USDS), an organization founded after Healthcare.gov, has partnered with the Postal Service to plan for the launch.

The Postal Service has expanded its staffing, similar to what’s done during the holidays.

All orders in the continental United States will be shipped through first-class mail, with shipments to Alaska, Hawaii, U.S. territories, and military and overseas addresses sent through priority mail.

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

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Americans can now have free COVID-19 rapid tests delivered directly to their homes.

The Biden administration’s new no-cost, at-home testing program launched Jan. 18, a day ahead of schedule.


The administration said 500 million tests are available to be delivered to homes across the country. This accounts for half of the president’s recent pledge to purchase 1 billion free at-home COVID-19 tests to distribute to the American public.

On a Jan. 14 call with reporters, senior White House officials offered some details about the new program.

Here’s what we know so far.

How do I order my free tests?

Americans can visit COVIDtests.gov to order their rapid at-home tests. You can also order directly from the U.S. Postal Service website. After you order, you’ll receive a confirmation email that promises to send tracking information once your order ships.

What information do I need to order the tests?

You only need your name and home mailing address.

There is also an option to provide your email address to get updates on the status of your order.

What if someone needs help ordering the tests?

There will be a free call-in line for people needing more help, including those having trouble accessing the internet, according to White House officials.

What tests will be available?

There are nine at-home tests available through FDA emergency use authorization. According to the Frequently Asked Questions section of COVIDtests.gov, "You will not be able to choose the  brand  you order as part of this program.”

 

 

How long will it take to get the tests once I order them?

Tests are expected to ship 7 to 12 days after you order them.

But White House officials say that the time frame will likely shorten as the program gains steam.

How many can I order?

There’s a limit of four tests per residential mailing address.

For larger families, White House officials suggest trying other free testing options, like visiting COVID-19 testing sites or your local health center.

Is this a one-time opportunity?

The White House doesn’t say, but officials did mention that if you run out of your four free tests, there are many other ways to access free at-home tests, such as COVID-19 testing sites, pharmacies, and community health centers.

The free tests available through COVIDtests.gov are in addition to an estimated 375 million at-home rapid tests on the market in the U.S. this month.

When should people use a rapid at-home test?

The CDC and experts with other public health groups agree that Americans should consider using at-home rapid tests in the following situations:

  • If they begin to have symptoms consistent with COVID-19;
  • At least 5 days after close contact with someone who has COVID;
  • If someone is indoors with a group of people who are at risk of severe disease or are unvaccinated.

Are at-home rapid tests accurate?

The U.S. Department of Health and Human Services and other federal officials confirmed through studies that all tests distributed through this program can detect the Omicron variant. These agencies also confirmed that their performance is consistent with the FDA’s emergency use authorization.

Is the website designed to handle high demand?

After the original website to sign up for health insurance under the Affordable Care Act crashed repeatedly at launch, the government says it has prepared for high demand for ordering at-home rapid tests.

The U.S. Digital Service (USDS), an organization founded after Healthcare.gov, has partnered with the Postal Service to plan for the launch.

The Postal Service has expanded its staffing, similar to what’s done during the holidays.

All orders in the continental United States will be shipped through first-class mail, with shipments to Alaska, Hawaii, U.S. territories, and military and overseas addresses sent through priority mail.

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

Americans can now have free COVID-19 rapid tests delivered directly to their homes.

The Biden administration’s new no-cost, at-home testing program launched Jan. 18, a day ahead of schedule.


The administration said 500 million tests are available to be delivered to homes across the country. This accounts for half of the president’s recent pledge to purchase 1 billion free at-home COVID-19 tests to distribute to the American public.

On a Jan. 14 call with reporters, senior White House officials offered some details about the new program.

Here’s what we know so far.

How do I order my free tests?

Americans can visit COVIDtests.gov to order their rapid at-home tests. You can also order directly from the U.S. Postal Service website. After you order, you’ll receive a confirmation email that promises to send tracking information once your order ships.

What information do I need to order the tests?

You only need your name and home mailing address.

There is also an option to provide your email address to get updates on the status of your order.

What if someone needs help ordering the tests?

There will be a free call-in line for people needing more help, including those having trouble accessing the internet, according to White House officials.

What tests will be available?

There are nine at-home tests available through FDA emergency use authorization. According to the Frequently Asked Questions section of COVIDtests.gov, "You will not be able to choose the  brand  you order as part of this program.”

 

 

How long will it take to get the tests once I order them?

Tests are expected to ship 7 to 12 days after you order them.

But White House officials say that the time frame will likely shorten as the program gains steam.

How many can I order?

There’s a limit of four tests per residential mailing address.

For larger families, White House officials suggest trying other free testing options, like visiting COVID-19 testing sites or your local health center.

Is this a one-time opportunity?

The White House doesn’t say, but officials did mention that if you run out of your four free tests, there are many other ways to access free at-home tests, such as COVID-19 testing sites, pharmacies, and community health centers.

The free tests available through COVIDtests.gov are in addition to an estimated 375 million at-home rapid tests on the market in the U.S. this month.

When should people use a rapid at-home test?

The CDC and experts with other public health groups agree that Americans should consider using at-home rapid tests in the following situations:

  • If they begin to have symptoms consistent with COVID-19;
  • At least 5 days after close contact with someone who has COVID;
  • If someone is indoors with a group of people who are at risk of severe disease or are unvaccinated.

Are at-home rapid tests accurate?

The U.S. Department of Health and Human Services and other federal officials confirmed through studies that all tests distributed through this program can detect the Omicron variant. These agencies also confirmed that their performance is consistent with the FDA’s emergency use authorization.

Is the website designed to handle high demand?

After the original website to sign up for health insurance under the Affordable Care Act crashed repeatedly at launch, the government says it has prepared for high demand for ordering at-home rapid tests.

The U.S. Digital Service (USDS), an organization founded after Healthcare.gov, has partnered with the Postal Service to plan for the launch.

The Postal Service has expanded its staffing, similar to what’s done during the holidays.

All orders in the continental United States will be shipped through first-class mail, with shipments to Alaska, Hawaii, U.S. territories, and military and overseas addresses sent through priority mail.

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

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Survey: Medical cannabis use for skin conditions lags behind interest, acceptance

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Changed
Tue, 01/18/2022 - 15:48

A majority of adults support the use of medical cannabis for the treatment of skin conditions, but relatively few have actually tried such a product, according to the results of a recent survey.

Almost 89% of respondents were in favor of medical cannabis use for dermatologic diseases, and 73% said that they would be comfortable seeing a dermatologist who recommended such products to them, Samuel Yeroushalmi, a 4th-year medical student at George Washington University, Washington, and associates reported.

“Consumers and patients are already using MCPs [medical cannabis products] to treat inflammatory skin conditions, such as acne, rosacea, atopic dermatitis, and psoriasis, even without guidance from a dermatologist. While acceptance was high, there were clear barriers reported limiting use and uptake, such as patient skepticism and a lack of understanding,” Adam Friedman, MD, senior author and chair of the department of dermatology at the university, said in a separate statement.

Dermatologic use of OTC cannabis products without the recommendation of a dermatologist was reported by 18% of the 504 of 700 adults who responded in the SurveyMonkey online panel. Of the two-thirds who had seen a dermatologist, 20% received a recommendation for an OTC product and 11% were recommended a product that required a department of health medical card, the investigators said.

Uptake among the patients who did receive a recommendation, however, was high: 76% for OTC products and 72% for those that required a medical card. Among those who had received an OTC recommendation, 32% used the cannabis product for psoriasis and 30% each for acne and rosacea, Mr. Yeroushalmi and his coauthors said.

The most common indication among the respondents with dermatologist recommendations for products requiring a medical card was for acne (68%), followed by psoriasis and rosacea (28% each). Cost was the main deterrent (60%) for those who declined to use the recommended cannabis product, with skepticism, limited understanding, and product illegality in their state each at 50%, the researchers said.

“Though cost and legality concerns are nonmodifiable barriers, dermatologists have an opportunity to educate those who know little in the way of medical cannabis or are skeptic[s],” they wrote. The survey results show that many patients are interested, and “the future should be bright for MCPs; we just need to show and disseminate the science,” Dr. Friedman commented in the statement.

One of the authors was from the University of Maryland, College Park. The authors had no disclosures to report.

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A majority of adults support the use of medical cannabis for the treatment of skin conditions, but relatively few have actually tried such a product, according to the results of a recent survey.

Almost 89% of respondents were in favor of medical cannabis use for dermatologic diseases, and 73% said that they would be comfortable seeing a dermatologist who recommended such products to them, Samuel Yeroushalmi, a 4th-year medical student at George Washington University, Washington, and associates reported.

“Consumers and patients are already using MCPs [medical cannabis products] to treat inflammatory skin conditions, such as acne, rosacea, atopic dermatitis, and psoriasis, even without guidance from a dermatologist. While acceptance was high, there were clear barriers reported limiting use and uptake, such as patient skepticism and a lack of understanding,” Adam Friedman, MD, senior author and chair of the department of dermatology at the university, said in a separate statement.

Dermatologic use of OTC cannabis products without the recommendation of a dermatologist was reported by 18% of the 504 of 700 adults who responded in the SurveyMonkey online panel. Of the two-thirds who had seen a dermatologist, 20% received a recommendation for an OTC product and 11% were recommended a product that required a department of health medical card, the investigators said.

Uptake among the patients who did receive a recommendation, however, was high: 76% for OTC products and 72% for those that required a medical card. Among those who had received an OTC recommendation, 32% used the cannabis product for psoriasis and 30% each for acne and rosacea, Mr. Yeroushalmi and his coauthors said.

The most common indication among the respondents with dermatologist recommendations for products requiring a medical card was for acne (68%), followed by psoriasis and rosacea (28% each). Cost was the main deterrent (60%) for those who declined to use the recommended cannabis product, with skepticism, limited understanding, and product illegality in their state each at 50%, the researchers said.

“Though cost and legality concerns are nonmodifiable barriers, dermatologists have an opportunity to educate those who know little in the way of medical cannabis or are skeptic[s],” they wrote. The survey results show that many patients are interested, and “the future should be bright for MCPs; we just need to show and disseminate the science,” Dr. Friedman commented in the statement.

One of the authors was from the University of Maryland, College Park. The authors had no disclosures to report.

A majority of adults support the use of medical cannabis for the treatment of skin conditions, but relatively few have actually tried such a product, according to the results of a recent survey.

Almost 89% of respondents were in favor of medical cannabis use for dermatologic diseases, and 73% said that they would be comfortable seeing a dermatologist who recommended such products to them, Samuel Yeroushalmi, a 4th-year medical student at George Washington University, Washington, and associates reported.

“Consumers and patients are already using MCPs [medical cannabis products] to treat inflammatory skin conditions, such as acne, rosacea, atopic dermatitis, and psoriasis, even without guidance from a dermatologist. While acceptance was high, there were clear barriers reported limiting use and uptake, such as patient skepticism and a lack of understanding,” Adam Friedman, MD, senior author and chair of the department of dermatology at the university, said in a separate statement.

Dermatologic use of OTC cannabis products without the recommendation of a dermatologist was reported by 18% of the 504 of 700 adults who responded in the SurveyMonkey online panel. Of the two-thirds who had seen a dermatologist, 20% received a recommendation for an OTC product and 11% were recommended a product that required a department of health medical card, the investigators said.

Uptake among the patients who did receive a recommendation, however, was high: 76% for OTC products and 72% for those that required a medical card. Among those who had received an OTC recommendation, 32% used the cannabis product for psoriasis and 30% each for acne and rosacea, Mr. Yeroushalmi and his coauthors said.

The most common indication among the respondents with dermatologist recommendations for products requiring a medical card was for acne (68%), followed by psoriasis and rosacea (28% each). Cost was the main deterrent (60%) for those who declined to use the recommended cannabis product, with skepticism, limited understanding, and product illegality in their state each at 50%, the researchers said.

“Though cost and legality concerns are nonmodifiable barriers, dermatologists have an opportunity to educate those who know little in the way of medical cannabis or are skeptic[s],” they wrote. The survey results show that many patients are interested, and “the future should be bright for MCPs; we just need to show and disseminate the science,” Dr. Friedman commented in the statement.

One of the authors was from the University of Maryland, College Park. The authors had no disclosures to report.

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Antibiotics used in newborns despite low risk for sepsis

Article Type
Changed
Wed, 01/19/2022 - 10:46

Antibiotics were administered to newborns at low risk for early-onset sepsis as frequently as to newborns with EOS risk factors, based on data from approximately 7,500 infants.

EOS remains a significant cause of morbidity and mortality, and predicting which newborns are at risk remains a challenge for neonatal care that often drives high rates of antibiotic use, Dustin D. Flannery, DO, of Children’s Hospital of Philadelphia and colleagues wrote.

Antibiotic exposures are associated with short- and long-term adverse effects in both preterm and term infants, which highlights the need for improved risk assessment in this population, the researchers said.

“A robust estimate of EOS risk in relation to delivery characteristics among infants of all gestational ages at birth could significantly contribute to newborn clinical management by identifying newborns unlikely to benefit from empirical antibiotic therapy,” they emphasized.

In a study published in Pediatrics, the researchers identified 7,540 infants born between Jan. 1, 2009, and Dec. 31, 2014, at two high-risk perinatal units in Philadelphia. Gestational age ranged from 22 to 43 weeks. Criteria for low risk of EOS were determined via an algorithm that included cesarean delivery (with or without labor or membrane rupture), and no antepartum concerns for intra-amniotic infection or nonreassuring fetal status.

A total of 6,428 infants did not meet the low-risk criteria; another 1,121 infants met the low-risk criteria. The primary outcome of EOS was defined as growth of a pathogen in at least 1 blood and/or cerebrospinal fluid culture obtained at 72 hours or less after birth. Overall, 41 infants who did not meet the low-risk criteria developed EOS; none of the infants who met the low-risk criteria developed EOS. Secondary outcomes included initiation of empirical antibiotics at 72 hours or less after birth and the duration of antibiotic use.

Although fewer low-risk infants received antibiotics, compared with infants with EOS (80.4% vs. 91.0%, P < .001), the duration of antibiotic use was not significantly different between the groups, with an adjusted difference of 0.6 hours.

Among infants who did not meet low-risk criteria, 157 were started on antibiotics for each case of EOS, the researchers noted in their discussion of the findings. “Because no cases of EOS were identified in the low-risk group, this proportion could not be calculated but suggests that antibiotic exposure in this group was disproportionately higher for incidence of EOS.”

The study findings were limited by several factors including the possible lack of generalizability to other centers and the use of data from a period before more refined EOS strategies, the researchers noted. Other limitations include the inability to assess the effect of lab results on antibiotic use, a lack of data on the exact indication for delivery, and potential misclassification bias.

Risk assessment tools should not be used alone, but should be used to inform clinical decision-making, the researchers emphasized. However, the results were strengthened by the inclusion of moderately preterm infants, who are rarely studied, and the clinical utility of the risk algorithm used in the study. “The implications of our study include potential adjustments to sepsis risk assessment in term infants, and confirmation and enhancement of previous studies that identify a subset of lower-risk preterm infants,” who may be spared empirical or prolonged antibiotic exposure, they concluded.
 

 

 

Data inform intelligent antibiotic use

“Early-onset sepsis is predominantly caused by exposure of the fetus or neonate to ascending maternal colonization or infection by gastrointestinal or genitourinary bacteria,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Scenarios where there is limited neonatal exposure to these organisms would decrease the risk of development of EOS, therefore it is not surprising that delivery characteristics of low-risk deliveries as defined by investigators – the absence of labor, absence of intra-amniotic infection, rupture of membranes at time of delivery, and cesarean delivery – would have resulted in decreased likelihood of EOS.”

Inappropriate antibiotic use contributes to the development of resistant and more virulent strains of bacteria. A growing body of literature also suggests that early antibiotic usage in newborns may affect the neonatal gut microbiome, which is important for development of the neonatal immune system. Early alterations of the microbiome may have long-term implications,” Dr. Krishna said.

“Understanding the delivery characteristics that increase the risk of EOS are crucial to optimizing the use of antibiotics and thereby minimize potential harm to newborns,” she said. “Studies such as the current study are needed develop EOS prediction tools to improve antibiotic utilization.” More research is needed not only to adequately predict EOS, but to explore how antibiotics affect the neonatal microbiome, and how clinicians can circumvent potential adverse implications with antibiotic use to improve long-term health, Dr. Krishna concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

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Antibiotics were administered to newborns at low risk for early-onset sepsis as frequently as to newborns with EOS risk factors, based on data from approximately 7,500 infants.

EOS remains a significant cause of morbidity and mortality, and predicting which newborns are at risk remains a challenge for neonatal care that often drives high rates of antibiotic use, Dustin D. Flannery, DO, of Children’s Hospital of Philadelphia and colleagues wrote.

Antibiotic exposures are associated with short- and long-term adverse effects in both preterm and term infants, which highlights the need for improved risk assessment in this population, the researchers said.

“A robust estimate of EOS risk in relation to delivery characteristics among infants of all gestational ages at birth could significantly contribute to newborn clinical management by identifying newborns unlikely to benefit from empirical antibiotic therapy,” they emphasized.

In a study published in Pediatrics, the researchers identified 7,540 infants born between Jan. 1, 2009, and Dec. 31, 2014, at two high-risk perinatal units in Philadelphia. Gestational age ranged from 22 to 43 weeks. Criteria for low risk of EOS were determined via an algorithm that included cesarean delivery (with or without labor or membrane rupture), and no antepartum concerns for intra-amniotic infection or nonreassuring fetal status.

A total of 6,428 infants did not meet the low-risk criteria; another 1,121 infants met the low-risk criteria. The primary outcome of EOS was defined as growth of a pathogen in at least 1 blood and/or cerebrospinal fluid culture obtained at 72 hours or less after birth. Overall, 41 infants who did not meet the low-risk criteria developed EOS; none of the infants who met the low-risk criteria developed EOS. Secondary outcomes included initiation of empirical antibiotics at 72 hours or less after birth and the duration of antibiotic use.

Although fewer low-risk infants received antibiotics, compared with infants with EOS (80.4% vs. 91.0%, P < .001), the duration of antibiotic use was not significantly different between the groups, with an adjusted difference of 0.6 hours.

Among infants who did not meet low-risk criteria, 157 were started on antibiotics for each case of EOS, the researchers noted in their discussion of the findings. “Because no cases of EOS were identified in the low-risk group, this proportion could not be calculated but suggests that antibiotic exposure in this group was disproportionately higher for incidence of EOS.”

The study findings were limited by several factors including the possible lack of generalizability to other centers and the use of data from a period before more refined EOS strategies, the researchers noted. Other limitations include the inability to assess the effect of lab results on antibiotic use, a lack of data on the exact indication for delivery, and potential misclassification bias.

Risk assessment tools should not be used alone, but should be used to inform clinical decision-making, the researchers emphasized. However, the results were strengthened by the inclusion of moderately preterm infants, who are rarely studied, and the clinical utility of the risk algorithm used in the study. “The implications of our study include potential adjustments to sepsis risk assessment in term infants, and confirmation and enhancement of previous studies that identify a subset of lower-risk preterm infants,” who may be spared empirical or prolonged antibiotic exposure, they concluded.
 

 

 

Data inform intelligent antibiotic use

“Early-onset sepsis is predominantly caused by exposure of the fetus or neonate to ascending maternal colonization or infection by gastrointestinal or genitourinary bacteria,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Scenarios where there is limited neonatal exposure to these organisms would decrease the risk of development of EOS, therefore it is not surprising that delivery characteristics of low-risk deliveries as defined by investigators – the absence of labor, absence of intra-amniotic infection, rupture of membranes at time of delivery, and cesarean delivery – would have resulted in decreased likelihood of EOS.”

Inappropriate antibiotic use contributes to the development of resistant and more virulent strains of bacteria. A growing body of literature also suggests that early antibiotic usage in newborns may affect the neonatal gut microbiome, which is important for development of the neonatal immune system. Early alterations of the microbiome may have long-term implications,” Dr. Krishna said.

“Understanding the delivery characteristics that increase the risk of EOS are crucial to optimizing the use of antibiotics and thereby minimize potential harm to newborns,” she said. “Studies such as the current study are needed develop EOS prediction tools to improve antibiotic utilization.” More research is needed not only to adequately predict EOS, but to explore how antibiotics affect the neonatal microbiome, and how clinicians can circumvent potential adverse implications with antibiotic use to improve long-term health, Dr. Krishna concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Antibiotics were administered to newborns at low risk for early-onset sepsis as frequently as to newborns with EOS risk factors, based on data from approximately 7,500 infants.

EOS remains a significant cause of morbidity and mortality, and predicting which newborns are at risk remains a challenge for neonatal care that often drives high rates of antibiotic use, Dustin D. Flannery, DO, of Children’s Hospital of Philadelphia and colleagues wrote.

Antibiotic exposures are associated with short- and long-term adverse effects in both preterm and term infants, which highlights the need for improved risk assessment in this population, the researchers said.

“A robust estimate of EOS risk in relation to delivery characteristics among infants of all gestational ages at birth could significantly contribute to newborn clinical management by identifying newborns unlikely to benefit from empirical antibiotic therapy,” they emphasized.

In a study published in Pediatrics, the researchers identified 7,540 infants born between Jan. 1, 2009, and Dec. 31, 2014, at two high-risk perinatal units in Philadelphia. Gestational age ranged from 22 to 43 weeks. Criteria for low risk of EOS were determined via an algorithm that included cesarean delivery (with or without labor or membrane rupture), and no antepartum concerns for intra-amniotic infection or nonreassuring fetal status.

A total of 6,428 infants did not meet the low-risk criteria; another 1,121 infants met the low-risk criteria. The primary outcome of EOS was defined as growth of a pathogen in at least 1 blood and/or cerebrospinal fluid culture obtained at 72 hours or less after birth. Overall, 41 infants who did not meet the low-risk criteria developed EOS; none of the infants who met the low-risk criteria developed EOS. Secondary outcomes included initiation of empirical antibiotics at 72 hours or less after birth and the duration of antibiotic use.

Although fewer low-risk infants received antibiotics, compared with infants with EOS (80.4% vs. 91.0%, P < .001), the duration of antibiotic use was not significantly different between the groups, with an adjusted difference of 0.6 hours.

Among infants who did not meet low-risk criteria, 157 were started on antibiotics for each case of EOS, the researchers noted in their discussion of the findings. “Because no cases of EOS were identified in the low-risk group, this proportion could not be calculated but suggests that antibiotic exposure in this group was disproportionately higher for incidence of EOS.”

The study findings were limited by several factors including the possible lack of generalizability to other centers and the use of data from a period before more refined EOS strategies, the researchers noted. Other limitations include the inability to assess the effect of lab results on antibiotic use, a lack of data on the exact indication for delivery, and potential misclassification bias.

Risk assessment tools should not be used alone, but should be used to inform clinical decision-making, the researchers emphasized. However, the results were strengthened by the inclusion of moderately preterm infants, who are rarely studied, and the clinical utility of the risk algorithm used in the study. “The implications of our study include potential adjustments to sepsis risk assessment in term infants, and confirmation and enhancement of previous studies that identify a subset of lower-risk preterm infants,” who may be spared empirical or prolonged antibiotic exposure, they concluded.
 

 

 

Data inform intelligent antibiotic use

“Early-onset sepsis is predominantly caused by exposure of the fetus or neonate to ascending maternal colonization or infection by gastrointestinal or genitourinary bacteria,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Scenarios where there is limited neonatal exposure to these organisms would decrease the risk of development of EOS, therefore it is not surprising that delivery characteristics of low-risk deliveries as defined by investigators – the absence of labor, absence of intra-amniotic infection, rupture of membranes at time of delivery, and cesarean delivery – would have resulted in decreased likelihood of EOS.”

Inappropriate antibiotic use contributes to the development of resistant and more virulent strains of bacteria. A growing body of literature also suggests that early antibiotic usage in newborns may affect the neonatal gut microbiome, which is important for development of the neonatal immune system. Early alterations of the microbiome may have long-term implications,” Dr. Krishna said.

“Understanding the delivery characteristics that increase the risk of EOS are crucial to optimizing the use of antibiotics and thereby minimize potential harm to newborns,” she said. “Studies such as the current study are needed develop EOS prediction tools to improve antibiotic utilization.” More research is needed not only to adequately predict EOS, but to explore how antibiotics affect the neonatal microbiome, and how clinicians can circumvent potential adverse implications with antibiotic use to improve long-term health, Dr. Krishna concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

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Emotions, science, and the politics of COVID

Article Type
Changed
Tue, 01/18/2022 - 15:18

A social worker called with a plea in April 2020, when the hospital was filled with COVID-19 patients, some so sick they were on ventilators. “I need your help with a family. Mom is in the ICU, intubated; her son died here 2 weeks ago of COVID and her daughters are overwhelmed, unable to visit because of restrictions. The staff anticipates extubating Elvira imminently, but she will be fragile and alone. When is the right time to tell Elvira that Tony died?”

That happened at the beginning of the COVID pandemic. I handled the case remotely with heroic help from overburdened nurses and doctors who were acting as medical staff, social workers, and substitute family to an isolated patient in the hospital. Such was the confusion with the new virus before vaccines and treatments.
 

The impact of pandemics: A historical perspective

Dr. Ruth Cohen

Beginning in antiquity, there were pandemics that decimated populations. Before antibiotics, vaccines or awareness of microorganisms, people feared contagion and sought isolation from the sick. People also thought that those who recovered were less likely to fall ill again, and if they did get sick, the illness would be milder.

There is abundant documentation of bubonic plague outbreaks, such as the “Black Death” in the Middle Ages. The Spanish flu of 1918 struck down robust young Americans and spread worldwide. Although the bubonic plague was at the center of major infectious outbreaks, including the pandemic of the Justinian era (500s) and the Great Plague of London (1665-1666), other infectious diseases, untreatable at the time, prevailed simultaneously. Wars, world trade, unsanitary conditions, and urban crowding enhanced the spread. Pandemics shaped history. Some historians attribute the fall of the Roman Empire to unrelenting infectious disease carried in migratory battles.

Even in the earliest outbreaks, the poor populace died more readily than the well off, who had means to escape and seclude themselves from congested areas. Samuel Pepys, a diarist of the London Plague, was a famed businessman and government official; he wrote of seeing the suffering in his city, but he escaped to live with his wife in their country home. What Samuel Pepys wrote of London during the Plague can apply to the early period of the COVID pandemic: “How few people I see, and those looking like people that had taken leave of the world.”

There are lurid descriptions of the chaos of pandemics, especially of the Black Death and the Plague of London. First published in 1722, Daniel Defoe’s “A Journal of the Plague Year” describes the suffering of the sick that included people abandoning the afflicted and others running rampant with delirium in the streets, screaming in pain. City officials took cruel measures that they considered necessary, such as locking away families in their homes, sick and well together, when an individual member showed symptoms. The Middle Ages saw deadly anti-Semitism. During the Black Death, fanatics murdered Jews in the belief that they brought on the pestilence. Ignorance created panic.

As happens in tragedy, there was also bravery. Some stayed to tend to the sick; charities provided food for poor people during the London Plague.
 

 

 

Back to the 21st century

After 3 weeks on the ventilator, Elvira got extubated. A team including her doctor, nurse, and Connie, one of her daughters, told Elvira that her 28-year-old son had died of COVID. I began telepsychiatry with Elvira and her two daughters. Treatment continued after Elvira returned home. In telephone sessions, we discussed bereavement and how to cope with the emotional and physical challenges in recovery.

Before he contracted COVID, Tony, Elvira’s son, had compromised health. He was on dialysis awaiting a kidney transplant. His mother prepared his meals and often accompanied Tony to doctor appointments. Still, Elvira said, “I wasn’t there to hold his hand.” At age 71, Elvira was also at high risk. She suffered from diabetes, high blood pressure, hyperlipidemia, and had coronary stents. Elvira was compliant with medications for her conditions.
 

What we know; where we are

“Infectious diseases are not static conditions but depend upon a constantly changing relationship between parasite and invaded species which is bound to result in modifications of both clinical and epidemiological manifestations.”

Hans Zinsser, Rats, Lice and History

We need to be informed by history and grateful to the geniuses who brought us into the modern age of medicine. We can prevent diseases with public health measures, and by understanding and treating crises. Edward Jenner, who recognized the protective effect of cowpox against smallpox, developed inoculations beginning in 1796; he ushered in immunology and saved the lives of millions. Smallpox is now eradicated. A succession of microbe hunters, including Louis Pasteur and Robert Koch, benefited from the development of the microscope by Antonie van Leeuwenhoek. With the advent and use of penicillin in the early 1940s, Alexander Fleming welcomed antibiotics; by the 1960s this modality became widespread. In the mid-20th century, immunologists recognized that bacteria and viruses change and adapt to the environment.

The planet has seen ravaging pandemics that then dissipated and, although untreatable at the time, disappeared into a reservoir, such as rats or lice. People also developed herd immunity from exposure to the offending microorganisms within the population. Less toxic, these agents no longer kill those who get infected but they can be transmissible and endemic to humans.

The mental health consequences of pandemics are reminiscent of other severe illnesses. The seriously ill develop cognitive aberrations and can become delirious. The population at risk and those who get sick can experience depression, PTSD, and anxiety – including panic.
 

Update on Elvira

Elvira continues to improve. She also participates in support groups, including one that addresses bereavement for parents of children who died of COVID and other causes. “I didn’t have a chance to say goodbye,” she said. But what she calls her “brain fog” has dissipated. She walks better, and she is getting evaluation of radiculopathy, probably from nerve root injury during her 3 weeks in bed on the ventilator. She’s still experiencing pain in her feet.

With regard to her symptoms she said: “I cry almost every day.” Her PTSD has abated, but she sometimes has nightmares. Elvira is writing a book about the induced coma and the “hallucinations from hell to heaven” she experienced. She wonders:“Did Tony go through the same thing?” Her empathy is enhanced by her background as a retired social worker with the Administration for Children’s Services in New York.
 

 

 

The role of psychiatry

In its early, most virulent form, SARS-CoV-2 devastated thousands of people, especially the elderly medically vulnerable. With scientific tools we developed vaccines and treatments and continue to study the dynamics of this virus.

As Andy Miller, MD, chief of the division of infectious diseases at the Hospital for Special Surgery, said when I spoke with him about the virus, because of the way in which viruses mutate, “we must remain aware” of the trajectory of SARS-CoV-2 and “counter irrational beliefs.”

How should psychiatry deal with COVID? As scientists, we seek the truth without bias and politics. Mental illness is our domain. Other specialties have the expertise to treat and even prevent infectious disease. We can assist our doctor colleagues to understand depression, anxiety, PTSD, and cognitive issues when they occur. Our medical mission should be, as always, to treat those who suffer mental illness. Now that extends to the consequences of COVID.
 

Suggested reading

Camus A. The Plague. New York: Vintage Books,. 1991.

Defoe D. A Journal of the Plague Year. Mineola, N.Y.: Dover Publications, 2001.

Kelly J. The Great Mortality: An Intimate History of the Black Death, The Most Devastating Plague of All Time. New York: Harper Perennial, 2005.

Pepys S. The Diary of Samuel Pepys: The Great Plague of London & The Great Fire of London, 1665-1666. Oxford, England: Benediction Classics, 2020.

Emerg Infect Dis. 2005 Mar 11(3):402-96.

Zinsser H. Rats, Lice and History. Boston/Toronto: Little Brown and Co., 1935.

Dr. Cohen is in private practice of psychotherapy and medication management in New York. She has been a consultant at the Hospital for Special Surgery and at New York–Presbyterian, and a forensic psychiatry expert. She changed key facts about Elvira’s case to protect her anonymity.

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A social worker called with a plea in April 2020, when the hospital was filled with COVID-19 patients, some so sick they were on ventilators. “I need your help with a family. Mom is in the ICU, intubated; her son died here 2 weeks ago of COVID and her daughters are overwhelmed, unable to visit because of restrictions. The staff anticipates extubating Elvira imminently, but she will be fragile and alone. When is the right time to tell Elvira that Tony died?”

That happened at the beginning of the COVID pandemic. I handled the case remotely with heroic help from overburdened nurses and doctors who were acting as medical staff, social workers, and substitute family to an isolated patient in the hospital. Such was the confusion with the new virus before vaccines and treatments.
 

The impact of pandemics: A historical perspective

Dr. Ruth Cohen

Beginning in antiquity, there were pandemics that decimated populations. Before antibiotics, vaccines or awareness of microorganisms, people feared contagion and sought isolation from the sick. People also thought that those who recovered were less likely to fall ill again, and if they did get sick, the illness would be milder.

There is abundant documentation of bubonic plague outbreaks, such as the “Black Death” in the Middle Ages. The Spanish flu of 1918 struck down robust young Americans and spread worldwide. Although the bubonic plague was at the center of major infectious outbreaks, including the pandemic of the Justinian era (500s) and the Great Plague of London (1665-1666), other infectious diseases, untreatable at the time, prevailed simultaneously. Wars, world trade, unsanitary conditions, and urban crowding enhanced the spread. Pandemics shaped history. Some historians attribute the fall of the Roman Empire to unrelenting infectious disease carried in migratory battles.

Even in the earliest outbreaks, the poor populace died more readily than the well off, who had means to escape and seclude themselves from congested areas. Samuel Pepys, a diarist of the London Plague, was a famed businessman and government official; he wrote of seeing the suffering in his city, but he escaped to live with his wife in their country home. What Samuel Pepys wrote of London during the Plague can apply to the early period of the COVID pandemic: “How few people I see, and those looking like people that had taken leave of the world.”

There are lurid descriptions of the chaos of pandemics, especially of the Black Death and the Plague of London. First published in 1722, Daniel Defoe’s “A Journal of the Plague Year” describes the suffering of the sick that included people abandoning the afflicted and others running rampant with delirium in the streets, screaming in pain. City officials took cruel measures that they considered necessary, such as locking away families in their homes, sick and well together, when an individual member showed symptoms. The Middle Ages saw deadly anti-Semitism. During the Black Death, fanatics murdered Jews in the belief that they brought on the pestilence. Ignorance created panic.

As happens in tragedy, there was also bravery. Some stayed to tend to the sick; charities provided food for poor people during the London Plague.
 

 

 

Back to the 21st century

After 3 weeks on the ventilator, Elvira got extubated. A team including her doctor, nurse, and Connie, one of her daughters, told Elvira that her 28-year-old son had died of COVID. I began telepsychiatry with Elvira and her two daughters. Treatment continued after Elvira returned home. In telephone sessions, we discussed bereavement and how to cope with the emotional and physical challenges in recovery.

Before he contracted COVID, Tony, Elvira’s son, had compromised health. He was on dialysis awaiting a kidney transplant. His mother prepared his meals and often accompanied Tony to doctor appointments. Still, Elvira said, “I wasn’t there to hold his hand.” At age 71, Elvira was also at high risk. She suffered from diabetes, high blood pressure, hyperlipidemia, and had coronary stents. Elvira was compliant with medications for her conditions.
 

What we know; where we are

“Infectious diseases are not static conditions but depend upon a constantly changing relationship between parasite and invaded species which is bound to result in modifications of both clinical and epidemiological manifestations.”

Hans Zinsser, Rats, Lice and History

We need to be informed by history and grateful to the geniuses who brought us into the modern age of medicine. We can prevent diseases with public health measures, and by understanding and treating crises. Edward Jenner, who recognized the protective effect of cowpox against smallpox, developed inoculations beginning in 1796; he ushered in immunology and saved the lives of millions. Smallpox is now eradicated. A succession of microbe hunters, including Louis Pasteur and Robert Koch, benefited from the development of the microscope by Antonie van Leeuwenhoek. With the advent and use of penicillin in the early 1940s, Alexander Fleming welcomed antibiotics; by the 1960s this modality became widespread. In the mid-20th century, immunologists recognized that bacteria and viruses change and adapt to the environment.

The planet has seen ravaging pandemics that then dissipated and, although untreatable at the time, disappeared into a reservoir, such as rats or lice. People also developed herd immunity from exposure to the offending microorganisms within the population. Less toxic, these agents no longer kill those who get infected but they can be transmissible and endemic to humans.

The mental health consequences of pandemics are reminiscent of other severe illnesses. The seriously ill develop cognitive aberrations and can become delirious. The population at risk and those who get sick can experience depression, PTSD, and anxiety – including panic.
 

Update on Elvira

Elvira continues to improve. She also participates in support groups, including one that addresses bereavement for parents of children who died of COVID and other causes. “I didn’t have a chance to say goodbye,” she said. But what she calls her “brain fog” has dissipated. She walks better, and she is getting evaluation of radiculopathy, probably from nerve root injury during her 3 weeks in bed on the ventilator. She’s still experiencing pain in her feet.

With regard to her symptoms she said: “I cry almost every day.” Her PTSD has abated, but she sometimes has nightmares. Elvira is writing a book about the induced coma and the “hallucinations from hell to heaven” she experienced. She wonders:“Did Tony go through the same thing?” Her empathy is enhanced by her background as a retired social worker with the Administration for Children’s Services in New York.
 

 

 

The role of psychiatry

In its early, most virulent form, SARS-CoV-2 devastated thousands of people, especially the elderly medically vulnerable. With scientific tools we developed vaccines and treatments and continue to study the dynamics of this virus.

As Andy Miller, MD, chief of the division of infectious diseases at the Hospital for Special Surgery, said when I spoke with him about the virus, because of the way in which viruses mutate, “we must remain aware” of the trajectory of SARS-CoV-2 and “counter irrational beliefs.”

How should psychiatry deal with COVID? As scientists, we seek the truth without bias and politics. Mental illness is our domain. Other specialties have the expertise to treat and even prevent infectious disease. We can assist our doctor colleagues to understand depression, anxiety, PTSD, and cognitive issues when they occur. Our medical mission should be, as always, to treat those who suffer mental illness. Now that extends to the consequences of COVID.
 

Suggested reading

Camus A. The Plague. New York: Vintage Books,. 1991.

Defoe D. A Journal of the Plague Year. Mineola, N.Y.: Dover Publications, 2001.

Kelly J. The Great Mortality: An Intimate History of the Black Death, The Most Devastating Plague of All Time. New York: Harper Perennial, 2005.

Pepys S. The Diary of Samuel Pepys: The Great Plague of London & The Great Fire of London, 1665-1666. Oxford, England: Benediction Classics, 2020.

Emerg Infect Dis. 2005 Mar 11(3):402-96.

Zinsser H. Rats, Lice and History. Boston/Toronto: Little Brown and Co., 1935.

Dr. Cohen is in private practice of psychotherapy and medication management in New York. She has been a consultant at the Hospital for Special Surgery and at New York–Presbyterian, and a forensic psychiatry expert. She changed key facts about Elvira’s case to protect her anonymity.

A social worker called with a plea in April 2020, when the hospital was filled with COVID-19 patients, some so sick they were on ventilators. “I need your help with a family. Mom is in the ICU, intubated; her son died here 2 weeks ago of COVID and her daughters are overwhelmed, unable to visit because of restrictions. The staff anticipates extubating Elvira imminently, but she will be fragile and alone. When is the right time to tell Elvira that Tony died?”

That happened at the beginning of the COVID pandemic. I handled the case remotely with heroic help from overburdened nurses and doctors who were acting as medical staff, social workers, and substitute family to an isolated patient in the hospital. Such was the confusion with the new virus before vaccines and treatments.
 

The impact of pandemics: A historical perspective

Dr. Ruth Cohen

Beginning in antiquity, there were pandemics that decimated populations. Before antibiotics, vaccines or awareness of microorganisms, people feared contagion and sought isolation from the sick. People also thought that those who recovered were less likely to fall ill again, and if they did get sick, the illness would be milder.

There is abundant documentation of bubonic plague outbreaks, such as the “Black Death” in the Middle Ages. The Spanish flu of 1918 struck down robust young Americans and spread worldwide. Although the bubonic plague was at the center of major infectious outbreaks, including the pandemic of the Justinian era (500s) and the Great Plague of London (1665-1666), other infectious diseases, untreatable at the time, prevailed simultaneously. Wars, world trade, unsanitary conditions, and urban crowding enhanced the spread. Pandemics shaped history. Some historians attribute the fall of the Roman Empire to unrelenting infectious disease carried in migratory battles.

Even in the earliest outbreaks, the poor populace died more readily than the well off, who had means to escape and seclude themselves from congested areas. Samuel Pepys, a diarist of the London Plague, was a famed businessman and government official; he wrote of seeing the suffering in his city, but he escaped to live with his wife in their country home. What Samuel Pepys wrote of London during the Plague can apply to the early period of the COVID pandemic: “How few people I see, and those looking like people that had taken leave of the world.”

There are lurid descriptions of the chaos of pandemics, especially of the Black Death and the Plague of London. First published in 1722, Daniel Defoe’s “A Journal of the Plague Year” describes the suffering of the sick that included people abandoning the afflicted and others running rampant with delirium in the streets, screaming in pain. City officials took cruel measures that they considered necessary, such as locking away families in their homes, sick and well together, when an individual member showed symptoms. The Middle Ages saw deadly anti-Semitism. During the Black Death, fanatics murdered Jews in the belief that they brought on the pestilence. Ignorance created panic.

As happens in tragedy, there was also bravery. Some stayed to tend to the sick; charities provided food for poor people during the London Plague.
 

 

 

Back to the 21st century

After 3 weeks on the ventilator, Elvira got extubated. A team including her doctor, nurse, and Connie, one of her daughters, told Elvira that her 28-year-old son had died of COVID. I began telepsychiatry with Elvira and her two daughters. Treatment continued after Elvira returned home. In telephone sessions, we discussed bereavement and how to cope with the emotional and physical challenges in recovery.

Before he contracted COVID, Tony, Elvira’s son, had compromised health. He was on dialysis awaiting a kidney transplant. His mother prepared his meals and often accompanied Tony to doctor appointments. Still, Elvira said, “I wasn’t there to hold his hand.” At age 71, Elvira was also at high risk. She suffered from diabetes, high blood pressure, hyperlipidemia, and had coronary stents. Elvira was compliant with medications for her conditions.
 

What we know; where we are

“Infectious diseases are not static conditions but depend upon a constantly changing relationship between parasite and invaded species which is bound to result in modifications of both clinical and epidemiological manifestations.”

Hans Zinsser, Rats, Lice and History

We need to be informed by history and grateful to the geniuses who brought us into the modern age of medicine. We can prevent diseases with public health measures, and by understanding and treating crises. Edward Jenner, who recognized the protective effect of cowpox against smallpox, developed inoculations beginning in 1796; he ushered in immunology and saved the lives of millions. Smallpox is now eradicated. A succession of microbe hunters, including Louis Pasteur and Robert Koch, benefited from the development of the microscope by Antonie van Leeuwenhoek. With the advent and use of penicillin in the early 1940s, Alexander Fleming welcomed antibiotics; by the 1960s this modality became widespread. In the mid-20th century, immunologists recognized that bacteria and viruses change and adapt to the environment.

The planet has seen ravaging pandemics that then dissipated and, although untreatable at the time, disappeared into a reservoir, such as rats or lice. People also developed herd immunity from exposure to the offending microorganisms within the population. Less toxic, these agents no longer kill those who get infected but they can be transmissible and endemic to humans.

The mental health consequences of pandemics are reminiscent of other severe illnesses. The seriously ill develop cognitive aberrations and can become delirious. The population at risk and those who get sick can experience depression, PTSD, and anxiety – including panic.
 

Update on Elvira

Elvira continues to improve. She also participates in support groups, including one that addresses bereavement for parents of children who died of COVID and other causes. “I didn’t have a chance to say goodbye,” she said. But what she calls her “brain fog” has dissipated. She walks better, and she is getting evaluation of radiculopathy, probably from nerve root injury during her 3 weeks in bed on the ventilator. She’s still experiencing pain in her feet.

With regard to her symptoms she said: “I cry almost every day.” Her PTSD has abated, but she sometimes has nightmares. Elvira is writing a book about the induced coma and the “hallucinations from hell to heaven” she experienced. She wonders:“Did Tony go through the same thing?” Her empathy is enhanced by her background as a retired social worker with the Administration for Children’s Services in New York.
 

 

 

The role of psychiatry

In its early, most virulent form, SARS-CoV-2 devastated thousands of people, especially the elderly medically vulnerable. With scientific tools we developed vaccines and treatments and continue to study the dynamics of this virus.

As Andy Miller, MD, chief of the division of infectious diseases at the Hospital for Special Surgery, said when I spoke with him about the virus, because of the way in which viruses mutate, “we must remain aware” of the trajectory of SARS-CoV-2 and “counter irrational beliefs.”

How should psychiatry deal with COVID? As scientists, we seek the truth without bias and politics. Mental illness is our domain. Other specialties have the expertise to treat and even prevent infectious disease. We can assist our doctor colleagues to understand depression, anxiety, PTSD, and cognitive issues when they occur. Our medical mission should be, as always, to treat those who suffer mental illness. Now that extends to the consequences of COVID.
 

Suggested reading

Camus A. The Plague. New York: Vintage Books,. 1991.

Defoe D. A Journal of the Plague Year. Mineola, N.Y.: Dover Publications, 2001.

Kelly J. The Great Mortality: An Intimate History of the Black Death, The Most Devastating Plague of All Time. New York: Harper Perennial, 2005.

Pepys S. The Diary of Samuel Pepys: The Great Plague of London & The Great Fire of London, 1665-1666. Oxford, England: Benediction Classics, 2020.

Emerg Infect Dis. 2005 Mar 11(3):402-96.

Zinsser H. Rats, Lice and History. Boston/Toronto: Little Brown and Co., 1935.

Dr. Cohen is in private practice of psychotherapy and medication management in New York. She has been a consultant at the Hospital for Special Surgery and at New York–Presbyterian, and a forensic psychiatry expert. She changed key facts about Elvira’s case to protect her anonymity.

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Can supercomputers really keep up with the human brain?

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Tue, 01/18/2022 - 15:06

An adult brain contains about 86 billion neurons and even more supercomputing power to closely monitor the entire human brain.

All those neurons have trillions of synapses – or connection points – that make up the circuitry the brain uses to control everything we do from reasoning to breathing to walking. And scientists with the Human Brain Project are trying to build new computing tools that can zoom in on every one of these synapses, peer inside cells, and zoom out to focus on entire regions of the brain at once.

Imaging the human brain at the cellular level would require several petabytes of data, researchers from the Human Brain Project report in Science. If you have an old smartphone or tablet with 32GB of storage, you’d need more than 31,000 of them to get a single petabyte of storage.

Using an electron microscope to image the entire brain would require more than one exabyte of data, the scientists point out. That’s more than a million petabytes.

Giacomo Indiveri, PhD, professor of neuroinformatics at the University of Zurich, Switzerland, says we need to fundamentally change the way we build computers. Delivering the keynote address at the Human Brain Project Summit in October, he warned we will use 20% of all the world’s electricity on computing by the year 2025.

To meet the computing challenges posed by the quest to map every bit of the human brain, researchers are working to produce the first two exascale supercomputers within the next 5 years. When they’re done, these machines will provide brain scientists with supercomputers powerful enough to explore the human brain in all its complexities.

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

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An adult brain contains about 86 billion neurons and even more supercomputing power to closely monitor the entire human brain.

All those neurons have trillions of synapses – or connection points – that make up the circuitry the brain uses to control everything we do from reasoning to breathing to walking. And scientists with the Human Brain Project are trying to build new computing tools that can zoom in on every one of these synapses, peer inside cells, and zoom out to focus on entire regions of the brain at once.

Imaging the human brain at the cellular level would require several petabytes of data, researchers from the Human Brain Project report in Science. If you have an old smartphone or tablet with 32GB of storage, you’d need more than 31,000 of them to get a single petabyte of storage.

Using an electron microscope to image the entire brain would require more than one exabyte of data, the scientists point out. That’s more than a million petabytes.

Giacomo Indiveri, PhD, professor of neuroinformatics at the University of Zurich, Switzerland, says we need to fundamentally change the way we build computers. Delivering the keynote address at the Human Brain Project Summit in October, he warned we will use 20% of all the world’s electricity on computing by the year 2025.

To meet the computing challenges posed by the quest to map every bit of the human brain, researchers are working to produce the first two exascale supercomputers within the next 5 years. When they’re done, these machines will provide brain scientists with supercomputers powerful enough to explore the human brain in all its complexities.

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

An adult brain contains about 86 billion neurons and even more supercomputing power to closely monitor the entire human brain.

All those neurons have trillions of synapses – or connection points – that make up the circuitry the brain uses to control everything we do from reasoning to breathing to walking. And scientists with the Human Brain Project are trying to build new computing tools that can zoom in on every one of these synapses, peer inside cells, and zoom out to focus on entire regions of the brain at once.

Imaging the human brain at the cellular level would require several petabytes of data, researchers from the Human Brain Project report in Science. If you have an old smartphone or tablet with 32GB of storage, you’d need more than 31,000 of them to get a single petabyte of storage.

Using an electron microscope to image the entire brain would require more than one exabyte of data, the scientists point out. That’s more than a million petabytes.

Giacomo Indiveri, PhD, professor of neuroinformatics at the University of Zurich, Switzerland, says we need to fundamentally change the way we build computers. Delivering the keynote address at the Human Brain Project Summit in October, he warned we will use 20% of all the world’s electricity on computing by the year 2025.

To meet the computing challenges posed by the quest to map every bit of the human brain, researchers are working to produce the first two exascale supercomputers within the next 5 years. When they’re done, these machines will provide brain scientists with supercomputers powerful enough to explore the human brain in all its complexities.

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

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Migraine Presentation and Diagnosis

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Preschool boys’ behaviors traced back to moms’ thyroid hormones

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Pregnant women’s thyroid hormone trajectories (levels in the first, second, and third trimester) may predict whether their male offspring are aggressive or withdrawn at age 4.

Certain maternal thyroid hormone trajectories were associated with problem behaviors in preschool boys in a study of close to 2,000 mother-child pairs in China.

The researchers identified low, moderate, and high thyroid-stimulating hormone (TSH) and free thyroxine (FT4) trajectories. 

pregnant woman in doctors office
shironosov/Getty Images


Most women had a low TSH trajectory and moderate FT4 trajectory, which the researchers deemed to be reference (normal) trajectories.  

The children’s primary caregiver (parent or grandparent) completed an extensive questionnaire about their child’s behavior at age 4.

The 4-year-old boys whose mothers had a high TSH trajectory during pregnancy were more likely to be withdrawn and to externalize problems (odds ratio, 2.01 and 2.69, respectively).

Boys whose mothers had a high FT4 trajectory during pregnancy were more likely to be anxious/depressed (OR, 2.22).

And boys whose mothers had a moderate TSH trajectory or low FT4 trajectory were more likely to show aggressive behavior (OR, 3.76 and 4.17, respectively), compared with boys whose mothers had normal TSH and FT4 trajectories, after adjusting for potential confounders.

However, there was no association between abnormal maternal thyroid hormone trajectories and behavior problems in 4-year-old girls.

The study by Peixuan Li, BM, and colleagues was published online Jan. 6 in the Journal of Clinical Endocrinology & Metabolism.
 

‘Study supports monitoring thyroid function in pregnancy’

“Our findings highlight the significance of close monitoring and management of maternal thyroid function during pregnancy,” senior author Kun Huang, PhD, said in a press release from the Endocrine Society.

“This research presents a new perspective in early intervention of children’s emotional and behavioral problems,” added Dr. Huang, from Anhui Medical University, Hefei, China.

The results add to a growing body of literature about a controversial link between maternal thyroid hormones in pregnancy, when the fetal brain is developing, and subsequent behavior in preschool children, Caroline T. Nguyen, MD, who was not involved with this research, commented in an email.

“Some studies show an association between thyroid levels and behavioral outcomes, others not,” added Dr. Nguyen, assistant professor of clinical medicine, Keck School of Medicine, University of Southern California, Los Angeles. And “some studies have found sex-specific associations with maternal thyroid levels and neurocognitive/behavioral outcomes, others have not.”

Women considering pregnancy should be evaluated for possible thyroid disease, she continued. Currently, no universal screening mandates exist for thyroid disease in pregnancy, but the 2017 American Thyroid Association guidelines do recommend screening women at risk for thyroid dysfunction.

“I think screening for thyroid peroxidase antibody (TPOAb) positivity is helpful in women desiring pregnancy,” Dr. Nguyen continued, “because we know that patients with TPOAb positivity are at increased risk for miscarriage and have a blunted response to the increased demands of pregnancy for thyroid hormone production.”

TPOAb positivity is also associated with the increased risk of postpartum and long-term thyroid dysfunction.

This current study, Dr. Nguyen summarized, “adds to a growing body of research of the relationship of thyroid hormone levels and neurocognitive outcomes [in offspring] and supports the monitoring of thyroid disease in pregnancy.”  

“However, we do not have sufficient data to demonstrate the benefits of intervention with levothyroxine treatment,” she noted. 

Nevertheless, the lack of positive data does not suggest there is no theoretical benefit of intervention, she said, as such studies are very challenging to do. 

“Physicians can help reduce stress and anxiety in patients desiring pregnancy by [recommending] preconception counseling, screening patients at risk for thyroid disease, and optimizing thyroid hormone levels before and during pregnancy,” according to Dr. Nguyen.
 

 

 

Maternal TSH and FT4 trajectories and preschoolers’ behaviors

Previous studies have reported that during pregnancy, maternal subclinical hypothyroidism (elevated TSH with normal FT4) as well as isolated hypothyroxinemia (decreased FT4 with normal TSH) are associated with adverse maternal and child outcomes, including preterm delivery and low birth weight.

However, most studies have not determined maternal thyroid hormone levels in different trimesters.

Researchers recruited pregnant women going for their first antenatal checkup at the Ma’anshan Maternal and Child Health Hospital in China from May 2013 to September 2014 and identified 1,860 mother-child pairs.

They determined maternal thyroid hormone levels from blood samples taken during the first, second, and third trimester: on average, gestational week 10, 25, and 34, respectively.

The researchers found that TSH levels increased somewhat from trimester 1 to trimester 2 and then decreased slightly in trimester 3. Most women (68%) had a low TSH trajectory, 28% had a moderate TSH trajectory, and 4% had a high TSH trajectory.

FT4 levels dropped sharply from trimester 1 to trimester 2 and then increased somewhat in trimester 3. About half of the women (52%) had a moderate FT4 trajectory, 33% had a low FT4 trajectory, and 15% had a high FT4 trajectory.

Most women (96.5%) had a low and stable TPOAb level, and the rest (3.5%) had high and decreasing TPOAb levels.  

When the children in the study were 4 years old, their main caregiver (parent or grandparent) completed the 100-question Achenbach Child Behavior checklist to identify whether the child often, sometimes, or never displayed three internalizing problem behaviors (emotionally reactive, anxious/depressed, or withdrawn) and/or two externalizing problem behaviors (attention problems or aggressive behavior).
 

Study limitations, more research needed

It is not clear why the associations between maternal hormones and offspring behavior were only seen in boys. Perhaps male fetuses are more sensitive than female fetuses to changing maternal thyroid hormone levels in pregnancy, the researchers speculate.

They acknowledge that study limitations include there were few children with aggressive behavior, so the confidence interval for the association of the moderate TSH trajectory with aggressive behavior was very wide.

In addition, evaluation of children’s behavior by caregivers was subjective. Also, the researchers did not have information about iodine levels, and low iodine levels can impair child brain development.

And there may have been residual confounders that researchers did not account for, such as differences in family upbringing, parental marital status, and the mother’s exposure to endocrine disruptors.

Therefore, further research is needed.

The study was supported by grants from the National Natural Science Foundation of China, the University Synergy Innovation Program of Anhui Province, the Sci-Tech Basic Resources Research Program of China, the National Key Research and Development Program, the Chinese Academy of Medical Sciences, and the Research Fund of Anhui Institute of Translational Medicine. The researchers and Dr. Nguyen have reported no relevant financial relationships.

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

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Pregnant women’s thyroid hormone trajectories (levels in the first, second, and third trimester) may predict whether their male offspring are aggressive or withdrawn at age 4.

Certain maternal thyroid hormone trajectories were associated with problem behaviors in preschool boys in a study of close to 2,000 mother-child pairs in China.

The researchers identified low, moderate, and high thyroid-stimulating hormone (TSH) and free thyroxine (FT4) trajectories. 

pregnant woman in doctors office
shironosov/Getty Images


Most women had a low TSH trajectory and moderate FT4 trajectory, which the researchers deemed to be reference (normal) trajectories.  

The children’s primary caregiver (parent or grandparent) completed an extensive questionnaire about their child’s behavior at age 4.

The 4-year-old boys whose mothers had a high TSH trajectory during pregnancy were more likely to be withdrawn and to externalize problems (odds ratio, 2.01 and 2.69, respectively).

Boys whose mothers had a high FT4 trajectory during pregnancy were more likely to be anxious/depressed (OR, 2.22).

And boys whose mothers had a moderate TSH trajectory or low FT4 trajectory were more likely to show aggressive behavior (OR, 3.76 and 4.17, respectively), compared with boys whose mothers had normal TSH and FT4 trajectories, after adjusting for potential confounders.

However, there was no association between abnormal maternal thyroid hormone trajectories and behavior problems in 4-year-old girls.

The study by Peixuan Li, BM, and colleagues was published online Jan. 6 in the Journal of Clinical Endocrinology & Metabolism.
 

‘Study supports monitoring thyroid function in pregnancy’

“Our findings highlight the significance of close monitoring and management of maternal thyroid function during pregnancy,” senior author Kun Huang, PhD, said in a press release from the Endocrine Society.

“This research presents a new perspective in early intervention of children’s emotional and behavioral problems,” added Dr. Huang, from Anhui Medical University, Hefei, China.

The results add to a growing body of literature about a controversial link between maternal thyroid hormones in pregnancy, when the fetal brain is developing, and subsequent behavior in preschool children, Caroline T. Nguyen, MD, who was not involved with this research, commented in an email.

“Some studies show an association between thyroid levels and behavioral outcomes, others not,” added Dr. Nguyen, assistant professor of clinical medicine, Keck School of Medicine, University of Southern California, Los Angeles. And “some studies have found sex-specific associations with maternal thyroid levels and neurocognitive/behavioral outcomes, others have not.”

Women considering pregnancy should be evaluated for possible thyroid disease, she continued. Currently, no universal screening mandates exist for thyroid disease in pregnancy, but the 2017 American Thyroid Association guidelines do recommend screening women at risk for thyroid dysfunction.

“I think screening for thyroid peroxidase antibody (TPOAb) positivity is helpful in women desiring pregnancy,” Dr. Nguyen continued, “because we know that patients with TPOAb positivity are at increased risk for miscarriage and have a blunted response to the increased demands of pregnancy for thyroid hormone production.”

TPOAb positivity is also associated with the increased risk of postpartum and long-term thyroid dysfunction.

This current study, Dr. Nguyen summarized, “adds to a growing body of research of the relationship of thyroid hormone levels and neurocognitive outcomes [in offspring] and supports the monitoring of thyroid disease in pregnancy.”  

“However, we do not have sufficient data to demonstrate the benefits of intervention with levothyroxine treatment,” she noted. 

Nevertheless, the lack of positive data does not suggest there is no theoretical benefit of intervention, she said, as such studies are very challenging to do. 

“Physicians can help reduce stress and anxiety in patients desiring pregnancy by [recommending] preconception counseling, screening patients at risk for thyroid disease, and optimizing thyroid hormone levels before and during pregnancy,” according to Dr. Nguyen.
 

 

 

Maternal TSH and FT4 trajectories and preschoolers’ behaviors

Previous studies have reported that during pregnancy, maternal subclinical hypothyroidism (elevated TSH with normal FT4) as well as isolated hypothyroxinemia (decreased FT4 with normal TSH) are associated with adverse maternal and child outcomes, including preterm delivery and low birth weight.

However, most studies have not determined maternal thyroid hormone levels in different trimesters.

Researchers recruited pregnant women going for their first antenatal checkup at the Ma’anshan Maternal and Child Health Hospital in China from May 2013 to September 2014 and identified 1,860 mother-child pairs.

They determined maternal thyroid hormone levels from blood samples taken during the first, second, and third trimester: on average, gestational week 10, 25, and 34, respectively.

The researchers found that TSH levels increased somewhat from trimester 1 to trimester 2 and then decreased slightly in trimester 3. Most women (68%) had a low TSH trajectory, 28% had a moderate TSH trajectory, and 4% had a high TSH trajectory.

FT4 levels dropped sharply from trimester 1 to trimester 2 and then increased somewhat in trimester 3. About half of the women (52%) had a moderate FT4 trajectory, 33% had a low FT4 trajectory, and 15% had a high FT4 trajectory.

Most women (96.5%) had a low and stable TPOAb level, and the rest (3.5%) had high and decreasing TPOAb levels.  

When the children in the study were 4 years old, their main caregiver (parent or grandparent) completed the 100-question Achenbach Child Behavior checklist to identify whether the child often, sometimes, or never displayed three internalizing problem behaviors (emotionally reactive, anxious/depressed, or withdrawn) and/or two externalizing problem behaviors (attention problems or aggressive behavior).
 

Study limitations, more research needed

It is not clear why the associations between maternal hormones and offspring behavior were only seen in boys. Perhaps male fetuses are more sensitive than female fetuses to changing maternal thyroid hormone levels in pregnancy, the researchers speculate.

They acknowledge that study limitations include there were few children with aggressive behavior, so the confidence interval for the association of the moderate TSH trajectory with aggressive behavior was very wide.

In addition, evaluation of children’s behavior by caregivers was subjective. Also, the researchers did not have information about iodine levels, and low iodine levels can impair child brain development.

And there may have been residual confounders that researchers did not account for, such as differences in family upbringing, parental marital status, and the mother’s exposure to endocrine disruptors.

Therefore, further research is needed.

The study was supported by grants from the National Natural Science Foundation of China, the University Synergy Innovation Program of Anhui Province, the Sci-Tech Basic Resources Research Program of China, the National Key Research and Development Program, the Chinese Academy of Medical Sciences, and the Research Fund of Anhui Institute of Translational Medicine. The researchers and Dr. Nguyen have reported no relevant financial relationships.

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

Pregnant women’s thyroid hormone trajectories (levels in the first, second, and third trimester) may predict whether their male offspring are aggressive or withdrawn at age 4.

Certain maternal thyroid hormone trajectories were associated with problem behaviors in preschool boys in a study of close to 2,000 mother-child pairs in China.

The researchers identified low, moderate, and high thyroid-stimulating hormone (TSH) and free thyroxine (FT4) trajectories. 

pregnant woman in doctors office
shironosov/Getty Images


Most women had a low TSH trajectory and moderate FT4 trajectory, which the researchers deemed to be reference (normal) trajectories.  

The children’s primary caregiver (parent or grandparent) completed an extensive questionnaire about their child’s behavior at age 4.

The 4-year-old boys whose mothers had a high TSH trajectory during pregnancy were more likely to be withdrawn and to externalize problems (odds ratio, 2.01 and 2.69, respectively).

Boys whose mothers had a high FT4 trajectory during pregnancy were more likely to be anxious/depressed (OR, 2.22).

And boys whose mothers had a moderate TSH trajectory or low FT4 trajectory were more likely to show aggressive behavior (OR, 3.76 and 4.17, respectively), compared with boys whose mothers had normal TSH and FT4 trajectories, after adjusting for potential confounders.

However, there was no association between abnormal maternal thyroid hormone trajectories and behavior problems in 4-year-old girls.

The study by Peixuan Li, BM, and colleagues was published online Jan. 6 in the Journal of Clinical Endocrinology & Metabolism.
 

‘Study supports monitoring thyroid function in pregnancy’

“Our findings highlight the significance of close monitoring and management of maternal thyroid function during pregnancy,” senior author Kun Huang, PhD, said in a press release from the Endocrine Society.

“This research presents a new perspective in early intervention of children’s emotional and behavioral problems,” added Dr. Huang, from Anhui Medical University, Hefei, China.

The results add to a growing body of literature about a controversial link between maternal thyroid hormones in pregnancy, when the fetal brain is developing, and subsequent behavior in preschool children, Caroline T. Nguyen, MD, who was not involved with this research, commented in an email.

“Some studies show an association between thyroid levels and behavioral outcomes, others not,” added Dr. Nguyen, assistant professor of clinical medicine, Keck School of Medicine, University of Southern California, Los Angeles. And “some studies have found sex-specific associations with maternal thyroid levels and neurocognitive/behavioral outcomes, others have not.”

Women considering pregnancy should be evaluated for possible thyroid disease, she continued. Currently, no universal screening mandates exist for thyroid disease in pregnancy, but the 2017 American Thyroid Association guidelines do recommend screening women at risk for thyroid dysfunction.

“I think screening for thyroid peroxidase antibody (TPOAb) positivity is helpful in women desiring pregnancy,” Dr. Nguyen continued, “because we know that patients with TPOAb positivity are at increased risk for miscarriage and have a blunted response to the increased demands of pregnancy for thyroid hormone production.”

TPOAb positivity is also associated with the increased risk of postpartum and long-term thyroid dysfunction.

This current study, Dr. Nguyen summarized, “adds to a growing body of research of the relationship of thyroid hormone levels and neurocognitive outcomes [in offspring] and supports the monitoring of thyroid disease in pregnancy.”  

“However, we do not have sufficient data to demonstrate the benefits of intervention with levothyroxine treatment,” she noted. 

Nevertheless, the lack of positive data does not suggest there is no theoretical benefit of intervention, she said, as such studies are very challenging to do. 

“Physicians can help reduce stress and anxiety in patients desiring pregnancy by [recommending] preconception counseling, screening patients at risk for thyroid disease, and optimizing thyroid hormone levels before and during pregnancy,” according to Dr. Nguyen.
 

 

 

Maternal TSH and FT4 trajectories and preschoolers’ behaviors

Previous studies have reported that during pregnancy, maternal subclinical hypothyroidism (elevated TSH with normal FT4) as well as isolated hypothyroxinemia (decreased FT4 with normal TSH) are associated with adverse maternal and child outcomes, including preterm delivery and low birth weight.

However, most studies have not determined maternal thyroid hormone levels in different trimesters.

Researchers recruited pregnant women going for their first antenatal checkup at the Ma’anshan Maternal and Child Health Hospital in China from May 2013 to September 2014 and identified 1,860 mother-child pairs.

They determined maternal thyroid hormone levels from blood samples taken during the first, second, and third trimester: on average, gestational week 10, 25, and 34, respectively.

The researchers found that TSH levels increased somewhat from trimester 1 to trimester 2 and then decreased slightly in trimester 3. Most women (68%) had a low TSH trajectory, 28% had a moderate TSH trajectory, and 4% had a high TSH trajectory.

FT4 levels dropped sharply from trimester 1 to trimester 2 and then increased somewhat in trimester 3. About half of the women (52%) had a moderate FT4 trajectory, 33% had a low FT4 trajectory, and 15% had a high FT4 trajectory.

Most women (96.5%) had a low and stable TPOAb level, and the rest (3.5%) had high and decreasing TPOAb levels.  

When the children in the study were 4 years old, their main caregiver (parent or grandparent) completed the 100-question Achenbach Child Behavior checklist to identify whether the child often, sometimes, or never displayed three internalizing problem behaviors (emotionally reactive, anxious/depressed, or withdrawn) and/or two externalizing problem behaviors (attention problems or aggressive behavior).
 

Study limitations, more research needed

It is not clear why the associations between maternal hormones and offspring behavior were only seen in boys. Perhaps male fetuses are more sensitive than female fetuses to changing maternal thyroid hormone levels in pregnancy, the researchers speculate.

They acknowledge that study limitations include there were few children with aggressive behavior, so the confidence interval for the association of the moderate TSH trajectory with aggressive behavior was very wide.

In addition, evaluation of children’s behavior by caregivers was subjective. Also, the researchers did not have information about iodine levels, and low iodine levels can impair child brain development.

And there may have been residual confounders that researchers did not account for, such as differences in family upbringing, parental marital status, and the mother’s exposure to endocrine disruptors.

Therefore, further research is needed.

The study was supported by grants from the National Natural Science Foundation of China, the University Synergy Innovation Program of Anhui Province, the Sci-Tech Basic Resources Research Program of China, the National Key Research and Development Program, the Chinese Academy of Medical Sciences, and the Research Fund of Anhui Institute of Translational Medicine. The researchers and Dr. Nguyen have reported no relevant financial relationships.

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

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Antidepressants: Is less more?

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Wed, 01/19/2022 - 11:10

When it comes to antidepressant prescribing, less may be more, new research suggests.

A new review suggests antidepressants are overprescribed and that the efficacy of these agents is questionable, leading researchers to recommend that, when physicians prescribe these medications, it should be for shorter periods.

“Antidepressants have never been shown to have a clinically significant difference from placebo in the treatment of depression,” study co\investigator Mark Horowitz, GDPsych, PhD, division of psychiatry, University College London, said in an interview.

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He added antidepressants “exert profound adverse effects on the body and brain” and can be difficult to stop because of physical dependence that occurs when the brain adapts to them.

“The best way to take people off these drugs is to do so gradually enough that the unpleasant effects are minimized and in a way that means the reductions in dose get smaller and smaller as the total dose gets lower,” Dr. Horowitz said.

However, at least one expert urged caution in interpreting the review’s findings.

“The reality is that millions of people do benefit from these medications, and this review minimizes those benefits,” Philip Muskin, MD, chief of consultation-liaison for psychiatry and professor of psychiatry, Columbia University Medical Center and New York–Presbyterian Hospital, said when approached for comment.

The findings were published online Dec. 20, 2021, in the Drug and Therapeutics Bulletin.
 

Personal experience

Prescribing of newer-generation antidepressants, such as SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs), is increasing, with an estimated one in six adults in the United Kingdom receiving at least one prescription in 2019-2020, the investigators noted.

Dr. Horowitz noted a personal motivation for conducting the review. “As well as being an academic psychiatrist, I’m also a patient who has been prescribed antidepressants since age 21, when my mood was poor, due to life circumstances.”

The antidepressant “didn’t have particularly helpful effects,” but Dr. Horowitz continued taking it for 18 years. “I was told it was helpful and internalized that message. I came to understand that much of the information around antidepressants came from the drug companies that manufactured them or from academics paid by these companies.”

Dr. Horowitz is currently discontinuing his medication – a tapering process now in its third year. He said he has come to realize, in retrospect, that symptoms not initially attributed to the drug, such as fatigue, impaired concentration, and impaired memory, have improved since reducing the medication.

“That experience sensitized me to look for these symptoms in my patients and I see them; but most of my patients were told by their doctors that the cause of those problems was the depression or anxiety itself and not the drug,” he said.

Dr. Horowitz collaborated with Michael Wilcock, DTB, Pharmacy, Royal Cornwall Hospitals, NHS Trust, Truro, England, in conducting the review “to provide an independent assessment of benefits and harms of antidepressants.”

“Much of the evidence of the efficacy of antidepressants comes from randomized placebo-controlled trials,” Dr. Horowitz said. Several meta-analyses of these studies showed a difference of about two points between the agent and the placebo on the Hamilton Depression Rating Scale (HAM-D).

“Although this might be statistically significant, it does not meet the threshold for a clinical significance – those aren’t the same thing,” Dr. Horowitz said. Some analyses suggest that a “minimally clinically important difference” on the HAM-D would range from 3 to 6 points.

The findings in adolescents and children are “even less convincing,” the investigators noted, citing a Cochrane review.

“This is especially concerning because the number of children and adolescents being treated with antidepressants is rapidly increasing,” Dr. Horowitz said.

Additionally, the short duration of most trials, typically 6-12 weeks, is “largely uninformative for the clinical treatment of depression.”
 

 

 

Relapse or withdrawal?

The researchers reviewed the adverse effects of long-term antidepressant use, including daytime sleepiness, dry mouth, profuse sweating, weight gain, sexual dysfunction, restlessness, and feeling “foggy or detached.”

“Antidepressants have toxic effects on the brain and cause brain damage when they artificially increase serotonin and modify brain chemistry, which is why people become sick for years after stopping,” Dr. Horowitz said. “When the drug is reduced or stopped, the brain has difficulty dealing with the sudden drop in neurotransmitters, and withdrawal symptoms result, similar to stopping caffeine, nicotine, or opioids.”

He added it is not necessarily the original condition of depression or anxiety that is recurring but rather withdrawal, which can last for months or even years after medication discontinuation.

“Unfortunately, doctors have been taught that there are minimal withdrawal symptoms, euphemized as ‘discontinuation symptoms,’ and so when patients have reported withdrawal symptoms, they have been told it is a return of their underlying condition,” Dr. Horowitz said.

“This has led to many patients being incorrectly told that they need to get back on their antidepressants,” he added.

He likened this approach to “telling people that the need to continue smoking because when they stop, they get more anxiety.” Rather, the “correct response would be that they simply need to taper off the antidepressant more carefully,” he said.
 

Helpful in the short term

Patients should be informed prior to initiation of antidepressant treatment about the risk of withdrawal effects if they stop the drug, the investigators advise. They reference the Royal College of Psychiatrists’ updated guidance, which recommends slow tapering over a period long enough to mitigate withdrawal symptoms to “tolerable levels.”

The guidance suggests that patients start with a small “test reduction.” Withdrawal symptoms should be monitored for the following 2-4 weeks, using a symptom checklist such as the Discontinuation Emergent Signs and Symptoms Scale, with subsequent reductions based on the tolerability of the process.

Gradual dose reductions and very small final doses may necessitate the use of formulations of medication other than those commonly available in tablet forms, the researchers noted. During the tapering process, patients may benefit from increased psychosocial support.

Dr. Horowitz noted that antidepressants can be helpful on a short-term basis, and likened their use to the use of a cast to stabilize a broken arm.

“It’s useful for a short period. But if you leave someone in a plastic cast permanently, their arm will shrivel and you will disable them. These drugs should be prescribed minimally, and for the shortest possible period of time,” he said.

Dr. Horowitz recommended the recent draft National Institute for Health and Care Excellence depression guidance that recommends multiple other options beyond antidepressants, including cognitive-behavioral therapy, problem solving, counseling, and exercise.
 

Lack of balance

Dr. Muskin commented that the review is helpful in guiding clinicians on how to approach tapering of antidepressants and making patients aware of discontinuation symptoms.

However, “a lot of people will read this who need treatment, but they won’t get treated because they’ll take away the message that ‘drugs don’t work,’ ” he said.

“As it is, there is already stigma and prejudice toward psychiatric illness and using medications for treatment,” said Dr. Muskin, who was not involved with the research.

The current review “isn’t balanced, in terms of the efficacy of these drugs – both for the spectrum of depressive disorders and for panic or anxiety disorder. And there is nowhere that the authors say these drugs help people,” he added.

Moreover, the investigators’ assertion that long-term use of antidepressants causes harm is incorrect, he said.

“Yes, there are ongoing side effects that impose a burden, but that’s not the same as harm. And while the side effects are sometimes burdensome, ongoing depression is also terribly burdensome,” Dr. Muskin concluded.

Dr. Horowitz, Dr. Wilcock, and Dr. Muskin have reported no relevant financial relationships.

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

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When it comes to antidepressant prescribing, less may be more, new research suggests.

A new review suggests antidepressants are overprescribed and that the efficacy of these agents is questionable, leading researchers to recommend that, when physicians prescribe these medications, it should be for shorter periods.

“Antidepressants have never been shown to have a clinically significant difference from placebo in the treatment of depression,” study co\investigator Mark Horowitz, GDPsych, PhD, division of psychiatry, University College London, said in an interview.

HconQ/ThinkStock

He added antidepressants “exert profound adverse effects on the body and brain” and can be difficult to stop because of physical dependence that occurs when the brain adapts to them.

“The best way to take people off these drugs is to do so gradually enough that the unpleasant effects are minimized and in a way that means the reductions in dose get smaller and smaller as the total dose gets lower,” Dr. Horowitz said.

However, at least one expert urged caution in interpreting the review’s findings.

“The reality is that millions of people do benefit from these medications, and this review minimizes those benefits,” Philip Muskin, MD, chief of consultation-liaison for psychiatry and professor of psychiatry, Columbia University Medical Center and New York–Presbyterian Hospital, said when approached for comment.

The findings were published online Dec. 20, 2021, in the Drug and Therapeutics Bulletin.
 

Personal experience

Prescribing of newer-generation antidepressants, such as SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs), is increasing, with an estimated one in six adults in the United Kingdom receiving at least one prescription in 2019-2020, the investigators noted.

Dr. Horowitz noted a personal motivation for conducting the review. “As well as being an academic psychiatrist, I’m also a patient who has been prescribed antidepressants since age 21, when my mood was poor, due to life circumstances.”

The antidepressant “didn’t have particularly helpful effects,” but Dr. Horowitz continued taking it for 18 years. “I was told it was helpful and internalized that message. I came to understand that much of the information around antidepressants came from the drug companies that manufactured them or from academics paid by these companies.”

Dr. Horowitz is currently discontinuing his medication – a tapering process now in its third year. He said he has come to realize, in retrospect, that symptoms not initially attributed to the drug, such as fatigue, impaired concentration, and impaired memory, have improved since reducing the medication.

“That experience sensitized me to look for these symptoms in my patients and I see them; but most of my patients were told by their doctors that the cause of those problems was the depression or anxiety itself and not the drug,” he said.

Dr. Horowitz collaborated with Michael Wilcock, DTB, Pharmacy, Royal Cornwall Hospitals, NHS Trust, Truro, England, in conducting the review “to provide an independent assessment of benefits and harms of antidepressants.”

“Much of the evidence of the efficacy of antidepressants comes from randomized placebo-controlled trials,” Dr. Horowitz said. Several meta-analyses of these studies showed a difference of about two points between the agent and the placebo on the Hamilton Depression Rating Scale (HAM-D).

“Although this might be statistically significant, it does not meet the threshold for a clinical significance – those aren’t the same thing,” Dr. Horowitz said. Some analyses suggest that a “minimally clinically important difference” on the HAM-D would range from 3 to 6 points.

The findings in adolescents and children are “even less convincing,” the investigators noted, citing a Cochrane review.

“This is especially concerning because the number of children and adolescents being treated with antidepressants is rapidly increasing,” Dr. Horowitz said.

Additionally, the short duration of most trials, typically 6-12 weeks, is “largely uninformative for the clinical treatment of depression.”
 

 

 

Relapse or withdrawal?

The researchers reviewed the adverse effects of long-term antidepressant use, including daytime sleepiness, dry mouth, profuse sweating, weight gain, sexual dysfunction, restlessness, and feeling “foggy or detached.”

“Antidepressants have toxic effects on the brain and cause brain damage when they artificially increase serotonin and modify brain chemistry, which is why people become sick for years after stopping,” Dr. Horowitz said. “When the drug is reduced or stopped, the brain has difficulty dealing with the sudden drop in neurotransmitters, and withdrawal symptoms result, similar to stopping caffeine, nicotine, or opioids.”

He added it is not necessarily the original condition of depression or anxiety that is recurring but rather withdrawal, which can last for months or even years after medication discontinuation.

“Unfortunately, doctors have been taught that there are minimal withdrawal symptoms, euphemized as ‘discontinuation symptoms,’ and so when patients have reported withdrawal symptoms, they have been told it is a return of their underlying condition,” Dr. Horowitz said.

“This has led to many patients being incorrectly told that they need to get back on their antidepressants,” he added.

He likened this approach to “telling people that the need to continue smoking because when they stop, they get more anxiety.” Rather, the “correct response would be that they simply need to taper off the antidepressant more carefully,” he said.
 

Helpful in the short term

Patients should be informed prior to initiation of antidepressant treatment about the risk of withdrawal effects if they stop the drug, the investigators advise. They reference the Royal College of Psychiatrists’ updated guidance, which recommends slow tapering over a period long enough to mitigate withdrawal symptoms to “tolerable levels.”

The guidance suggests that patients start with a small “test reduction.” Withdrawal symptoms should be monitored for the following 2-4 weeks, using a symptom checklist such as the Discontinuation Emergent Signs and Symptoms Scale, with subsequent reductions based on the tolerability of the process.

Gradual dose reductions and very small final doses may necessitate the use of formulations of medication other than those commonly available in tablet forms, the researchers noted. During the tapering process, patients may benefit from increased psychosocial support.

Dr. Horowitz noted that antidepressants can be helpful on a short-term basis, and likened their use to the use of a cast to stabilize a broken arm.

“It’s useful for a short period. But if you leave someone in a plastic cast permanently, their arm will shrivel and you will disable them. These drugs should be prescribed minimally, and for the shortest possible period of time,” he said.

Dr. Horowitz recommended the recent draft National Institute for Health and Care Excellence depression guidance that recommends multiple other options beyond antidepressants, including cognitive-behavioral therapy, problem solving, counseling, and exercise.
 

Lack of balance

Dr. Muskin commented that the review is helpful in guiding clinicians on how to approach tapering of antidepressants and making patients aware of discontinuation symptoms.

However, “a lot of people will read this who need treatment, but they won’t get treated because they’ll take away the message that ‘drugs don’t work,’ ” he said.

“As it is, there is already stigma and prejudice toward psychiatric illness and using medications for treatment,” said Dr. Muskin, who was not involved with the research.

The current review “isn’t balanced, in terms of the efficacy of these drugs – both for the spectrum of depressive disorders and for panic or anxiety disorder. And there is nowhere that the authors say these drugs help people,” he added.

Moreover, the investigators’ assertion that long-term use of antidepressants causes harm is incorrect, he said.

“Yes, there are ongoing side effects that impose a burden, but that’s not the same as harm. And while the side effects are sometimes burdensome, ongoing depression is also terribly burdensome,” Dr. Muskin concluded.

Dr. Horowitz, Dr. Wilcock, and Dr. Muskin have reported no relevant financial relationships.

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

When it comes to antidepressant prescribing, less may be more, new research suggests.

A new review suggests antidepressants are overprescribed and that the efficacy of these agents is questionable, leading researchers to recommend that, when physicians prescribe these medications, it should be for shorter periods.

“Antidepressants have never been shown to have a clinically significant difference from placebo in the treatment of depression,” study co\investigator Mark Horowitz, GDPsych, PhD, division of psychiatry, University College London, said in an interview.

HconQ/ThinkStock

He added antidepressants “exert profound adverse effects on the body and brain” and can be difficult to stop because of physical dependence that occurs when the brain adapts to them.

“The best way to take people off these drugs is to do so gradually enough that the unpleasant effects are minimized and in a way that means the reductions in dose get smaller and smaller as the total dose gets lower,” Dr. Horowitz said.

However, at least one expert urged caution in interpreting the review’s findings.

“The reality is that millions of people do benefit from these medications, and this review minimizes those benefits,” Philip Muskin, MD, chief of consultation-liaison for psychiatry and professor of psychiatry, Columbia University Medical Center and New York–Presbyterian Hospital, said when approached for comment.

The findings were published online Dec. 20, 2021, in the Drug and Therapeutics Bulletin.
 

Personal experience

Prescribing of newer-generation antidepressants, such as SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs), is increasing, with an estimated one in six adults in the United Kingdom receiving at least one prescription in 2019-2020, the investigators noted.

Dr. Horowitz noted a personal motivation for conducting the review. “As well as being an academic psychiatrist, I’m also a patient who has been prescribed antidepressants since age 21, when my mood was poor, due to life circumstances.”

The antidepressant “didn’t have particularly helpful effects,” but Dr. Horowitz continued taking it for 18 years. “I was told it was helpful and internalized that message. I came to understand that much of the information around antidepressants came from the drug companies that manufactured them or from academics paid by these companies.”

Dr. Horowitz is currently discontinuing his medication – a tapering process now in its third year. He said he has come to realize, in retrospect, that symptoms not initially attributed to the drug, such as fatigue, impaired concentration, and impaired memory, have improved since reducing the medication.

“That experience sensitized me to look for these symptoms in my patients and I see them; but most of my patients were told by their doctors that the cause of those problems was the depression or anxiety itself and not the drug,” he said.

Dr. Horowitz collaborated with Michael Wilcock, DTB, Pharmacy, Royal Cornwall Hospitals, NHS Trust, Truro, England, in conducting the review “to provide an independent assessment of benefits and harms of antidepressants.”

“Much of the evidence of the efficacy of antidepressants comes from randomized placebo-controlled trials,” Dr. Horowitz said. Several meta-analyses of these studies showed a difference of about two points between the agent and the placebo on the Hamilton Depression Rating Scale (HAM-D).

“Although this might be statistically significant, it does not meet the threshold for a clinical significance – those aren’t the same thing,” Dr. Horowitz said. Some analyses suggest that a “minimally clinically important difference” on the HAM-D would range from 3 to 6 points.

The findings in adolescents and children are “even less convincing,” the investigators noted, citing a Cochrane review.

“This is especially concerning because the number of children and adolescents being treated with antidepressants is rapidly increasing,” Dr. Horowitz said.

Additionally, the short duration of most trials, typically 6-12 weeks, is “largely uninformative for the clinical treatment of depression.”
 

 

 

Relapse or withdrawal?

The researchers reviewed the adverse effects of long-term antidepressant use, including daytime sleepiness, dry mouth, profuse sweating, weight gain, sexual dysfunction, restlessness, and feeling “foggy or detached.”

“Antidepressants have toxic effects on the brain and cause brain damage when they artificially increase serotonin and modify brain chemistry, which is why people become sick for years after stopping,” Dr. Horowitz said. “When the drug is reduced or stopped, the brain has difficulty dealing with the sudden drop in neurotransmitters, and withdrawal symptoms result, similar to stopping caffeine, nicotine, or opioids.”

He added it is not necessarily the original condition of depression or anxiety that is recurring but rather withdrawal, which can last for months or even years after medication discontinuation.

“Unfortunately, doctors have been taught that there are minimal withdrawal symptoms, euphemized as ‘discontinuation symptoms,’ and so when patients have reported withdrawal symptoms, they have been told it is a return of their underlying condition,” Dr. Horowitz said.

“This has led to many patients being incorrectly told that they need to get back on their antidepressants,” he added.

He likened this approach to “telling people that the need to continue smoking because when they stop, they get more anxiety.” Rather, the “correct response would be that they simply need to taper off the antidepressant more carefully,” he said.
 

Helpful in the short term

Patients should be informed prior to initiation of antidepressant treatment about the risk of withdrawal effects if they stop the drug, the investigators advise. They reference the Royal College of Psychiatrists’ updated guidance, which recommends slow tapering over a period long enough to mitigate withdrawal symptoms to “tolerable levels.”

The guidance suggests that patients start with a small “test reduction.” Withdrawal symptoms should be monitored for the following 2-4 weeks, using a symptom checklist such as the Discontinuation Emergent Signs and Symptoms Scale, with subsequent reductions based on the tolerability of the process.

Gradual dose reductions and very small final doses may necessitate the use of formulations of medication other than those commonly available in tablet forms, the researchers noted. During the tapering process, patients may benefit from increased psychosocial support.

Dr. Horowitz noted that antidepressants can be helpful on a short-term basis, and likened their use to the use of a cast to stabilize a broken arm.

“It’s useful for a short period. But if you leave someone in a plastic cast permanently, their arm will shrivel and you will disable them. These drugs should be prescribed minimally, and for the shortest possible period of time,” he said.

Dr. Horowitz recommended the recent draft National Institute for Health and Care Excellence depression guidance that recommends multiple other options beyond antidepressants, including cognitive-behavioral therapy, problem solving, counseling, and exercise.
 

Lack of balance

Dr. Muskin commented that the review is helpful in guiding clinicians on how to approach tapering of antidepressants and making patients aware of discontinuation symptoms.

However, “a lot of people will read this who need treatment, but they won’t get treated because they’ll take away the message that ‘drugs don’t work,’ ” he said.

“As it is, there is already stigma and prejudice toward psychiatric illness and using medications for treatment,” said Dr. Muskin, who was not involved with the research.

The current review “isn’t balanced, in terms of the efficacy of these drugs – both for the spectrum of depressive disorders and for panic or anxiety disorder. And there is nowhere that the authors say these drugs help people,” he added.

Moreover, the investigators’ assertion that long-term use of antidepressants causes harm is incorrect, he said.

“Yes, there are ongoing side effects that impose a burden, but that’s not the same as harm. And while the side effects are sometimes burdensome, ongoing depression is also terribly burdensome,” Dr. Muskin concluded.

Dr. Horowitz, Dr. Wilcock, and Dr. Muskin have reported no relevant financial relationships.

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

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