MDedge Psychiatry

For younger generations, TikTok is a go-to site for those who like short and catchy video clips. As a social media platform that allows concise video sharing, TikTok has over 1 billion monthly global users. Because of its platform size, a plethora of resources, and influence on media discourse, TikTok is the place for content creators to share visual media. Its cursory, condensed content delivery with videos capped at 1-minute focuses on high-yield information and rapid identification of fundamental points that are both engaging and entertaining.

Currently, on TikTok, 40 billion views are associated with the hashtag #mentalhealth. Content creators and regular users are employing this platform to share their own experiences, opinions, and strategies to overcome their struggles. While it is understandable for creators to share their personal stories that may be abusive, traumatic, or violent, they may not be prepared for their video to “go viral.”

Like any other social media platform, hateful speech such as racism, sexism, or xenophobia can accumulate on TikTok, which may cause more self-harm than self-help. Oversharing about personal strategies may lead to misconceived advice for TikTok viewers, while watching these TikTok videos can have negative mental health effects, even though there are no malicious intentions behind the creators who post these videos.

Hence, public health should pay more attention to the potential health-related implications this platform can create, as the quality of the information and the qualifications of the creators are mostly unrevealed. The concerns include undisclosed conflicts of interest, unchecked spread of misinformation, difficulty identifying source credibility, and excessive false information that viewers must filter through.^1,2

Individual TikTok users may follow accounts and interpret these content creators as therapists and the content they see as therapy. They may also believe that a close relationship with the content creator exists when it does not. Specifically, these relationships may be defined as parasocial relationships, which are one-sided relationships where one person (the TikTok viewer) extends emotional energy, interest, and time, and the other party (the content creator) is completely unaware of the other’s existence.³ Additionally, Americans who are uninsured/underinsured may turn to this diluted version of therapy to compensate for the one-on-one or group therapy they need.

While TikTok may seem like a dangerous platform to browse through or post on, its growing influence cannot be underestimated. With 41% of TikTok users between the ages of 16 and 24, this is an ideal platform to disseminate public health information pertaining to this age group (for example, safe sex practices, substance abuse, and mental health issues).⁴ Because younger generations have incorporated social media into their daily lives, the medical community can harness TikTok’s potential to disseminate accurate information to potential patients for targeted medical education.

For example, Jake Goodman, MD, MBA, and Melissa Shepard, MD, each have more than a million TikTok followers and are notable psychiatrists who post a variety of content ranging from recognizing signs of depression to reducing stigma around mental health. Similarly, Justin Puder, PhD, is a licensed psychologist who advocates for ways to overcome mental health issues. By creating diverse content with appealing strategies, spreading accurate medical knowledge, and answering common medical questions for the public, these ‘mental health influencers’ educate potential patients to create patient-centered interactions.

Given the ever-changing digital media landscape, an emphasis must be placed on understanding how adolescents respond to social media in maladaptive or adaptive ways by pointing out the common strengths and weaknesses adolescents share. While there are many pros and cons to social media platforms, it is undeniable that these platforms – such as TikTok – are here to stay. It is crucial for members of the medical community to recognize the outlets that younger generations use to express themselves and to exploit these media channels therapeutically.
 

Ms. Wong is a fourth-year medical student at the New York Institute of Technology College of Osteopathic Medicine in Old Westbury, N.Y. Dr. Chua is a psychiatrist with the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia, and assistant professor of clinical psychiatry at the University of Pennsylvania, also in Philadelphia.

References

1. Gottlieb M and Dyer S. Information and Disinformation: Social Media in the COVID-19 Crisis. Acad Emerg Med. 2020 Jul;27(7):640-1. doi: 10.1111/acem.14036.

2. De Veirman M et al. Front Psychol. 2019;10:2685. doi: 10.3389/fpsyg.2019.02685.

3. Bennett N-K et al. “Parasocial Relationships: The Nature of Celebrity Fascinations.” National Register of Health Service Psychologists. https://www.findapsychologist.org/parasocial-relationships-the-nature-of-celebrity-fascinations/.

4. Eghtesadi M and Florea A. Can J Public Health. 2020 Jun;111(3):389-91. doi: 10.17269/s41997-020-00343-0.

For younger generations, TikTok is a go-to site for those who like short and catchy video clips. As a social media platform that allows concise video sharing, TikTok has over 1 billion monthly global users. Because of its platform size, a plethora of resources, and influence on media discourse, TikTok is the place for content creators to share visual media. Its cursory, condensed content delivery with videos capped at 1-minute focuses on high-yield information and rapid identification of fundamental points that are both engaging and entertaining.

Currently, on TikTok, 40 billion views are associated with the hashtag #mentalhealth. Content creators and regular users are employing this platform to share their own experiences, opinions, and strategies to overcome their struggles. While it is understandable for creators to share their personal stories that may be abusive, traumatic, or violent, they may not be prepared for their video to “go viral.”

Like any other social media platform, hateful speech such as racism, sexism, or xenophobia can accumulate on TikTok, which may cause more self-harm than self-help. Oversharing about personal strategies may lead to misconceived advice for TikTok viewers, while watching these TikTok videos can have negative mental health effects, even though there are no malicious intentions behind the creators who post these videos.

Hence, public health should pay more attention to the potential health-related implications this platform can create, as the quality of the information and the qualifications of the creators are mostly unrevealed. The concerns include undisclosed conflicts of interest, unchecked spread of misinformation, difficulty identifying source credibility, and excessive false information that viewers must filter through.^1,2

Individual TikTok users may follow accounts and interpret these content creators as therapists and the content they see as therapy. They may also believe that a close relationship with the content creator exists when it does not. Specifically, these relationships may be defined as parasocial relationships, which are one-sided relationships where one person (the TikTok viewer) extends emotional energy, interest, and time, and the other party (the content creator) is completely unaware of the other’s existence.³ Additionally, Americans who are uninsured/underinsured may turn to this diluted version of therapy to compensate for the one-on-one or group therapy they need.

While TikTok may seem like a dangerous platform to browse through or post on, its growing influence cannot be underestimated. With 41% of TikTok users between the ages of 16 and 24, this is an ideal platform to disseminate public health information pertaining to this age group (for example, safe sex practices, substance abuse, and mental health issues).⁴ Because younger generations have incorporated social media into their daily lives, the medical community can harness TikTok’s potential to disseminate accurate information to potential patients for targeted medical education.

For example, Jake Goodman, MD, MBA, and Melissa Shepard, MD, each have more than a million TikTok followers and are notable psychiatrists who post a variety of content ranging from recognizing signs of depression to reducing stigma around mental health. Similarly, Justin Puder, PhD, is a licensed psychologist who advocates for ways to overcome mental health issues. By creating diverse content with appealing strategies, spreading accurate medical knowledge, and answering common medical questions for the public, these ‘mental health influencers’ educate potential patients to create patient-centered interactions.

Given the ever-changing digital media landscape, an emphasis must be placed on understanding how adolescents respond to social media in maladaptive or adaptive ways by pointing out the common strengths and weaknesses adolescents share. While there are many pros and cons to social media platforms, it is undeniable that these platforms – such as TikTok – are here to stay. It is crucial for members of the medical community to recognize the outlets that younger generations use to express themselves and to exploit these media channels therapeutically.
 

Ms. Wong is a fourth-year medical student at the New York Institute of Technology College of Osteopathic Medicine in Old Westbury, N.Y. Dr. Chua is a psychiatrist with the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia, and assistant professor of clinical psychiatry at the University of Pennsylvania, also in Philadelphia.

References

1. Gottlieb M and Dyer S. Information and Disinformation: Social Media in the COVID-19 Crisis. Acad Emerg Med. 2020 Jul;27(7):640-1. doi: 10.1111/acem.14036.

2. De Veirman M et al. Front Psychol. 2019;10:2685. doi: 10.3389/fpsyg.2019.02685.

3. Bennett N-K et al. “Parasocial Relationships: The Nature of Celebrity Fascinations.” National Register of Health Service Psychologists. https://www.findapsychologist.org/parasocial-relationships-the-nature-of-celebrity-fascinations/.

4. Eghtesadi M and Florea A. Can J Public Health. 2020 Jun;111(3):389-91. doi: 10.17269/s41997-020-00343-0.

For younger generations, TikTok is a go-to site for those who like short and catchy video clips. As a social media platform that allows concise video sharing, TikTok has over 1 billion monthly global users. Because of its platform size, a plethora of resources, and influence on media discourse, TikTok is the place for content creators to share visual media. Its cursory, condensed content delivery with videos capped at 1-minute focuses on high-yield information and rapid identification of fundamental points that are both engaging and entertaining.

Currently, on TikTok, 40 billion views are associated with the hashtag #mentalhealth. Content creators and regular users are employing this platform to share their own experiences, opinions, and strategies to overcome their struggles. While it is understandable for creators to share their personal stories that may be abusive, traumatic, or violent, they may not be prepared for their video to “go viral.”

Like any other social media platform, hateful speech such as racism, sexism, or xenophobia can accumulate on TikTok, which may cause more self-harm than self-help. Oversharing about personal strategies may lead to misconceived advice for TikTok viewers, while watching these TikTok videos can have negative mental health effects, even though there are no malicious intentions behind the creators who post these videos.

Hence, public health should pay more attention to the potential health-related implications this platform can create, as the quality of the information and the qualifications of the creators are mostly unrevealed. The concerns include undisclosed conflicts of interest, unchecked spread of misinformation, difficulty identifying source credibility, and excessive false information that viewers must filter through.^1,2

Individual TikTok users may follow accounts and interpret these content creators as therapists and the content they see as therapy. They may also believe that a close relationship with the content creator exists when it does not. Specifically, these relationships may be defined as parasocial relationships, which are one-sided relationships where one person (the TikTok viewer) extends emotional energy, interest, and time, and the other party (the content creator) is completely unaware of the other’s existence.³ Additionally, Americans who are uninsured/underinsured may turn to this diluted version of therapy to compensate for the one-on-one or group therapy they need.

While TikTok may seem like a dangerous platform to browse through or post on, its growing influence cannot be underestimated. With 41% of TikTok users between the ages of 16 and 24, this is an ideal platform to disseminate public health information pertaining to this age group (for example, safe sex practices, substance abuse, and mental health issues).⁴ Because younger generations have incorporated social media into their daily lives, the medical community can harness TikTok’s potential to disseminate accurate information to potential patients for targeted medical education.

For example, Jake Goodman, MD, MBA, and Melissa Shepard, MD, each have more than a million TikTok followers and are notable psychiatrists who post a variety of content ranging from recognizing signs of depression to reducing stigma around mental health. Similarly, Justin Puder, PhD, is a licensed psychologist who advocates for ways to overcome mental health issues. By creating diverse content with appealing strategies, spreading accurate medical knowledge, and answering common medical questions for the public, these ‘mental health influencers’ educate potential patients to create patient-centered interactions.

Given the ever-changing digital media landscape, an emphasis must be placed on understanding how adolescents respond to social media in maladaptive or adaptive ways by pointing out the common strengths and weaknesses adolescents share. While there are many pros and cons to social media platforms, it is undeniable that these platforms – such as TikTok – are here to stay. It is crucial for members of the medical community to recognize the outlets that younger generations use to express themselves and to exploit these media channels therapeutically.
 

Ms. Wong is a fourth-year medical student at the New York Institute of Technology College of Osteopathic Medicine in Old Westbury, N.Y. Dr. Chua is a psychiatrist with the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia, and assistant professor of clinical psychiatry at the University of Pennsylvania, also in Philadelphia.

References

1. Gottlieb M and Dyer S. Information and Disinformation: Social Media in the COVID-19 Crisis. Acad Emerg Med. 2020 Jul;27(7):640-1. doi: 10.1111/acem.14036.

2. De Veirman M et al. Front Psychol. 2019;10:2685. doi: 10.3389/fpsyg.2019.02685.

3. Bennett N-K et al. “Parasocial Relationships: The Nature of Celebrity Fascinations.” National Register of Health Service Psychologists. https://www.findapsychologist.org/parasocial-relationships-the-nature-of-celebrity-fascinations/.

4. Eghtesadi M and Florea A. Can J Public Health. 2020 Jun;111(3):389-91. doi: 10.17269/s41997-020-00343-0.

BARCELONA – Treatment of patients with chronic heart failure with sacubitril/valsartan (Entresto), a mainstay agent for people with this disorder, produced no hint of incremental adverse cognitive effects during 3 years of treatment in a prospective, controlled, multicenter study with nearly 600 patients, although some experts note that possible adverse cognitive effects of sacubitril were not an issue for many heart failure clinicians, even before the study ran.

The potential for an adverse effect of sacubitril on cognition had arisen as a hypothetical concern because sacubitril inhibits the human enzyme neprilysin. This activity results in beneficial effects for patients with heart failure by increasing levels of several endogenous vasoactive peptides. But neprilysin also degrades amyloid beta peptides and so inhibition of this enzyme could possibly result in accumulation of amyloid peptides in the brain with potential neurotoxic effects, which raised concern among some cardiologists and patients that sacubitril/valsartan could hasten cognitive decline.

Catherine Hackett/MDedge News

Results from the new study, PERSPECTIVE, showed “no evidence that neprilysin inhibition increased the risk of cognitive impairment due to the accumulation of beta amyloid” in patients with heart failure with either mid-range or preserved ejection fraction,” John McMurray, MD, said at the annual congress of the European Society of Cardiology.

Dr. McMurray, professor of medical cardiology at the University of Glasgow, highlighted that the study enrolled only patients with heart failure with a left ventricular ejection fraction of greater than 40% because the study designers considered it “unethical” to withhold treatment with sacubitril/valsartan from patients with an ejection fraction of 40% or less (heart failure with reduced ejection fraction, HFrEF), whereas “no mandate” exists in current treatment guidelines for using sacubitril/valsartan in patients with heart failure and higher ejection fractions. He added that he could see no reason why the results seen in patients with higher ejection fractions would not also apply to those with HFrEF.
 

Reassuring results, but cost still a drag on uptake

“This was a well-designed trial” with results that are “very reassuring” for a lack of harm from sacubitril/valsartan, commented Biykem Bozkurt, MD, PhD, the study’s designated discussant and professor of medicine at Baylor College of Medicine, Houston. The findings “solidify the lack of risk and are very exciting for the heart failure community because the question has bothered a large number of people, especially older patients” with heart failure.

Catherine Hackett/MDedge News

Following these results, “hopefully more patients with heart failure will receive” sacubitril/valsartan, agreed Dr. McMurray, but he added the caveat that the relatively high cost of the agent (which has a U.S. list price of roughly $6,000/year) has been the primary barrier to wider uptake of the drug for patients with heart failure. Treatment with sacubitril/valsartan is recommended in several society guidelines as a core intervention for patients with HFrEF and as a treatment option for patients with heart failure and higher ejection fractions.

“Cost remains the single biggest deterrent for use” of sacubitril/valsartan, agreed Dipti N. Itchhaporia, MD, director of disease management at the Hoag Heart and Vascular Institute in Newport Beach, Calif. “Concerns about cognitive impairment has not been why people have not been using sacubitril/valsartan,” Dr. Itchhaporia commented in an interview.

PERSPECTIVE enrolled patients with heart failure with an ejection fraction greater than 40% and at least 60 years old at any of 137 sites in 20 countries, with about a third of enrolled patients coming from U.S. centers. The study, which ran enrollment during January 2017–May 2019, excluded people with clinically discernible cognitive impairment at the time of entry.

Researchers randomized patients to either a standard regimen of sacubitril/valsartan (295) or valsartan (297) on top of their background treatment, with most patients also receiving a beta-blocker, a diuretic, and a statin. The enrolled patients averaged about 72 years of age, and more than one-third were at least 75 years old.

The study’s primary endpoint was the performance of these patients in seven different tests of cognitive function using a proprietary metric, the CogState Global Cognitive Composite Score, measured at baseline and then every 6 months during follow-up designed to run for 3 years on treatment (the researchers collected data for at least 30 months of follow-up from 71%-73% of enrolled patients). Average changes in these scores over time tracked nearly the same in both treatment arms and met the study’s prespecified criteria for noninferiority of the sacubitril valsartan treatment, Dr. McMurray reported. The results also showed that roughly 60% of patients in both arms had “some degree of cognitive impairment” during follow-up.

A secondary outcome measure used PET imaging to quantify cerebral accumulation of beta amyloid, and again the results met the study’s prespecified threshold for noninferiority for the patients treated with sacubitril/valsartan, said Dr. McMurray.

Another concern raised by some experts was the relatively brief follow-up of 3 years, and the complexity of heart failure patients who could face several other causes of cognitive decline. The findings “help reassure, but 3 years is not long enough, and I’m not sure the study eliminated all the other possible variables,” commented Dr. Itchhaporia.

But Dr. McMurray contended that 3 years represents robust follow-up in patients with heart failure who notoriously have limited life expectancy following their diagnosis. “Three years is a long time for patients with heart failure.”

The findings also raise the prospect of developing sacubitril/valsartan as an antihypertensive treatment, an indication that has been avoided until now because of the uncertain cognitive effects of the agent and the need for prolonged use when the treated disorder is hypertension instead of heart failure.

PERSPECTIVE was funded by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. McMurray has received consulting and lecture fees from Novartis and he and his institution have received research funding from Novartis. Dr. Bozkurt has been a consultant to numerous companies but has no relationship with Novartis. Dr. Itchhaporia had no disclosures.

BARCELONA – Treatment of patients with chronic heart failure with sacubitril/valsartan (Entresto), a mainstay agent for people with this disorder, produced no hint of incremental adverse cognitive effects during 3 years of treatment in a prospective, controlled, multicenter study with nearly 600 patients, although some experts note that possible adverse cognitive effects of sacubitril were not an issue for many heart failure clinicians, even before the study ran.

The potential for an adverse effect of sacubitril on cognition had arisen as a hypothetical concern because sacubitril inhibits the human enzyme neprilysin. This activity results in beneficial effects for patients with heart failure by increasing levels of several endogenous vasoactive peptides. But neprilysin also degrades amyloid beta peptides and so inhibition of this enzyme could possibly result in accumulation of amyloid peptides in the brain with potential neurotoxic effects, which raised concern among some cardiologists and patients that sacubitril/valsartan could hasten cognitive decline.

Catherine Hackett/MDedge News

Results from the new study, PERSPECTIVE, showed “no evidence that neprilysin inhibition increased the risk of cognitive impairment due to the accumulation of beta amyloid” in patients with heart failure with either mid-range or preserved ejection fraction,” John McMurray, MD, said at the annual congress of the European Society of Cardiology.

Dr. McMurray, professor of medical cardiology at the University of Glasgow, highlighted that the study enrolled only patients with heart failure with a left ventricular ejection fraction of greater than 40% because the study designers considered it “unethical” to withhold treatment with sacubitril/valsartan from patients with an ejection fraction of 40% or less (heart failure with reduced ejection fraction, HFrEF), whereas “no mandate” exists in current treatment guidelines for using sacubitril/valsartan in patients with heart failure and higher ejection fractions. He added that he could see no reason why the results seen in patients with higher ejection fractions would not also apply to those with HFrEF.
 

Reassuring results, but cost still a drag on uptake

“This was a well-designed trial” with results that are “very reassuring” for a lack of harm from sacubitril/valsartan, commented Biykem Bozkurt, MD, PhD, the study’s designated discussant and professor of medicine at Baylor College of Medicine, Houston. The findings “solidify the lack of risk and are very exciting for the heart failure community because the question has bothered a large number of people, especially older patients” with heart failure.

Catherine Hackett/MDedge News

Following these results, “hopefully more patients with heart failure will receive” sacubitril/valsartan, agreed Dr. McMurray, but he added the caveat that the relatively high cost of the agent (which has a U.S. list price of roughly $6,000/year) has been the primary barrier to wider uptake of the drug for patients with heart failure. Treatment with sacubitril/valsartan is recommended in several society guidelines as a core intervention for patients with HFrEF and as a treatment option for patients with heart failure and higher ejection fractions.

“Cost remains the single biggest deterrent for use” of sacubitril/valsartan, agreed Dipti N. Itchhaporia, MD, director of disease management at the Hoag Heart and Vascular Institute in Newport Beach, Calif. “Concerns about cognitive impairment has not been why people have not been using sacubitril/valsartan,” Dr. Itchhaporia commented in an interview.

PERSPECTIVE enrolled patients with heart failure with an ejection fraction greater than 40% and at least 60 years old at any of 137 sites in 20 countries, with about a third of enrolled patients coming from U.S. centers. The study, which ran enrollment during January 2017–May 2019, excluded people with clinically discernible cognitive impairment at the time of entry.

Researchers randomized patients to either a standard regimen of sacubitril/valsartan (295) or valsartan (297) on top of their background treatment, with most patients also receiving a beta-blocker, a diuretic, and a statin. The enrolled patients averaged about 72 years of age, and more than one-third were at least 75 years old.

The study’s primary endpoint was the performance of these patients in seven different tests of cognitive function using a proprietary metric, the CogState Global Cognitive Composite Score, measured at baseline and then every 6 months during follow-up designed to run for 3 years on treatment (the researchers collected data for at least 30 months of follow-up from 71%-73% of enrolled patients). Average changes in these scores over time tracked nearly the same in both treatment arms and met the study’s prespecified criteria for noninferiority of the sacubitril valsartan treatment, Dr. McMurray reported. The results also showed that roughly 60% of patients in both arms had “some degree of cognitive impairment” during follow-up.

A secondary outcome measure used PET imaging to quantify cerebral accumulation of beta amyloid, and again the results met the study’s prespecified threshold for noninferiority for the patients treated with sacubitril/valsartan, said Dr. McMurray.

Another concern raised by some experts was the relatively brief follow-up of 3 years, and the complexity of heart failure patients who could face several other causes of cognitive decline. The findings “help reassure, but 3 years is not long enough, and I’m not sure the study eliminated all the other possible variables,” commented Dr. Itchhaporia.

But Dr. McMurray contended that 3 years represents robust follow-up in patients with heart failure who notoriously have limited life expectancy following their diagnosis. “Three years is a long time for patients with heart failure.”

The findings also raise the prospect of developing sacubitril/valsartan as an antihypertensive treatment, an indication that has been avoided until now because of the uncertain cognitive effects of the agent and the need for prolonged use when the treated disorder is hypertension instead of heart failure.

PERSPECTIVE was funded by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. McMurray has received consulting and lecture fees from Novartis and he and his institution have received research funding from Novartis. Dr. Bozkurt has been a consultant to numerous companies but has no relationship with Novartis. Dr. Itchhaporia had no disclosures.

BARCELONA – Treatment of patients with chronic heart failure with sacubitril/valsartan (Entresto), a mainstay agent for people with this disorder, produced no hint of incremental adverse cognitive effects during 3 years of treatment in a prospective, controlled, multicenter study with nearly 600 patients, although some experts note that possible adverse cognitive effects of sacubitril were not an issue for many heart failure clinicians, even before the study ran.

The potential for an adverse effect of sacubitril on cognition had arisen as a hypothetical concern because sacubitril inhibits the human enzyme neprilysin. This activity results in beneficial effects for patients with heart failure by increasing levels of several endogenous vasoactive peptides. But neprilysin also degrades amyloid beta peptides and so inhibition of this enzyme could possibly result in accumulation of amyloid peptides in the brain with potential neurotoxic effects, which raised concern among some cardiologists and patients that sacubitril/valsartan could hasten cognitive decline.

Catherine Hackett/MDedge News

Results from the new study, PERSPECTIVE, showed “no evidence that neprilysin inhibition increased the risk of cognitive impairment due to the accumulation of beta amyloid” in patients with heart failure with either mid-range or preserved ejection fraction,” John McMurray, MD, said at the annual congress of the European Society of Cardiology.

Dr. McMurray, professor of medical cardiology at the University of Glasgow, highlighted that the study enrolled only patients with heart failure with a left ventricular ejection fraction of greater than 40% because the study designers considered it “unethical” to withhold treatment with sacubitril/valsartan from patients with an ejection fraction of 40% or less (heart failure with reduced ejection fraction, HFrEF), whereas “no mandate” exists in current treatment guidelines for using sacubitril/valsartan in patients with heart failure and higher ejection fractions. He added that he could see no reason why the results seen in patients with higher ejection fractions would not also apply to those with HFrEF.
 

Reassuring results, but cost still a drag on uptake

“This was a well-designed trial” with results that are “very reassuring” for a lack of harm from sacubitril/valsartan, commented Biykem Bozkurt, MD, PhD, the study’s designated discussant and professor of medicine at Baylor College of Medicine, Houston. The findings “solidify the lack of risk and are very exciting for the heart failure community because the question has bothered a large number of people, especially older patients” with heart failure.

Catherine Hackett/MDedge News

Following these results, “hopefully more patients with heart failure will receive” sacubitril/valsartan, agreed Dr. McMurray, but he added the caveat that the relatively high cost of the agent (which has a U.S. list price of roughly $6,000/year) has been the primary barrier to wider uptake of the drug for patients with heart failure. Treatment with sacubitril/valsartan is recommended in several society guidelines as a core intervention for patients with HFrEF and as a treatment option for patients with heart failure and higher ejection fractions.

“Cost remains the single biggest deterrent for use” of sacubitril/valsartan, agreed Dipti N. Itchhaporia, MD, director of disease management at the Hoag Heart and Vascular Institute in Newport Beach, Calif. “Concerns about cognitive impairment has not been why people have not been using sacubitril/valsartan,” Dr. Itchhaporia commented in an interview.

PERSPECTIVE enrolled patients with heart failure with an ejection fraction greater than 40% and at least 60 years old at any of 137 sites in 20 countries, with about a third of enrolled patients coming from U.S. centers. The study, which ran enrollment during January 2017–May 2019, excluded people with clinically discernible cognitive impairment at the time of entry.

Researchers randomized patients to either a standard regimen of sacubitril/valsartan (295) or valsartan (297) on top of their background treatment, with most patients also receiving a beta-blocker, a diuretic, and a statin. The enrolled patients averaged about 72 years of age, and more than one-third were at least 75 years old.

The study’s primary endpoint was the performance of these patients in seven different tests of cognitive function using a proprietary metric, the CogState Global Cognitive Composite Score, measured at baseline and then every 6 months during follow-up designed to run for 3 years on treatment (the researchers collected data for at least 30 months of follow-up from 71%-73% of enrolled patients). Average changes in these scores over time tracked nearly the same in both treatment arms and met the study’s prespecified criteria for noninferiority of the sacubitril valsartan treatment, Dr. McMurray reported. The results also showed that roughly 60% of patients in both arms had “some degree of cognitive impairment” during follow-up.

A secondary outcome measure used PET imaging to quantify cerebral accumulation of beta amyloid, and again the results met the study’s prespecified threshold for noninferiority for the patients treated with sacubitril/valsartan, said Dr. McMurray.

Another concern raised by some experts was the relatively brief follow-up of 3 years, and the complexity of heart failure patients who could face several other causes of cognitive decline. The findings “help reassure, but 3 years is not long enough, and I’m not sure the study eliminated all the other possible variables,” commented Dr. Itchhaporia.

But Dr. McMurray contended that 3 years represents robust follow-up in patients with heart failure who notoriously have limited life expectancy following their diagnosis. “Three years is a long time for patients with heart failure.”

The findings also raise the prospect of developing sacubitril/valsartan as an antihypertensive treatment, an indication that has been avoided until now because of the uncertain cognitive effects of the agent and the need for prolonged use when the treated disorder is hypertension instead of heart failure.

PERSPECTIVE was funded by Novartis, the company that markets sacubitril/valsartan (Entresto). Dr. McMurray has received consulting and lecture fees from Novartis and he and his institution have received research funding from Novartis. Dr. Bozkurt has been a consultant to numerous companies but has no relationship with Novartis. Dr. Itchhaporia had no disclosures.

Psilocybin paired with psychotherapy is associated with a robust and sustained decrease in drinking among adults with alcohol use disorder (AUD), new research suggests.

Results from the first randomized, placebo-controlled trial of psilocybin for alcohol dependence showed that during the 8 months after first treatment dose, participants who received psilocybin had less than half as many heavy drinking days as their counterparts who received placebo.

In addition, 7 months after the last dose of medication, twice as many psilocybin-treated patients as placebo-treated patients were abstinent.

The effects observed with psilocybin were “considerably larger” than those of currently approved treatments for AUD, senior investigator Michael Bogenschutz, MD, psychiatrist and director of the NYU Langone Center for Psychedelic Medicine, New York, said during an Aug. 24 press briefing.

If the findings hold up in future trials, psilocybin will be a “real breakthrough” in the treatment of the condition, Dr. Bogenschutz said.

The findings were published online in JAMA Psychiatry.

83% reduction in drinking days

The study included 93 adults (mean age, 46 years) with alcohol dependence who consumed an average of seven drinks on the days they drank and had had at least four heavy drinking days during the month prior to treatment.

Of the participants, 48 were randomly assigned to receive two doses of psilocybin, and 45 were assigned to receive an antihistamine (diphenhydramine) placebo. Study medication was administered during 2 day-long sessions at week 4 and week 8.

The participants also received 12 psychotherapy sessions over a 12-week period. All were assessed at intervals from the beginning of the study until 32 weeks after the first medication session.

The primary outcome was percentage of days in which the patient drank heavily during the 32-week period following first medication dose. Heavy drinking was defined as having five or more drinks in a day for a man and four or more drinks in a day for a woman.

The percentage of heavy drinking days during the 32-week period was 9.7% for the psilocybin group and 23.6% for the placebo group, for a mean difference of 13.9% (P = .01).

“Compared to their baseline before the study, after receiving medication, the psilocybin group decreased their heavy drinking days by 83%, while the placebo group reduced their heavy drinking by 51%,” Dr. Bogenschutz reported.

During the last month of follow-up, which was 7 months after the final dose of study medication, 48% of the psilocybin group were entirely abstinent vs. 24% of the placebo group.

“It is remarkable that the effects of psilocybin treatment persisted for 7 months after people received the last dose of medication. This suggests that psilocybin is treating the underlying disorder of alcohol addiction rather than merely treating symptoms,” Dr. Bogenschutz noted.

Total alcohol consumption and problems related to alcohol use were also significantly less in the psilocybin group.

‘Encouraged and hopeful’

Adverse events related to psilocybin were mostly mild, self-limiting, and consistent with other recent trials that evaluated the drug’s effects in various conditions.

However, the current investigators note that they implemented measures to ensure safety, including careful medical and psychiatric screening, therapy, and monitoring that was provided by well-trained therapists, including a licensed psychiatrist. In addition, medications were available to treat acute psychiatric reactions.

A cited limitation of the study was that blinding was not maintained because the average intensity of experience with psilocybin was high, whereas it was low with diphenhydramine.

This difference undermined the masking of treatment such that more than 90% of participants and therapists correctly guessed the treatment assignment.

Another limitation was that objective measures to validate self-reported drinking outcomes were available for only 54% of study participants.

Despite these limitations, the study builds on earlier work by the NYU team that showed that two doses of psilocybin taken over a period of 8 weeks significantly reduced alcohol use and cravings in patients with AUD.

“We’re very encouraged by these findings and hopeful about where they could lead. Personally, it’s been very meaningful and rewarding for me to do this work and inspiring to witness the remarkable recoveries that some of our participants have experienced,” Dr. Bogenschutz told briefing attendees.

Urgent need

The authors of an accompanying editorial note that novel medications for alcohol dependence are “sorely needed. Recent renewed interest in the potential of hallucinogens for treating psychiatric disorders, including AUD, represents a potential move in that direction.”

Henry Kranzler, MD, and Emily Hartwell, PhD, both with the Center for Studies of Addiction, University of Pennsylvania, Philadelphia, write that the new findings “underscore the potential of developing psilocybin as an addition to the alcohol treatment pharmacopeia.”

They question, however, the feasibility of using hallucinogens in routine clinical practice because intensive psychotherapy, such as that provided in this study, requires a significant investment of time and labor.

“Such concomitant therapy, if necessary to realize the therapeutic benefits of psilocybin for treating AUD, could limit its uptake by clinicians,” Dr. Kranzler and Dr. Hartwell write.

The study was funded by the Heffter Research Institute and by individual donations from Carey and Claudia Turnbull, Dr. Efrem Nulman, Rodrigo Niño, and Cody Swift. Dr. Bogenschutz reports having received research funds from and serving as a consultant to Mind Medicine, the Multidisciplinary Association for Psychedelic Studies, B. More, AJNA Labs, Beckley Psytech, Journey Colab, and Bright Minds Biosciences. Dr. Kranzler and Dr. Hartwell have reported no relevant financial relationships.

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

Psilocybin paired with psychotherapy is associated with a robust and sustained decrease in drinking among adults with alcohol use disorder (AUD), new research suggests.

Results from the first randomized, placebo-controlled trial of psilocybin for alcohol dependence showed that during the 8 months after first treatment dose, participants who received psilocybin had less than half as many heavy drinking days as their counterparts who received placebo.

In addition, 7 months after the last dose of medication, twice as many psilocybin-treated patients as placebo-treated patients were abstinent.

The effects observed with psilocybin were “considerably larger” than those of currently approved treatments for AUD, senior investigator Michael Bogenschutz, MD, psychiatrist and director of the NYU Langone Center for Psychedelic Medicine, New York, said during an Aug. 24 press briefing.

If the findings hold up in future trials, psilocybin will be a “real breakthrough” in the treatment of the condition, Dr. Bogenschutz said.

The findings were published online in JAMA Psychiatry.

83% reduction in drinking days

The study included 93 adults (mean age, 46 years) with alcohol dependence who consumed an average of seven drinks on the days they drank and had had at least four heavy drinking days during the month prior to treatment.

Of the participants, 48 were randomly assigned to receive two doses of psilocybin, and 45 were assigned to receive an antihistamine (diphenhydramine) placebo. Study medication was administered during 2 day-long sessions at week 4 and week 8.

The participants also received 12 psychotherapy sessions over a 12-week period. All were assessed at intervals from the beginning of the study until 32 weeks after the first medication session.

The primary outcome was percentage of days in which the patient drank heavily during the 32-week period following first medication dose. Heavy drinking was defined as having five or more drinks in a day for a man and four or more drinks in a day for a woman.

The percentage of heavy drinking days during the 32-week period was 9.7% for the psilocybin group and 23.6% for the placebo group, for a mean difference of 13.9% (P = .01).

“Compared to their baseline before the study, after receiving medication, the psilocybin group decreased their heavy drinking days by 83%, while the placebo group reduced their heavy drinking by 51%,” Dr. Bogenschutz reported.

During the last month of follow-up, which was 7 months after the final dose of study medication, 48% of the psilocybin group were entirely abstinent vs. 24% of the placebo group.

“It is remarkable that the effects of psilocybin treatment persisted for 7 months after people received the last dose of medication. This suggests that psilocybin is treating the underlying disorder of alcohol addiction rather than merely treating symptoms,” Dr. Bogenschutz noted.

Total alcohol consumption and problems related to alcohol use were also significantly less in the psilocybin group.

‘Encouraged and hopeful’

Adverse events related to psilocybin were mostly mild, self-limiting, and consistent with other recent trials that evaluated the drug’s effects in various conditions.

However, the current investigators note that they implemented measures to ensure safety, including careful medical and psychiatric screening, therapy, and monitoring that was provided by well-trained therapists, including a licensed psychiatrist. In addition, medications were available to treat acute psychiatric reactions.

A cited limitation of the study was that blinding was not maintained because the average intensity of experience with psilocybin was high, whereas it was low with diphenhydramine.

This difference undermined the masking of treatment such that more than 90% of participants and therapists correctly guessed the treatment assignment.

Another limitation was that objective measures to validate self-reported drinking outcomes were available for only 54% of study participants.

Despite these limitations, the study builds on earlier work by the NYU team that showed that two doses of psilocybin taken over a period of 8 weeks significantly reduced alcohol use and cravings in patients with AUD.

“We’re very encouraged by these findings and hopeful about where they could lead. Personally, it’s been very meaningful and rewarding for me to do this work and inspiring to witness the remarkable recoveries that some of our participants have experienced,” Dr. Bogenschutz told briefing attendees.

Urgent need

The authors of an accompanying editorial note that novel medications for alcohol dependence are “sorely needed. Recent renewed interest in the potential of hallucinogens for treating psychiatric disorders, including AUD, represents a potential move in that direction.”

Henry Kranzler, MD, and Emily Hartwell, PhD, both with the Center for Studies of Addiction, University of Pennsylvania, Philadelphia, write that the new findings “underscore the potential of developing psilocybin as an addition to the alcohol treatment pharmacopeia.”

They question, however, the feasibility of using hallucinogens in routine clinical practice because intensive psychotherapy, such as that provided in this study, requires a significant investment of time and labor.

“Such concomitant therapy, if necessary to realize the therapeutic benefits of psilocybin for treating AUD, could limit its uptake by clinicians,” Dr. Kranzler and Dr. Hartwell write.

The study was funded by the Heffter Research Institute and by individual donations from Carey and Claudia Turnbull, Dr. Efrem Nulman, Rodrigo Niño, and Cody Swift. Dr. Bogenschutz reports having received research funds from and serving as a consultant to Mind Medicine, the Multidisciplinary Association for Psychedelic Studies, B. More, AJNA Labs, Beckley Psytech, Journey Colab, and Bright Minds Biosciences. Dr. Kranzler and Dr. Hartwell have reported no relevant financial relationships.

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

Psilocybin paired with psychotherapy is associated with a robust and sustained decrease in drinking among adults with alcohol use disorder (AUD), new research suggests.

Results from the first randomized, placebo-controlled trial of psilocybin for alcohol dependence showed that during the 8 months after first treatment dose, participants who received psilocybin had less than half as many heavy drinking days as their counterparts who received placebo.

In addition, 7 months after the last dose of medication, twice as many psilocybin-treated patients as placebo-treated patients were abstinent.

The effects observed with psilocybin were “considerably larger” than those of currently approved treatments for AUD, senior investigator Michael Bogenschutz, MD, psychiatrist and director of the NYU Langone Center for Psychedelic Medicine, New York, said during an Aug. 24 press briefing.

If the findings hold up in future trials, psilocybin will be a “real breakthrough” in the treatment of the condition, Dr. Bogenschutz said.

The findings were published online in JAMA Psychiatry.

83% reduction in drinking days

The study included 93 adults (mean age, 46 years) with alcohol dependence who consumed an average of seven drinks on the days they drank and had had at least four heavy drinking days during the month prior to treatment.

Of the participants, 48 were randomly assigned to receive two doses of psilocybin, and 45 were assigned to receive an antihistamine (diphenhydramine) placebo. Study medication was administered during 2 day-long sessions at week 4 and week 8.

The participants also received 12 psychotherapy sessions over a 12-week period. All were assessed at intervals from the beginning of the study until 32 weeks after the first medication session.

The primary outcome was percentage of days in which the patient drank heavily during the 32-week period following first medication dose. Heavy drinking was defined as having five or more drinks in a day for a man and four or more drinks in a day for a woman.

The percentage of heavy drinking days during the 32-week period was 9.7% for the psilocybin group and 23.6% for the placebo group, for a mean difference of 13.9% (P = .01).

“Compared to their baseline before the study, after receiving medication, the psilocybin group decreased their heavy drinking days by 83%, while the placebo group reduced their heavy drinking by 51%,” Dr. Bogenschutz reported.

During the last month of follow-up, which was 7 months after the final dose of study medication, 48% of the psilocybin group were entirely abstinent vs. 24% of the placebo group.

“It is remarkable that the effects of psilocybin treatment persisted for 7 months after people received the last dose of medication. This suggests that psilocybin is treating the underlying disorder of alcohol addiction rather than merely treating symptoms,” Dr. Bogenschutz noted.

Total alcohol consumption and problems related to alcohol use were also significantly less in the psilocybin group.

‘Encouraged and hopeful’

Adverse events related to psilocybin were mostly mild, self-limiting, and consistent with other recent trials that evaluated the drug’s effects in various conditions.

However, the current investigators note that they implemented measures to ensure safety, including careful medical and psychiatric screening, therapy, and monitoring that was provided by well-trained therapists, including a licensed psychiatrist. In addition, medications were available to treat acute psychiatric reactions.

A cited limitation of the study was that blinding was not maintained because the average intensity of experience with psilocybin was high, whereas it was low with diphenhydramine.

This difference undermined the masking of treatment such that more than 90% of participants and therapists correctly guessed the treatment assignment.

Another limitation was that objective measures to validate self-reported drinking outcomes were available for only 54% of study participants.

Despite these limitations, the study builds on earlier work by the NYU team that showed that two doses of psilocybin taken over a period of 8 weeks significantly reduced alcohol use and cravings in patients with AUD.

“We’re very encouraged by these findings and hopeful about where they could lead. Personally, it’s been very meaningful and rewarding for me to do this work and inspiring to witness the remarkable recoveries that some of our participants have experienced,” Dr. Bogenschutz told briefing attendees.

Urgent need

The authors of an accompanying editorial note that novel medications for alcohol dependence are “sorely needed. Recent renewed interest in the potential of hallucinogens for treating psychiatric disorders, including AUD, represents a potential move in that direction.”

Henry Kranzler, MD, and Emily Hartwell, PhD, both with the Center for Studies of Addiction, University of Pennsylvania, Philadelphia, write that the new findings “underscore the potential of developing psilocybin as an addition to the alcohol treatment pharmacopeia.”

They question, however, the feasibility of using hallucinogens in routine clinical practice because intensive psychotherapy, such as that provided in this study, requires a significant investment of time and labor.

“Such concomitant therapy, if necessary to realize the therapeutic benefits of psilocybin for treating AUD, could limit its uptake by clinicians,” Dr. Kranzler and Dr. Hartwell write.

The study was funded by the Heffter Research Institute and by individual donations from Carey and Claudia Turnbull, Dr. Efrem Nulman, Rodrigo Niño, and Cody Swift. Dr. Bogenschutz reports having received research funds from and serving as a consultant to Mind Medicine, the Multidisciplinary Association for Psychedelic Studies, B. More, AJNA Labs, Beckley Psytech, Journey Colab, and Bright Minds Biosciences. Dr. Kranzler and Dr. Hartwell have reported no relevant financial relationships.

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

Researchers have identified 72 genes very strongly linked to autism spectrum disorders and more than 250 other genes with a strong link to ASD, according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.

“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”

Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
 

Investigating large cohorts

The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.

In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.

Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.

“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
 

ASD, developmental delay, and schizophrenia

When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.

”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.

The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.

“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
 

Chasing therapy targets by backtracking through genes

The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.

“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”

Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.

“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”

The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.

”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”

The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.

Researchers have identified 72 genes very strongly linked to autism spectrum disorders and more than 250 other genes with a strong link to ASD, according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.

“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”

Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
 

Investigating large cohorts

The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.

In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.

Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.

“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
 

ASD, developmental delay, and schizophrenia

When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.

”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.

The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.

“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
 

Chasing therapy targets by backtracking through genes

The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.

“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”

Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.

“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”

The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.

”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”

The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.

Researchers have identified 72 genes very strongly linked to autism spectrum disorders and more than 250 other genes with a strong link to ASD, according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.

“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”

Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
 

Investigating large cohorts

The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.

In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.

Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.

“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
 

ASD, developmental delay, and schizophrenia

When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.

”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.

The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.

“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
 

Chasing therapy targets by backtracking through genes

The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.

“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”

Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.

“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”

The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.

”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”

The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.

Something about this COVID testing smells fishy

The Chinese have been challenging America’s political and economic hegemony (yes, we did have to look that one up – you’re rude to ask) for some time, but now they’ve gone too far. Are we going to just sit here and let China do something more ridiculous than us in response to COVID? No way!

Alexander Zvir/Pexels

Here’s the deal: The government of the Chinese coastal city of Xiamen has decided that it’s not just the workers on returning fishing boats who have the potential to introduce COVID to the rest of the population. The fish also present a problem. So when the authorities say that everyone needs to be tested before they can enter the city, they mean everyone.

An employee of the municipal ocean development bureau told local media that “all people in Xiamen City need nucleic acid testing, and the fish catches must be tested as well,” according to the Guardian, which also said that “TV news reports showed officials swabbing the mouths of fish and the underside of crabs.”

In the words of George Takei: “Oh my.”

Hold on there a second, George Takei, because we here in the good old US of A have still got Los Angeles, where COVID testing also has taken a nonhuman turn. The LA County public health department recently announced that pets are now eligible for a free SARS-CoV-2 test through veterinarians and other animal care facilities.

“Our goal is to test many different species of animals including wildlife (deer, bats, raccoons), pets (dogs, cats, hamsters, pocket pets), marine mammals (seals), and more,” Veterinary Public Health announced.

Hegemony restored.
 

Not even God could save them from worms

The Dark Ages may not have been as dark and violent as many people think, but there’s no denying that life in medieval Europe kind of sucked. The only real alternative to serfdom was a job with the Catholic Church. Medieval friars, for example, lived in stone buildings, had access to fresh fruits and vegetables, and even had latrines and running water. Luxuries compared with the life of the average peasant.

Cambridge Archaeological Unit

So why then, despite having access to more modern sanitation and amenities, did the friars have so many gut parasites? That’s the question raised by a group of researchers from the University of Cambridge, who conducted a study of 19 medieval friars buried at a local friary (Oh, doesn’t your town have one of those?) and 25 local people buried at a nonreligious cemetery during a similar time period. Of those 19 friars, 11 were infected with worms and parasites, compared with just 8 of 25 townspeople.

This doesn’t make a lot of sense. The friars had a good life by old-time standards: They had basic sanitation down and a solid diet. These things should lead to a healthier population. The problem, the researchers found, is two pronged and a vicious cycle. First off, the friars had plenty of fresh food, but they used human feces to fertilize their produce. There’s a reason modern practice for human waste fertilization is to let the waste compost for 6 months: The waiting period allows the parasites a chance to kindly die off, which prevents reinfection.

Secondly, the friars’ diet of fresh fruits and vegetables mixed together into a salad, while appealing to our modern-day sensibilities, was not a great choice. By comparison, laypeople tended to eat a boiled mishmash of whatever they could find, and while that’s kind of gross, the key here is that their food was cooked. And heat kills parasites. The uncooked salads did no such thing, so the monks ate infected food, expelled infected poop, and grew more infected food with their infected poop.

Once the worms arrived, they never left, making them the worst kind of house guest. Read the room, worms, take your dinner and move on. You don’t have to go home, but you can’t stay here.
 

What’s a shared genotype between friends?

Do you find it hard to tell the difference between Katy Perry and Zooey Deschanel? They look alike, but they’re not related. Or are they? According to new research, people who look and act very similar but are not related may share DNA.

François Brunelle

“Our study provides a rare insight into human likeness by showing that people with extreme look-alike faces share common genotypes, whereas they are discordant at the epigenome and microbiome levels,” senior author Manel Esteller of the Josep Carreras Leukemia Research Institute in Barcelona said in a written statement. “Genomics clusters them together, and the rest sets them apart.”

The Internet has been a great source in being able to find look-alikes. The research team found photos of doppelgangers photographed by François Brunelle, a Canadian artist. Using facial recognition algorithms, the investigators were able to measure likeness between the each pair of look-alikes. The participants also completed a questionnaire about lifestyle and provided a saliva sample.

The results showed that the look-alikes had similar genotypes but different DNA methylation and microbiome landscapes. The look-alikes also seemed to have similarities in weight, height, and behaviors such as smoking, proving that doppelgangers not only look alike but also share common interests.

Next time someone tells you that you look like their best friend Steve, you won’t have to wonder much what Steve is like.
 

The secret to a good relationship? It’s a secret

Strong relationships are built on honesty and trust, right? Being open with your partner and/or friends is usually a good practice for keeping the relationship healthy, but the latest evidence suggests that maybe you shouldn’t share everything.

bilderlounge

According to the first known study on the emotional, behavioral, and relational aspect of consumer behavior, not disclosing certain purchases to your partner can actually be a good thing for the relationship. How? Well, it all has to do with guilt.

In a series of studies, the researchers asked couples about their secret consumptions. The most commonly hidden thing by far was a product (65%).

“We found that 90% of people have recently kept everyday consumer behaviors a secret from a close other – like a friend or spouse – even though they also report that they don’t think their partner would care if they knew about it,” Kelley Gullo Wight, one of the study’s two lead authors, said in a written statement.

Keeping a hidden stash of chocolate produces guilt, which the researchers found to be the key factor, making the perpetrator want to do more in the relationship to ease that sense of betrayal or dishonesty. They called it a “greater relationship investment,” meaning the person is more likely to do a little extra for their partner, like shell out more money for the next anniversary gift or yield to watching their partner’s favorite program.

So don’t feel too bad about that secret Amazon purchase. As long as the other person doesn’t see the box, nobody has to know. Your relationship can only improve.

Something about this COVID testing smells fishy

The Chinese have been challenging America’s political and economic hegemony (yes, we did have to look that one up – you’re rude to ask) for some time, but now they’ve gone too far. Are we going to just sit here and let China do something more ridiculous than us in response to COVID? No way!

Alexander Zvir/Pexels

Here’s the deal: The government of the Chinese coastal city of Xiamen has decided that it’s not just the workers on returning fishing boats who have the potential to introduce COVID to the rest of the population. The fish also present a problem. So when the authorities say that everyone needs to be tested before they can enter the city, they mean everyone.

An employee of the municipal ocean development bureau told local media that “all people in Xiamen City need nucleic acid testing, and the fish catches must be tested as well,” according to the Guardian, which also said that “TV news reports showed officials swabbing the mouths of fish and the underside of crabs.”

In the words of George Takei: “Oh my.”

Hold on there a second, George Takei, because we here in the good old US of A have still got Los Angeles, where COVID testing also has taken a nonhuman turn. The LA County public health department recently announced that pets are now eligible for a free SARS-CoV-2 test through veterinarians and other animal care facilities.

“Our goal is to test many different species of animals including wildlife (deer, bats, raccoons), pets (dogs, cats, hamsters, pocket pets), marine mammals (seals), and more,” Veterinary Public Health announced.

Hegemony restored.
 

Not even God could save them from worms

The Dark Ages may not have been as dark and violent as many people think, but there’s no denying that life in medieval Europe kind of sucked. The only real alternative to serfdom was a job with the Catholic Church. Medieval friars, for example, lived in stone buildings, had access to fresh fruits and vegetables, and even had latrines and running water. Luxuries compared with the life of the average peasant.

Cambridge Archaeological Unit

So why then, despite having access to more modern sanitation and amenities, did the friars have so many gut parasites? That’s the question raised by a group of researchers from the University of Cambridge, who conducted a study of 19 medieval friars buried at a local friary (Oh, doesn’t your town have one of those?) and 25 local people buried at a nonreligious cemetery during a similar time period. Of those 19 friars, 11 were infected with worms and parasites, compared with just 8 of 25 townspeople.

This doesn’t make a lot of sense. The friars had a good life by old-time standards: They had basic sanitation down and a solid diet. These things should lead to a healthier population. The problem, the researchers found, is two pronged and a vicious cycle. First off, the friars had plenty of fresh food, but they used human feces to fertilize their produce. There’s a reason modern practice for human waste fertilization is to let the waste compost for 6 months: The waiting period allows the parasites a chance to kindly die off, which prevents reinfection.

Secondly, the friars’ diet of fresh fruits and vegetables mixed together into a salad, while appealing to our modern-day sensibilities, was not a great choice. By comparison, laypeople tended to eat a boiled mishmash of whatever they could find, and while that’s kind of gross, the key here is that their food was cooked. And heat kills parasites. The uncooked salads did no such thing, so the monks ate infected food, expelled infected poop, and grew more infected food with their infected poop.

Once the worms arrived, they never left, making them the worst kind of house guest. Read the room, worms, take your dinner and move on. You don’t have to go home, but you can’t stay here.
 

What’s a shared genotype between friends?

Do you find it hard to tell the difference between Katy Perry and Zooey Deschanel? They look alike, but they’re not related. Or are they? According to new research, people who look and act very similar but are not related may share DNA.

François Brunelle

“Our study provides a rare insight into human likeness by showing that people with extreme look-alike faces share common genotypes, whereas they are discordant at the epigenome and microbiome levels,” senior author Manel Esteller of the Josep Carreras Leukemia Research Institute in Barcelona said in a written statement. “Genomics clusters them together, and the rest sets them apart.”

The Internet has been a great source in being able to find look-alikes. The research team found photos of doppelgangers photographed by François Brunelle, a Canadian artist. Using facial recognition algorithms, the investigators were able to measure likeness between the each pair of look-alikes. The participants also completed a questionnaire about lifestyle and provided a saliva sample.

The results showed that the look-alikes had similar genotypes but different DNA methylation and microbiome landscapes. The look-alikes also seemed to have similarities in weight, height, and behaviors such as smoking, proving that doppelgangers not only look alike but also share common interests.

Next time someone tells you that you look like their best friend Steve, you won’t have to wonder much what Steve is like.
 

The secret to a good relationship? It’s a secret

Strong relationships are built on honesty and trust, right? Being open with your partner and/or friends is usually a good practice for keeping the relationship healthy, but the latest evidence suggests that maybe you shouldn’t share everything.

bilderlounge

According to the first known study on the emotional, behavioral, and relational aspect of consumer behavior, not disclosing certain purchases to your partner can actually be a good thing for the relationship. How? Well, it all has to do with guilt.

In a series of studies, the researchers asked couples about their secret consumptions. The most commonly hidden thing by far was a product (65%).

“We found that 90% of people have recently kept everyday consumer behaviors a secret from a close other – like a friend or spouse – even though they also report that they don’t think their partner would care if they knew about it,” Kelley Gullo Wight, one of the study’s two lead authors, said in a written statement.

Keeping a hidden stash of chocolate produces guilt, which the researchers found to be the key factor, making the perpetrator want to do more in the relationship to ease that sense of betrayal or dishonesty. They called it a “greater relationship investment,” meaning the person is more likely to do a little extra for their partner, like shell out more money for the next anniversary gift or yield to watching their partner’s favorite program.

So don’t feel too bad about that secret Amazon purchase. As long as the other person doesn’t see the box, nobody has to know. Your relationship can only improve.

Something about this COVID testing smells fishy

The Chinese have been challenging America’s political and economic hegemony (yes, we did have to look that one up – you’re rude to ask) for some time, but now they’ve gone too far. Are we going to just sit here and let China do something more ridiculous than us in response to COVID? No way!

Alexander Zvir/Pexels

Here’s the deal: The government of the Chinese coastal city of Xiamen has decided that it’s not just the workers on returning fishing boats who have the potential to introduce COVID to the rest of the population. The fish also present a problem. So when the authorities say that everyone needs to be tested before they can enter the city, they mean everyone.

An employee of the municipal ocean development bureau told local media that “all people in Xiamen City need nucleic acid testing, and the fish catches must be tested as well,” according to the Guardian, which also said that “TV news reports showed officials swabbing the mouths of fish and the underside of crabs.”

In the words of George Takei: “Oh my.”

Hold on there a second, George Takei, because we here in the good old US of A have still got Los Angeles, where COVID testing also has taken a nonhuman turn. The LA County public health department recently announced that pets are now eligible for a free SARS-CoV-2 test through veterinarians and other animal care facilities.

“Our goal is to test many different species of animals including wildlife (deer, bats, raccoons), pets (dogs, cats, hamsters, pocket pets), marine mammals (seals), and more,” Veterinary Public Health announced.

Hegemony restored.
 

Not even God could save them from worms

The Dark Ages may not have been as dark and violent as many people think, but there’s no denying that life in medieval Europe kind of sucked. The only real alternative to serfdom was a job with the Catholic Church. Medieval friars, for example, lived in stone buildings, had access to fresh fruits and vegetables, and even had latrines and running water. Luxuries compared with the life of the average peasant.

Cambridge Archaeological Unit

So why then, despite having access to more modern sanitation and amenities, did the friars have so many gut parasites? That’s the question raised by a group of researchers from the University of Cambridge, who conducted a study of 19 medieval friars buried at a local friary (Oh, doesn’t your town have one of those?) and 25 local people buried at a nonreligious cemetery during a similar time period. Of those 19 friars, 11 were infected with worms and parasites, compared with just 8 of 25 townspeople.

This doesn’t make a lot of sense. The friars had a good life by old-time standards: They had basic sanitation down and a solid diet. These things should lead to a healthier population. The problem, the researchers found, is two pronged and a vicious cycle. First off, the friars had plenty of fresh food, but they used human feces to fertilize their produce. There’s a reason modern practice for human waste fertilization is to let the waste compost for 6 months: The waiting period allows the parasites a chance to kindly die off, which prevents reinfection.

Secondly, the friars’ diet of fresh fruits and vegetables mixed together into a salad, while appealing to our modern-day sensibilities, was not a great choice. By comparison, laypeople tended to eat a boiled mishmash of whatever they could find, and while that’s kind of gross, the key here is that their food was cooked. And heat kills parasites. The uncooked salads did no such thing, so the monks ate infected food, expelled infected poop, and grew more infected food with their infected poop.

Once the worms arrived, they never left, making them the worst kind of house guest. Read the room, worms, take your dinner and move on. You don’t have to go home, but you can’t stay here.
 

What’s a shared genotype between friends?

Do you find it hard to tell the difference between Katy Perry and Zooey Deschanel? They look alike, but they’re not related. Or are they? According to new research, people who look and act very similar but are not related may share DNA.

François Brunelle

“Our study provides a rare insight into human likeness by showing that people with extreme look-alike faces share common genotypes, whereas they are discordant at the epigenome and microbiome levels,” senior author Manel Esteller of the Josep Carreras Leukemia Research Institute in Barcelona said in a written statement. “Genomics clusters them together, and the rest sets them apart.”

The Internet has been a great source in being able to find look-alikes. The research team found photos of doppelgangers photographed by François Brunelle, a Canadian artist. Using facial recognition algorithms, the investigators were able to measure likeness between the each pair of look-alikes. The participants also completed a questionnaire about lifestyle and provided a saliva sample.

The results showed that the look-alikes had similar genotypes but different DNA methylation and microbiome landscapes. The look-alikes also seemed to have similarities in weight, height, and behaviors such as smoking, proving that doppelgangers not only look alike but also share common interests.

Next time someone tells you that you look like their best friend Steve, you won’t have to wonder much what Steve is like.
 

The secret to a good relationship? It’s a secret

Strong relationships are built on honesty and trust, right? Being open with your partner and/or friends is usually a good practice for keeping the relationship healthy, but the latest evidence suggests that maybe you shouldn’t share everything.

bilderlounge

According to the first known study on the emotional, behavioral, and relational aspect of consumer behavior, not disclosing certain purchases to your partner can actually be a good thing for the relationship. How? Well, it all has to do with guilt.

In a series of studies, the researchers asked couples about their secret consumptions. The most commonly hidden thing by far was a product (65%).

“We found that 90% of people have recently kept everyday consumer behaviors a secret from a close other – like a friend or spouse – even though they also report that they don’t think their partner would care if they knew about it,” Kelley Gullo Wight, one of the study’s two lead authors, said in a written statement.

Keeping a hidden stash of chocolate produces guilt, which the researchers found to be the key factor, making the perpetrator want to do more in the relationship to ease that sense of betrayal or dishonesty. They called it a “greater relationship investment,” meaning the person is more likely to do a little extra for their partner, like shell out more money for the next anniversary gift or yield to watching their partner’s favorite program.

So don’t feel too bad about that secret Amazon purchase. As long as the other person doesn’t see the box, nobody has to know. Your relationship can only improve.

Transcranial direct current stimulation (tDCS) using a home-based device can help improve attention in adults with attention-deficit/hyperactivity disorder who are not taking stimulants, new research suggests.

Results from the sham-controlled trial also showed that the tDCS treatment was both safe and well tolerated.

Overall, the findings suggest that the device could be a nondrug alternative for treating this patient population, Douglas Teixeira Leffa, MD, PhD, department of psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, and colleagues note.

“This is particularly relevant since a vast body of literature describes low long-term adherence rates and persistence to pharmacological treatment in patients with ADHD,” they write.

The findings were published online in JAMA Psychiatry.
 

Avoiding office visits

A noninvasive technique that is easy to use and relatively inexpensive, tDCS involves applying a low-intensity current over the scalp to modulate cortical excitability and induce neuroplasticity. Home-use tDCS devices, which avoid the need for daily office visits for stimulation sessions, have been validated in previous clinical samples.

The current study included 64 adults with ADHD who are not taking stimulants. They had moderate or severe symptoms of inattention, with an inattention score of 21 or higher on the clinician-administered Adult ADHD Self-Report Scale version 1.1 (CASRS).

The CASRS includes nine questions related to inattention symptoms (CASRS-I) and nine related to hyperactivity-impulsivity symptoms (CASRS-HI). The score can vary from 0 to 36 for each domain, with higher scores indicating increased symptoms.

Researchers randomly assigned participants to receive either active or sham stimulation.

The tDCS device used in the study delivered a current with 35-cm² electrodes (7 cm by 5 cm). The anodal and cathodal electrodes were positioned corresponding to the right and left dorsolateral prefrontal cortex (DLPFC), respectively.

The investigators note that decreased activation in the right DLPFC has been reported before in patients with ADHD during tasks that require attention.

After learning to use the device, participants underwent 30-minute daily sessions of tDCS (2-mA direct constant current) for 4 weeks for a total of 28 sessions.

Devices programmed for sham treatment delivered a 30-second ramp-up (0-2 mA) stimulation followed by a 30-second ramp-down (2-0 mA) at the beginning, middle, and end of the application. This mimicked the tactile sensations reported with tDCS and has been shown to be a reliable sham protocol.

Participants were encouraged to perform the stimulation sessions at the same time of day. To improve adherence, they received daily text message reminders.

Nine patients discontinued treatment, two in the sham group and seven in the active group. However, patients who finished the trial completed a mean 25 of 28 sessions.
 

Window of opportunity?

The mean inattention score on CASRS-I at week 4, the primary outcome, was 18.88 in the active tDCS group vs. 23.63 in the sham tDCS group. There was a statistically significant treatment by time interaction for CASRS-I (beta interaction, –3.18; 95% confidence interval, –4.60 to –1.75; P < .001), showing decreased inattention symptoms in the active vs. sham groups.

The estimated Cohen’s d was 1.23 (95% CI, .67-1.78), indicating at least a moderate effect. This effect was similar to that reported with trigeminal nerve stimulation (TNS), the first approved device-based therapy for ADHD, and to that of atomoxetine, the second-line treatment for ADHD, the researchers note.

About one-third of patients (34.3%) in the active tDCS group achieved a 30% reduction in CASRS-I score, compared with 6.2% in the sham tDCS group.

There was no statistically significant difference in the secondary outcome of hyperactivity-impulsivity symptoms evaluated with the CASRS-HI. This may be because hyperactivity-impulsivity in ADHD is associated with a hypoactivation in the right inferior frontal cortex rather than the right DLPFC, the investigators write.

There were also no significant group differences in other secondary outcomes, including depression, anxiety, and executive function.

Adverse events (AE) were mostly mild and included skin redness and scalp burn. There were no severe or serious AEs.

Using a home-based tDCS device allows for considerably more sessions, with 28 being the highest number so far applied to patients with ADHD. This, the researchers note, is important because evidence suggests increased efficacy of tDCS with extended periods of treatment.

The home-based device “opens a new window of opportunity, especially for participants who live in geographically remote areas or have physical or cognitive disabilities that may hinder access to clinical centers,” they write.

Although a study limitation was the relatively high dropout rate in the active group, which might bias interpretation of the findings, only two of seven dropouts in the active group left because of an AE, the investigators note.

Patients received training in using the device, but there was no remote monitoring of sessions. In addition, the study population, which was relatively homogeneous with participants having no moderate to severe symptoms of depression or anxiety, differed from the usual patients with ADHD who are treated in clinical centers, the researchers point out.

As well, the study included only patients not taking pharmacologic treatment for ADHD – so the findings might not be generalizable to other patients, they add.
 

‘Just a first step’

Commenting on the study, Mark George, MD, distinguished professor of psychiatry, radiology, and neurology, Medical University of South Carolina, Charleston, noted that although this was a single-center study with a relatively small sample size, it is still important.

Showing it is possible to do high-quality tDCS studies at home “is a huge advance,” said Dr. George, who was not involved with the research.

“Home treatment is cheaper and easier for patients and allows many people to get treatment who would not be able to make it to the clinic daily for treatment,” he added.

He noted the study showed “a clear improvement in ADHD,” which is important because better treatments are needed.

However, he cautioned that this is “just a first step” and more studies are needed. For example, he said, it is not clear whether improvements persist and if patients need to self-treat forever, as they would with a medication.

Dr. George also noted that although the study used “a pioneering research device” with several safety features, many home-based tDCS devices on the market do not have those.

“I don’t advise patients to do this now. Further studies are needed for FDA approval and general public use,” he said.

The study was funded by the National Council for Scientific and Technological Development, the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, the Brain & Behavior Research Foundation, Fundação de Amparo à Pesquisa do Estado de São Paulo, and the Brazilian Innovation Agency. Dr. Leffa reported having received grants from the Brain & Behavior Research Foundation, the National Council for Scientific and Technological Development, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul during the conduction of the study. Dr. George reported no relevant financial relationships.

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

Transcranial direct current stimulation (tDCS) using a home-based device can help improve attention in adults with attention-deficit/hyperactivity disorder who are not taking stimulants, new research suggests.

Results from the sham-controlled trial also showed that the tDCS treatment was both safe and well tolerated.

Overall, the findings suggest that the device could be a nondrug alternative for treating this patient population, Douglas Teixeira Leffa, MD, PhD, department of psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, and colleagues note.

“This is particularly relevant since a vast body of literature describes low long-term adherence rates and persistence to pharmacological treatment in patients with ADHD,” they write.

The findings were published online in JAMA Psychiatry.
 

Avoiding office visits

A noninvasive technique that is easy to use and relatively inexpensive, tDCS involves applying a low-intensity current over the scalp to modulate cortical excitability and induce neuroplasticity. Home-use tDCS devices, which avoid the need for daily office visits for stimulation sessions, have been validated in previous clinical samples.

The current study included 64 adults with ADHD who are not taking stimulants. They had moderate or severe symptoms of inattention, with an inattention score of 21 or higher on the clinician-administered Adult ADHD Self-Report Scale version 1.1 (CASRS).

The CASRS includes nine questions related to inattention symptoms (CASRS-I) and nine related to hyperactivity-impulsivity symptoms (CASRS-HI). The score can vary from 0 to 36 for each domain, with higher scores indicating increased symptoms.

Researchers randomly assigned participants to receive either active or sham stimulation.

The tDCS device used in the study delivered a current with 35-cm² electrodes (7 cm by 5 cm). The anodal and cathodal electrodes were positioned corresponding to the right and left dorsolateral prefrontal cortex (DLPFC), respectively.

The investigators note that decreased activation in the right DLPFC has been reported before in patients with ADHD during tasks that require attention.

After learning to use the device, participants underwent 30-minute daily sessions of tDCS (2-mA direct constant current) for 4 weeks for a total of 28 sessions.

Devices programmed for sham treatment delivered a 30-second ramp-up (0-2 mA) stimulation followed by a 30-second ramp-down (2-0 mA) at the beginning, middle, and end of the application. This mimicked the tactile sensations reported with tDCS and has been shown to be a reliable sham protocol.

Participants were encouraged to perform the stimulation sessions at the same time of day. To improve adherence, they received daily text message reminders.

Nine patients discontinued treatment, two in the sham group and seven in the active group. However, patients who finished the trial completed a mean 25 of 28 sessions.
 

Window of opportunity?

The mean inattention score on CASRS-I at week 4, the primary outcome, was 18.88 in the active tDCS group vs. 23.63 in the sham tDCS group. There was a statistically significant treatment by time interaction for CASRS-I (beta interaction, –3.18; 95% confidence interval, –4.60 to –1.75; P < .001), showing decreased inattention symptoms in the active vs. sham groups.

The estimated Cohen’s d was 1.23 (95% CI, .67-1.78), indicating at least a moderate effect. This effect was similar to that reported with trigeminal nerve stimulation (TNS), the first approved device-based therapy for ADHD, and to that of atomoxetine, the second-line treatment for ADHD, the researchers note.

About one-third of patients (34.3%) in the active tDCS group achieved a 30% reduction in CASRS-I score, compared with 6.2% in the sham tDCS group.

There was no statistically significant difference in the secondary outcome of hyperactivity-impulsivity symptoms evaluated with the CASRS-HI. This may be because hyperactivity-impulsivity in ADHD is associated with a hypoactivation in the right inferior frontal cortex rather than the right DLPFC, the investigators write.

There were also no significant group differences in other secondary outcomes, including depression, anxiety, and executive function.

Adverse events (AE) were mostly mild and included skin redness and scalp burn. There were no severe or serious AEs.

Using a home-based tDCS device allows for considerably more sessions, with 28 being the highest number so far applied to patients with ADHD. This, the researchers note, is important because evidence suggests increased efficacy of tDCS with extended periods of treatment.

The home-based device “opens a new window of opportunity, especially for participants who live in geographically remote areas or have physical or cognitive disabilities that may hinder access to clinical centers,” they write.

Although a study limitation was the relatively high dropout rate in the active group, which might bias interpretation of the findings, only two of seven dropouts in the active group left because of an AE, the investigators note.

Patients received training in using the device, but there was no remote monitoring of sessions. In addition, the study population, which was relatively homogeneous with participants having no moderate to severe symptoms of depression or anxiety, differed from the usual patients with ADHD who are treated in clinical centers, the researchers point out.

As well, the study included only patients not taking pharmacologic treatment for ADHD – so the findings might not be generalizable to other patients, they add.
 

‘Just a first step’

Commenting on the study, Mark George, MD, distinguished professor of psychiatry, radiology, and neurology, Medical University of South Carolina, Charleston, noted that although this was a single-center study with a relatively small sample size, it is still important.

Showing it is possible to do high-quality tDCS studies at home “is a huge advance,” said Dr. George, who was not involved with the research.

“Home treatment is cheaper and easier for patients and allows many people to get treatment who would not be able to make it to the clinic daily for treatment,” he added.

He noted the study showed “a clear improvement in ADHD,” which is important because better treatments are needed.

However, he cautioned that this is “just a first step” and more studies are needed. For example, he said, it is not clear whether improvements persist and if patients need to self-treat forever, as they would with a medication.

Dr. George also noted that although the study used “a pioneering research device” with several safety features, many home-based tDCS devices on the market do not have those.

“I don’t advise patients to do this now. Further studies are needed for FDA approval and general public use,” he said.

The study was funded by the National Council for Scientific and Technological Development, the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, the Brain & Behavior Research Foundation, Fundação de Amparo à Pesquisa do Estado de São Paulo, and the Brazilian Innovation Agency. Dr. Leffa reported having received grants from the Brain & Behavior Research Foundation, the National Council for Scientific and Technological Development, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul during the conduction of the study. Dr. George reported no relevant financial relationships.

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

Transcranial direct current stimulation (tDCS) using a home-based device can help improve attention in adults with attention-deficit/hyperactivity disorder who are not taking stimulants, new research suggests.

Results from the sham-controlled trial also showed that the tDCS treatment was both safe and well tolerated.

Overall, the findings suggest that the device could be a nondrug alternative for treating this patient population, Douglas Teixeira Leffa, MD, PhD, department of psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, and colleagues note.

“This is particularly relevant since a vast body of literature describes low long-term adherence rates and persistence to pharmacological treatment in patients with ADHD,” they write.

The findings were published online in JAMA Psychiatry.
 

Avoiding office visits

A noninvasive technique that is easy to use and relatively inexpensive, tDCS involves applying a low-intensity current over the scalp to modulate cortical excitability and induce neuroplasticity. Home-use tDCS devices, which avoid the need for daily office visits for stimulation sessions, have been validated in previous clinical samples.

The current study included 64 adults with ADHD who are not taking stimulants. They had moderate or severe symptoms of inattention, with an inattention score of 21 or higher on the clinician-administered Adult ADHD Self-Report Scale version 1.1 (CASRS).

The CASRS includes nine questions related to inattention symptoms (CASRS-I) and nine related to hyperactivity-impulsivity symptoms (CASRS-HI). The score can vary from 0 to 36 for each domain, with higher scores indicating increased symptoms.

Researchers randomly assigned participants to receive either active or sham stimulation.

The tDCS device used in the study delivered a current with 35-cm² electrodes (7 cm by 5 cm). The anodal and cathodal electrodes were positioned corresponding to the right and left dorsolateral prefrontal cortex (DLPFC), respectively.

The investigators note that decreased activation in the right DLPFC has been reported before in patients with ADHD during tasks that require attention.

After learning to use the device, participants underwent 30-minute daily sessions of tDCS (2-mA direct constant current) for 4 weeks for a total of 28 sessions.

Devices programmed for sham treatment delivered a 30-second ramp-up (0-2 mA) stimulation followed by a 30-second ramp-down (2-0 mA) at the beginning, middle, and end of the application. This mimicked the tactile sensations reported with tDCS and has been shown to be a reliable sham protocol.

Participants were encouraged to perform the stimulation sessions at the same time of day. To improve adherence, they received daily text message reminders.

Nine patients discontinued treatment, two in the sham group and seven in the active group. However, patients who finished the trial completed a mean 25 of 28 sessions.
 

Window of opportunity?

The mean inattention score on CASRS-I at week 4, the primary outcome, was 18.88 in the active tDCS group vs. 23.63 in the sham tDCS group. There was a statistically significant treatment by time interaction for CASRS-I (beta interaction, –3.18; 95% confidence interval, –4.60 to –1.75; P < .001), showing decreased inattention symptoms in the active vs. sham groups.

The estimated Cohen’s d was 1.23 (95% CI, .67-1.78), indicating at least a moderate effect. This effect was similar to that reported with trigeminal nerve stimulation (TNS), the first approved device-based therapy for ADHD, and to that of atomoxetine, the second-line treatment for ADHD, the researchers note.

About one-third of patients (34.3%) in the active tDCS group achieved a 30% reduction in CASRS-I score, compared with 6.2% in the sham tDCS group.

There was no statistically significant difference in the secondary outcome of hyperactivity-impulsivity symptoms evaluated with the CASRS-HI. This may be because hyperactivity-impulsivity in ADHD is associated with a hypoactivation in the right inferior frontal cortex rather than the right DLPFC, the investigators write.

There were also no significant group differences in other secondary outcomes, including depression, anxiety, and executive function.

Adverse events (AE) were mostly mild and included skin redness and scalp burn. There were no severe or serious AEs.

Using a home-based tDCS device allows for considerably more sessions, with 28 being the highest number so far applied to patients with ADHD. This, the researchers note, is important because evidence suggests increased efficacy of tDCS with extended periods of treatment.

The home-based device “opens a new window of opportunity, especially for participants who live in geographically remote areas or have physical or cognitive disabilities that may hinder access to clinical centers,” they write.

Although a study limitation was the relatively high dropout rate in the active group, which might bias interpretation of the findings, only two of seven dropouts in the active group left because of an AE, the investigators note.

Patients received training in using the device, but there was no remote monitoring of sessions. In addition, the study population, which was relatively homogeneous with participants having no moderate to severe symptoms of depression or anxiety, differed from the usual patients with ADHD who are treated in clinical centers, the researchers point out.

As well, the study included only patients not taking pharmacologic treatment for ADHD – so the findings might not be generalizable to other patients, they add.
 

‘Just a first step’

Commenting on the study, Mark George, MD, distinguished professor of psychiatry, radiology, and neurology, Medical University of South Carolina, Charleston, noted that although this was a single-center study with a relatively small sample size, it is still important.

Showing it is possible to do high-quality tDCS studies at home “is a huge advance,” said Dr. George, who was not involved with the research.

“Home treatment is cheaper and easier for patients and allows many people to get treatment who would not be able to make it to the clinic daily for treatment,” he added.

He noted the study showed “a clear improvement in ADHD,” which is important because better treatments are needed.

However, he cautioned that this is “just a first step” and more studies are needed. For example, he said, it is not clear whether improvements persist and if patients need to self-treat forever, as they would with a medication.

Dr. George also noted that although the study used “a pioneering research device” with several safety features, many home-based tDCS devices on the market do not have those.

“I don’t advise patients to do this now. Further studies are needed for FDA approval and general public use,” he said.

The study was funded by the National Council for Scientific and Technological Development, the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, the Brain & Behavior Research Foundation, Fundação de Amparo à Pesquisa do Estado de São Paulo, and the Brazilian Innovation Agency. Dr. Leffa reported having received grants from the Brain & Behavior Research Foundation, the National Council for Scientific and Technological Development, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul during the conduction of the study. Dr. George reported no relevant financial relationships.

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

Thursday night

It was 9 o’clock at night when my phone rang. I didn’t recognize the number but decided to answer it anyway. It was my doctor.

“Chase, I got your labs back and you have a critically low level. I spoke with someone at the hospital, I think I know what is happening, but I need you to go to the pharmacy right now and get a medicine.” She explained further and as I listened electric currents ran through my thighs until I could barely feel my legs.

“I’m so sorry, Chase. I missed it. It was low the last time we did your labs 9 months ago, and I missed it.”

In disbelief, I continued to listen as she instructed me about the next steps I was to take and prepared me for what was to come the next day.

“If you notice any changes overnight, go straight to the ED.”

My chest tingled and I could barely breathe. My mind struggled to comprehend what was happening. I looked at my husband sitting close by on the couch. He looked concerned. I tuned back in and heard her say: “Is your husband there? Can I talk to him?”

“Yes,” is all I could manage, and I handed him the phone. I sat while he listened and asked his questions. My breathing came back under my control, my legs felt wiry, and restlessness set in. “I have to get out of here,” I thought. “I have to go and pick up this medicine.”
 

Monday afternoon

I am sitting across from a PGY3 resident I have been treating since his intern year, as part of his treatment plan for managing a chronic mental illness that began in medical school. Earlier in the day, I received an urgent message from him requesting an emergency appointment.

Within a few minutes of sitting down, the story from his weekend call shift tumbled out of him. His speech became pressured, and his eyes welled with tears as he recounted in detail the steps he had taken to care for a very sick patient overnight.

“I missed it.” The dam broke and he sat sobbing in front of me, his body trembling.

I sat silently across from him. Willing him to breathe.

In time, his breathing came back under his control, and he slowly regained his composure. He continued: “I got the imaging, and I missed a bleed.”
 

Failure and shame

I can recall memorable moments from my training when I came to understand that what I initially perceived to be a mistake was instead part of the work. An example from our practice involves a patient whom I was comanaging with her primary care provider (PCP). She was not doing well following a critical work event. When I met with her after the event, she admitted having thoughts of suicide, refused a voluntary inpatient admission, and would not have met criteria for an involuntary admission. My hands were tied.

Together we created a plan to keep her safe, which included paging her PCP after hours if needed. I told her PCP before leaving that night that he might hear from her and that if she reached out, she would require hospitalization.

I arrived at work the following day, and her PCP shared with me that our patient had overdosed on medication, paged him, and was admitted to the unit.

He seemed forlorn.

I was both relieved by the news and confused by his reaction. I had hoped that she would choose a higher level of care than what we could provide her as an outpatient. I said: “This is good. She followed the plan.”

Her overdose was, of course, not part of the plan. She was struggling with several internal conflicts, including having mixed feelings about coming into the hospital; but, when the critical moment happened and she was faced with a decision to call for help or possibly die, she chose to call her PCP and have him paged as we had talked about.

I looked at her PCP. “You helped get her to where she needed to be.”

In the years of working side by side with medically trained colleagues, I have time and again needed to reframe for them that what they perceive to be a “failure” or a “crisis” is often a catalyst for change. The patient I comanaged with the PCP was a highly skilled caregiver and, as such, had been having a hard time asking for help. The hospitalization that her PCP facilitated allowed her to receive the care she needed and created an opportunity for family and friends to show up for her. Their support fed her, and she only made gains from that point on.

My training had taught me that respecting a patient’s autonomy was of the utmost importance. This instills confidence in patients as the authority in their lives. For a clinician to do this, a certain amount of helplessness must be tolerated. As I became better at identifying these moments of helplessness, feelings of failure and shame transformed.
 

Medical error

Sitting across from the PGY3 resident who I had met with weekly for the past 3 years, I thought about his error.

I thought about my phone call 4 nights earlier. My doctor was called at home by a lab technician, who never met their patients but was simply following protocol and alerted my doctor to the worsening number that she should have been aware of 9 months earlier.

Just like my doctor’s lapse of attention, my patient’s error was not a moment of helplessness to be tolerated. These were mistakes, and there was no way around it.

“People make mistakes.” I said simply.

We sat silently for a time.

I don’t remember who broke the silence. The conversation that followed was centered on our humanity and our capability for both compassion and fallibility. Afterward, I wondered who my doctor confided in and hoped she had a similar conversation.

Dr. Levesque is a clinical psychologist and clinical assistant professor of psychiatry at the Geisel School of Medicine at Dartmouth, Hanover, N.H., where she also serves on the Committee for a Respectful Learning Environment.

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

Thursday night

It was 9 o’clock at night when my phone rang. I didn’t recognize the number but decided to answer it anyway. It was my doctor.

“Chase, I got your labs back and you have a critically low level. I spoke with someone at the hospital, I think I know what is happening, but I need you to go to the pharmacy right now and get a medicine.” She explained further and as I listened electric currents ran through my thighs until I could barely feel my legs.

“I’m so sorry, Chase. I missed it. It was low the last time we did your labs 9 months ago, and I missed it.”

In disbelief, I continued to listen as she instructed me about the next steps I was to take and prepared me for what was to come the next day.

“If you notice any changes overnight, go straight to the ED.”

My chest tingled and I could barely breathe. My mind struggled to comprehend what was happening. I looked at my husband sitting close by on the couch. He looked concerned. I tuned back in and heard her say: “Is your husband there? Can I talk to him?”

“Yes,” is all I could manage, and I handed him the phone. I sat while he listened and asked his questions. My breathing came back under my control, my legs felt wiry, and restlessness set in. “I have to get out of here,” I thought. “I have to go and pick up this medicine.”
 

Monday afternoon

I am sitting across from a PGY3 resident I have been treating since his intern year, as part of his treatment plan for managing a chronic mental illness that began in medical school. Earlier in the day, I received an urgent message from him requesting an emergency appointment.

Within a few minutes of sitting down, the story from his weekend call shift tumbled out of him. His speech became pressured, and his eyes welled with tears as he recounted in detail the steps he had taken to care for a very sick patient overnight.

“I missed it.” The dam broke and he sat sobbing in front of me, his body trembling.

I sat silently across from him. Willing him to breathe.

In time, his breathing came back under his control, and he slowly regained his composure. He continued: “I got the imaging, and I missed a bleed.”
 

Failure and shame

I can recall memorable moments from my training when I came to understand that what I initially perceived to be a mistake was instead part of the work. An example from our practice involves a patient whom I was comanaging with her primary care provider (PCP). She was not doing well following a critical work event. When I met with her after the event, she admitted having thoughts of suicide, refused a voluntary inpatient admission, and would not have met criteria for an involuntary admission. My hands were tied.

Together we created a plan to keep her safe, which included paging her PCP after hours if needed. I told her PCP before leaving that night that he might hear from her and that if she reached out, she would require hospitalization.

I arrived at work the following day, and her PCP shared with me that our patient had overdosed on medication, paged him, and was admitted to the unit.

He seemed forlorn.

I was both relieved by the news and confused by his reaction. I had hoped that she would choose a higher level of care than what we could provide her as an outpatient. I said: “This is good. She followed the plan.”

Her overdose was, of course, not part of the plan. She was struggling with several internal conflicts, including having mixed feelings about coming into the hospital; but, when the critical moment happened and she was faced with a decision to call for help or possibly die, she chose to call her PCP and have him paged as we had talked about.

I looked at her PCP. “You helped get her to where she needed to be.”

In the years of working side by side with medically trained colleagues, I have time and again needed to reframe for them that what they perceive to be a “failure” or a “crisis” is often a catalyst for change. The patient I comanaged with the PCP was a highly skilled caregiver and, as such, had been having a hard time asking for help. The hospitalization that her PCP facilitated allowed her to receive the care she needed and created an opportunity for family and friends to show up for her. Their support fed her, and she only made gains from that point on.

My training had taught me that respecting a patient’s autonomy was of the utmost importance. This instills confidence in patients as the authority in their lives. For a clinician to do this, a certain amount of helplessness must be tolerated. As I became better at identifying these moments of helplessness, feelings of failure and shame transformed.
 

Medical error

Sitting across from the PGY3 resident who I had met with weekly for the past 3 years, I thought about his error.

I thought about my phone call 4 nights earlier. My doctor was called at home by a lab technician, who never met their patients but was simply following protocol and alerted my doctor to the worsening number that she should have been aware of 9 months earlier.

Just like my doctor’s lapse of attention, my patient’s error was not a moment of helplessness to be tolerated. These were mistakes, and there was no way around it.

“People make mistakes.” I said simply.

We sat silently for a time.

I don’t remember who broke the silence. The conversation that followed was centered on our humanity and our capability for both compassion and fallibility. Afterward, I wondered who my doctor confided in and hoped she had a similar conversation.

Dr. Levesque is a clinical psychologist and clinical assistant professor of psychiatry at the Geisel School of Medicine at Dartmouth, Hanover, N.H., where she also serves on the Committee for a Respectful Learning Environment.

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

Thursday night

It was 9 o’clock at night when my phone rang. I didn’t recognize the number but decided to answer it anyway. It was my doctor.

“Chase, I got your labs back and you have a critically low level. I spoke with someone at the hospital, I think I know what is happening, but I need you to go to the pharmacy right now and get a medicine.” She explained further and as I listened electric currents ran through my thighs until I could barely feel my legs.

“I’m so sorry, Chase. I missed it. It was low the last time we did your labs 9 months ago, and I missed it.”

In disbelief, I continued to listen as she instructed me about the next steps I was to take and prepared me for what was to come the next day.

“If you notice any changes overnight, go straight to the ED.”

My chest tingled and I could barely breathe. My mind struggled to comprehend what was happening. I looked at my husband sitting close by on the couch. He looked concerned. I tuned back in and heard her say: “Is your husband there? Can I talk to him?”

“Yes,” is all I could manage, and I handed him the phone. I sat while he listened and asked his questions. My breathing came back under my control, my legs felt wiry, and restlessness set in. “I have to get out of here,” I thought. “I have to go and pick up this medicine.”
 

Monday afternoon

I am sitting across from a PGY3 resident I have been treating since his intern year, as part of his treatment plan for managing a chronic mental illness that began in medical school. Earlier in the day, I received an urgent message from him requesting an emergency appointment.

Within a few minutes of sitting down, the story from his weekend call shift tumbled out of him. His speech became pressured, and his eyes welled with tears as he recounted in detail the steps he had taken to care for a very sick patient overnight.

“I missed it.” The dam broke and he sat sobbing in front of me, his body trembling.

I sat silently across from him. Willing him to breathe.

In time, his breathing came back under his control, and he slowly regained his composure. He continued: “I got the imaging, and I missed a bleed.”
 

Failure and shame

I can recall memorable moments from my training when I came to understand that what I initially perceived to be a mistake was instead part of the work. An example from our practice involves a patient whom I was comanaging with her primary care provider (PCP). She was not doing well following a critical work event. When I met with her after the event, she admitted having thoughts of suicide, refused a voluntary inpatient admission, and would not have met criteria for an involuntary admission. My hands were tied.

Together we created a plan to keep her safe, which included paging her PCP after hours if needed. I told her PCP before leaving that night that he might hear from her and that if she reached out, she would require hospitalization.

I arrived at work the following day, and her PCP shared with me that our patient had overdosed on medication, paged him, and was admitted to the unit.

He seemed forlorn.

I was both relieved by the news and confused by his reaction. I had hoped that she would choose a higher level of care than what we could provide her as an outpatient. I said: “This is good. She followed the plan.”

Her overdose was, of course, not part of the plan. She was struggling with several internal conflicts, including having mixed feelings about coming into the hospital; but, when the critical moment happened and she was faced with a decision to call for help or possibly die, she chose to call her PCP and have him paged as we had talked about.

I looked at her PCP. “You helped get her to where she needed to be.”

In the years of working side by side with medically trained colleagues, I have time and again needed to reframe for them that what they perceive to be a “failure” or a “crisis” is often a catalyst for change. The patient I comanaged with the PCP was a highly skilled caregiver and, as such, had been having a hard time asking for help. The hospitalization that her PCP facilitated allowed her to receive the care she needed and created an opportunity for family and friends to show up for her. Their support fed her, and she only made gains from that point on.

My training had taught me that respecting a patient’s autonomy was of the utmost importance. This instills confidence in patients as the authority in their lives. For a clinician to do this, a certain amount of helplessness must be tolerated. As I became better at identifying these moments of helplessness, feelings of failure and shame transformed.
 

Medical error

Sitting across from the PGY3 resident who I had met with weekly for the past 3 years, I thought about his error.

I thought about my phone call 4 nights earlier. My doctor was called at home by a lab technician, who never met their patients but was simply following protocol and alerted my doctor to the worsening number that she should have been aware of 9 months earlier.

Just like my doctor’s lapse of attention, my patient’s error was not a moment of helplessness to be tolerated. These were mistakes, and there was no way around it.

“People make mistakes.” I said simply.

We sat silently for a time.

I don’t remember who broke the silence. The conversation that followed was centered on our humanity and our capability for both compassion and fallibility. Afterward, I wondered who my doctor confided in and hoped she had a similar conversation.

Dr. Levesque is a clinical psychologist and clinical assistant professor of psychiatry at the Geisel School of Medicine at Dartmouth, Hanover, N.H., where she also serves on the Committee for a Respectful Learning Environment.

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

The Brief Psychiatric Rating Scale (BPRS) was an effective tool for measuring general and specific psychiatric symptoms across the diagnostic spectrum, based on data from 600 psychiatric inpatients.

“Current DSM and ICD diagnoses do not depict psychopathology accurately, therefore their validity in research and utility in clinical practice is questioned,” wrote Andreas B. Hofmann, PhD, of the University of Zürich and colleagues.

The BPRS was developed to assess changes in psychopathology across a range of severe psychiatric disorders, but its potential to assess symptoms in nonpsychotic disorders has not been explored, the researchers said.

In a study published in Psychiatry Research, the investigators analyzed data from 600 adult psychiatric inpatients divided equally into six diagnostic categories: alcohol use disorder, major depressive disorder, anxiety disorders, bipolar disorder, schizophrenia, and personality disorders. The mean age of the patients was 41.5 years and 45.5% were women. The demographic characteristics were similar across most groups, although patients with a personality disorder were significantly more likely than other patients to be younger and female.

Patients were assessed using the BPRS based on their main diagnosis. The mini-ICF-APP, another validated measure for assessing psychiatric disorders, served as a comparator, and both were compared to the Clinical Global Impression Scale (CGI).

Overall, the BPRS and mini-ICF-APP showed moderate correlation and good agreement, the researchers said. The Pearson correlation coefficient for the BPRS and mini-ICF-APP scales was 0.53 and the concordance correlation coefficient was 0.52. The mean sum scores for the BPRS, the mini-ICF-APP, and the CGI were 45.4 (standard deviation, 14.4), 19.93 (SD, 8.21), and 5.55 (SD, 0.84), respectively, which indicated “markedly ill” to “severely ill” patients, the researchers said.

The researchers were able to detect three clusters of symptoms corresponding to externalizing, internalizing, and thought disturbance domains using the BPRS, and four clusters using the mini-ICF-APP.

The symptoms using BPRS and the functionality domains using the mini-ICF-APP “showed a close interplay,” the researchers noted.

“The symptoms and functional domains we found to be central within the network structure are among the first targets of any psychiatric or psychotherapeutic intervention, namely the building of a common language and understanding as well as the establishment of confidence in relationships and a trustworthy therapeutic alliance,” they wrote in their discussion.

The study findings were limited by several factors including the collection of data from routine practice rather than clinical trials, the focus on only the main diagnosis without comorbidities, and the inclusion only of patients requiring hospitalization, the researchers noted.

However, the results were strengthened by the large sample size, and demonstrate the validity of the BPRS as a measurement tool across a range of psychiatric diagnoses, they said.

“Since the BPRS is a widely known and readily available psychometric scale, our results support its use as a transdiagnostic measurement instrument of psychopathology,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

The Brief Psychiatric Rating Scale (BPRS) was an effective tool for measuring general and specific psychiatric symptoms across the diagnostic spectrum, based on data from 600 psychiatric inpatients.

“Current DSM and ICD diagnoses do not depict psychopathology accurately, therefore their validity in research and utility in clinical practice is questioned,” wrote Andreas B. Hofmann, PhD, of the University of Zürich and colleagues.

The BPRS was developed to assess changes in psychopathology across a range of severe psychiatric disorders, but its potential to assess symptoms in nonpsychotic disorders has not been explored, the researchers said.

In a study published in Psychiatry Research, the investigators analyzed data from 600 adult psychiatric inpatients divided equally into six diagnostic categories: alcohol use disorder, major depressive disorder, anxiety disorders, bipolar disorder, schizophrenia, and personality disorders. The mean age of the patients was 41.5 years and 45.5% were women. The demographic characteristics were similar across most groups, although patients with a personality disorder were significantly more likely than other patients to be younger and female.

Patients were assessed using the BPRS based on their main diagnosis. The mini-ICF-APP, another validated measure for assessing psychiatric disorders, served as a comparator, and both were compared to the Clinical Global Impression Scale (CGI).

Overall, the BPRS and mini-ICF-APP showed moderate correlation and good agreement, the researchers said. The Pearson correlation coefficient for the BPRS and mini-ICF-APP scales was 0.53 and the concordance correlation coefficient was 0.52. The mean sum scores for the BPRS, the mini-ICF-APP, and the CGI were 45.4 (standard deviation, 14.4), 19.93 (SD, 8.21), and 5.55 (SD, 0.84), respectively, which indicated “markedly ill” to “severely ill” patients, the researchers said.

The researchers were able to detect three clusters of symptoms corresponding to externalizing, internalizing, and thought disturbance domains using the BPRS, and four clusters using the mini-ICF-APP.

The symptoms using BPRS and the functionality domains using the mini-ICF-APP “showed a close interplay,” the researchers noted.

“The symptoms and functional domains we found to be central within the network structure are among the first targets of any psychiatric or psychotherapeutic intervention, namely the building of a common language and understanding as well as the establishment of confidence in relationships and a trustworthy therapeutic alliance,” they wrote in their discussion.

The study findings were limited by several factors including the collection of data from routine practice rather than clinical trials, the focus on only the main diagnosis without comorbidities, and the inclusion only of patients requiring hospitalization, the researchers noted.

However, the results were strengthened by the large sample size, and demonstrate the validity of the BPRS as a measurement tool across a range of psychiatric diagnoses, they said.

“Since the BPRS is a widely known and readily available psychometric scale, our results support its use as a transdiagnostic measurement instrument of psychopathology,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

The Brief Psychiatric Rating Scale (BPRS) was an effective tool for measuring general and specific psychiatric symptoms across the diagnostic spectrum, based on data from 600 psychiatric inpatients.

“Current DSM and ICD diagnoses do not depict psychopathology accurately, therefore their validity in research and utility in clinical practice is questioned,” wrote Andreas B. Hofmann, PhD, of the University of Zürich and colleagues.

The BPRS was developed to assess changes in psychopathology across a range of severe psychiatric disorders, but its potential to assess symptoms in nonpsychotic disorders has not been explored, the researchers said.

In a study published in Psychiatry Research, the investigators analyzed data from 600 adult psychiatric inpatients divided equally into six diagnostic categories: alcohol use disorder, major depressive disorder, anxiety disorders, bipolar disorder, schizophrenia, and personality disorders. The mean age of the patients was 41.5 years and 45.5% were women. The demographic characteristics were similar across most groups, although patients with a personality disorder were significantly more likely than other patients to be younger and female.

Patients were assessed using the BPRS based on their main diagnosis. The mini-ICF-APP, another validated measure for assessing psychiatric disorders, served as a comparator, and both were compared to the Clinical Global Impression Scale (CGI).

Overall, the BPRS and mini-ICF-APP showed moderate correlation and good agreement, the researchers said. The Pearson correlation coefficient for the BPRS and mini-ICF-APP scales was 0.53 and the concordance correlation coefficient was 0.52. The mean sum scores for the BPRS, the mini-ICF-APP, and the CGI were 45.4 (standard deviation, 14.4), 19.93 (SD, 8.21), and 5.55 (SD, 0.84), respectively, which indicated “markedly ill” to “severely ill” patients, the researchers said.

The researchers were able to detect three clusters of symptoms corresponding to externalizing, internalizing, and thought disturbance domains using the BPRS, and four clusters using the mini-ICF-APP.

The symptoms using BPRS and the functionality domains using the mini-ICF-APP “showed a close interplay,” the researchers noted.

“The symptoms and functional domains we found to be central within the network structure are among the first targets of any psychiatric or psychotherapeutic intervention, namely the building of a common language and understanding as well as the establishment of confidence in relationships and a trustworthy therapeutic alliance,” they wrote in their discussion.

The study findings were limited by several factors including the collection of data from routine practice rather than clinical trials, the focus on only the main diagnosis without comorbidities, and the inclusion only of patients requiring hospitalization, the researchers noted.

However, the results were strengthened by the large sample size, and demonstrate the validity of the BPRS as a measurement tool across a range of psychiatric diagnoses, they said.

“Since the BPRS is a widely known and readily available psychometric scale, our results support its use as a transdiagnostic measurement instrument of psychopathology,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

The Food and Drug Administration has approved Abbott Laboratories’ new Proclaim Plus spinal cord stimulation (SCS) system featuring FlexBurst360 therapy for the treatment of patients with chronic pain, the company announced Aug. 23.

The “next generation” of its proprietary BurstDR stimulation, FlexBurst360 therapy, provides pain coverage across up to six areas of the trunk and limbs, with programming that can be adjusted as a patient’s individual therapeutic needs evolve, the manufacturer noted.

“Using FlexBurst360 therapy on the Proclaim Plus system, physicians can identify the lowest effective dose of stimulation for each patient and adapt it based on evolving pain needs,” the company said in a news release.

The system also has therapy settings accessed with a mobile device.

Through their mobile devices, patients can access the manufacturer’s NeuroSphere Virtual Clinic, which allows them to communicate with their providers and receive remote adjustments to their therapeutic settings as needed.
 

Game changer?

The newly approved system has a battery life of up to 10 years, akin to the company’s Proclaim XR neurostimulation system for chronic pain. As reported at the time by this news organization, that system was approved by the FDA in 2019.

More than 50 million people in the United States experience chronic pain and most have pain in more than one area of the body. Steven Falowski, MD, with Argires Marotti Neurosurgical Associates of Lancaster, Pa., noted in the release that spinal cord stimulation has provided “tremendous relief” for patients with chronic pain.

Dr. Falowski added that “with its ability to mimic natural patterns found in the brain, the Abbott BurstDR platform has been a game changer” for these patients.

“However, despite the many benefits of BurstDR, such as being effective as a low-energy stimulation therapy, some patients continue to be burdened ... because of multiple painful areas and evolving pain,” he said.

“Now, with Proclaim Plus and FlexBurst360, an already established platform has been improved to treat more patients who suffer from pain across different body parts and changing pain over time,” said Dr. Falowski.

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

The Food and Drug Administration has approved Abbott Laboratories’ new Proclaim Plus spinal cord stimulation (SCS) system featuring FlexBurst360 therapy for the treatment of patients with chronic pain, the company announced Aug. 23.

The “next generation” of its proprietary BurstDR stimulation, FlexBurst360 therapy, provides pain coverage across up to six areas of the trunk and limbs, with programming that can be adjusted as a patient’s individual therapeutic needs evolve, the manufacturer noted.

“Using FlexBurst360 therapy on the Proclaim Plus system, physicians can identify the lowest effective dose of stimulation for each patient and adapt it based on evolving pain needs,” the company said in a news release.

The system also has therapy settings accessed with a mobile device.

Through their mobile devices, patients can access the manufacturer’s NeuroSphere Virtual Clinic, which allows them to communicate with their providers and receive remote adjustments to their therapeutic settings as needed.
 

Game changer?

The newly approved system has a battery life of up to 10 years, akin to the company’s Proclaim XR neurostimulation system for chronic pain. As reported at the time by this news organization, that system was approved by the FDA in 2019.

More than 50 million people in the United States experience chronic pain and most have pain in more than one area of the body. Steven Falowski, MD, with Argires Marotti Neurosurgical Associates of Lancaster, Pa., noted in the release that spinal cord stimulation has provided “tremendous relief” for patients with chronic pain.

Dr. Falowski added that “with its ability to mimic natural patterns found in the brain, the Abbott BurstDR platform has been a game changer” for these patients.

“However, despite the many benefits of BurstDR, such as being effective as a low-energy stimulation therapy, some patients continue to be burdened ... because of multiple painful areas and evolving pain,” he said.

“Now, with Proclaim Plus and FlexBurst360, an already established platform has been improved to treat more patients who suffer from pain across different body parts and changing pain over time,” said Dr. Falowski.

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

The Food and Drug Administration has approved Abbott Laboratories’ new Proclaim Plus spinal cord stimulation (SCS) system featuring FlexBurst360 therapy for the treatment of patients with chronic pain, the company announced Aug. 23.

The “next generation” of its proprietary BurstDR stimulation, FlexBurst360 therapy, provides pain coverage across up to six areas of the trunk and limbs, with programming that can be adjusted as a patient’s individual therapeutic needs evolve, the manufacturer noted.

“Using FlexBurst360 therapy on the Proclaim Plus system, physicians can identify the lowest effective dose of stimulation for each patient and adapt it based on evolving pain needs,” the company said in a news release.

The system also has therapy settings accessed with a mobile device.

Through their mobile devices, patients can access the manufacturer’s NeuroSphere Virtual Clinic, which allows them to communicate with their providers and receive remote adjustments to their therapeutic settings as needed.
 

Game changer?

The newly approved system has a battery life of up to 10 years, akin to the company’s Proclaim XR neurostimulation system for chronic pain. As reported at the time by this news organization, that system was approved by the FDA in 2019.

More than 50 million people in the United States experience chronic pain and most have pain in more than one area of the body. Steven Falowski, MD, with Argires Marotti Neurosurgical Associates of Lancaster, Pa., noted in the release that spinal cord stimulation has provided “tremendous relief” for patients with chronic pain.

Dr. Falowski added that “with its ability to mimic natural patterns found in the brain, the Abbott BurstDR platform has been a game changer” for these patients.

“However, despite the many benefits of BurstDR, such as being effective as a low-energy stimulation therapy, some patients continue to be burdened ... because of multiple painful areas and evolving pain,” he said.

“Now, with Proclaim Plus and FlexBurst360, an already established platform has been improved to treat more patients who suffer from pain across different body parts and changing pain over time,” said Dr. Falowski.

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

The U.S. Food and Drug Administration has approved the first oral N-methyl D-aspartate (NMDA) receptor antagonist for the treatment of major depressive disorder (MDD) in adults, its manufacturer has announced.

Auvelity (Axsome Therapeutics) is a proprietary extended-release oral tablet containing dextromethorphan (45 mg) and bupropion (105 mg).

It is the “first and only rapid-acting oral medicine approved for the treatment of MDD with labeling of statistically significant antidepressant efficacy compared to placebo starting at one week,” the company said in a news release.

“The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile,” Maurizio Fava, MD, psychiatrist-in-chief, Massachusetts General Hospital, Boston, added in the release. 
 

‘Milestone’ in depression treatment?

Dr. Fava noted that nearly two-thirds of patients treated with currently available antidepressants fail to respond adequately, and those who do may not achieve clinically meaningful responses for up to 6-8 weeks.

“Given the debilitating nature of depression, the efficacy of Auvelity observed at 1 week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition,” he said.

The company noted the drug was studied in a comprehensive clinical program that included more than 1,100 patients with MDD.

The efficacy of the drug was demonstrated in the GEMINI placebo-controlled study – with confirmatory evidence provided by the ASCEND study, which  compared it with bupropion sustained-release tablets.

Axsome said it expects to launch the new oral medication in the fourth quarter of this year. It is not approved for use in children.

The full prescribing information and medication guide are available online.

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

The U.S. Food and Drug Administration has approved the first oral N-methyl D-aspartate (NMDA) receptor antagonist for the treatment of major depressive disorder (MDD) in adults, its manufacturer has announced.

Auvelity (Axsome Therapeutics) is a proprietary extended-release oral tablet containing dextromethorphan (45 mg) and bupropion (105 mg).

It is the “first and only rapid-acting oral medicine approved for the treatment of MDD with labeling of statistically significant antidepressant efficacy compared to placebo starting at one week,” the company said in a news release.

“The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile,” Maurizio Fava, MD, psychiatrist-in-chief, Massachusetts General Hospital, Boston, added in the release. 
 

‘Milestone’ in depression treatment?

Dr. Fava noted that nearly two-thirds of patients treated with currently available antidepressants fail to respond adequately, and those who do may not achieve clinically meaningful responses for up to 6-8 weeks.

“Given the debilitating nature of depression, the efficacy of Auvelity observed at 1 week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition,” he said.

The company noted the drug was studied in a comprehensive clinical program that included more than 1,100 patients with MDD.

The efficacy of the drug was demonstrated in the GEMINI placebo-controlled study – with confirmatory evidence provided by the ASCEND study, which  compared it with bupropion sustained-release tablets.

Axsome said it expects to launch the new oral medication in the fourth quarter of this year. It is not approved for use in children.

The full prescribing information and medication guide are available online.

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

The U.S. Food and Drug Administration has approved the first oral N-methyl D-aspartate (NMDA) receptor antagonist for the treatment of major depressive disorder (MDD) in adults, its manufacturer has announced.

Auvelity (Axsome Therapeutics) is a proprietary extended-release oral tablet containing dextromethorphan (45 mg) and bupropion (105 mg).

It is the “first and only rapid-acting oral medicine approved for the treatment of MDD with labeling of statistically significant antidepressant efficacy compared to placebo starting at one week,” the company said in a news release.

“The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile,” Maurizio Fava, MD, psychiatrist-in-chief, Massachusetts General Hospital, Boston, added in the release. 
 

‘Milestone’ in depression treatment?

Dr. Fava noted that nearly two-thirds of patients treated with currently available antidepressants fail to respond adequately, and those who do may not achieve clinically meaningful responses for up to 6-8 weeks.

“Given the debilitating nature of depression, the efficacy of Auvelity observed at 1 week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition,” he said.

The company noted the drug was studied in a comprehensive clinical program that included more than 1,100 patients with MDD.

The efficacy of the drug was demonstrated in the GEMINI placebo-controlled study – with confirmatory evidence provided by the ASCEND study, which  compared it with bupropion sustained-release tablets.

Axsome said it expects to launch the new oral medication in the fourth quarter of this year. It is not approved for use in children.

The full prescribing information and medication guide are available online.

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