Deborah Brauser

A novel digital treatment designed to reduce the frequency of auditory hallucinations and associated distress in patients with psychosis has been shown to be safe and effective, results from the largest study of avatar therapy to date show. 

The therapy allows patients to interact with a “digital embodiment” of the voice they hear, which is represented by a computer-generated face, also known as an avatar.

In the randomized, multisite, phase 2/3 AVATAR2 trial, patients who received AVATAR-Extended therapy, which included a personalized series of voiced dialogues based on their life history, plus treatment as usual (TAU) showed significantly greater improvement in distress and voice severity levels at 16 weeks vs those who received TAU only. They also had significant reductions in voice frequency at 16 and 28 weeks.

Patients in a third arm who were assigned to TAU plus AVATAR-Brief therapy, which included six sessions of a standardized version of the therapy, also showed improvements at 16 weeks, compared with TAU alone — but the clinical impact was stronger with the extended version. 

“I was surprised at the extent to which the extended version seemed to be a more optimal version, and it should be the way forward with this therapy,” said study investigator Philippa A. Garety, PhD, professor emerita of clinical psychology at the Institute of Psychiatry, Psychology, and Neuroscience at King’s College, London, England.

With more than 300 participants, AVATAR2 is the largest trial to access avatar therapy to date, Garety noted.

“What’s unique about this work is that technology allows us to create safe face-to-face encounters with a representation of a person’s voice and allows them to relate to that voice in a new way,” she added. 

The findings were published online in Nature Medicine. 
 

A Decade of Research

Auditory verbal hallucinations are common in patients with schizophrenia, but currently available therapies can be ineffective, investigators wrote. 

The therapy allows patients to customize how the avatar looks and sounds. Face-to-face dialogues are then conducted between the patients and avatars in order to build empowerment. A trained therapist provides support during these sessions.

As previously reported, the creator of avatar therapy, Julian Leff, MD, presented promising results from a pilot study of 26 patients at the International Congress of the Royal College of Psychiatrists in 2014. 

“Opening up a dialogue between a patient and the voice they’ve been hearing is powerful,” said Leff, who was emeritus professor at the Institute of Psychiatry in London at the time.

In 2018, a randomized single-site study (AVATAR1) of 150 participants showed that the intervention was associated with a greater decrease in voice severity at 12 weeks vs supportive therapy. Past research led to the idea of incorporating personalization to better optimize the experience. 

Garety noted that AVATAR2 is the largest trial to date of the therapy, as well as the first multisite trial to test the intervention, which was important in order to determine whether it could work outside of a research setting. 

The study included 345 participants (61.4% men; mean age, 39.6 years) from three sites in England and one in Scotland. All were randomly assigned to receive TAU alone (n = 115), TAU plus AVATAR-Brief (n = 116), or TAU plus AVATAR-Extended (n = 114). 

TAU typically included use of antipsychotics, as well as outpatient psychiatric visits and follow-up by case managers and care coordinators. 

“We didn’t interfere with treatment as usual. We wanted to test whether adding this therapy to [TAU] would enhance effects and provide better treatment for their voices,” Garety noted. 

AVATAR-Brief included a standardized process that focused on such things as self-esteem and assertiveness. AVATAR-Extended had two phases. In the first, participants received AVATAR-Brief therapy, whereas the second phase offered a more personalized intervention.
 

An ‘Unusual Finding’ 

The study’s primary outcome was voice-related distress at 16 and 28 weeks. Although the TAU plus AVATAR-Extended group did show a significant decrease in distress at 16 weeks vs TAU alone (–1.6 points; P = .029), the improvement was no longer significant at the 28-week follow-up (P = .175). The same was also true for the key secondary outcome of reduction in voice severity (–2.32 points; P = .009 at 16 weeks but P =.1 at 28 weeks).

The investigators noted that this might be caused by the number of dropouts in the AVATAR-Extended group by the 28-week timepoint. The completion rate for those patients was only 58%. The completion rate for the shorter, AVATAR-Brief group was 82%.

On the other hand, the other key secondary outcome of voice frequency was significantly reduced with AVATAR-Extended at both 16 weeks (–0.62 point; P = .01) and 28 weeks (–0.89 point; P = .003).

“This is an unusual finding. We’re not aware of any other psychological therapy that shows a reduction in the occurrence of the voice,” Garety said. 

For TAU plus AVATAR-Brief, there were improvements at 16 weeks for distress (-1.05 points; P = .035) vs TAU alone. However, the researchers noted that this version of the therapy was just below the prespecified threshold for a clinically significant change and was at the threshold for statistical significance. 

Although the shorter therapy was associated with a reduction in voice severity level at 16 weeks (–2.04 points; P = .017) vs TAU alone, there was no reduction in distress or voice severity at 28 weeks. There was no improvement in voice frequency at either timepoint. 

Both the brief and the extended versions of AVATAR therapy showed improved mood and anxiety levels at 16 weeks and sustained improvement in well-being and recovery, the researchers noted.

“The short version, as expected, did deliver benefits posttreatment, but clearly the extended, optimized version outperformed the brief version. It had stronger and more lasting effects across quite a wide range of outcomes that matter to people who hear voices,” Garety said. 

“In the extended version, people felt more empowered. And in just that version, the frequency of voices was reduced, which is a very important outcome,” she added. 
 

Safety Issues?

There were 58 serious adverse events (SAEs) in total, with 51% of those occurring in the AVATAR-Extended group. Two participants in that group died; however, independent reviews deemed these events as not related to the intervention. 

In addition, there were no “definitely related” SAEs and only a small number of “possibly related” SAEs, which typically included hospitalization with other contributory factors.

Garety noted during a press briefing that AVATAR therapy has now been demonstrated to be safe across two large trials. 

Study limitations cited included no direct comparison between AVATAR-Brief and AVATAR-Extended or between AVATAR therapy and a different type of psychological treatment. 

Overall, “we recommend that future development and provision of AVATAR therapy is primarily guided” by the AVATAR-Extended protocol, the investigators wrote.

Because the therapy was recommended by a National Institute for Health and Care Excellence Early Value Assessment, the investigators are now seeking to provide it in routine National Health Service settings to gather further real-world evidence of effectiveness over the next 3 years.
 

Next Steps

Although the intervention isn’t currently available to everybody who might be seeking it, “there’s a pipeline of movement from research into treatment and it’s moving towards the next stage of delivery,” Garety said. 

Investigators are also looking into cultural adaptations for the therapy so it can be used in different locales, including Ethiopia and India, she added. There isn’t a US version yet, but Garety noted that investigators in Canada are looking at similar research and suspects that will also occur in the United States soon. 

“We’re pioneers in this work, and it now needs to be going international and into services,” she said. “We have had many people who hear voices say what an amazing experience this has been. So, I feel very proud and excited to have been able to be part of this.” 

At the press briefing, Miranda Wolpert, director of mental health at Wellcome, which funded the study, noted that it is encouraging to see the development of a new intervention that could potentially change the lives of patients across the world.

“We know that psychosis can start early in life, stopping people from having the jobs and relationships they want and from achieving the goals they want. This intervention was developed with those people to help them address an issue that really troubles them,” Wolpert said. 

“For me, this represents part of a revolution we are starting to see in terms of mental health interventions and the potential impact on mental health science,” she added. 
 

Digital Placebo Effect?

Commenting on the findings, John Torous, MD, a psychiatrist and director of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, Massachusetts, said there is a need for new treatments for schizophrenia that work with different mechanisms.

“We have a lot of medication studies but not as many innovative therapy studies. I think it’s exciting that the results, at least in the shorter-term outcome, were positive. And I think that’s something that can give people hope in using these new technologies,” said Torous, who is also an assistant professor of psychiatry at Harvard Medical School, Boston, and was not involved with the research. 

Still, he did note some study limitations, including whether there could have been some type of “digital placebo effect” from the therapy. 

“If you tell people they’re getting high-tech advanced digital care, that may have some effect,” he said, adding that “it’s always interesting” to tease out the benefit being delivered by the technology vs the delivery mechanism itself — or some combination of both.

Torous added, though, that it’s very difficult to have a rigorous digital control group. “It’s not necessarily a fault of their study, but it’s something to keep in mind when interpreting what the results are.”

He also noted that he would have liked to have seen a direct comparison between this new kind of psychological therapy vs standard psychological therapy, such as cognitive-behavioral therapy. 

In addition, he wondered about expenses and scalability of the intervention, and whether patients would need to go to a specialized center to undergo treatment. Torous mentioned that a version involving virtual reality could perhaps make this more scalable in the future. 

Overall, he said that what the investigators are currently doing is very innovative. “It’s exciting that we’re talking about the next steps. Giving people new options for psychological therapy that may be effective for their disorders is really wonderful to see,” Torous said. 

The study was funded by the National Institute for Health and Care Research (NIHR), the Wellcome Trust King’s Clinical Research Facility, the NIHR Maudsley Biomedical Research Centre and Maudsley NHS Foundation Trust, King’s College London, the Manchester Biomedical Research Centre, and NHS Research Scotland, as well as by a grant from Wellcome. Garety reports being an unpaid scientific adviser to Avatar Therapy. Financial disclosures for the other investigators are fully listed in the original article. Torous reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A novel digital treatment designed to reduce the frequency of auditory hallucinations and associated distress in patients with psychosis has been shown to be safe and effective, results from the largest study of avatar therapy to date show. 

The therapy allows patients to interact with a “digital embodiment” of the voice they hear, which is represented by a computer-generated face, also known as an avatar.

In the randomized, multisite, phase 2/3 AVATAR2 trial, patients who received AVATAR-Extended therapy, which included a personalized series of voiced dialogues based on their life history, plus treatment as usual (TAU) showed significantly greater improvement in distress and voice severity levels at 16 weeks vs those who received TAU only. They also had significant reductions in voice frequency at 16 and 28 weeks.

Patients in a third arm who were assigned to TAU plus AVATAR-Brief therapy, which included six sessions of a standardized version of the therapy, also showed improvements at 16 weeks, compared with TAU alone — but the clinical impact was stronger with the extended version. 

“I was surprised at the extent to which the extended version seemed to be a more optimal version, and it should be the way forward with this therapy,” said study investigator Philippa A. Garety, PhD, professor emerita of clinical psychology at the Institute of Psychiatry, Psychology, and Neuroscience at King’s College, London, England.

With more than 300 participants, AVATAR2 is the largest trial to access avatar therapy to date, Garety noted.

“What’s unique about this work is that technology allows us to create safe face-to-face encounters with a representation of a person’s voice and allows them to relate to that voice in a new way,” she added. 

The findings were published online in Nature Medicine. 
 

A Decade of Research

Auditory verbal hallucinations are common in patients with schizophrenia, but currently available therapies can be ineffective, investigators wrote. 

The therapy allows patients to customize how the avatar looks and sounds. Face-to-face dialogues are then conducted between the patients and avatars in order to build empowerment. A trained therapist provides support during these sessions.

As previously reported, the creator of avatar therapy, Julian Leff, MD, presented promising results from a pilot study of 26 patients at the International Congress of the Royal College of Psychiatrists in 2014. 

“Opening up a dialogue between a patient and the voice they’ve been hearing is powerful,” said Leff, who was emeritus professor at the Institute of Psychiatry in London at the time.

In 2018, a randomized single-site study (AVATAR1) of 150 participants showed that the intervention was associated with a greater decrease in voice severity at 12 weeks vs supportive therapy. Past research led to the idea of incorporating personalization to better optimize the experience. 

Garety noted that AVATAR2 is the largest trial to date of the therapy, as well as the first multisite trial to test the intervention, which was important in order to determine whether it could work outside of a research setting. 

The study included 345 participants (61.4% men; mean age, 39.6 years) from three sites in England and one in Scotland. All were randomly assigned to receive TAU alone (n = 115), TAU plus AVATAR-Brief (n = 116), or TAU plus AVATAR-Extended (n = 114). 

TAU typically included use of antipsychotics, as well as outpatient psychiatric visits and follow-up by case managers and care coordinators. 

“We didn’t interfere with treatment as usual. We wanted to test whether adding this therapy to [TAU] would enhance effects and provide better treatment for their voices,” Garety noted. 

AVATAR-Brief included a standardized process that focused on such things as self-esteem and assertiveness. AVATAR-Extended had two phases. In the first, participants received AVATAR-Brief therapy, whereas the second phase offered a more personalized intervention.
 

An ‘Unusual Finding’ 

The study’s primary outcome was voice-related distress at 16 and 28 weeks. Although the TAU plus AVATAR-Extended group did show a significant decrease in distress at 16 weeks vs TAU alone (–1.6 points; P = .029), the improvement was no longer significant at the 28-week follow-up (P = .175). The same was also true for the key secondary outcome of reduction in voice severity (–2.32 points; P = .009 at 16 weeks but P =.1 at 28 weeks).

The investigators noted that this might be caused by the number of dropouts in the AVATAR-Extended group by the 28-week timepoint. The completion rate for those patients was only 58%. The completion rate for the shorter, AVATAR-Brief group was 82%.

On the other hand, the other key secondary outcome of voice frequency was significantly reduced with AVATAR-Extended at both 16 weeks (–0.62 point; P = .01) and 28 weeks (–0.89 point; P = .003).

“This is an unusual finding. We’re not aware of any other psychological therapy that shows a reduction in the occurrence of the voice,” Garety said. 

For TAU plus AVATAR-Brief, there were improvements at 16 weeks for distress (-1.05 points; P = .035) vs TAU alone. However, the researchers noted that this version of the therapy was just below the prespecified threshold for a clinically significant change and was at the threshold for statistical significance. 

Although the shorter therapy was associated with a reduction in voice severity level at 16 weeks (–2.04 points; P = .017) vs TAU alone, there was no reduction in distress or voice severity at 28 weeks. There was no improvement in voice frequency at either timepoint. 

Both the brief and the extended versions of AVATAR therapy showed improved mood and anxiety levels at 16 weeks and sustained improvement in well-being and recovery, the researchers noted.

“The short version, as expected, did deliver benefits posttreatment, but clearly the extended, optimized version outperformed the brief version. It had stronger and more lasting effects across quite a wide range of outcomes that matter to people who hear voices,” Garety said. 

“In the extended version, people felt more empowered. And in just that version, the frequency of voices was reduced, which is a very important outcome,” she added. 
 

Safety Issues?

There were 58 serious adverse events (SAEs) in total, with 51% of those occurring in the AVATAR-Extended group. Two participants in that group died; however, independent reviews deemed these events as not related to the intervention. 

In addition, there were no “definitely related” SAEs and only a small number of “possibly related” SAEs, which typically included hospitalization with other contributory factors.

Garety noted during a press briefing that AVATAR therapy has now been demonstrated to be safe across two large trials. 

Study limitations cited included no direct comparison between AVATAR-Brief and AVATAR-Extended or between AVATAR therapy and a different type of psychological treatment. 

Overall, “we recommend that future development and provision of AVATAR therapy is primarily guided” by the AVATAR-Extended protocol, the investigators wrote.

Because the therapy was recommended by a National Institute for Health and Care Excellence Early Value Assessment, the investigators are now seeking to provide it in routine National Health Service settings to gather further real-world evidence of effectiveness over the next 3 years.
 

Next Steps

Although the intervention isn’t currently available to everybody who might be seeking it, “there’s a pipeline of movement from research into treatment and it’s moving towards the next stage of delivery,” Garety said. 

Investigators are also looking into cultural adaptations for the therapy so it can be used in different locales, including Ethiopia and India, she added. There isn’t a US version yet, but Garety noted that investigators in Canada are looking at similar research and suspects that will also occur in the United States soon. 

“We’re pioneers in this work, and it now needs to be going international and into services,” she said. “We have had many people who hear voices say what an amazing experience this has been. So, I feel very proud and excited to have been able to be part of this.” 

At the press briefing, Miranda Wolpert, director of mental health at Wellcome, which funded the study, noted that it is encouraging to see the development of a new intervention that could potentially change the lives of patients across the world.

“We know that psychosis can start early in life, stopping people from having the jobs and relationships they want and from achieving the goals they want. This intervention was developed with those people to help them address an issue that really troubles them,” Wolpert said. 

“For me, this represents part of a revolution we are starting to see in terms of mental health interventions and the potential impact on mental health science,” she added. 
 

Digital Placebo Effect?

Commenting on the findings, John Torous, MD, a psychiatrist and director of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, Massachusetts, said there is a need for new treatments for schizophrenia that work with different mechanisms.

“We have a lot of medication studies but not as many innovative therapy studies. I think it’s exciting that the results, at least in the shorter-term outcome, were positive. And I think that’s something that can give people hope in using these new technologies,” said Torous, who is also an assistant professor of psychiatry at Harvard Medical School, Boston, and was not involved with the research. 

Still, he did note some study limitations, including whether there could have been some type of “digital placebo effect” from the therapy. 

“If you tell people they’re getting high-tech advanced digital care, that may have some effect,” he said, adding that “it’s always interesting” to tease out the benefit being delivered by the technology vs the delivery mechanism itself — or some combination of both.

Torous added, though, that it’s very difficult to have a rigorous digital control group. “It’s not necessarily a fault of their study, but it’s something to keep in mind when interpreting what the results are.”

He also noted that he would have liked to have seen a direct comparison between this new kind of psychological therapy vs standard psychological therapy, such as cognitive-behavioral therapy. 

In addition, he wondered about expenses and scalability of the intervention, and whether patients would need to go to a specialized center to undergo treatment. Torous mentioned that a version involving virtual reality could perhaps make this more scalable in the future. 

Overall, he said that what the investigators are currently doing is very innovative. “It’s exciting that we’re talking about the next steps. Giving people new options for psychological therapy that may be effective for their disorders is really wonderful to see,” Torous said. 

The study was funded by the National Institute for Health and Care Research (NIHR), the Wellcome Trust King’s Clinical Research Facility, the NIHR Maudsley Biomedical Research Centre and Maudsley NHS Foundation Trust, King’s College London, the Manchester Biomedical Research Centre, and NHS Research Scotland, as well as by a grant from Wellcome. Garety reports being an unpaid scientific adviser to Avatar Therapy. Financial disclosures for the other investigators are fully listed in the original article. Torous reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A novel digital treatment designed to reduce the frequency of auditory hallucinations and associated distress in patients with psychosis has been shown to be safe and effective, results from the largest study of avatar therapy to date show. 

The therapy allows patients to interact with a “digital embodiment” of the voice they hear, which is represented by a computer-generated face, also known as an avatar.

In the randomized, multisite, phase 2/3 AVATAR2 trial, patients who received AVATAR-Extended therapy, which included a personalized series of voiced dialogues based on their life history, plus treatment as usual (TAU) showed significantly greater improvement in distress and voice severity levels at 16 weeks vs those who received TAU only. They also had significant reductions in voice frequency at 16 and 28 weeks.

Patients in a third arm who were assigned to TAU plus AVATAR-Brief therapy, which included six sessions of a standardized version of the therapy, also showed improvements at 16 weeks, compared with TAU alone — but the clinical impact was stronger with the extended version. 

“I was surprised at the extent to which the extended version seemed to be a more optimal version, and it should be the way forward with this therapy,” said study investigator Philippa A. Garety, PhD, professor emerita of clinical psychology at the Institute of Psychiatry, Psychology, and Neuroscience at King’s College, London, England.

With more than 300 participants, AVATAR2 is the largest trial to access avatar therapy to date, Garety noted.

“What’s unique about this work is that technology allows us to create safe face-to-face encounters with a representation of a person’s voice and allows them to relate to that voice in a new way,” she added. 

The findings were published online in Nature Medicine. 
 

A Decade of Research

Auditory verbal hallucinations are common in patients with schizophrenia, but currently available therapies can be ineffective, investigators wrote. 

The therapy allows patients to customize how the avatar looks and sounds. Face-to-face dialogues are then conducted between the patients and avatars in order to build empowerment. A trained therapist provides support during these sessions.

As previously reported, the creator of avatar therapy, Julian Leff, MD, presented promising results from a pilot study of 26 patients at the International Congress of the Royal College of Psychiatrists in 2014. 

“Opening up a dialogue between a patient and the voice they’ve been hearing is powerful,” said Leff, who was emeritus professor at the Institute of Psychiatry in London at the time.

In 2018, a randomized single-site study (AVATAR1) of 150 participants showed that the intervention was associated with a greater decrease in voice severity at 12 weeks vs supportive therapy. Past research led to the idea of incorporating personalization to better optimize the experience. 

Garety noted that AVATAR2 is the largest trial to date of the therapy, as well as the first multisite trial to test the intervention, which was important in order to determine whether it could work outside of a research setting. 

The study included 345 participants (61.4% men; mean age, 39.6 years) from three sites in England and one in Scotland. All were randomly assigned to receive TAU alone (n = 115), TAU plus AVATAR-Brief (n = 116), or TAU plus AVATAR-Extended (n = 114). 

TAU typically included use of antipsychotics, as well as outpatient psychiatric visits and follow-up by case managers and care coordinators. 

“We didn’t interfere with treatment as usual. We wanted to test whether adding this therapy to [TAU] would enhance effects and provide better treatment for their voices,” Garety noted. 

AVATAR-Brief included a standardized process that focused on such things as self-esteem and assertiveness. AVATAR-Extended had two phases. In the first, participants received AVATAR-Brief therapy, whereas the second phase offered a more personalized intervention.
 

An ‘Unusual Finding’ 

The study’s primary outcome was voice-related distress at 16 and 28 weeks. Although the TAU plus AVATAR-Extended group did show a significant decrease in distress at 16 weeks vs TAU alone (–1.6 points; P = .029), the improvement was no longer significant at the 28-week follow-up (P = .175). The same was also true for the key secondary outcome of reduction in voice severity (–2.32 points; P = .009 at 16 weeks but P =.1 at 28 weeks).

The investigators noted that this might be caused by the number of dropouts in the AVATAR-Extended group by the 28-week timepoint. The completion rate for those patients was only 58%. The completion rate for the shorter, AVATAR-Brief group was 82%.

On the other hand, the other key secondary outcome of voice frequency was significantly reduced with AVATAR-Extended at both 16 weeks (–0.62 point; P = .01) and 28 weeks (–0.89 point; P = .003).

“This is an unusual finding. We’re not aware of any other psychological therapy that shows a reduction in the occurrence of the voice,” Garety said. 

For TAU plus AVATAR-Brief, there were improvements at 16 weeks for distress (-1.05 points; P = .035) vs TAU alone. However, the researchers noted that this version of the therapy was just below the prespecified threshold for a clinically significant change and was at the threshold for statistical significance. 

Although the shorter therapy was associated with a reduction in voice severity level at 16 weeks (–2.04 points; P = .017) vs TAU alone, there was no reduction in distress or voice severity at 28 weeks. There was no improvement in voice frequency at either timepoint. 

Both the brief and the extended versions of AVATAR therapy showed improved mood and anxiety levels at 16 weeks and sustained improvement in well-being and recovery, the researchers noted.

“The short version, as expected, did deliver benefits posttreatment, but clearly the extended, optimized version outperformed the brief version. It had stronger and more lasting effects across quite a wide range of outcomes that matter to people who hear voices,” Garety said. 

“In the extended version, people felt more empowered. And in just that version, the frequency of voices was reduced, which is a very important outcome,” she added. 
 

Safety Issues?

There were 58 serious adverse events (SAEs) in total, with 51% of those occurring in the AVATAR-Extended group. Two participants in that group died; however, independent reviews deemed these events as not related to the intervention. 

In addition, there were no “definitely related” SAEs and only a small number of “possibly related” SAEs, which typically included hospitalization with other contributory factors.

Garety noted during a press briefing that AVATAR therapy has now been demonstrated to be safe across two large trials. 

Study limitations cited included no direct comparison between AVATAR-Brief and AVATAR-Extended or between AVATAR therapy and a different type of psychological treatment. 

Overall, “we recommend that future development and provision of AVATAR therapy is primarily guided” by the AVATAR-Extended protocol, the investigators wrote.

Because the therapy was recommended by a National Institute for Health and Care Excellence Early Value Assessment, the investigators are now seeking to provide it in routine National Health Service settings to gather further real-world evidence of effectiveness over the next 3 years.
 

Next Steps

Although the intervention isn’t currently available to everybody who might be seeking it, “there’s a pipeline of movement from research into treatment and it’s moving towards the next stage of delivery,” Garety said. 

Investigators are also looking into cultural adaptations for the therapy so it can be used in different locales, including Ethiopia and India, she added. There isn’t a US version yet, but Garety noted that investigators in Canada are looking at similar research and suspects that will also occur in the United States soon. 

“We’re pioneers in this work, and it now needs to be going international and into services,” she said. “We have had many people who hear voices say what an amazing experience this has been. So, I feel very proud and excited to have been able to be part of this.” 

At the press briefing, Miranda Wolpert, director of mental health at Wellcome, which funded the study, noted that it is encouraging to see the development of a new intervention that could potentially change the lives of patients across the world.

“We know that psychosis can start early in life, stopping people from having the jobs and relationships they want and from achieving the goals they want. This intervention was developed with those people to help them address an issue that really troubles them,” Wolpert said. 

“For me, this represents part of a revolution we are starting to see in terms of mental health interventions and the potential impact on mental health science,” she added. 
 

Digital Placebo Effect?

Commenting on the findings, John Torous, MD, a psychiatrist and director of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, Massachusetts, said there is a need for new treatments for schizophrenia that work with different mechanisms.

“We have a lot of medication studies but not as many innovative therapy studies. I think it’s exciting that the results, at least in the shorter-term outcome, were positive. And I think that’s something that can give people hope in using these new technologies,” said Torous, who is also an assistant professor of psychiatry at Harvard Medical School, Boston, and was not involved with the research. 

Still, he did note some study limitations, including whether there could have been some type of “digital placebo effect” from the therapy. 

“If you tell people they’re getting high-tech advanced digital care, that may have some effect,” he said, adding that “it’s always interesting” to tease out the benefit being delivered by the technology vs the delivery mechanism itself — or some combination of both.

Torous added, though, that it’s very difficult to have a rigorous digital control group. “It’s not necessarily a fault of their study, but it’s something to keep in mind when interpreting what the results are.”

He also noted that he would have liked to have seen a direct comparison between this new kind of psychological therapy vs standard psychological therapy, such as cognitive-behavioral therapy. 

In addition, he wondered about expenses and scalability of the intervention, and whether patients would need to go to a specialized center to undergo treatment. Torous mentioned that a version involving virtual reality could perhaps make this more scalable in the future. 

Overall, he said that what the investigators are currently doing is very innovative. “It’s exciting that we’re talking about the next steps. Giving people new options for psychological therapy that may be effective for their disorders is really wonderful to see,” Torous said. 

The study was funded by the National Institute for Health and Care Research (NIHR), the Wellcome Trust King’s Clinical Research Facility, the NIHR Maudsley Biomedical Research Centre and Maudsley NHS Foundation Trust, King’s College London, the Manchester Biomedical Research Centre, and NHS Research Scotland, as well as by a grant from Wellcome. Garety reports being an unpaid scientific adviser to Avatar Therapy. Financial disclosures for the other investigators are fully listed in the original article. Torous reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

As at-home, do-it-yourself (DIY) brain stimulation devices like transcranial direct current stimulation (tDCS) gain popularity for common psychiatric conditions like depression, anxiety, and posttraumatic stress disorder (PTSD), questions arise about their safety and efficacy.

However, the US Food and Drug Administration (FDA) has yet to “fully” clear any of these devices and has only granted breakthrough device designation to a few. In addition, most of the portable products don’t market themselves as medical interventions, putting them into a regulatory “gray area” that has little oversight.

This has led to a free-for-all environment, allowing individuals to purchase these products online and self-administer “treatment” — often without the guidance or even knowledge of their healthcare providers.

So how effective and safe are these noninvasive brain stimulators, and what guidance, if any, should clinicians provide to patients who are or are contemplating using them at home; what does the research show, and what are the ethical considerations?
 

What the Research Shows

Data from studies examining unsupervised at-home and use under medical supervision are mixed. Results from a recent randomized trial of more than 200 participants showed no significant difference in safety or efficacy between adjunctive at-home tDCS and at-home sham tDCS for depressive symptoms.

“To be fair, they did not find any unexpected safety issues. What they did find was that there was no clear signal that it worked,” said Noah S. Philip, MD, professor of psychiatry and human behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Philip, who is also lead for mental health research at Brown’s Center for Neurorestoration and Neurotechnology, Providence, Rhode Island, and was not involved in the study, noted that while other research papers have shown more promising results for depression and other conditions such as adult attention-deficit/hyperactivity disorder (ADHD) and pain, they often are not placebo controlled or include large numbers of patients.

Still, he added the growing use of these devices reflects the fact that standard treatment often doesn’t meet patients’ needs.

“Broadly speaking, part of the hope with brain stimulation is that instead of taking a pill, we’re trying to more directly affect the brain tissues involved — and therefore, avoid the issue of having systemic side effects that you get from the meds. There’s certainly a hunger” for better interventions, Philip said.

tDCS involves a low-intensity electrical current applied through electrodes on the scalp in order to influence brain activity. Generally speaking, it emits less energy than other types of noninvasive brain stimulation, such as transcranial magnetic stimulation. “The trade-off is that’s it also a little harder to find a clear signal about how it works,” Philip said.

As such, he added, it’s important for clinicians to familiarize themselves with these devices, to ask about patient use, and to set up structured assessments of efficacy and adverse events.

Results from a randomized trial published last year in The Lancet showed no significant benefit for in-office use of tDCS plus a selective serotonin reuptake inhibitor vs sham tDCS for major depression.

On the other hand, a randomized trial published earlier this year in Brain Stimulation showed that older adults who received active tDCS had greater reductions in depressive and anxiety symptoms than those in the sham group.

In addition, results from a small study of eight participants published last year in SAGE Open Medicine showed adjuvant tDCS helped patients with refractory PTSD. Finally, a randomized trial of 54 veterans from Philip’s own team showed tDCS plus virtual reality was effective for combat-related PTSD.

Although there have also been several studies showing possible benefit of tDCS for Alzheimer’s disease, Gayatri Devi, MD, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, noted in a Medscape Neurology Decision Point that “the problem with all these studies is that they’re all very small, and there [are] so many different variables in terms of how you interpret response.”
 

On-Demand Brain Stim

As for at-home use, there’s now a wide offering of these types of devices available online, allowing an individual to apply daily brain stimulation via headsets, dispensing with the need to consult a clinician. Most are battery-powered and emit a low-level current.

Philip noted that there are essentially two ways to obtain such devices. Some are readily available from online stores, while others require a prescription, which typically includes guidelines on how to use the device.

So far, none of these portable products have been fully cleared by the FDA — although the agency did grant Breakthrough Device designation to Sooma Medical for its device to treat depression in 2023 and to Flow Neuroscience in 2022.

In August 2023, Flow announced that its device is now being reviewed for full FDA clearance on the basis of trial results showing at-home tDCS was “twice as effective” as antidepressants. The company received regulatory approval in Europe in 2019.

Other research has shown “encouraging” results for these at-home devices for conditions such as adult ADHD and pain relief with remote supervision.

Philip noted that more high-quality randomized controlled trials are definitely needed, with “a number of companies probably getting close to releasing data sometime soon.”

Is it possible that a placebo effect is at work here? “Yes, partially,” said Philip. Users often become more mindful of managing their depression and other conditions, which leads to behavior change, he said.
 

A Quick Fix for a Broken System?

Joseph J. Fins, MD, The E. William Davis Jr, MD, professor of Medical Ethics and chief of the Division of Medical Ethics at Weill Cornell Medicine, New York City, also believes there could be a placebo effect at play.

“It’s important that we don’t ascribe efficacy to a device without being aware of the placebo effect,” he said. That’s why more and larger, placebo-controlled trials are needed, he added.

There’s a multitude of reasons why patients may turn to at-home devices on their own, including drug shortages and the inability to see a psychiatrist in a timely manner.

“I think it speaks to the isolation of these folks that leads to them doing this on their own. These devices become a technological quick fix for a system that’s desperately broken. There’s nothing wrong with being a consumer, but at a certain point they need to be a patient, and they need to have a clinician there to help them,” he said.

Fins said that he also worries about regulatory oversight because of the way the devices are classified. He likened them to supplements, which, because they don’t make certain claims, are not regulated with the same stringency as other products and fall into an area “in between regulatory spheres.”

“I think we’re trying to take old regulatory frameworks and jerry-rig it to accommodate new and evolving technologies. And I think we need to have serious study of how we protect patients as they become consumers — to make sure there’s enough safety and enough efficacy and that they don’t get ripped off out of desperation,” Fins said.

As for safety, at-home devices are unlikely to cause physical harm — at least when used as intended. “The riskier situations happen when people build their own, overuse it, or use it in combination with drugs or alcohol or other factors that can produce unpredictable results,” Philip said.

He added that DIY-built products carry a higher risk for burns or excessive energy output. A 2016 “open letter” from a group of neurologists, published in Annals of Neurology, warned about the dangers of DIY tDCS.

In addition, Philip noted that he has seen instances where patients become manic after using at-home tDCS, especially when trying to improve cognition.

“We have seen a number of peculiar side effects emerge in those situations. Typically, it’s anxiety, panic attacks, and sensitivity to bright lights, in addition to the emergence of mania, which would require major psychiatric intervention,” he said.

“So, it’s important that if folks do engage with these sorts of things, it’s with some degree of medical involvement,” Philip added.
 

Ethical Considerations

Roy Hamilton, MD, professor of neurology, psychiatry, and physical medicine & rehabilitation at the University of Pennsylvania, in Philadelphia, said that in the setting of proper training, proper clinician communication, and proper oversight, he doesn’t view at-home tDCS as ethically problematic.

“For individuals who have conditions that are clearly causing them remarkable detriment to quality of life or to their health, it seems like the risk-benefit ratio with respect to the likelihood of harm is quite good,” said Hamilton, who is also the director of the Penn Brain Science, Translation, Innovation, and Modulation Center.

In addition, tDCS and other transcranial electrical stimulation techniques seem to have a better safety profile than “many of the other things we send patients home with to treat their pain,” he said.

On the other hand, this risk calculus changes in a scenario where patients are neurologically intact, he said.

The brain, Hamilton noted, exhibits functional differences based on the region undergoing stimulation. This means users should follow a specific, prescribed method. However, he pointed out that those using commercially available devices often lack clear guidance on where to place the electrodes and what intensity to use.

“This raises concerns because the way you use the device is important,” he said.

Hamilton also highlighted important ethical considerations regarding enhanced cognition through technology or pharmaceutical interventions. The possibility of coercive use raises questions about equity and fairness, particularly if individuals feel pressured to use such devices to remain competitive in academic or professional settings.

This mirrors the current issues surrounding the use of stimulants among students, where those without ADHD may feel compelled to use these drugs to improve performance. In addition, there is the possibility that the capacity to access devices that enhance cognition could exacerbate existing inequalities.

“Any time you introduce a technological intervention, you have to worry about discriminative justice. That’s where only people who can afford such devices or have access to specialists who can give them such devices get to receive improvements in their cognition,” Hamilton said.

Neither the American Academy of Neurology nor the American Psychiatric Association has established practice guidelines for tDCS, either for use in clinical settings or for use at home. Hamilton believes this is due to the current lack of data, noting that organizations likely want to see more approvals and widespread use before creating guidelines.

Fins emphasized the need for organized medicine to sponsor research, noting that the use of these devices is becoming a public health issue. He expressed concern that some devices are marketed as nonmedical interventions, despite involving medical procedures like brain stimulation. He concluded that while scrutiny is necessary, the current landscape should be approached without judgment.

Fins reported no relevant financial relationships. Philip reported serving on a scientific advisory board for Pulvinar Neuro and past involvement in clinical trials related to these devices and their use as home. Hamilton reported he is on the board of trustees for the McKnight Brain Research Foundation, which is dedicated to advancing healthy cognitive aging.
 

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

As at-home, do-it-yourself (DIY) brain stimulation devices like transcranial direct current stimulation (tDCS) gain popularity for common psychiatric conditions like depression, anxiety, and posttraumatic stress disorder (PTSD), questions arise about their safety and efficacy.

However, the US Food and Drug Administration (FDA) has yet to “fully” clear any of these devices and has only granted breakthrough device designation to a few. In addition, most of the portable products don’t market themselves as medical interventions, putting them into a regulatory “gray area” that has little oversight.

This has led to a free-for-all environment, allowing individuals to purchase these products online and self-administer “treatment” — often without the guidance or even knowledge of their healthcare providers.

So how effective and safe are these noninvasive brain stimulators, and what guidance, if any, should clinicians provide to patients who are or are contemplating using them at home; what does the research show, and what are the ethical considerations?
 

What the Research Shows

Data from studies examining unsupervised at-home and use under medical supervision are mixed. Results from a recent randomized trial of more than 200 participants showed no significant difference in safety or efficacy between adjunctive at-home tDCS and at-home sham tDCS for depressive symptoms.

“To be fair, they did not find any unexpected safety issues. What they did find was that there was no clear signal that it worked,” said Noah S. Philip, MD, professor of psychiatry and human behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Philip, who is also lead for mental health research at Brown’s Center for Neurorestoration and Neurotechnology, Providence, Rhode Island, and was not involved in the study, noted that while other research papers have shown more promising results for depression and other conditions such as adult attention-deficit/hyperactivity disorder (ADHD) and pain, they often are not placebo controlled or include large numbers of patients.

Still, he added the growing use of these devices reflects the fact that standard treatment often doesn’t meet patients’ needs.

“Broadly speaking, part of the hope with brain stimulation is that instead of taking a pill, we’re trying to more directly affect the brain tissues involved — and therefore, avoid the issue of having systemic side effects that you get from the meds. There’s certainly a hunger” for better interventions, Philip said.

tDCS involves a low-intensity electrical current applied through electrodes on the scalp in order to influence brain activity. Generally speaking, it emits less energy than other types of noninvasive brain stimulation, such as transcranial magnetic stimulation. “The trade-off is that’s it also a little harder to find a clear signal about how it works,” Philip said.

As such, he added, it’s important for clinicians to familiarize themselves with these devices, to ask about patient use, and to set up structured assessments of efficacy and adverse events.

Results from a randomized trial published last year in The Lancet showed no significant benefit for in-office use of tDCS plus a selective serotonin reuptake inhibitor vs sham tDCS for major depression.

On the other hand, a randomized trial published earlier this year in Brain Stimulation showed that older adults who received active tDCS had greater reductions in depressive and anxiety symptoms than those in the sham group.

In addition, results from a small study of eight participants published last year in SAGE Open Medicine showed adjuvant tDCS helped patients with refractory PTSD. Finally, a randomized trial of 54 veterans from Philip’s own team showed tDCS plus virtual reality was effective for combat-related PTSD.

Although there have also been several studies showing possible benefit of tDCS for Alzheimer’s disease, Gayatri Devi, MD, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, noted in a Medscape Neurology Decision Point that “the problem with all these studies is that they’re all very small, and there [are] so many different variables in terms of how you interpret response.”
 

On-Demand Brain Stim

As for at-home use, there’s now a wide offering of these types of devices available online, allowing an individual to apply daily brain stimulation via headsets, dispensing with the need to consult a clinician. Most are battery-powered and emit a low-level current.

Philip noted that there are essentially two ways to obtain such devices. Some are readily available from online stores, while others require a prescription, which typically includes guidelines on how to use the device.

So far, none of these portable products have been fully cleared by the FDA — although the agency did grant Breakthrough Device designation to Sooma Medical for its device to treat depression in 2023 and to Flow Neuroscience in 2022.

In August 2023, Flow announced that its device is now being reviewed for full FDA clearance on the basis of trial results showing at-home tDCS was “twice as effective” as antidepressants. The company received regulatory approval in Europe in 2019.

Other research has shown “encouraging” results for these at-home devices for conditions such as adult ADHD and pain relief with remote supervision.

Philip noted that more high-quality randomized controlled trials are definitely needed, with “a number of companies probably getting close to releasing data sometime soon.”

Is it possible that a placebo effect is at work here? “Yes, partially,” said Philip. Users often become more mindful of managing their depression and other conditions, which leads to behavior change, he said.
 

A Quick Fix for a Broken System?

Joseph J. Fins, MD, The E. William Davis Jr, MD, professor of Medical Ethics and chief of the Division of Medical Ethics at Weill Cornell Medicine, New York City, also believes there could be a placebo effect at play.

“It’s important that we don’t ascribe efficacy to a device without being aware of the placebo effect,” he said. That’s why more and larger, placebo-controlled trials are needed, he added.

There’s a multitude of reasons why patients may turn to at-home devices on their own, including drug shortages and the inability to see a psychiatrist in a timely manner.

“I think it speaks to the isolation of these folks that leads to them doing this on their own. These devices become a technological quick fix for a system that’s desperately broken. There’s nothing wrong with being a consumer, but at a certain point they need to be a patient, and they need to have a clinician there to help them,” he said.

Fins said that he also worries about regulatory oversight because of the way the devices are classified. He likened them to supplements, which, because they don’t make certain claims, are not regulated with the same stringency as other products and fall into an area “in between regulatory spheres.”

“I think we’re trying to take old regulatory frameworks and jerry-rig it to accommodate new and evolving technologies. And I think we need to have serious study of how we protect patients as they become consumers — to make sure there’s enough safety and enough efficacy and that they don’t get ripped off out of desperation,” Fins said.

As for safety, at-home devices are unlikely to cause physical harm — at least when used as intended. “The riskier situations happen when people build their own, overuse it, or use it in combination with drugs or alcohol or other factors that can produce unpredictable results,” Philip said.

He added that DIY-built products carry a higher risk for burns or excessive energy output. A 2016 “open letter” from a group of neurologists, published in Annals of Neurology, warned about the dangers of DIY tDCS.

In addition, Philip noted that he has seen instances where patients become manic after using at-home tDCS, especially when trying to improve cognition.

“We have seen a number of peculiar side effects emerge in those situations. Typically, it’s anxiety, panic attacks, and sensitivity to bright lights, in addition to the emergence of mania, which would require major psychiatric intervention,” he said.

“So, it’s important that if folks do engage with these sorts of things, it’s with some degree of medical involvement,” Philip added.
 

Ethical Considerations

Roy Hamilton, MD, professor of neurology, psychiatry, and physical medicine & rehabilitation at the University of Pennsylvania, in Philadelphia, said that in the setting of proper training, proper clinician communication, and proper oversight, he doesn’t view at-home tDCS as ethically problematic.

“For individuals who have conditions that are clearly causing them remarkable detriment to quality of life or to their health, it seems like the risk-benefit ratio with respect to the likelihood of harm is quite good,” said Hamilton, who is also the director of the Penn Brain Science, Translation, Innovation, and Modulation Center.

In addition, tDCS and other transcranial electrical stimulation techniques seem to have a better safety profile than “many of the other things we send patients home with to treat their pain,” he said.

On the other hand, this risk calculus changes in a scenario where patients are neurologically intact, he said.

The brain, Hamilton noted, exhibits functional differences based on the region undergoing stimulation. This means users should follow a specific, prescribed method. However, he pointed out that those using commercially available devices often lack clear guidance on where to place the electrodes and what intensity to use.

“This raises concerns because the way you use the device is important,” he said.

Hamilton also highlighted important ethical considerations regarding enhanced cognition through technology or pharmaceutical interventions. The possibility of coercive use raises questions about equity and fairness, particularly if individuals feel pressured to use such devices to remain competitive in academic or professional settings.

This mirrors the current issues surrounding the use of stimulants among students, where those without ADHD may feel compelled to use these drugs to improve performance. In addition, there is the possibility that the capacity to access devices that enhance cognition could exacerbate existing inequalities.

“Any time you introduce a technological intervention, you have to worry about discriminative justice. That’s where only people who can afford such devices or have access to specialists who can give them such devices get to receive improvements in their cognition,” Hamilton said.

Neither the American Academy of Neurology nor the American Psychiatric Association has established practice guidelines for tDCS, either for use in clinical settings or for use at home. Hamilton believes this is due to the current lack of data, noting that organizations likely want to see more approvals and widespread use before creating guidelines.

Fins emphasized the need for organized medicine to sponsor research, noting that the use of these devices is becoming a public health issue. He expressed concern that some devices are marketed as nonmedical interventions, despite involving medical procedures like brain stimulation. He concluded that while scrutiny is necessary, the current landscape should be approached without judgment.

Fins reported no relevant financial relationships. Philip reported serving on a scientific advisory board for Pulvinar Neuro and past involvement in clinical trials related to these devices and their use as home. Hamilton reported he is on the board of trustees for the McKnight Brain Research Foundation, which is dedicated to advancing healthy cognitive aging.
 

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

As at-home, do-it-yourself (DIY) brain stimulation devices like transcranial direct current stimulation (tDCS) gain popularity for common psychiatric conditions like depression, anxiety, and posttraumatic stress disorder (PTSD), questions arise about their safety and efficacy.

However, the US Food and Drug Administration (FDA) has yet to “fully” clear any of these devices and has only granted breakthrough device designation to a few. In addition, most of the portable products don’t market themselves as medical interventions, putting them into a regulatory “gray area” that has little oversight.

This has led to a free-for-all environment, allowing individuals to purchase these products online and self-administer “treatment” — often without the guidance or even knowledge of their healthcare providers.

So how effective and safe are these noninvasive brain stimulators, and what guidance, if any, should clinicians provide to patients who are or are contemplating using them at home; what does the research show, and what are the ethical considerations?
 

What the Research Shows

Data from studies examining unsupervised at-home and use under medical supervision are mixed. Results from a recent randomized trial of more than 200 participants showed no significant difference in safety or efficacy between adjunctive at-home tDCS and at-home sham tDCS for depressive symptoms.

“To be fair, they did not find any unexpected safety issues. What they did find was that there was no clear signal that it worked,” said Noah S. Philip, MD, professor of psychiatry and human behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Philip, who is also lead for mental health research at Brown’s Center for Neurorestoration and Neurotechnology, Providence, Rhode Island, and was not involved in the study, noted that while other research papers have shown more promising results for depression and other conditions such as adult attention-deficit/hyperactivity disorder (ADHD) and pain, they often are not placebo controlled or include large numbers of patients.

Still, he added the growing use of these devices reflects the fact that standard treatment often doesn’t meet patients’ needs.

“Broadly speaking, part of the hope with brain stimulation is that instead of taking a pill, we’re trying to more directly affect the brain tissues involved — and therefore, avoid the issue of having systemic side effects that you get from the meds. There’s certainly a hunger” for better interventions, Philip said.

tDCS involves a low-intensity electrical current applied through electrodes on the scalp in order to influence brain activity. Generally speaking, it emits less energy than other types of noninvasive brain stimulation, such as transcranial magnetic stimulation. “The trade-off is that’s it also a little harder to find a clear signal about how it works,” Philip said.

As such, he added, it’s important for clinicians to familiarize themselves with these devices, to ask about patient use, and to set up structured assessments of efficacy and adverse events.

Results from a randomized trial published last year in The Lancet showed no significant benefit for in-office use of tDCS plus a selective serotonin reuptake inhibitor vs sham tDCS for major depression.

On the other hand, a randomized trial published earlier this year in Brain Stimulation showed that older adults who received active tDCS had greater reductions in depressive and anxiety symptoms than those in the sham group.

In addition, results from a small study of eight participants published last year in SAGE Open Medicine showed adjuvant tDCS helped patients with refractory PTSD. Finally, a randomized trial of 54 veterans from Philip’s own team showed tDCS plus virtual reality was effective for combat-related PTSD.

Although there have also been several studies showing possible benefit of tDCS for Alzheimer’s disease, Gayatri Devi, MD, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, noted in a Medscape Neurology Decision Point that “the problem with all these studies is that they’re all very small, and there [are] so many different variables in terms of how you interpret response.”
 

On-Demand Brain Stim

As for at-home use, there’s now a wide offering of these types of devices available online, allowing an individual to apply daily brain stimulation via headsets, dispensing with the need to consult a clinician. Most are battery-powered and emit a low-level current.

Philip noted that there are essentially two ways to obtain such devices. Some are readily available from online stores, while others require a prescription, which typically includes guidelines on how to use the device.

So far, none of these portable products have been fully cleared by the FDA — although the agency did grant Breakthrough Device designation to Sooma Medical for its device to treat depression in 2023 and to Flow Neuroscience in 2022.

In August 2023, Flow announced that its device is now being reviewed for full FDA clearance on the basis of trial results showing at-home tDCS was “twice as effective” as antidepressants. The company received regulatory approval in Europe in 2019.

Other research has shown “encouraging” results for these at-home devices for conditions such as adult ADHD and pain relief with remote supervision.

Philip noted that more high-quality randomized controlled trials are definitely needed, with “a number of companies probably getting close to releasing data sometime soon.”

Is it possible that a placebo effect is at work here? “Yes, partially,” said Philip. Users often become more mindful of managing their depression and other conditions, which leads to behavior change, he said.
 

A Quick Fix for a Broken System?

Joseph J. Fins, MD, The E. William Davis Jr, MD, professor of Medical Ethics and chief of the Division of Medical Ethics at Weill Cornell Medicine, New York City, also believes there could be a placebo effect at play.

“It’s important that we don’t ascribe efficacy to a device without being aware of the placebo effect,” he said. That’s why more and larger, placebo-controlled trials are needed, he added.

There’s a multitude of reasons why patients may turn to at-home devices on their own, including drug shortages and the inability to see a psychiatrist in a timely manner.

“I think it speaks to the isolation of these folks that leads to them doing this on their own. These devices become a technological quick fix for a system that’s desperately broken. There’s nothing wrong with being a consumer, but at a certain point they need to be a patient, and they need to have a clinician there to help them,” he said.

Fins said that he also worries about regulatory oversight because of the way the devices are classified. He likened them to supplements, which, because they don’t make certain claims, are not regulated with the same stringency as other products and fall into an area “in between regulatory spheres.”

“I think we’re trying to take old regulatory frameworks and jerry-rig it to accommodate new and evolving technologies. And I think we need to have serious study of how we protect patients as they become consumers — to make sure there’s enough safety and enough efficacy and that they don’t get ripped off out of desperation,” Fins said.

As for safety, at-home devices are unlikely to cause physical harm — at least when used as intended. “The riskier situations happen when people build their own, overuse it, or use it in combination with drugs or alcohol or other factors that can produce unpredictable results,” Philip said.

He added that DIY-built products carry a higher risk for burns or excessive energy output. A 2016 “open letter” from a group of neurologists, published in Annals of Neurology, warned about the dangers of DIY tDCS.

In addition, Philip noted that he has seen instances where patients become manic after using at-home tDCS, especially when trying to improve cognition.

“We have seen a number of peculiar side effects emerge in those situations. Typically, it’s anxiety, panic attacks, and sensitivity to bright lights, in addition to the emergence of mania, which would require major psychiatric intervention,” he said.

“So, it’s important that if folks do engage with these sorts of things, it’s with some degree of medical involvement,” Philip added.
 

Ethical Considerations

Roy Hamilton, MD, professor of neurology, psychiatry, and physical medicine & rehabilitation at the University of Pennsylvania, in Philadelphia, said that in the setting of proper training, proper clinician communication, and proper oversight, he doesn’t view at-home tDCS as ethically problematic.

“For individuals who have conditions that are clearly causing them remarkable detriment to quality of life or to their health, it seems like the risk-benefit ratio with respect to the likelihood of harm is quite good,” said Hamilton, who is also the director of the Penn Brain Science, Translation, Innovation, and Modulation Center.

In addition, tDCS and other transcranial electrical stimulation techniques seem to have a better safety profile than “many of the other things we send patients home with to treat their pain,” he said.

On the other hand, this risk calculus changes in a scenario where patients are neurologically intact, he said.

The brain, Hamilton noted, exhibits functional differences based on the region undergoing stimulation. This means users should follow a specific, prescribed method. However, he pointed out that those using commercially available devices often lack clear guidance on where to place the electrodes and what intensity to use.

“This raises concerns because the way you use the device is important,” he said.

Hamilton also highlighted important ethical considerations regarding enhanced cognition through technology or pharmaceutical interventions. The possibility of coercive use raises questions about equity and fairness, particularly if individuals feel pressured to use such devices to remain competitive in academic or professional settings.

This mirrors the current issues surrounding the use of stimulants among students, where those without ADHD may feel compelled to use these drugs to improve performance. In addition, there is the possibility that the capacity to access devices that enhance cognition could exacerbate existing inequalities.

“Any time you introduce a technological intervention, you have to worry about discriminative justice. That’s where only people who can afford such devices or have access to specialists who can give them such devices get to receive improvements in their cognition,” Hamilton said.

Neither the American Academy of Neurology nor the American Psychiatric Association has established practice guidelines for tDCS, either for use in clinical settings or for use at home. Hamilton believes this is due to the current lack of data, noting that organizations likely want to see more approvals and widespread use before creating guidelines.

Fins emphasized the need for organized medicine to sponsor research, noting that the use of these devices is becoming a public health issue. He expressed concern that some devices are marketed as nonmedical interventions, despite involving medical procedures like brain stimulation. He concluded that while scrutiny is necessary, the current landscape should be approached without judgment.

Fins reported no relevant financial relationships. Philip reported serving on a scientific advisory board for Pulvinar Neuro and past involvement in clinical trials related to these devices and their use as home. Hamilton reported he is on the board of trustees for the McKnight Brain Research Foundation, which is dedicated to advancing healthy cognitive aging.
 

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

A growing body of research has increasingly connected hearing loss with a higher risk for dementia. In addition, some studies suggest that wearing hearing aids may help prevent dementia, though one study was recently voluntarily retracted due to methodological errors.

Given the overall evidence, how robust are these associations? And what guidance should clinicians provide to their patients?

Frank Lin, MD, PhD, a clinician and professor of otolaryngology and epidemiology at Johns Hopkins University School of Medicine, Baltimore, emphasized that the evidence from the past 10-15 years strongly links hearing loss to cognitive decline.

While quantifying the exact increase in risk is challenging, Dr. Lin said, “there’s no doubt about it; it’s not trivial.”

With respect to the potential link between hearing aids and dementia prevention, Dr. Lin is involved in the ongoing ACHIEVE randomized trial. Results presented at the 2023 Alzheimer’s Association International Conference and simultaneously published in The Lancet revealed participants who used hearing aids experienced a significant slowing of cognitive decline compared with those who received health education.

“It’s a no-risk intervention that can benefit social function, and for people at risk for cognitive decline, it can actually benefit cognitive health,” Dr. Lin said.
 

Potential Mechanisms

Dr. Lin pointed out that the Lancet Commission on Dementia identifies hearing impairment as one of the most significant risk factors for dementia. Overall, the consensus from most studies is that hearing loss definitely increases the risk for cognitive decline and dementia, he said.

Several hypotheses may explain this connection, and Dr. Lin believes that a combination of three key mechanisms is likely to be central to understanding this link.

The first theory focuses on cognitive load. As people experience age-related hearing changes, “the inner ear is no longer sending signals clearly to the brain,” Dr. Lin explained. This forces the brain to work harder, increasing its cognitive load as it reallocates resources to assist with hearing.

Dr. Lin emphasized that this is a hypothesis and does not prove hearing loss directly causes cognitive decline or dementia. Rather, it suggests that hearing loss accelerates the “unmasking” of cognitive issues. Brain resources that might otherwise buffer against dementia’s pathologic triggers are consumed earlier due to the demands of managing hearing loss.

The second potential mechanism suggests that hearing loss may have detrimental effects on brain structure and function over time — a theory supported by several recent studies.

These studies show that individuals with more severe hearing loss experience faster rates of brain atrophy. The reduced stimulation from poor auditory signals accelerates brain atrophy, Dr. Lin explained.

The third hypothesis focuses on social isolation. Individuals with hearing loss may engage less in social activities, reducing cognitive stimulation and overall social interaction. It’s well-known that social engagement and cognitive stimulation are crucial for maintaining cognitive health over time, Dr. Lin said.

Overall, Dr. Lin believes that the association between hearing loss and an increased risk for cognitive decline likely involves a combination of all three potential mechanisms. It’s not a matter of one theory being right and the others being wrong, he said.
 

The Role of Hearing Aids

However, the jury is out on the role of hearing aids in preventing dementia.

A large observational study published in 2023 in Lancet Public Health was hailed by its investigators as providing “the best evidence to date” that hearing aids could mitigate the impact of hearing loss on dementia (Lancet Public Health. 2023 May;8[5]:e329-e338. doi: 10.1016/S2468-2667[23]00048-8). However, the authors voluntarily retracted the paper in December 2023 due to a coding error.

Despite this, a large meta-analysis published in JAMA Neurology suggested that hearing aids might reduce cognitive decline and dementia risk and even enhance short-term cognitive function.

Additionally, the ACHIEVE study, the first randomized trial to investigate these issues, included nearly 1000 older participants from two populations — those from the ARIC study and healthy volunteers. Participants were randomly assigned to receive either a hearing intervention or education on healthy aging.

Although the primary endpoint of change in standardized neurocognitive scores at year 3 showed no significant difference between the hearing intervention and health education groups, the ARIC cohort experienced a notable 48% reduction in cognitive decline with hearing aids compared with education.

Dr. Lin explained that, due to the study’s design, the control group was healthier than the ARIC cohort, which was at higher risk for cognitive decline due to factors such as age and diabetes. This is where they observed a strong effect of hearing intervention in reducing cognitive decline within just 3 years, Dr. Lin said.

Conversely, the hearing aids had minimal impact on the healthy controls, likely because they had not experienced cognitive decline to begin with. Essentially, the benefits of hearing aids were more apparent once cognitive issues were already present.

“It seems sort of obvious. In a group of people who aren’t at risk for cognitive decline, a hearing intervention isn’t going to benefit their cognition” in the short term, Dr. Lin noted. That said, the investigators are continuing to follow the healthy controls to determine whether hearing aids lower dementia risk over the long term.
 

Which Comes First?

Some experts have questioned the directionality of the link between hearing aids and dementia — do hearing aids reduce dementia risk or are individuals with dementia simply less likely to use them?

Dr. Lin noted that observational studies often have confounders. For instance, people who use hearing aids are often healthier and better educated. This makes it difficult to distinguish the effect of the intervention from the factors that led people to use it, he said.

In contrast, the ACHIEVE trial, a randomized study, was designed to separate these factors from the hearing intervention, Dr. Lin explained.

However, he added that ACHIEVE was not specifically powered to assess dementia development, focusing instead on cognitive decline. The investigators plan long-term follow-up of participants to evaluate the impact on dementia in the future.

So, given the current evidence, what should clinicians tell their patients?

Because all people experience some degree of hearing changes as they age, which can gradually affect communication and social engagement, it’s important for everyone to be aware of their hearing health, Dr. Lin said.

He noted there are apps available that allow individuals to measure their hearing with their phones, including determining their “hearing number.”

With respect to hearing aids, Dr. Lin noted that if individuals have trouble participating in everyday activities, addressing hearing issues and considering a hearing intervention is crucial.

There’s no medical risk associated with hearing aids, he said. Even if they only improve social activities and engagement, that’s a benefit. If they also have potential positive effects on cognitive health, “even better,” he added.

Dr. Lin noted that as of 2022, hearing aids are now available over the counter, a move that has improved accessibility. In addition, new technologies, such as stylish “hearing aid glasses,” are being developed to offer more appealing options and reduce the stigma associated with traditional devices.

People often view hearing loss as a significant life event and are reluctant to admit they need hearing aids. However, focusing on “what’s your hearing?” as a neutral tracking metric could make it easier to adopt new technologies in the future, Lin said.
 

Alzheimer’s Association Weighs in

Heather Snyder, PhD, vice president, Medical & Scientific Relations at the Alzheimer’s Association, echoed Dr. Lin, noting that there has been substantial research showing a link between hearing loss and cognitive decline.

“This association is something that we have seen repeated and replicated in a number of different studies. What we don’t know is the cause and effect,” Dr. Snyder said.

She noted it is unknown whether there is a causal link between hearing loss and cognitive decline and/or whether cognitive decline may contribute to hearing loss. These are some of the “big questions” that remain, said Dr. Snyder.

Still, she noted that hearing health is an important part of quality of life and overall brain health and “should be part of the conversation” between clinicians and their patients.

Discussing the results of the ACHIEVE study, Dr. Snyder highlighted that while the subgroup at higher risk for cognitive decline did experience significant improvement, the overall population did not show a benefit from the intervention.

The brain “is complex,” and it’s unlikely that a single intervention or target will provide all the benefits, Dr. Snyder said.

She emphasized that addressing hearing loss with hearing aids, combined with managing other modifiable risk factors — such as heart and metabolic health, physical activity, and a balanced diet — appears to offer the greatest potential for synergy and preserving cognition.

Drs. Lin and Snyder reported no relevant conflicts of interest.
 

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

A growing body of research has increasingly connected hearing loss with a higher risk for dementia. In addition, some studies suggest that wearing hearing aids may help prevent dementia, though one study was recently voluntarily retracted due to methodological errors.

Given the overall evidence, how robust are these associations? And what guidance should clinicians provide to their patients?

Frank Lin, MD, PhD, a clinician and professor of otolaryngology and epidemiology at Johns Hopkins University School of Medicine, Baltimore, emphasized that the evidence from the past 10-15 years strongly links hearing loss to cognitive decline.

While quantifying the exact increase in risk is challenging, Dr. Lin said, “there’s no doubt about it; it’s not trivial.”

With respect to the potential link between hearing aids and dementia prevention, Dr. Lin is involved in the ongoing ACHIEVE randomized trial. Results presented at the 2023 Alzheimer’s Association International Conference and simultaneously published in The Lancet revealed participants who used hearing aids experienced a significant slowing of cognitive decline compared with those who received health education.

“It’s a no-risk intervention that can benefit social function, and for people at risk for cognitive decline, it can actually benefit cognitive health,” Dr. Lin said.
 

Potential Mechanisms

Dr. Lin pointed out that the Lancet Commission on Dementia identifies hearing impairment as one of the most significant risk factors for dementia. Overall, the consensus from most studies is that hearing loss definitely increases the risk for cognitive decline and dementia, he said.

Several hypotheses may explain this connection, and Dr. Lin believes that a combination of three key mechanisms is likely to be central to understanding this link.

The first theory focuses on cognitive load. As people experience age-related hearing changes, “the inner ear is no longer sending signals clearly to the brain,” Dr. Lin explained. This forces the brain to work harder, increasing its cognitive load as it reallocates resources to assist with hearing.

Dr. Lin emphasized that this is a hypothesis and does not prove hearing loss directly causes cognitive decline or dementia. Rather, it suggests that hearing loss accelerates the “unmasking” of cognitive issues. Brain resources that might otherwise buffer against dementia’s pathologic triggers are consumed earlier due to the demands of managing hearing loss.

The second potential mechanism suggests that hearing loss may have detrimental effects on brain structure and function over time — a theory supported by several recent studies.

These studies show that individuals with more severe hearing loss experience faster rates of brain atrophy. The reduced stimulation from poor auditory signals accelerates brain atrophy, Dr. Lin explained.

The third hypothesis focuses on social isolation. Individuals with hearing loss may engage less in social activities, reducing cognitive stimulation and overall social interaction. It’s well-known that social engagement and cognitive stimulation are crucial for maintaining cognitive health over time, Dr. Lin said.

Overall, Dr. Lin believes that the association between hearing loss and an increased risk for cognitive decline likely involves a combination of all three potential mechanisms. It’s not a matter of one theory being right and the others being wrong, he said.
 

The Role of Hearing Aids

However, the jury is out on the role of hearing aids in preventing dementia.

A large observational study published in 2023 in Lancet Public Health was hailed by its investigators as providing “the best evidence to date” that hearing aids could mitigate the impact of hearing loss on dementia (Lancet Public Health. 2023 May;8[5]:e329-e338. doi: 10.1016/S2468-2667[23]00048-8). However, the authors voluntarily retracted the paper in December 2023 due to a coding error.

Despite this, a large meta-analysis published in JAMA Neurology suggested that hearing aids might reduce cognitive decline and dementia risk and even enhance short-term cognitive function.

Additionally, the ACHIEVE study, the first randomized trial to investigate these issues, included nearly 1000 older participants from two populations — those from the ARIC study and healthy volunteers. Participants were randomly assigned to receive either a hearing intervention or education on healthy aging.

Although the primary endpoint of change in standardized neurocognitive scores at year 3 showed no significant difference between the hearing intervention and health education groups, the ARIC cohort experienced a notable 48% reduction in cognitive decline with hearing aids compared with education.

Dr. Lin explained that, due to the study’s design, the control group was healthier than the ARIC cohort, which was at higher risk for cognitive decline due to factors such as age and diabetes. This is where they observed a strong effect of hearing intervention in reducing cognitive decline within just 3 years, Dr. Lin said.

Conversely, the hearing aids had minimal impact on the healthy controls, likely because they had not experienced cognitive decline to begin with. Essentially, the benefits of hearing aids were more apparent once cognitive issues were already present.

“It seems sort of obvious. In a group of people who aren’t at risk for cognitive decline, a hearing intervention isn’t going to benefit their cognition” in the short term, Dr. Lin noted. That said, the investigators are continuing to follow the healthy controls to determine whether hearing aids lower dementia risk over the long term.
 

Which Comes First?

Some experts have questioned the directionality of the link between hearing aids and dementia — do hearing aids reduce dementia risk or are individuals with dementia simply less likely to use them?

Dr. Lin noted that observational studies often have confounders. For instance, people who use hearing aids are often healthier and better educated. This makes it difficult to distinguish the effect of the intervention from the factors that led people to use it, he said.

In contrast, the ACHIEVE trial, a randomized study, was designed to separate these factors from the hearing intervention, Dr. Lin explained.

However, he added that ACHIEVE was not specifically powered to assess dementia development, focusing instead on cognitive decline. The investigators plan long-term follow-up of participants to evaluate the impact on dementia in the future.

So, given the current evidence, what should clinicians tell their patients?

Because all people experience some degree of hearing changes as they age, which can gradually affect communication and social engagement, it’s important for everyone to be aware of their hearing health, Dr. Lin said.

He noted there are apps available that allow individuals to measure their hearing with their phones, including determining their “hearing number.”

With respect to hearing aids, Dr. Lin noted that if individuals have trouble participating in everyday activities, addressing hearing issues and considering a hearing intervention is crucial.

There’s no medical risk associated with hearing aids, he said. Even if they only improve social activities and engagement, that’s a benefit. If they also have potential positive effects on cognitive health, “even better,” he added.

Dr. Lin noted that as of 2022, hearing aids are now available over the counter, a move that has improved accessibility. In addition, new technologies, such as stylish “hearing aid glasses,” are being developed to offer more appealing options and reduce the stigma associated with traditional devices.

People often view hearing loss as a significant life event and are reluctant to admit they need hearing aids. However, focusing on “what’s your hearing?” as a neutral tracking metric could make it easier to adopt new technologies in the future, Lin said.
 

Alzheimer’s Association Weighs in

Heather Snyder, PhD, vice president, Medical & Scientific Relations at the Alzheimer’s Association, echoed Dr. Lin, noting that there has been substantial research showing a link between hearing loss and cognitive decline.

“This association is something that we have seen repeated and replicated in a number of different studies. What we don’t know is the cause and effect,” Dr. Snyder said.

She noted it is unknown whether there is a causal link between hearing loss and cognitive decline and/or whether cognitive decline may contribute to hearing loss. These are some of the “big questions” that remain, said Dr. Snyder.

Still, she noted that hearing health is an important part of quality of life and overall brain health and “should be part of the conversation” between clinicians and their patients.

Discussing the results of the ACHIEVE study, Dr. Snyder highlighted that while the subgroup at higher risk for cognitive decline did experience significant improvement, the overall population did not show a benefit from the intervention.

The brain “is complex,” and it’s unlikely that a single intervention or target will provide all the benefits, Dr. Snyder said.

She emphasized that addressing hearing loss with hearing aids, combined with managing other modifiable risk factors — such as heart and metabolic health, physical activity, and a balanced diet — appears to offer the greatest potential for synergy and preserving cognition.

Drs. Lin and Snyder reported no relevant conflicts of interest.
 

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

A growing body of research has increasingly connected hearing loss with a higher risk for dementia. In addition, some studies suggest that wearing hearing aids may help prevent dementia, though one study was recently voluntarily retracted due to methodological errors.

Given the overall evidence, how robust are these associations? And what guidance should clinicians provide to their patients?

Frank Lin, MD, PhD, a clinician and professor of otolaryngology and epidemiology at Johns Hopkins University School of Medicine, Baltimore, emphasized that the evidence from the past 10-15 years strongly links hearing loss to cognitive decline.

While quantifying the exact increase in risk is challenging, Dr. Lin said, “there’s no doubt about it; it’s not trivial.”

With respect to the potential link between hearing aids and dementia prevention, Dr. Lin is involved in the ongoing ACHIEVE randomized trial. Results presented at the 2023 Alzheimer’s Association International Conference and simultaneously published in The Lancet revealed participants who used hearing aids experienced a significant slowing of cognitive decline compared with those who received health education.

“It’s a no-risk intervention that can benefit social function, and for people at risk for cognitive decline, it can actually benefit cognitive health,” Dr. Lin said.
 

Potential Mechanisms

Dr. Lin pointed out that the Lancet Commission on Dementia identifies hearing impairment as one of the most significant risk factors for dementia. Overall, the consensus from most studies is that hearing loss definitely increases the risk for cognitive decline and dementia, he said.

Several hypotheses may explain this connection, and Dr. Lin believes that a combination of three key mechanisms is likely to be central to understanding this link.

The first theory focuses on cognitive load. As people experience age-related hearing changes, “the inner ear is no longer sending signals clearly to the brain,” Dr. Lin explained. This forces the brain to work harder, increasing its cognitive load as it reallocates resources to assist with hearing.

Dr. Lin emphasized that this is a hypothesis and does not prove hearing loss directly causes cognitive decline or dementia. Rather, it suggests that hearing loss accelerates the “unmasking” of cognitive issues. Brain resources that might otherwise buffer against dementia’s pathologic triggers are consumed earlier due to the demands of managing hearing loss.

The second potential mechanism suggests that hearing loss may have detrimental effects on brain structure and function over time — a theory supported by several recent studies.

These studies show that individuals with more severe hearing loss experience faster rates of brain atrophy. The reduced stimulation from poor auditory signals accelerates brain atrophy, Dr. Lin explained.

The third hypothesis focuses on social isolation. Individuals with hearing loss may engage less in social activities, reducing cognitive stimulation and overall social interaction. It’s well-known that social engagement and cognitive stimulation are crucial for maintaining cognitive health over time, Dr. Lin said.

Overall, Dr. Lin believes that the association between hearing loss and an increased risk for cognitive decline likely involves a combination of all three potential mechanisms. It’s not a matter of one theory being right and the others being wrong, he said.
 

The Role of Hearing Aids

However, the jury is out on the role of hearing aids in preventing dementia.

A large observational study published in 2023 in Lancet Public Health was hailed by its investigators as providing “the best evidence to date” that hearing aids could mitigate the impact of hearing loss on dementia (Lancet Public Health. 2023 May;8[5]:e329-e338. doi: 10.1016/S2468-2667[23]00048-8). However, the authors voluntarily retracted the paper in December 2023 due to a coding error.

Despite this, a large meta-analysis published in JAMA Neurology suggested that hearing aids might reduce cognitive decline and dementia risk and even enhance short-term cognitive function.

Additionally, the ACHIEVE study, the first randomized trial to investigate these issues, included nearly 1000 older participants from two populations — those from the ARIC study and healthy volunteers. Participants were randomly assigned to receive either a hearing intervention or education on healthy aging.

Although the primary endpoint of change in standardized neurocognitive scores at year 3 showed no significant difference between the hearing intervention and health education groups, the ARIC cohort experienced a notable 48% reduction in cognitive decline with hearing aids compared with education.

Dr. Lin explained that, due to the study’s design, the control group was healthier than the ARIC cohort, which was at higher risk for cognitive decline due to factors such as age and diabetes. This is where they observed a strong effect of hearing intervention in reducing cognitive decline within just 3 years, Dr. Lin said.

Conversely, the hearing aids had minimal impact on the healthy controls, likely because they had not experienced cognitive decline to begin with. Essentially, the benefits of hearing aids were more apparent once cognitive issues were already present.

“It seems sort of obvious. In a group of people who aren’t at risk for cognitive decline, a hearing intervention isn’t going to benefit their cognition” in the short term, Dr. Lin noted. That said, the investigators are continuing to follow the healthy controls to determine whether hearing aids lower dementia risk over the long term.
 

Which Comes First?

Some experts have questioned the directionality of the link between hearing aids and dementia — do hearing aids reduce dementia risk or are individuals with dementia simply less likely to use them?

Dr. Lin noted that observational studies often have confounders. For instance, people who use hearing aids are often healthier and better educated. This makes it difficult to distinguish the effect of the intervention from the factors that led people to use it, he said.

In contrast, the ACHIEVE trial, a randomized study, was designed to separate these factors from the hearing intervention, Dr. Lin explained.

However, he added that ACHIEVE was not specifically powered to assess dementia development, focusing instead on cognitive decline. The investigators plan long-term follow-up of participants to evaluate the impact on dementia in the future.

So, given the current evidence, what should clinicians tell their patients?

Because all people experience some degree of hearing changes as they age, which can gradually affect communication and social engagement, it’s important for everyone to be aware of their hearing health, Dr. Lin said.

He noted there are apps available that allow individuals to measure their hearing with their phones, including determining their “hearing number.”

With respect to hearing aids, Dr. Lin noted that if individuals have trouble participating in everyday activities, addressing hearing issues and considering a hearing intervention is crucial.

There’s no medical risk associated with hearing aids, he said. Even if they only improve social activities and engagement, that’s a benefit. If they also have potential positive effects on cognitive health, “even better,” he added.

Dr. Lin noted that as of 2022, hearing aids are now available over the counter, a move that has improved accessibility. In addition, new technologies, such as stylish “hearing aid glasses,” are being developed to offer more appealing options and reduce the stigma associated with traditional devices.

People often view hearing loss as a significant life event and are reluctant to admit they need hearing aids. However, focusing on “what’s your hearing?” as a neutral tracking metric could make it easier to adopt new technologies in the future, Lin said.
 

Alzheimer’s Association Weighs in

Heather Snyder, PhD, vice president, Medical & Scientific Relations at the Alzheimer’s Association, echoed Dr. Lin, noting that there has been substantial research showing a link between hearing loss and cognitive decline.

“This association is something that we have seen repeated and replicated in a number of different studies. What we don’t know is the cause and effect,” Dr. Snyder said.

She noted it is unknown whether there is a causal link between hearing loss and cognitive decline and/or whether cognitive decline may contribute to hearing loss. These are some of the “big questions” that remain, said Dr. Snyder.

Still, she noted that hearing health is an important part of quality of life and overall brain health and “should be part of the conversation” between clinicians and their patients.

Discussing the results of the ACHIEVE study, Dr. Snyder highlighted that while the subgroup at higher risk for cognitive decline did experience significant improvement, the overall population did not show a benefit from the intervention.

The brain “is complex,” and it’s unlikely that a single intervention or target will provide all the benefits, Dr. Snyder said.

She emphasized that addressing hearing loss with hearing aids, combined with managing other modifiable risk factors — such as heart and metabolic health, physical activity, and a balanced diet — appears to offer the greatest potential for synergy and preserving cognition.

Drs. Lin and Snyder reported no relevant conflicts of interest.
 

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

For years, electroconvulsive therapy (ECT) has been a lifesaving treatment for patients with treatment-resistant depression (TRD), yet exactly how it works has largely remained a mystery. Now researchers believe they have uncovered the underlying mechanisms behind its therapeutic effects — a discovery that may help clinicians better predict treatment response in individual patients and quell much of the fear and stigma associated with one of psychiatry’s most effective, yet misunderstood, treatments.

Two recent papers published in Translational Psychiatry have highlighted the significance of aperiodic neural activity. The first study showed this activity increased following ECT treatment. The second study expanded on these data by demonstrating a significant increase in aperiodic activity after patients received either ECT or magnetic seizure therapy (MST), which has a better side-effect profile than ECT but lower efficacy.

Aperiodic activity is “like the brain’s background noise, and for years scientists treated it that way and didn’t pay much attention to it,” first author Sydney E. Smith, a PhD candidate at the Voytek Lab in the Neuroscience Graduate Program at the University of California San Diego (UCSD), said in a press release.

However, aperiodic activity boosts inhibitory activity in the brain, effectively slowing it down,” the investigators noted.

In an interview with this news organization, Ms. Smith used a car analogy to explain the mechanism behind ECT. “ECT might be increasing the activity levels in the brain cells that help calm it down. It taps on the brakes that tend to malfunction in depression. By restoring the balance between the gas and the brakes in the brain, some of those depressive symptoms are alleviated,” she said.

Ms. Smith added her team’s research helps demystify one of the most effective yet stigmatized treatments for severe depression.

“Aperiodic activity as a physiologically interpretable EEG metric could be a really valuable new predictive indicator for treatment response,” she added.
 

Fear and Stigma

ECT is primarily used for TRD and is effective in up to 80% of patients, yet it remains one of the least prescribed treatments.

Although it’s been around for almost 90 years, fear and concern about its potential cognitive side effects have contributed to its poor uptake. It is estimated that less than 1% of patients with TRD receive ECT.

Smith noted that the 1970s movie One Flew Over the Cuckoo’s Nest still contributes to ECT’s stigma. In the film, actor Jack Nicholson’s character is forced to undergo ECT as a punishment.

It’s important for clinicians to acknowledge the stigma while advising patients that “the actual treatment doesn’t look anything like what’s in the movies,” noted Ms. Smith. Patients must give informed consent for the procedure, and it’s delivered with the lowest level of effective stimulation.

“So many steps are taken to consider comfort and efficacy for patients and to minimize how scary it can be,” she said.

ECT uses an electrical current to induce a seizure that spreads to deep subcortical structures. MST, which was developed as an alternative to ECT, uses a magnetic field to induce a more focal seizure primarily confined to the cortex.

Although MST has a better side-effect profile, experts noted it has remission rates of 30%-60% compared with ECT. Even one of MST’s inventors, Harold Sackeim, PhD, professor in the Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, is skeptical about its efficacy for TRD.

“I don’t think it works,” Dr. Sackeim, founding editor of Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation, told this news organization.

In addition to being more expensive, MST produces a peak electrical intensity at one-tenth of what a typical ECT stimulus produces. “We’re limited by electrical engineering at this point with MST. That’s my view; others are more optimistic,” he said.
 

A Lifesaving Treatment

One of the reasons ECT isn’t more popular is because for many patients, it’s easier and more convenient to just take a pill, senior investigator Bradley Voytek, PhD, professor of cognitive science at UCSD, said in the release.

“However, in people for whom medications don’t work, [ECT] can be lifesaving. Understanding how it works will help us discover ways to increase the benefits while minimizing side effects,” he added.

In the first study, which included nine patients with major depressive disorder (MDD), EEG results showed an increase in aperiodic activity following ECT.

The investigators then wanted to test whether these findings could be replicated in a larger study. They retrospectively assessed two previous datasets — 1 of 22 patients with MDD who received ECT and 1 of 23 patients who received MST. After treatment, both groups showed increased aperiodic activity.

“Although not directly related to clinical efficacy in this dataset, increased aperiodic activity is linked to greater amounts of neural inhibition, which is suggestive of a potential shared neural mechanism of action across ECT and MST,” the investigators wrote.

The researchers noted that this increase in aperiodic activity is a more parsimonious explanation for observations of clinical slowing than delta band power or delta oscillations for both ECT and MST.”

So why is it important to know exactly how ECT works, and is there any clinical utility to these research findings?

“It’s important for clinicians to give a patient who has questions, a meaningful understanding of what the treatment is going to do, especially with something so scary and stigmatized. The ability to tell a patient why this treatment is working could provide a level of comfort that can assuage some of these fears,” Ms. Smith said.
 

A New Predictor of Response?

In addition, she noted that psychiatry is becoming more focused on predictive indicators for treatment.

“It’s asking: Are there any biological measures that can be used to predict whether someone is going to respond to a treatment or not?” said Ms. Smith.

“Aperiodic activity might be a valuable asset to add to that arsenal. Maybe we can better predict which patients might respond to ECT by using this as an additional biological indicator,” she added.

Smith noted that while more studies are needed, it’s exciting that some investigators are already starting to include aperiodic activity as a variable in their research analyses on a variety of topics, such as pharmacological intervention and transcranial magnetic stimulation.

“I don’t know exactly how much utility aperiodic activity is going to have in terms of being a great biological indicator, but I hope that the research will start to play out and reveal a little bit more,” she said.

Dr. Sackeim noted that ECT is one of the most misunderstood, controversial, and infrequently used treatments in psychiatry.

“But there’s also no doubt that when you look at ECT, it saves the lives of people with psychiatric illness. Period, full stop,” he said.

He added that although restarting a patient’s heart doesn’t seem to cause unease in the public, the idea of applying electricity to the brain under anesthesia in order to provoke a seizure for therapeutic purpose causes anxiety.

Still, the benefits and harms of a treatment are more important than how it looks, Sackeim said. “If it was only about how it looks, we’d never have surgery,” he added.
 

‘A Huge Success Story’

ECT was first introduced by Hungarian neuropsychiatrist László Meduna in 1935, and today clinicians “know where the current goes in the brain, at what dosage, and with what path you can get 70%, 80% fully remitted,” said Dr. Sackeim.

He noted that in a randomized study published in JAMA Psychiatry, investigators compared the outcomes of MST vs ECT for major depressive episodes in 73 patients. They reported that although depression symptom scores decreased for both treatments, there was “no significant difference” between the two in response or remission rates.

However, in an opinion letter the journal published in April, Dr. Sackeim and colleagues Mark S. George, MD, Medical University of South Carolina, and William V. McCall, MD, Augusta University, Augusta, Georgia, strongly questioned the findings.

At less than 30%, “the ECT remission rate after acute treatment was exceptionally low, limiting confidence in the validity and/or generalizability of the findings,” they wrote.

“It’s undoubtedly the case that either if you recruited a sample from whom the treatment may not be as efficacious or if there are issues in delivering them, then you may be finding equivalence” between ECT and MST, Dr. Sackeim said.

In addition, he noted that although there have been concerns about cognitive side effects with ECT, they have improved over the years. Sackeim reported that when he entered the field, the average time for a patient to remember their name or the day of the week was 6 hours after receiving unilateral ECT and 8 hours after bilateral ECT. “With modern methods, that’s now down to 10 minutes,” he said.

“The fundamental knowledge is that this treatment can be administered far softer than it ever was in the past. Impressions from the 50s and 60s and portrayed in movies have very little to do with modern practice and with the real effects of the treatment,” Dr. Sackeim said.

As for the new studies about aperiodic activity, the investigators are “essentially saying, ‘We have a better marker’ of the process. That way of thinking had in many ways been left behind in the run to study connectivity,” Dr. Sackeim said.

He noted that years ago, while he was with Columbia University, his team found that patients who had frontal inhibition were more likely to get well after ECT.

“And that’s essentially the same thing you’re hearing from the UCSD group. They’re saying that the aperiodic measure is hopefully of clearer physiological significance than simply delta [waves] in the EEG,” Dr. Sackeim said.

“The idea that inhibition was the key to its efficacy has been around. This is saying it’s a better measure of that, and that may be true. It’s certainly an interesting contribution,” he added.

Dr. Sackeim said the takeaway message for clinicians regarding ECT today is that it can be lifesaving but is still often only used as a last resort and reserved for those who have run out of options.

However, he said, ECT is “a huge success story: Maintaining its efficacy, reducing its side effects, getting an understanding as to what the physics of it are. We have some compelling stories about ECT, but even more so, we know what’s not true. And what’s not true are most of the assumptions people have about the treatment,” he concluded.

Ms. Smith and Dr. Voytek reported no relevant conflicts of interest. Dr. Sackeim reported holding patents in ECT technology and consulting with the MECTA Corporation and SigmaStim LLC and other neuromodulation companies.
 

A version of this article appeared on Medscape.com.

For years, electroconvulsive therapy (ECT) has been a lifesaving treatment for patients with treatment-resistant depression (TRD), yet exactly how it works has largely remained a mystery. Now researchers believe they have uncovered the underlying mechanisms behind its therapeutic effects — a discovery that may help clinicians better predict treatment response in individual patients and quell much of the fear and stigma associated with one of psychiatry’s most effective, yet misunderstood, treatments.

Two recent papers published in Translational Psychiatry have highlighted the significance of aperiodic neural activity. The first study showed this activity increased following ECT treatment. The second study expanded on these data by demonstrating a significant increase in aperiodic activity after patients received either ECT or magnetic seizure therapy (MST), which has a better side-effect profile than ECT but lower efficacy.

Aperiodic activity is “like the brain’s background noise, and for years scientists treated it that way and didn’t pay much attention to it,” first author Sydney E. Smith, a PhD candidate at the Voytek Lab in the Neuroscience Graduate Program at the University of California San Diego (UCSD), said in a press release.

However, aperiodic activity boosts inhibitory activity in the brain, effectively slowing it down,” the investigators noted.

In an interview with this news organization, Ms. Smith used a car analogy to explain the mechanism behind ECT. “ECT might be increasing the activity levels in the brain cells that help calm it down. It taps on the brakes that tend to malfunction in depression. By restoring the balance between the gas and the brakes in the brain, some of those depressive symptoms are alleviated,” she said.

Ms. Smith added her team’s research helps demystify one of the most effective yet stigmatized treatments for severe depression.

“Aperiodic activity as a physiologically interpretable EEG metric could be a really valuable new predictive indicator for treatment response,” she added.
 

Fear and Stigma

ECT is primarily used for TRD and is effective in up to 80% of patients, yet it remains one of the least prescribed treatments.

Although it’s been around for almost 90 years, fear and concern about its potential cognitive side effects have contributed to its poor uptake. It is estimated that less than 1% of patients with TRD receive ECT.

Smith noted that the 1970s movie One Flew Over the Cuckoo’s Nest still contributes to ECT’s stigma. In the film, actor Jack Nicholson’s character is forced to undergo ECT as a punishment.

It’s important for clinicians to acknowledge the stigma while advising patients that “the actual treatment doesn’t look anything like what’s in the movies,” noted Ms. Smith. Patients must give informed consent for the procedure, and it’s delivered with the lowest level of effective stimulation.

“So many steps are taken to consider comfort and efficacy for patients and to minimize how scary it can be,” she said.

ECT uses an electrical current to induce a seizure that spreads to deep subcortical structures. MST, which was developed as an alternative to ECT, uses a magnetic field to induce a more focal seizure primarily confined to the cortex.

Although MST has a better side-effect profile, experts noted it has remission rates of 30%-60% compared with ECT. Even one of MST’s inventors, Harold Sackeim, PhD, professor in the Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, is skeptical about its efficacy for TRD.

“I don’t think it works,” Dr. Sackeim, founding editor of Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation, told this news organization.

In addition to being more expensive, MST produces a peak electrical intensity at one-tenth of what a typical ECT stimulus produces. “We’re limited by electrical engineering at this point with MST. That’s my view; others are more optimistic,” he said.
 

A Lifesaving Treatment

One of the reasons ECT isn’t more popular is because for many patients, it’s easier and more convenient to just take a pill, senior investigator Bradley Voytek, PhD, professor of cognitive science at UCSD, said in the release.

“However, in people for whom medications don’t work, [ECT] can be lifesaving. Understanding how it works will help us discover ways to increase the benefits while minimizing side effects,” he added.

In the first study, which included nine patients with major depressive disorder (MDD), EEG results showed an increase in aperiodic activity following ECT.

The investigators then wanted to test whether these findings could be replicated in a larger study. They retrospectively assessed two previous datasets — 1 of 22 patients with MDD who received ECT and 1 of 23 patients who received MST. After treatment, both groups showed increased aperiodic activity.

“Although not directly related to clinical efficacy in this dataset, increased aperiodic activity is linked to greater amounts of neural inhibition, which is suggestive of a potential shared neural mechanism of action across ECT and MST,” the investigators wrote.

The researchers noted that this increase in aperiodic activity is a more parsimonious explanation for observations of clinical slowing than delta band power or delta oscillations for both ECT and MST.”

So why is it important to know exactly how ECT works, and is there any clinical utility to these research findings?

“It’s important for clinicians to give a patient who has questions, a meaningful understanding of what the treatment is going to do, especially with something so scary and stigmatized. The ability to tell a patient why this treatment is working could provide a level of comfort that can assuage some of these fears,” Ms. Smith said.
 

A New Predictor of Response?

In addition, she noted that psychiatry is becoming more focused on predictive indicators for treatment.

“It’s asking: Are there any biological measures that can be used to predict whether someone is going to respond to a treatment or not?” said Ms. Smith.

“Aperiodic activity might be a valuable asset to add to that arsenal. Maybe we can better predict which patients might respond to ECT by using this as an additional biological indicator,” she added.

Smith noted that while more studies are needed, it’s exciting that some investigators are already starting to include aperiodic activity as a variable in their research analyses on a variety of topics, such as pharmacological intervention and transcranial magnetic stimulation.

“I don’t know exactly how much utility aperiodic activity is going to have in terms of being a great biological indicator, but I hope that the research will start to play out and reveal a little bit more,” she said.

Dr. Sackeim noted that ECT is one of the most misunderstood, controversial, and infrequently used treatments in psychiatry.

“But there’s also no doubt that when you look at ECT, it saves the lives of people with psychiatric illness. Period, full stop,” he said.

He added that although restarting a patient’s heart doesn’t seem to cause unease in the public, the idea of applying electricity to the brain under anesthesia in order to provoke a seizure for therapeutic purpose causes anxiety.

Still, the benefits and harms of a treatment are more important than how it looks, Sackeim said. “If it was only about how it looks, we’d never have surgery,” he added.
 

‘A Huge Success Story’

ECT was first introduced by Hungarian neuropsychiatrist László Meduna in 1935, and today clinicians “know where the current goes in the brain, at what dosage, and with what path you can get 70%, 80% fully remitted,” said Dr. Sackeim.

He noted that in a randomized study published in JAMA Psychiatry, investigators compared the outcomes of MST vs ECT for major depressive episodes in 73 patients. They reported that although depression symptom scores decreased for both treatments, there was “no significant difference” between the two in response or remission rates.

However, in an opinion letter the journal published in April, Dr. Sackeim and colleagues Mark S. George, MD, Medical University of South Carolina, and William V. McCall, MD, Augusta University, Augusta, Georgia, strongly questioned the findings.

At less than 30%, “the ECT remission rate after acute treatment was exceptionally low, limiting confidence in the validity and/or generalizability of the findings,” they wrote.

“It’s undoubtedly the case that either if you recruited a sample from whom the treatment may not be as efficacious or if there are issues in delivering them, then you may be finding equivalence” between ECT and MST, Dr. Sackeim said.

In addition, he noted that although there have been concerns about cognitive side effects with ECT, they have improved over the years. Sackeim reported that when he entered the field, the average time for a patient to remember their name or the day of the week was 6 hours after receiving unilateral ECT and 8 hours after bilateral ECT. “With modern methods, that’s now down to 10 minutes,” he said.

“The fundamental knowledge is that this treatment can be administered far softer than it ever was in the past. Impressions from the 50s and 60s and portrayed in movies have very little to do with modern practice and with the real effects of the treatment,” Dr. Sackeim said.

As for the new studies about aperiodic activity, the investigators are “essentially saying, ‘We have a better marker’ of the process. That way of thinking had in many ways been left behind in the run to study connectivity,” Dr. Sackeim said.

He noted that years ago, while he was with Columbia University, his team found that patients who had frontal inhibition were more likely to get well after ECT.

“And that’s essentially the same thing you’re hearing from the UCSD group. They’re saying that the aperiodic measure is hopefully of clearer physiological significance than simply delta [waves] in the EEG,” Dr. Sackeim said.

“The idea that inhibition was the key to its efficacy has been around. This is saying it’s a better measure of that, and that may be true. It’s certainly an interesting contribution,” he added.

Dr. Sackeim said the takeaway message for clinicians regarding ECT today is that it can be lifesaving but is still often only used as a last resort and reserved for those who have run out of options.

However, he said, ECT is “a huge success story: Maintaining its efficacy, reducing its side effects, getting an understanding as to what the physics of it are. We have some compelling stories about ECT, but even more so, we know what’s not true. And what’s not true are most of the assumptions people have about the treatment,” he concluded.

Ms. Smith and Dr. Voytek reported no relevant conflicts of interest. Dr. Sackeim reported holding patents in ECT technology and consulting with the MECTA Corporation and SigmaStim LLC and other neuromodulation companies.
 

A version of this article appeared on Medscape.com.

For years, electroconvulsive therapy (ECT) has been a lifesaving treatment for patients with treatment-resistant depression (TRD), yet exactly how it works has largely remained a mystery. Now researchers believe they have uncovered the underlying mechanisms behind its therapeutic effects — a discovery that may help clinicians better predict treatment response in individual patients and quell much of the fear and stigma associated with one of psychiatry’s most effective, yet misunderstood, treatments.

Two recent papers published in Translational Psychiatry have highlighted the significance of aperiodic neural activity. The first study showed this activity increased following ECT treatment. The second study expanded on these data by demonstrating a significant increase in aperiodic activity after patients received either ECT or magnetic seizure therapy (MST), which has a better side-effect profile than ECT but lower efficacy.

Aperiodic activity is “like the brain’s background noise, and for years scientists treated it that way and didn’t pay much attention to it,” first author Sydney E. Smith, a PhD candidate at the Voytek Lab in the Neuroscience Graduate Program at the University of California San Diego (UCSD), said in a press release.

However, aperiodic activity boosts inhibitory activity in the brain, effectively slowing it down,” the investigators noted.

In an interview with this news organization, Ms. Smith used a car analogy to explain the mechanism behind ECT. “ECT might be increasing the activity levels in the brain cells that help calm it down. It taps on the brakes that tend to malfunction in depression. By restoring the balance between the gas and the brakes in the brain, some of those depressive symptoms are alleviated,” she said.

Ms. Smith added her team’s research helps demystify one of the most effective yet stigmatized treatments for severe depression.

“Aperiodic activity as a physiologically interpretable EEG metric could be a really valuable new predictive indicator for treatment response,” she added.
 

Fear and Stigma

ECT is primarily used for TRD and is effective in up to 80% of patients, yet it remains one of the least prescribed treatments.

Although it’s been around for almost 90 years, fear and concern about its potential cognitive side effects have contributed to its poor uptake. It is estimated that less than 1% of patients with TRD receive ECT.

Smith noted that the 1970s movie One Flew Over the Cuckoo’s Nest still contributes to ECT’s stigma. In the film, actor Jack Nicholson’s character is forced to undergo ECT as a punishment.

It’s important for clinicians to acknowledge the stigma while advising patients that “the actual treatment doesn’t look anything like what’s in the movies,” noted Ms. Smith. Patients must give informed consent for the procedure, and it’s delivered with the lowest level of effective stimulation.

“So many steps are taken to consider comfort and efficacy for patients and to minimize how scary it can be,” she said.

ECT uses an electrical current to induce a seizure that spreads to deep subcortical structures. MST, which was developed as an alternative to ECT, uses a magnetic field to induce a more focal seizure primarily confined to the cortex.

Although MST has a better side-effect profile, experts noted it has remission rates of 30%-60% compared with ECT. Even one of MST’s inventors, Harold Sackeim, PhD, professor in the Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, is skeptical about its efficacy for TRD.

“I don’t think it works,” Dr. Sackeim, founding editor of Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation, told this news organization.

In addition to being more expensive, MST produces a peak electrical intensity at one-tenth of what a typical ECT stimulus produces. “We’re limited by electrical engineering at this point with MST. That’s my view; others are more optimistic,” he said.
 

A Lifesaving Treatment

One of the reasons ECT isn’t more popular is because for many patients, it’s easier and more convenient to just take a pill, senior investigator Bradley Voytek, PhD, professor of cognitive science at UCSD, said in the release.

“However, in people for whom medications don’t work, [ECT] can be lifesaving. Understanding how it works will help us discover ways to increase the benefits while minimizing side effects,” he added.

In the first study, which included nine patients with major depressive disorder (MDD), EEG results showed an increase in aperiodic activity following ECT.

The investigators then wanted to test whether these findings could be replicated in a larger study. They retrospectively assessed two previous datasets — 1 of 22 patients with MDD who received ECT and 1 of 23 patients who received MST. After treatment, both groups showed increased aperiodic activity.

“Although not directly related to clinical efficacy in this dataset, increased aperiodic activity is linked to greater amounts of neural inhibition, which is suggestive of a potential shared neural mechanism of action across ECT and MST,” the investigators wrote.

The researchers noted that this increase in aperiodic activity is a more parsimonious explanation for observations of clinical slowing than delta band power or delta oscillations for both ECT and MST.”

So why is it important to know exactly how ECT works, and is there any clinical utility to these research findings?

“It’s important for clinicians to give a patient who has questions, a meaningful understanding of what the treatment is going to do, especially with something so scary and stigmatized. The ability to tell a patient why this treatment is working could provide a level of comfort that can assuage some of these fears,” Ms. Smith said.
 

A New Predictor of Response?

In addition, she noted that psychiatry is becoming more focused on predictive indicators for treatment.

“It’s asking: Are there any biological measures that can be used to predict whether someone is going to respond to a treatment or not?” said Ms. Smith.

“Aperiodic activity might be a valuable asset to add to that arsenal. Maybe we can better predict which patients might respond to ECT by using this as an additional biological indicator,” she added.

Smith noted that while more studies are needed, it’s exciting that some investigators are already starting to include aperiodic activity as a variable in their research analyses on a variety of topics, such as pharmacological intervention and transcranial magnetic stimulation.

“I don’t know exactly how much utility aperiodic activity is going to have in terms of being a great biological indicator, but I hope that the research will start to play out and reveal a little bit more,” she said.

Dr. Sackeim noted that ECT is one of the most misunderstood, controversial, and infrequently used treatments in psychiatry.

“But there’s also no doubt that when you look at ECT, it saves the lives of people with psychiatric illness. Period, full stop,” he said.

He added that although restarting a patient’s heart doesn’t seem to cause unease in the public, the idea of applying electricity to the brain under anesthesia in order to provoke a seizure for therapeutic purpose causes anxiety.

Still, the benefits and harms of a treatment are more important than how it looks, Sackeim said. “If it was only about how it looks, we’d never have surgery,” he added.
 

‘A Huge Success Story’

ECT was first introduced by Hungarian neuropsychiatrist László Meduna in 1935, and today clinicians “know where the current goes in the brain, at what dosage, and with what path you can get 70%, 80% fully remitted,” said Dr. Sackeim.

He noted that in a randomized study published in JAMA Psychiatry, investigators compared the outcomes of MST vs ECT for major depressive episodes in 73 patients. They reported that although depression symptom scores decreased for both treatments, there was “no significant difference” between the two in response or remission rates.

However, in an opinion letter the journal published in April, Dr. Sackeim and colleagues Mark S. George, MD, Medical University of South Carolina, and William V. McCall, MD, Augusta University, Augusta, Georgia, strongly questioned the findings.

At less than 30%, “the ECT remission rate after acute treatment was exceptionally low, limiting confidence in the validity and/or generalizability of the findings,” they wrote.

“It’s undoubtedly the case that either if you recruited a sample from whom the treatment may not be as efficacious or if there are issues in delivering them, then you may be finding equivalence” between ECT and MST, Dr. Sackeim said.

In addition, he noted that although there have been concerns about cognitive side effects with ECT, they have improved over the years. Sackeim reported that when he entered the field, the average time for a patient to remember their name or the day of the week was 6 hours after receiving unilateral ECT and 8 hours after bilateral ECT. “With modern methods, that’s now down to 10 minutes,” he said.

“The fundamental knowledge is that this treatment can be administered far softer than it ever was in the past. Impressions from the 50s and 60s and portrayed in movies have very little to do with modern practice and with the real effects of the treatment,” Dr. Sackeim said.

As for the new studies about aperiodic activity, the investigators are “essentially saying, ‘We have a better marker’ of the process. That way of thinking had in many ways been left behind in the run to study connectivity,” Dr. Sackeim said.

He noted that years ago, while he was with Columbia University, his team found that patients who had frontal inhibition were more likely to get well after ECT.

“And that’s essentially the same thing you’re hearing from the UCSD group. They’re saying that the aperiodic measure is hopefully of clearer physiological significance than simply delta [waves] in the EEG,” Dr. Sackeim said.

“The idea that inhibition was the key to its efficacy has been around. This is saying it’s a better measure of that, and that may be true. It’s certainly an interesting contribution,” he added.

Dr. Sackeim said the takeaway message for clinicians regarding ECT today is that it can be lifesaving but is still often only used as a last resort and reserved for those who have run out of options.

However, he said, ECT is “a huge success story: Maintaining its efficacy, reducing its side effects, getting an understanding as to what the physics of it are. We have some compelling stories about ECT, but even more so, we know what’s not true. And what’s not true are most of the assumptions people have about the treatment,” he concluded.

Ms. Smith and Dr. Voytek reported no relevant conflicts of interest. Dr. Sackeim reported holding patents in ECT technology and consulting with the MECTA Corporation and SigmaStim LLC and other neuromodulation companies.
 

A version of this article appeared on Medscape.com.

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

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

sdominick/iStock/Getty Images

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

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

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

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

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

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

High death rate from synthetic opioids

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

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

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

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

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

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

Two-part, two-period study

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

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

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

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

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

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

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

First clinical evidence?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

sdominick/iStock/Getty Images

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

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

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

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

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

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

High death rate from synthetic opioids

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

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

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

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

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

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

Two-part, two-period study

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

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

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

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

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

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

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

First clinical evidence?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

sdominick/iStock/Getty Images

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

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

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

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

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

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

High death rate from synthetic opioids

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

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

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

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

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

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

Two-part, two-period study

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

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

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

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

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

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

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

First clinical evidence?

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

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

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

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

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

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

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

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

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

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

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

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

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

The U.S. Food and Drug Administration has expanded the indication for the noninvasive BrainsWay Deep Transcranial Magnetic Stimulation (Deep TMS) System to include treatment of comorbid anxiety symptoms in adult patients with depression, the company has announced.

As reported by this news organization, the neurostimulation system has previously received FDA approval for treatment-resistant major depression, obsessive-compulsive disorder, and smoking addiction.

In the August 18 announcement, BrainsWay reported that it has also received 510(k) clearance from the FDA to market its TMS system for the reduction of anxious depression symptoms.

“This clearance is confirmation of what many have believed anecdotally for years – that Deep TMS is a unique form of therapy that can address comorbid anxiety symptoms using the same depression treatment protocol,” Aron Tendler, MD, chief medical officer at BrainsWay, said in a press release.

‘Consistent, robust’ effect

Before receiving approval, the company submitted data on 573 patients who underwent this treatment while participating in 11 studies, which included both randomized controlled trials and open-label studies.

“The data demonstrated a treatment effect that was consistent, robust, and clinically meaningful for decreasing anxiety symptoms in adult patients suffering from major depressive disorder [MDD],” the company said in its release.

Data from three of the randomized trials showed an effect size of 0.3 when compared with a sham device and an effect size of 0.9 when compared with medication. The overall, weighted, pooled effect size was 0.55.

The company noted that in more than 70 published studies with about 16,000 total participants, effect sizes have ranged from 0.2-0.37 for drug-based anxiety treatments.

“The expanded FDA labeling now allows BrainsWay to market its Deep TMS System for the treatment of depressive episodes and for decreasing anxiety symptoms for those who may exhibit comorbid anxiety symptoms in adult patients suffering from [MDD] and who failed to achieve satisfactory improvement from previous antidepressant medication treatment in the current episode,” the company said.

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

The U.S. Food and Drug Administration has expanded the indication for the noninvasive BrainsWay Deep Transcranial Magnetic Stimulation (Deep TMS) System to include treatment of comorbid anxiety symptoms in adult patients with depression, the company has announced.

As reported by this news organization, the neurostimulation system has previously received FDA approval for treatment-resistant major depression, obsessive-compulsive disorder, and smoking addiction.

In the August 18 announcement, BrainsWay reported that it has also received 510(k) clearance from the FDA to market its TMS system for the reduction of anxious depression symptoms.

“This clearance is confirmation of what many have believed anecdotally for years – that Deep TMS is a unique form of therapy that can address comorbid anxiety symptoms using the same depression treatment protocol,” Aron Tendler, MD, chief medical officer at BrainsWay, said in a press release.

‘Consistent, robust’ effect

Before receiving approval, the company submitted data on 573 patients who underwent this treatment while participating in 11 studies, which included both randomized controlled trials and open-label studies.

“The data demonstrated a treatment effect that was consistent, robust, and clinically meaningful for decreasing anxiety symptoms in adult patients suffering from major depressive disorder [MDD],” the company said in its release.

Data from three of the randomized trials showed an effect size of 0.3 when compared with a sham device and an effect size of 0.9 when compared with medication. The overall, weighted, pooled effect size was 0.55.

The company noted that in more than 70 published studies with about 16,000 total participants, effect sizes have ranged from 0.2-0.37 for drug-based anxiety treatments.

“The expanded FDA labeling now allows BrainsWay to market its Deep TMS System for the treatment of depressive episodes and for decreasing anxiety symptoms for those who may exhibit comorbid anxiety symptoms in adult patients suffering from [MDD] and who failed to achieve satisfactory improvement from previous antidepressant medication treatment in the current episode,” the company said.

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

The U.S. Food and Drug Administration has expanded the indication for the noninvasive BrainsWay Deep Transcranial Magnetic Stimulation (Deep TMS) System to include treatment of comorbid anxiety symptoms in adult patients with depression, the company has announced.

As reported by this news organization, the neurostimulation system has previously received FDA approval for treatment-resistant major depression, obsessive-compulsive disorder, and smoking addiction.

In the August 18 announcement, BrainsWay reported that it has also received 510(k) clearance from the FDA to market its TMS system for the reduction of anxious depression symptoms.

“This clearance is confirmation of what many have believed anecdotally for years – that Deep TMS is a unique form of therapy that can address comorbid anxiety symptoms using the same depression treatment protocol,” Aron Tendler, MD, chief medical officer at BrainsWay, said in a press release.

‘Consistent, robust’ effect

Before receiving approval, the company submitted data on 573 patients who underwent this treatment while participating in 11 studies, which included both randomized controlled trials and open-label studies.

“The data demonstrated a treatment effect that was consistent, robust, and clinically meaningful for decreasing anxiety symptoms in adult patients suffering from major depressive disorder [MDD],” the company said in its release.

Data from three of the randomized trials showed an effect size of 0.3 when compared with a sham device and an effect size of 0.9 when compared with medication. The overall, weighted, pooled effect size was 0.55.

The company noted that in more than 70 published studies with about 16,000 total participants, effect sizes have ranged from 0.2-0.37 for drug-based anxiety treatments.

“The expanded FDA labeling now allows BrainsWay to market its Deep TMS System for the treatment of depressive episodes and for decreasing anxiety symptoms for those who may exhibit comorbid anxiety symptoms in adult patients suffering from [MDD] and who failed to achieve satisfactory improvement from previous antidepressant medication treatment in the current episode,” the company said.

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

Pfizer has recalled four more lots of the smoking cessation drug varenicline (Chantix), according to an Aug. 16 update on the U.S. Food and Drug Administration website.

In a new FDA MedWatch, the agency notes that these 0.5 mg/1 mg tablets are being recalled because of the presence of N-nitroso-varenicline, a nitrosamine impurity, at a level higher than Pfizer’s acceptable intake limit.

On July 2, the FDA reported that Pfizer had voluntarily recalled nine lots of the drug for this reason. As reported by this news organization, the company added three more lots to the recall a few weeks later. The new recall now brings to 16 the number of lots that have been recalled.

In the update, the FDA noted that, although long-term ingestion of the impurity “may be associated with a theoretical potential increased cancer risk in humans,” there is no immediate risk in taking this medication. The agency added that no related adverse events (AEs) have been reported.

The four additional lots included in the newest recall are as follows:

• 00018522 (expiration date: August 2021).
• 00018523 (expiration date: August 2021).
• 00018739 (expiration date: August 2021).
• 00018740 (expiration date: August 2021).

The recalled lots were distributed in the United States and Puerto Rico from June 2019 to June 2021.

As before, the FDA noted that the benefits of stopping smoking “outweigh the theoretical potential cancer risk” from varenicline’s impurity.

It added that, although the impurities may increase risk for cancer if a high level of exposure continues over a long period, the drug is intended as a short-term treatment to aid in smoking cessation.

For now, clinicians should report any AEs from varenicline to the FDA’s MedWatch program, and patients taking this treatment should consult with their health care practitioner or pharmacy, the update notes.

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

Pfizer has recalled four more lots of the smoking cessation drug varenicline (Chantix), according to an Aug. 16 update on the U.S. Food and Drug Administration website.

In a new FDA MedWatch, the agency notes that these 0.5 mg/1 mg tablets are being recalled because of the presence of N-nitroso-varenicline, a nitrosamine impurity, at a level higher than Pfizer’s acceptable intake limit.

On July 2, the FDA reported that Pfizer had voluntarily recalled nine lots of the drug for this reason. As reported by this news organization, the company added three more lots to the recall a few weeks later. The new recall now brings to 16 the number of lots that have been recalled.

In the update, the FDA noted that, although long-term ingestion of the impurity “may be associated with a theoretical potential increased cancer risk in humans,” there is no immediate risk in taking this medication. The agency added that no related adverse events (AEs) have been reported.

The four additional lots included in the newest recall are as follows:

• 00018522 (expiration date: August 2021).
• 00018523 (expiration date: August 2021).
• 00018739 (expiration date: August 2021).
• 00018740 (expiration date: August 2021).

The recalled lots were distributed in the United States and Puerto Rico from June 2019 to June 2021.

As before, the FDA noted that the benefits of stopping smoking “outweigh the theoretical potential cancer risk” from varenicline’s impurity.

It added that, although the impurities may increase risk for cancer if a high level of exposure continues over a long period, the drug is intended as a short-term treatment to aid in smoking cessation.

For now, clinicians should report any AEs from varenicline to the FDA’s MedWatch program, and patients taking this treatment should consult with their health care practitioner or pharmacy, the update notes.

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

Pfizer has recalled four more lots of the smoking cessation drug varenicline (Chantix), according to an Aug. 16 update on the U.S. Food and Drug Administration website.

In a new FDA MedWatch, the agency notes that these 0.5 mg/1 mg tablets are being recalled because of the presence of N-nitroso-varenicline, a nitrosamine impurity, at a level higher than Pfizer’s acceptable intake limit.

On July 2, the FDA reported that Pfizer had voluntarily recalled nine lots of the drug for this reason. As reported by this news organization, the company added three more lots to the recall a few weeks later. The new recall now brings to 16 the number of lots that have been recalled.

In the update, the FDA noted that, although long-term ingestion of the impurity “may be associated with a theoretical potential increased cancer risk in humans,” there is no immediate risk in taking this medication. The agency added that no related adverse events (AEs) have been reported.

The four additional lots included in the newest recall are as follows:

• 00018522 (expiration date: August 2021).
• 00018523 (expiration date: August 2021).
• 00018739 (expiration date: August 2021).
• 00018740 (expiration date: August 2021).

The recalled lots were distributed in the United States and Puerto Rico from June 2019 to June 2021.

As before, the FDA noted that the benefits of stopping smoking “outweigh the theoretical potential cancer risk” from varenicline’s impurity.

It added that, although the impurities may increase risk for cancer if a high level of exposure continues over a long period, the drug is intended as a short-term treatment to aid in smoking cessation.

For now, clinicians should report any AEs from varenicline to the FDA’s MedWatch program, and patients taking this treatment should consult with their health care practitioner or pharmacy, the update notes.

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

After several weeks of outcry and heated debate over the Food and Drug Administration’s controversial approval of the Alzheimer’s drug aducanumab (Aduhelm), the head of the agency is now calling for a federal investigation into its own approval proceedings.

Janet Woodcock, MD, the FDA’s acting commissioner, sent a letter to the Office of the Inspector General on July 9, she announced in a tweet.

Dr. Woodcock is asking for an investigation into questionable meetings and other interactions between Biogen and FDA staff members prior to the drug’s approval that “may have occurred outside of the formal correspondence process.”

The letter explains that concerns around these issues “could undermine the public’s confidence in the FDA’s decision.” Therefore, an independent investigation is needed to determine whether anything occurred that was “inconsistent with FDA policies and procedures.”

Dr. Woodcock noted that she has “tremendous confidence in the integrity of the staff and leadership of the Center for Drug Evaluation and Research” involved in the review process.

However, “FDA is dedicated to scientific integrity, to reviewing data without bias, and to basing its regulatory decisions on data,” she wrote. “You have my personal commitment that the Agency will fully cooperate should your office undertake a review.”

Dr. Woodcock concluded by urging that a review be conducted as soon as possible, noting that “should such a review result in actionable items, you also have my commitment to addressing these issues.”

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

After several weeks of outcry and heated debate over the Food and Drug Administration’s controversial approval of the Alzheimer’s drug aducanumab (Aduhelm), the head of the agency is now calling for a federal investigation into its own approval proceedings.

Janet Woodcock, MD, the FDA’s acting commissioner, sent a letter to the Office of the Inspector General on July 9, she announced in a tweet.

Dr. Woodcock is asking for an investigation into questionable meetings and other interactions between Biogen and FDA staff members prior to the drug’s approval that “may have occurred outside of the formal correspondence process.”

The letter explains that concerns around these issues “could undermine the public’s confidence in the FDA’s decision.” Therefore, an independent investigation is needed to determine whether anything occurred that was “inconsistent with FDA policies and procedures.”

Dr. Woodcock noted that she has “tremendous confidence in the integrity of the staff and leadership of the Center for Drug Evaluation and Research” involved in the review process.

However, “FDA is dedicated to scientific integrity, to reviewing data without bias, and to basing its regulatory decisions on data,” she wrote. “You have my personal commitment that the Agency will fully cooperate should your office undertake a review.”

Dr. Woodcock concluded by urging that a review be conducted as soon as possible, noting that “should such a review result in actionable items, you also have my commitment to addressing these issues.”

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

After several weeks of outcry and heated debate over the Food and Drug Administration’s controversial approval of the Alzheimer’s drug aducanumab (Aduhelm), the head of the agency is now calling for a federal investigation into its own approval proceedings.

Janet Woodcock, MD, the FDA’s acting commissioner, sent a letter to the Office of the Inspector General on July 9, she announced in a tweet.

Dr. Woodcock is asking for an investigation into questionable meetings and other interactions between Biogen and FDA staff members prior to the drug’s approval that “may have occurred outside of the formal correspondence process.”

The letter explains that concerns around these issues “could undermine the public’s confidence in the FDA’s decision.” Therefore, an independent investigation is needed to determine whether anything occurred that was “inconsistent with FDA policies and procedures.”

Dr. Woodcock noted that she has “tremendous confidence in the integrity of the staff and leadership of the Center for Drug Evaluation and Research” involved in the review process.

However, “FDA is dedicated to scientific integrity, to reviewing data without bias, and to basing its regulatory decisions on data,” she wrote. “You have my personal commitment that the Agency will fully cooperate should your office undertake a review.”

Dr. Woodcock concluded by urging that a review be conducted as soon as possible, noting that “should such a review result in actionable items, you also have my commitment to addressing these issues.”

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

The U.S. Food and Drug Administration has provided a detailed and documented account of how it arrived at its decision to approve the controversial Alzheimer’s drug aducanumab (Aduhelm, Biogen/Eisai), including the release of several internal documents.

In a letter sent to members of the FDA’s Center for Drug Evaluation Research (CDER), CDER Director Patrizia Cavazzoni, MD, noted that in view of the “fierce public debate” that erupted immediately following the drug’s approval, she felt compelled to explain how the agency came to its decision.

Also publicly released today on the FDA’s updated aducanumab landing page was “the first set of review memos,” for the drug.

“We’re releasing these documents with the intent of informing public discourse – providing interested parties with the opportunity to explore the data that helped shape our decision to grant accelerated approval,” Dr. Cavazzoni wrote. “The rest of the approval package will be released over the next several days,” she added.
 

Immediate backlash

The FDA’s June 7 approval of aducanumab was met with instant backlash. In November 2020, the agency’s Peripheral and Central Nervous System Drugs Advisory Committee voted nearly unanimously to not vote in favor of approval because of a lack of evidence proving its efficacy.

Since the drug was approved, three of the advisory committee’s members resigned in protest. In addition, the high-profile consumer advocacy group Public Citizen sent a letter to the secretary of the U.S. Department of Health & Human Services demanding the removal of three FDA officials, including acting FDA Commissioner Janet Woodcock, MD.

In its letter, the group noted that the FDA’s decision “showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.”

Even the Alzheimer’s Association, which was a staunch supporter of the drug throughout its development process and applauded its approval, expressed outrage over its more than $56,000-a-year cost to patients and called the price “simply unacceptable” in a statement.

In the June 23 letter, the CDER director noted, “this was one of the most complex applications in recent history” and admitted that deliberations were lengthy and difficult.

“It’s also not surprising, in fact it was to be expected, that there would be different viewpoints about the data, including dissenting opinions about the approval decision,” Dr. Cavazzoni wrote.

However, this “is what scientific debate is all about, and while difficult at times, it should be celebrated,” she added. “Please know that every opinion was heard, and the approval is a direct reflection of this open and robust scientific and regulatory debate.”
 

Accelerated approval pathway

Documents newly posted to the FDA’s aducanumab landing page include CDER’s Office of Neurology’s Summary Review Memorandum, which includes details on the basis for the approval; the Concurrence Memorandum from the director of CDER’s Office of New Drugs; and the Concurrence Memorandum from Dr. Cavazzoni.

“The remaining scientific review documents in the Aduhelm action package are not yet available but will be made available to the public as soon as the internal process of review and redaction is complete,” the FDA noted on its site.

In the document FDA’s Decision to Approve New Treatment for Alzheimer’s Disease, Dr. Cavazzoni noted that the “highly complex” data included in the submission package for the drug “left residual uncertainties regarding clinical benefit.”

However, after listening to the patient community and reviewing all the data, the FDA chose to use the Accelerated Approval pathway, deciding that the potential benefit to patients outweighed the drug’s risks.

Of two phase 3 trials, only one met its primary endpoint. However, in all trials, including earlier studies, “Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion,” Dr. Cavazzoni wrote.

“It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline,” she added.

Dr. Cavazzoni noted that although the Advisory Committee did not agree that clinical benefit from one trial meeting its primary endpoint was enough for approval, “the option of Accelerated Approval was not discussed” at that time.

This type of approval “is based on a surrogate or intermediate clinical endpoint, in this case reduction of amyloid plaque in the brain” and requires post-approval studies to verify clinical benefit.

Dr. Cavazzoni added that the drug could still be removed from the market if its confirmatory trial does not verify this type of benefit.

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

The U.S. Food and Drug Administration has provided a detailed and documented account of how it arrived at its decision to approve the controversial Alzheimer’s drug aducanumab (Aduhelm, Biogen/Eisai), including the release of several internal documents.

In a letter sent to members of the FDA’s Center for Drug Evaluation Research (CDER), CDER Director Patrizia Cavazzoni, MD, noted that in view of the “fierce public debate” that erupted immediately following the drug’s approval, she felt compelled to explain how the agency came to its decision.

Also publicly released today on the FDA’s updated aducanumab landing page was “the first set of review memos,” for the drug.

“We’re releasing these documents with the intent of informing public discourse – providing interested parties with the opportunity to explore the data that helped shape our decision to grant accelerated approval,” Dr. Cavazzoni wrote. “The rest of the approval package will be released over the next several days,” she added.
 

Immediate backlash

The FDA’s June 7 approval of aducanumab was met with instant backlash. In November 2020, the agency’s Peripheral and Central Nervous System Drugs Advisory Committee voted nearly unanimously to not vote in favor of approval because of a lack of evidence proving its efficacy.

Since the drug was approved, three of the advisory committee’s members resigned in protest. In addition, the high-profile consumer advocacy group Public Citizen sent a letter to the secretary of the U.S. Department of Health & Human Services demanding the removal of three FDA officials, including acting FDA Commissioner Janet Woodcock, MD.

In its letter, the group noted that the FDA’s decision “showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.”

Even the Alzheimer’s Association, which was a staunch supporter of the drug throughout its development process and applauded its approval, expressed outrage over its more than $56,000-a-year cost to patients and called the price “simply unacceptable” in a statement.

In the June 23 letter, the CDER director noted, “this was one of the most complex applications in recent history” and admitted that deliberations were lengthy and difficult.

“It’s also not surprising, in fact it was to be expected, that there would be different viewpoints about the data, including dissenting opinions about the approval decision,” Dr. Cavazzoni wrote.

However, this “is what scientific debate is all about, and while difficult at times, it should be celebrated,” she added. “Please know that every opinion was heard, and the approval is a direct reflection of this open and robust scientific and regulatory debate.”
 

Accelerated approval pathway

Documents newly posted to the FDA’s aducanumab landing page include CDER’s Office of Neurology’s Summary Review Memorandum, which includes details on the basis for the approval; the Concurrence Memorandum from the director of CDER’s Office of New Drugs; and the Concurrence Memorandum from Dr. Cavazzoni.

“The remaining scientific review documents in the Aduhelm action package are not yet available but will be made available to the public as soon as the internal process of review and redaction is complete,” the FDA noted on its site.

In the document FDA’s Decision to Approve New Treatment for Alzheimer’s Disease, Dr. Cavazzoni noted that the “highly complex” data included in the submission package for the drug “left residual uncertainties regarding clinical benefit.”

However, after listening to the patient community and reviewing all the data, the FDA chose to use the Accelerated Approval pathway, deciding that the potential benefit to patients outweighed the drug’s risks.

Of two phase 3 trials, only one met its primary endpoint. However, in all trials, including earlier studies, “Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion,” Dr. Cavazzoni wrote.

“It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline,” she added.

Dr. Cavazzoni noted that although the Advisory Committee did not agree that clinical benefit from one trial meeting its primary endpoint was enough for approval, “the option of Accelerated Approval was not discussed” at that time.

This type of approval “is based on a surrogate or intermediate clinical endpoint, in this case reduction of amyloid plaque in the brain” and requires post-approval studies to verify clinical benefit.

Dr. Cavazzoni added that the drug could still be removed from the market if its confirmatory trial does not verify this type of benefit.

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

The U.S. Food and Drug Administration has provided a detailed and documented account of how it arrived at its decision to approve the controversial Alzheimer’s drug aducanumab (Aduhelm, Biogen/Eisai), including the release of several internal documents.

In a letter sent to members of the FDA’s Center for Drug Evaluation Research (CDER), CDER Director Patrizia Cavazzoni, MD, noted that in view of the “fierce public debate” that erupted immediately following the drug’s approval, she felt compelled to explain how the agency came to its decision.

Also publicly released today on the FDA’s updated aducanumab landing page was “the first set of review memos,” for the drug.

“We’re releasing these documents with the intent of informing public discourse – providing interested parties with the opportunity to explore the data that helped shape our decision to grant accelerated approval,” Dr. Cavazzoni wrote. “The rest of the approval package will be released over the next several days,” she added.
 

Immediate backlash

The FDA’s June 7 approval of aducanumab was met with instant backlash. In November 2020, the agency’s Peripheral and Central Nervous System Drugs Advisory Committee voted nearly unanimously to not vote in favor of approval because of a lack of evidence proving its efficacy.

Since the drug was approved, three of the advisory committee’s members resigned in protest. In addition, the high-profile consumer advocacy group Public Citizen sent a letter to the secretary of the U.S. Department of Health & Human Services demanding the removal of three FDA officials, including acting FDA Commissioner Janet Woodcock, MD.

In its letter, the group noted that the FDA’s decision “showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.”

Even the Alzheimer’s Association, which was a staunch supporter of the drug throughout its development process and applauded its approval, expressed outrage over its more than $56,000-a-year cost to patients and called the price “simply unacceptable” in a statement.

In the June 23 letter, the CDER director noted, “this was one of the most complex applications in recent history” and admitted that deliberations were lengthy and difficult.

“It’s also not surprising, in fact it was to be expected, that there would be different viewpoints about the data, including dissenting opinions about the approval decision,” Dr. Cavazzoni wrote.

However, this “is what scientific debate is all about, and while difficult at times, it should be celebrated,” she added. “Please know that every opinion was heard, and the approval is a direct reflection of this open and robust scientific and regulatory debate.”
 

Accelerated approval pathway

Documents newly posted to the FDA’s aducanumab landing page include CDER’s Office of Neurology’s Summary Review Memorandum, which includes details on the basis for the approval; the Concurrence Memorandum from the director of CDER’s Office of New Drugs; and the Concurrence Memorandum from Dr. Cavazzoni.

“The remaining scientific review documents in the Aduhelm action package are not yet available but will be made available to the public as soon as the internal process of review and redaction is complete,” the FDA noted on its site.

In the document FDA’s Decision to Approve New Treatment for Alzheimer’s Disease, Dr. Cavazzoni noted that the “highly complex” data included in the submission package for the drug “left residual uncertainties regarding clinical benefit.”

However, after listening to the patient community and reviewing all the data, the FDA chose to use the Accelerated Approval pathway, deciding that the potential benefit to patients outweighed the drug’s risks.

Of two phase 3 trials, only one met its primary endpoint. However, in all trials, including earlier studies, “Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion,” Dr. Cavazzoni wrote.

“It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline,” she added.

Dr. Cavazzoni noted that although the Advisory Committee did not agree that clinical benefit from one trial meeting its primary endpoint was enough for approval, “the option of Accelerated Approval was not discussed” at that time.

This type of approval “is based on a surrogate or intermediate clinical endpoint, in this case reduction of amyloid plaque in the brain” and requires post-approval studies to verify clinical benefit.

Dr. Cavazzoni added that the drug could still be removed from the market if its confirmatory trial does not verify this type of benefit.

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

Amid significant controversy, the U.S. Food and Drug Administration (FDA) has approved the anti-amyloid agent aducanumab (Biogen, Eisai) for the treatment of Alzheimer’s disease, disregarding the recommendation by its own advisory panel not to approve the drug.

In November, the Peripheral and Central Nervous System Drugs Advisory Committee voted eight to one against approving the drug because, based on clinical trial results, evidence of efficacy was not strong enough. Two other members said they were uncertain on the issue of efficacy.

In a company release Michel Vounatsos, Biogen’s Chief Executive Officer, said, “this historic moment is the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer’s disease. We believe this first-in-class medicine will transform the treatment of people living with Alzheimer’s disease and spark continuous innovation in the years to come.
 

Rocky road

The road to approval has been extremely rocky for aducanumab, an anti-amyloid-beta human monoclonal antibody, previously known as BIIB037.

As reported by this news organization, two phase 3 trials evaluating the drug were initially scrapped in March 2019 because of interim futility analysis. At the time, Biogen released a statement saying that aducanumab was unlikely to meet primary endpoints in the ENGAGE and EMERGE randomized controlled trials.

However, in an about-face 7 months later, Biogen and Eisai announced that a  new analysis showed the drug met its primary endpoint of reduction in clinical decline, including cognition and function, in the EMERGE trial.

Although ENGAGE still didn’t meet its primary endpoint, data from its new analysis “supported” the EMERGE findings, the drug companies said at the time.

However, 1 year later, a majority of the members of the FDA’s advisory panel were against the drug’s approval. Details of that decision were published online March 30 in the Journal of the American Medical Association.

As reported by this news organization, a Viewpoint written by three of the committee members notes that results from the drug’s only large positive clinical trial fell short.

“There is no persuasive evidence to support approval of aducanumab at this time,” they write.

Groups such as Public Citizen’s Health Research Group not only agree with the Viewpoint’s authors, they also criticized the FDA for its collaboration with the drug’s manufacturers on briefing documents and more.

On April 1, Health Research Group members sent a letter to the U.S. Secretary of Health and Human Services requesting the temporary suspension of the FDA’s neuroscience chief, Bill Dunn, MD, because of his role in supervising the collaboration.
 

Alzheimer association weighs in

The Alzheimer’s Association has been a proponent of the drug throughout its development.

Ahead of today’s news, the organization noted in a statement that a decision to approve “would be historic” because it would make aducanumab “the first drug to slow Alzheimer’s disease” and would mark the beginning of a new future for AD treatments.

“The Alzheimer’s Association urgently supports FDA approval of the treatment based on clinical trial results that showed a 22% reduction in cognitive and function decline — something that could make a meaningful difference” for patients with AD, it said.

Kristen Clifford, chief program officer for the Alzheimer’s Association, said in an interview at the time that approval would be considered a “victory” for patients with AD and for the field overall.

“For individuals who would potentially be eligible for the treatment, this drug could mean more quality time. Slowing decline, particularly in early diagnosis, could add weeks or months or maybe even years of active life,” Clifford said.

“If approved, this would really be a landmark moment. And it could provide hope for those living with Alzheimer’s and their families,” she added.

Clifford noted that approval of this type of drug would also underscore the importance of early detection for AD. “This treatment would encourage earlier diagnosis of the disease,” she said.

In a new statement released just after approval for aducanumab was announced, the organization said that today’s news is a win-win for all patients with AD and their families.

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

Amid significant controversy, the U.S. Food and Drug Administration (FDA) has approved the anti-amyloid agent aducanumab (Biogen, Eisai) for the treatment of Alzheimer’s disease, disregarding the recommendation by its own advisory panel not to approve the drug.

In November, the Peripheral and Central Nervous System Drugs Advisory Committee voted eight to one against approving the drug because, based on clinical trial results, evidence of efficacy was not strong enough. Two other members said they were uncertain on the issue of efficacy.

In a company release Michel Vounatsos, Biogen’s Chief Executive Officer, said, “this historic moment is the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer’s disease. We believe this first-in-class medicine will transform the treatment of people living with Alzheimer’s disease and spark continuous innovation in the years to come.
 

Rocky road

The road to approval has been extremely rocky for aducanumab, an anti-amyloid-beta human monoclonal antibody, previously known as BIIB037.

As reported by this news organization, two phase 3 trials evaluating the drug were initially scrapped in March 2019 because of interim futility analysis. At the time, Biogen released a statement saying that aducanumab was unlikely to meet primary endpoints in the ENGAGE and EMERGE randomized controlled trials.

However, in an about-face 7 months later, Biogen and Eisai announced that a  new analysis showed the drug met its primary endpoint of reduction in clinical decline, including cognition and function, in the EMERGE trial.

Although ENGAGE still didn’t meet its primary endpoint, data from its new analysis “supported” the EMERGE findings, the drug companies said at the time.

However, 1 year later, a majority of the members of the FDA’s advisory panel were against the drug’s approval. Details of that decision were published online March 30 in the Journal of the American Medical Association.

As reported by this news organization, a Viewpoint written by three of the committee members notes that results from the drug’s only large positive clinical trial fell short.

“There is no persuasive evidence to support approval of aducanumab at this time,” they write.

Groups such as Public Citizen’s Health Research Group not only agree with the Viewpoint’s authors, they also criticized the FDA for its collaboration with the drug’s manufacturers on briefing documents and more.

On April 1, Health Research Group members sent a letter to the U.S. Secretary of Health and Human Services requesting the temporary suspension of the FDA’s neuroscience chief, Bill Dunn, MD, because of his role in supervising the collaboration.
 

Alzheimer association weighs in

The Alzheimer’s Association has been a proponent of the drug throughout its development.

Ahead of today’s news, the organization noted in a statement that a decision to approve “would be historic” because it would make aducanumab “the first drug to slow Alzheimer’s disease” and would mark the beginning of a new future for AD treatments.

“The Alzheimer’s Association urgently supports FDA approval of the treatment based on clinical trial results that showed a 22% reduction in cognitive and function decline — something that could make a meaningful difference” for patients with AD, it said.

Kristen Clifford, chief program officer for the Alzheimer’s Association, said in an interview at the time that approval would be considered a “victory” for patients with AD and for the field overall.

“For individuals who would potentially be eligible for the treatment, this drug could mean more quality time. Slowing decline, particularly in early diagnosis, could add weeks or months or maybe even years of active life,” Clifford said.

“If approved, this would really be a landmark moment. And it could provide hope for those living with Alzheimer’s and their families,” she added.

Clifford noted that approval of this type of drug would also underscore the importance of early detection for AD. “This treatment would encourage earlier diagnosis of the disease,” she said.

In a new statement released just after approval for aducanumab was announced, the organization said that today’s news is a win-win for all patients with AD and their families.

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

Amid significant controversy, the U.S. Food and Drug Administration (FDA) has approved the anti-amyloid agent aducanumab (Biogen, Eisai) for the treatment of Alzheimer’s disease, disregarding the recommendation by its own advisory panel not to approve the drug.

In November, the Peripheral and Central Nervous System Drugs Advisory Committee voted eight to one against approving the drug because, based on clinical trial results, evidence of efficacy was not strong enough. Two other members said they were uncertain on the issue of efficacy.

In a company release Michel Vounatsos, Biogen’s Chief Executive Officer, said, “this historic moment is the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer’s disease. We believe this first-in-class medicine will transform the treatment of people living with Alzheimer’s disease and spark continuous innovation in the years to come.
 

Rocky road

The road to approval has been extremely rocky for aducanumab, an anti-amyloid-beta human monoclonal antibody, previously known as BIIB037.

As reported by this news organization, two phase 3 trials evaluating the drug were initially scrapped in March 2019 because of interim futility analysis. At the time, Biogen released a statement saying that aducanumab was unlikely to meet primary endpoints in the ENGAGE and EMERGE randomized controlled trials.

However, in an about-face 7 months later, Biogen and Eisai announced that a  new analysis showed the drug met its primary endpoint of reduction in clinical decline, including cognition and function, in the EMERGE trial.

Although ENGAGE still didn’t meet its primary endpoint, data from its new analysis “supported” the EMERGE findings, the drug companies said at the time.

However, 1 year later, a majority of the members of the FDA’s advisory panel were against the drug’s approval. Details of that decision were published online March 30 in the Journal of the American Medical Association.

As reported by this news organization, a Viewpoint written by three of the committee members notes that results from the drug’s only large positive clinical trial fell short.

“There is no persuasive evidence to support approval of aducanumab at this time,” they write.

Groups such as Public Citizen’s Health Research Group not only agree with the Viewpoint’s authors, they also criticized the FDA for its collaboration with the drug’s manufacturers on briefing documents and more.

On April 1, Health Research Group members sent a letter to the U.S. Secretary of Health and Human Services requesting the temporary suspension of the FDA’s neuroscience chief, Bill Dunn, MD, because of his role in supervising the collaboration.
 

Alzheimer association weighs in

The Alzheimer’s Association has been a proponent of the drug throughout its development.

Ahead of today’s news, the organization noted in a statement that a decision to approve “would be historic” because it would make aducanumab “the first drug to slow Alzheimer’s disease” and would mark the beginning of a new future for AD treatments.

“The Alzheimer’s Association urgently supports FDA approval of the treatment based on clinical trial results that showed a 22% reduction in cognitive and function decline — something that could make a meaningful difference” for patients with AD, it said.

Kristen Clifford, chief program officer for the Alzheimer’s Association, said in an interview at the time that approval would be considered a “victory” for patients with AD and for the field overall.

“For individuals who would potentially be eligible for the treatment, this drug could mean more quality time. Slowing decline, particularly in early diagnosis, could add weeks or months or maybe even years of active life,” Clifford said.

“If approved, this would really be a landmark moment. And it could provide hope for those living with Alzheimer’s and their families,” she added.

Clifford noted that approval of this type of drug would also underscore the importance of early detection for AD. “This treatment would encourage earlier diagnosis of the disease,” she said.

In a new statement released just after approval for aducanumab was announced, the organization said that today’s news is a win-win for all patients with AD and their families.

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