Eve Bender

Any amount of exercise in middle age is associated with better cognition in later life, new research suggests.

A prospective study of 1,400 participants showed that those who exercised to any extent in adulthood had significantly better cognitive scores later in life, compared with their peers who were physically inactive.

Maintaining an exercise routine throughout adulthood showed the strongest link to subsequent mental acuity.

Although these associations lessened when investigators controlled for childhood cognitive ability, socioeconomic background, and education, they remained statistically significant.

“Our findings support recommendations for greater participation in physical activity across adulthood,” lead investigator Sarah-Naomi James, PhD, research fellow at the Medical Research Council Unit for Lifelong Health and Ageing at the University College London, told this news organization.

“We provide evidence to encourage inactive adults to be active even to a small extent … at any point during adulthood,” which can improve cognition and memory later in life, Dr. James said.

The findings were published online in the Journal of Neurology, Neurosurgery & Psychiatry.
 

Exercise timing

Previous studies have established a link between fitness training and cognitive benefit later in life, but the researchers wanted to explore whether the timing or type of exercise influenced cognitive outcomes in later life.

The investigators asked more than 1,400 participants in the 1946 British birth cohort how much they had exercised at ages 36, 43, 60, and 69 years.

The questions changed slightly for each assessment period, but in general, participants were asked whether in the past month they had exercised or participated in such activities as badminton, swimming, fitness exercises, yoga, dancing, football, mountain climbing, jogging, or brisk walks for 30 minutes or more; and if so, how many times they participated per month.

Prior research showed that when the participants were aged 60 years, the most commonly reported activities were walking (71%), swimming (33%), floor exercises (24%), and cycling (15%).

When they turned 69, researchers tested participants’ cognitive performance using the Addenbrooke’s Cognitive Examination–III, which measures attention and orientation, verbal fluency, memory, language, and visuospatial function. In this study sample, 53% were women, and all were White.

Physical activity levels were classified as inactive, moderately active (one to four times per month), and most active (five or more times per month). In addition, they were summed across all five assessments to create a total score ranging from 0 (inactive at all ages) to 5 (active at all ages).

Overall, 11% of participants were physically inactive at all five time points; 17% were active at one time point; 20% were active at two and three time points; 17% were active at four time points; and 15% were active at all five time points.
 

‘Cradle to grave’ study?

Results showed that being physically active at all study time points was significantly associated with higher cognitive performance, verbal memory, and processing speed when participants were aged 69 (P < .01).

Those who exercised to any extent in adulthood – even just once a month during one of the time periods, fared better cognitively in later life, compared with physically inactive participants. (P < .01).

Study limitations cited include a lack of diversity among participants and a disproportionately high attrition rate among those who were socially disadvantaged.

“Our findings show that being active during every decade from their 30s on was associated with better cognition at around 70. Indeed, those who were active for longer had the highest cognitive function,” Dr. James said.

“However, it is also never too late to start. People in our study who only started being active in their 50s or 60s still had higher cognitive scores at age 70, compared to people of the same age who had never been active,” she added.

Dr. James intends to continue following the study sample to determine whether physical activity is linked to preserved cognitive aging “and buffers the effects of cognitive deterioration in the presence of disease markers that cause dementia, ultimately delaying dementia onset.

“We hope the cohort we study will be the first ‘cradle to grave’ study in the world, where we have followed people for their entire lives,” she said.
 

Encouraging finding

In a comment, Joel Hughes, PhD, professor of psychology and director of clinical training at Kent (Ohio) State University, said the study contributes to the idea that “accumulation of physical activity over one’s lifetime fits the data better than a ‘sensitive period’ – which suggests that it’s never too late to start exercising.”

Dr. Hughes, who was not involved in the research, noted that “exercise can improve cerebral blood flow and hemodynamic function, as well as greater activation of relevant brain regions such as the frontal lobes.”

While observing that the effects of exercise on cognition are likely complex from a mechanistic point of view, the finding that “exercise preserves or improves cognition later in life is encouraging,” he said.

The study received funding from the UK Medical Research Council and Alzheimer’s Research UK. The investigators and Dr. Hughes report no relevant financial relationships.

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

Any amount of exercise in middle age is associated with better cognition in later life, new research suggests.

A prospective study of 1,400 participants showed that those who exercised to any extent in adulthood had significantly better cognitive scores later in life, compared with their peers who were physically inactive.

Maintaining an exercise routine throughout adulthood showed the strongest link to subsequent mental acuity.

Although these associations lessened when investigators controlled for childhood cognitive ability, socioeconomic background, and education, they remained statistically significant.

“Our findings support recommendations for greater participation in physical activity across adulthood,” lead investigator Sarah-Naomi James, PhD, research fellow at the Medical Research Council Unit for Lifelong Health and Ageing at the University College London, told this news organization.

“We provide evidence to encourage inactive adults to be active even to a small extent … at any point during adulthood,” which can improve cognition and memory later in life, Dr. James said.

The findings were published online in the Journal of Neurology, Neurosurgery & Psychiatry.
 

Exercise timing

Previous studies have established a link between fitness training and cognitive benefit later in life, but the researchers wanted to explore whether the timing or type of exercise influenced cognitive outcomes in later life.

The investigators asked more than 1,400 participants in the 1946 British birth cohort how much they had exercised at ages 36, 43, 60, and 69 years.

The questions changed slightly for each assessment period, but in general, participants were asked whether in the past month they had exercised or participated in such activities as badminton, swimming, fitness exercises, yoga, dancing, football, mountain climbing, jogging, or brisk walks for 30 minutes or more; and if so, how many times they participated per month.

Prior research showed that when the participants were aged 60 years, the most commonly reported activities were walking (71%), swimming (33%), floor exercises (24%), and cycling (15%).

When they turned 69, researchers tested participants’ cognitive performance using the Addenbrooke’s Cognitive Examination–III, which measures attention and orientation, verbal fluency, memory, language, and visuospatial function. In this study sample, 53% were women, and all were White.

Physical activity levels were classified as inactive, moderately active (one to four times per month), and most active (five or more times per month). In addition, they were summed across all five assessments to create a total score ranging from 0 (inactive at all ages) to 5 (active at all ages).

Overall, 11% of participants were physically inactive at all five time points; 17% were active at one time point; 20% were active at two and three time points; 17% were active at four time points; and 15% were active at all five time points.
 

‘Cradle to grave’ study?

Results showed that being physically active at all study time points was significantly associated with higher cognitive performance, verbal memory, and processing speed when participants were aged 69 (P < .01).

Those who exercised to any extent in adulthood – even just once a month during one of the time periods, fared better cognitively in later life, compared with physically inactive participants. (P < .01).

Study limitations cited include a lack of diversity among participants and a disproportionately high attrition rate among those who were socially disadvantaged.

“Our findings show that being active during every decade from their 30s on was associated with better cognition at around 70. Indeed, those who were active for longer had the highest cognitive function,” Dr. James said.

“However, it is also never too late to start. People in our study who only started being active in their 50s or 60s still had higher cognitive scores at age 70, compared to people of the same age who had never been active,” she added.

Dr. James intends to continue following the study sample to determine whether physical activity is linked to preserved cognitive aging “and buffers the effects of cognitive deterioration in the presence of disease markers that cause dementia, ultimately delaying dementia onset.

“We hope the cohort we study will be the first ‘cradle to grave’ study in the world, where we have followed people for their entire lives,” she said.
 

Encouraging finding

In a comment, Joel Hughes, PhD, professor of psychology and director of clinical training at Kent (Ohio) State University, said the study contributes to the idea that “accumulation of physical activity over one’s lifetime fits the data better than a ‘sensitive period’ – which suggests that it’s never too late to start exercising.”

Dr. Hughes, who was not involved in the research, noted that “exercise can improve cerebral blood flow and hemodynamic function, as well as greater activation of relevant brain regions such as the frontal lobes.”

While observing that the effects of exercise on cognition are likely complex from a mechanistic point of view, the finding that “exercise preserves or improves cognition later in life is encouraging,” he said.

The study received funding from the UK Medical Research Council and Alzheimer’s Research UK. The investigators and Dr. Hughes report no relevant financial relationships.

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

Any amount of exercise in middle age is associated with better cognition in later life, new research suggests.

A prospective study of 1,400 participants showed that those who exercised to any extent in adulthood had significantly better cognitive scores later in life, compared with their peers who were physically inactive.

Maintaining an exercise routine throughout adulthood showed the strongest link to subsequent mental acuity.

Although these associations lessened when investigators controlled for childhood cognitive ability, socioeconomic background, and education, they remained statistically significant.

“Our findings support recommendations for greater participation in physical activity across adulthood,” lead investigator Sarah-Naomi James, PhD, research fellow at the Medical Research Council Unit for Lifelong Health and Ageing at the University College London, told this news organization.

“We provide evidence to encourage inactive adults to be active even to a small extent … at any point during adulthood,” which can improve cognition and memory later in life, Dr. James said.

The findings were published online in the Journal of Neurology, Neurosurgery & Psychiatry.
 

Exercise timing

Previous studies have established a link between fitness training and cognitive benefit later in life, but the researchers wanted to explore whether the timing or type of exercise influenced cognitive outcomes in later life.

The investigators asked more than 1,400 participants in the 1946 British birth cohort how much they had exercised at ages 36, 43, 60, and 69 years.

The questions changed slightly for each assessment period, but in general, participants were asked whether in the past month they had exercised or participated in such activities as badminton, swimming, fitness exercises, yoga, dancing, football, mountain climbing, jogging, or brisk walks for 30 minutes or more; and if so, how many times they participated per month.

Prior research showed that when the participants were aged 60 years, the most commonly reported activities were walking (71%), swimming (33%), floor exercises (24%), and cycling (15%).

When they turned 69, researchers tested participants’ cognitive performance using the Addenbrooke’s Cognitive Examination–III, which measures attention and orientation, verbal fluency, memory, language, and visuospatial function. In this study sample, 53% were women, and all were White.

Physical activity levels were classified as inactive, moderately active (one to four times per month), and most active (five or more times per month). In addition, they were summed across all five assessments to create a total score ranging from 0 (inactive at all ages) to 5 (active at all ages).

Overall, 11% of participants were physically inactive at all five time points; 17% were active at one time point; 20% were active at two and three time points; 17% were active at four time points; and 15% were active at all five time points.
 

‘Cradle to grave’ study?

Results showed that being physically active at all study time points was significantly associated with higher cognitive performance, verbal memory, and processing speed when participants were aged 69 (P < .01).

Those who exercised to any extent in adulthood – even just once a month during one of the time periods, fared better cognitively in later life, compared with physically inactive participants. (P < .01).

Study limitations cited include a lack of diversity among participants and a disproportionately high attrition rate among those who were socially disadvantaged.

“Our findings show that being active during every decade from their 30s on was associated with better cognition at around 70. Indeed, those who were active for longer had the highest cognitive function,” Dr. James said.

“However, it is also never too late to start. People in our study who only started being active in their 50s or 60s still had higher cognitive scores at age 70, compared to people of the same age who had never been active,” she added.

Dr. James intends to continue following the study sample to determine whether physical activity is linked to preserved cognitive aging “and buffers the effects of cognitive deterioration in the presence of disease markers that cause dementia, ultimately delaying dementia onset.

“We hope the cohort we study will be the first ‘cradle to grave’ study in the world, where we have followed people for their entire lives,” she said.
 

Encouraging finding

In a comment, Joel Hughes, PhD, professor of psychology and director of clinical training at Kent (Ohio) State University, said the study contributes to the idea that “accumulation of physical activity over one’s lifetime fits the data better than a ‘sensitive period’ – which suggests that it’s never too late to start exercising.”

Dr. Hughes, who was not involved in the research, noted that “exercise can improve cerebral blood flow and hemodynamic function, as well as greater activation of relevant brain regions such as the frontal lobes.”

While observing that the effects of exercise on cognition are likely complex from a mechanistic point of view, the finding that “exercise preserves or improves cognition later in life is encouraging,” he said.

The study received funding from the UK Medical Research Council and Alzheimer’s Research UK. The investigators and Dr. Hughes report no relevant financial relationships.

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

Repetitive transcranial magnetic stimulation (rTMS) is associated with reduced symptom severity in patients with comorbid major depressive disorder (MDD) and substance use disorders (SUDs), new research suggests.

In a retrospective observational study, participants receiving 20-30 rTMS sessions delivered over a course of 4-6 weeks showed significant reductions in both craving and depression symptom scores.

In addition, the researchers found that the number of rTMS sessions significantly predicted the number of days of drug abstinence, even after controlling for confounders.

“For each additional TMS session, there was an additional 10 days of abstinence in the community,” principal investigator Wael Foad, MD, medical director, Erada Center for Treatment and Rehabilitation, Dubai, United Arab Emirates, told this news organization.

However, Dr. Foad noted that he would need to construct a randomized controlled trial to further explore that “interesting” finding.

The results were published in the Annals of Clinical Psychiatry.
 

Inpatient program

The researchers retrospectively analyzed medical records of men admitted to the inpatient unit at the Erada Center between June 2019 and September 2020. The vast majority were native to the UAE.

The inpatient program focuses on treating patients with SUDs and is the only dedicated addiction rehabilitation service in Dubai, the investigators noted.

They analyzed outcomes for 55 men with mild to moderate MDD who received rTMS as standard treatment.

Participants were excluded from the data analysis if they had another comorbid diagnosis from the DSM-5 other than SUD or MDD. They were also excluded if they used an illicit substance 2 weeks before the study or used certain medications, including antipsychotics, benzodiazepines, or mood stabilizers.

When patients first arrived on the unit, they were detoxed for a period of time before they began receiving rTMS sessions.

The 55 men received 20-30 high-frequency rTMS sessions over the course of 4-6 weeks in the area of the dorsolateral prefrontal cortex. Each session consisted of 3,000 pulses delivered over a period of 37.5 minutes.  Severity of depression was measured with the Clinical Global Impression–Severity Scale (CGI-S), which uses a 7-point Likert scale.

In addition, participants’ scores were tracked on the Brief Substance Craving Scale (BSCS), a self-report scale that measures craving for primary and secondary substances of abuse over a 24-hr period.

Of all participants, 47% said opiates and 35% said methamphetamine were their primary substances of abuse.
 

Significant improvement

Results showed a statistically significant improvement (P < .05) between baseline and post-rTMS treatment scores in severity of depression and drug craving, as measured by the BSCS and the CGI-S.

The researchers noted that eight participants dropped out of the study after their first rTMS session for various reasons.

Dr. Foad explained that investigators contracted with study participants to receive 20 rTMS sessions; if the sessions were not fully completed during the inpatient stay, the rTMS sessions were continued on an outpatient basis. A study clinician closely monitored patients until they finished their sessions.

For each additional rTMS session the patients completed beyond 20 sessions, there was an associated excess of 10 more days of abstinence from the primary drug in the community.

The investigators speculated that rTMS may reduce drug craving by increasing dopaminergic binding in the striatum, or by releasing dopamine in the caudate nucleus.

Study limitations cited include the lack of a control group and the fact that the study sample was limited to male inpatients, which limits generalizability of the findings to other populations.
 

Promising intervention

Commenting on the study, Colleen Ann Hanlon, PhD, noted that, from years of work using TMS for depression, “we know that more sessions of TMS during the acute treatment phase tends to lead to stronger and possibly more durable results long-term.”

Dr. Hanlon, who was not involved with the current research, formerly headed a clinical neuromodulation lab at Wake Forest University, Winston-Salem, N.C. She is now vice president of medical affairs at BrainsWay, an international health technology company specializing in Deep TMS.

She noted that Deep TMS was approved by the Food and Drug Administration for smoking cessation in 2020, “which was a tremendous win for our field at large, and requires only 15 acute sessions followed by 3 weekly sessions” of deep TMS.

“I suspect this is just the beginning of a new era in neuromodulation-based therapeutics for people struggling with drug and alcohol use disorders,” Dr. Hanlon said. 

The study behind the FDA approval for smoking approval was a large double-blind, sham-controlled multisite clinical trial where investigators used an H4 coil – a TMS coil that modulates multiple brain areas involved in addictive behaviors simultaneously.

Results from that study showed that 15 sessions of deep TMS significantly improved smoking cessation rates relative to sham (10 Hz, 120% motor threshold, H4 coil, 1,800 pulses/session).

“The difference in cigarette consumption and craving was significant as early as 2 weeks after treatment initiation,” said Dr. Hanlon. “I am looking forward to the future of this field for all people suffering from drug and alcohol use disorders.”

The study and services provided through the Erada Center were funded by the government of Dubai. The investigators reported no relevant financial relationships.

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

Repetitive transcranial magnetic stimulation (rTMS) is associated with reduced symptom severity in patients with comorbid major depressive disorder (MDD) and substance use disorders (SUDs), new research suggests.

In a retrospective observational study, participants receiving 20-30 rTMS sessions delivered over a course of 4-6 weeks showed significant reductions in both craving and depression symptom scores.

In addition, the researchers found that the number of rTMS sessions significantly predicted the number of days of drug abstinence, even after controlling for confounders.

“For each additional TMS session, there was an additional 10 days of abstinence in the community,” principal investigator Wael Foad, MD, medical director, Erada Center for Treatment and Rehabilitation, Dubai, United Arab Emirates, told this news organization.

However, Dr. Foad noted that he would need to construct a randomized controlled trial to further explore that “interesting” finding.

The results were published in the Annals of Clinical Psychiatry.
 

Inpatient program

The researchers retrospectively analyzed medical records of men admitted to the inpatient unit at the Erada Center between June 2019 and September 2020. The vast majority were native to the UAE.

The inpatient program focuses on treating patients with SUDs and is the only dedicated addiction rehabilitation service in Dubai, the investigators noted.

They analyzed outcomes for 55 men with mild to moderate MDD who received rTMS as standard treatment.

Participants were excluded from the data analysis if they had another comorbid diagnosis from the DSM-5 other than SUD or MDD. They were also excluded if they used an illicit substance 2 weeks before the study or used certain medications, including antipsychotics, benzodiazepines, or mood stabilizers.

When patients first arrived on the unit, they were detoxed for a period of time before they began receiving rTMS sessions.

The 55 men received 20-30 high-frequency rTMS sessions over the course of 4-6 weeks in the area of the dorsolateral prefrontal cortex. Each session consisted of 3,000 pulses delivered over a period of 37.5 minutes.  Severity of depression was measured with the Clinical Global Impression–Severity Scale (CGI-S), which uses a 7-point Likert scale.

In addition, participants’ scores were tracked on the Brief Substance Craving Scale (BSCS), a self-report scale that measures craving for primary and secondary substances of abuse over a 24-hr period.

Of all participants, 47% said opiates and 35% said methamphetamine were their primary substances of abuse.
 

Significant improvement

Results showed a statistically significant improvement (P < .05) between baseline and post-rTMS treatment scores in severity of depression and drug craving, as measured by the BSCS and the CGI-S.

The researchers noted that eight participants dropped out of the study after their first rTMS session for various reasons.

Dr. Foad explained that investigators contracted with study participants to receive 20 rTMS sessions; if the sessions were not fully completed during the inpatient stay, the rTMS sessions were continued on an outpatient basis. A study clinician closely monitored patients until they finished their sessions.

For each additional rTMS session the patients completed beyond 20 sessions, there was an associated excess of 10 more days of abstinence from the primary drug in the community.

The investigators speculated that rTMS may reduce drug craving by increasing dopaminergic binding in the striatum, or by releasing dopamine in the caudate nucleus.

Study limitations cited include the lack of a control group and the fact that the study sample was limited to male inpatients, which limits generalizability of the findings to other populations.
 

Promising intervention

Commenting on the study, Colleen Ann Hanlon, PhD, noted that, from years of work using TMS for depression, “we know that more sessions of TMS during the acute treatment phase tends to lead to stronger and possibly more durable results long-term.”

Dr. Hanlon, who was not involved with the current research, formerly headed a clinical neuromodulation lab at Wake Forest University, Winston-Salem, N.C. She is now vice president of medical affairs at BrainsWay, an international health technology company specializing in Deep TMS.

She noted that Deep TMS was approved by the Food and Drug Administration for smoking cessation in 2020, “which was a tremendous win for our field at large, and requires only 15 acute sessions followed by 3 weekly sessions” of deep TMS.

“I suspect this is just the beginning of a new era in neuromodulation-based therapeutics for people struggling with drug and alcohol use disorders,” Dr. Hanlon said. 

The study behind the FDA approval for smoking approval was a large double-blind, sham-controlled multisite clinical trial where investigators used an H4 coil – a TMS coil that modulates multiple brain areas involved in addictive behaviors simultaneously.

Results from that study showed that 15 sessions of deep TMS significantly improved smoking cessation rates relative to sham (10 Hz, 120% motor threshold, H4 coil, 1,800 pulses/session).

“The difference in cigarette consumption and craving was significant as early as 2 weeks after treatment initiation,” said Dr. Hanlon. “I am looking forward to the future of this field for all people suffering from drug and alcohol use disorders.”

The study and services provided through the Erada Center were funded by the government of Dubai. The investigators reported no relevant financial relationships.

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

Repetitive transcranial magnetic stimulation (rTMS) is associated with reduced symptom severity in patients with comorbid major depressive disorder (MDD) and substance use disorders (SUDs), new research suggests.

In a retrospective observational study, participants receiving 20-30 rTMS sessions delivered over a course of 4-6 weeks showed significant reductions in both craving and depression symptom scores.

In addition, the researchers found that the number of rTMS sessions significantly predicted the number of days of drug abstinence, even after controlling for confounders.

“For each additional TMS session, there was an additional 10 days of abstinence in the community,” principal investigator Wael Foad, MD, medical director, Erada Center for Treatment and Rehabilitation, Dubai, United Arab Emirates, told this news organization.

However, Dr. Foad noted that he would need to construct a randomized controlled trial to further explore that “interesting” finding.

The results were published in the Annals of Clinical Psychiatry.
 

Inpatient program

The researchers retrospectively analyzed medical records of men admitted to the inpatient unit at the Erada Center between June 2019 and September 2020. The vast majority were native to the UAE.

The inpatient program focuses on treating patients with SUDs and is the only dedicated addiction rehabilitation service in Dubai, the investigators noted.

They analyzed outcomes for 55 men with mild to moderate MDD who received rTMS as standard treatment.

Participants were excluded from the data analysis if they had another comorbid diagnosis from the DSM-5 other than SUD or MDD. They were also excluded if they used an illicit substance 2 weeks before the study or used certain medications, including antipsychotics, benzodiazepines, or mood stabilizers.

When patients first arrived on the unit, they were detoxed for a period of time before they began receiving rTMS sessions.

The 55 men received 20-30 high-frequency rTMS sessions over the course of 4-6 weeks in the area of the dorsolateral prefrontal cortex. Each session consisted of 3,000 pulses delivered over a period of 37.5 minutes.  Severity of depression was measured with the Clinical Global Impression–Severity Scale (CGI-S), which uses a 7-point Likert scale.

In addition, participants’ scores were tracked on the Brief Substance Craving Scale (BSCS), a self-report scale that measures craving for primary and secondary substances of abuse over a 24-hr period.

Of all participants, 47% said opiates and 35% said methamphetamine were their primary substances of abuse.
 

Significant improvement

Results showed a statistically significant improvement (P < .05) between baseline and post-rTMS treatment scores in severity of depression and drug craving, as measured by the BSCS and the CGI-S.

The researchers noted that eight participants dropped out of the study after their first rTMS session for various reasons.

Dr. Foad explained that investigators contracted with study participants to receive 20 rTMS sessions; if the sessions were not fully completed during the inpatient stay, the rTMS sessions were continued on an outpatient basis. A study clinician closely monitored patients until they finished their sessions.

For each additional rTMS session the patients completed beyond 20 sessions, there was an associated excess of 10 more days of abstinence from the primary drug in the community.

The investigators speculated that rTMS may reduce drug craving by increasing dopaminergic binding in the striatum, or by releasing dopamine in the caudate nucleus.

Study limitations cited include the lack of a control group and the fact that the study sample was limited to male inpatients, which limits generalizability of the findings to other populations.
 

Promising intervention

Commenting on the study, Colleen Ann Hanlon, PhD, noted that, from years of work using TMS for depression, “we know that more sessions of TMS during the acute treatment phase tends to lead to stronger and possibly more durable results long-term.”

Dr. Hanlon, who was not involved with the current research, formerly headed a clinical neuromodulation lab at Wake Forest University, Winston-Salem, N.C. She is now vice president of medical affairs at BrainsWay, an international health technology company specializing in Deep TMS.

She noted that Deep TMS was approved by the Food and Drug Administration for smoking cessation in 2020, “which was a tremendous win for our field at large, and requires only 15 acute sessions followed by 3 weekly sessions” of deep TMS.

“I suspect this is just the beginning of a new era in neuromodulation-based therapeutics for people struggling with drug and alcohol use disorders,” Dr. Hanlon said. 

The study behind the FDA approval for smoking approval was a large double-blind, sham-controlled multisite clinical trial where investigators used an H4 coil – a TMS coil that modulates multiple brain areas involved in addictive behaviors simultaneously.

Results from that study showed that 15 sessions of deep TMS significantly improved smoking cessation rates relative to sham (10 Hz, 120% motor threshold, H4 coil, 1,800 pulses/session).

“The difference in cigarette consumption and craving was significant as early as 2 weeks after treatment initiation,” said Dr. Hanlon. “I am looking forward to the future of this field for all people suffering from drug and alcohol use disorders.”

The study and services provided through the Erada Center were funded by the government of Dubai. The investigators reported no relevant financial relationships.

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

A new “smart patch” composed of microneedles that can detect proinflammatory markers via simulated skin interstitial fluid (ISF) may help diagnose neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease very early on.

Originally developed to deliver medications and vaccines via the skin in a minimally invasive manner, the microneedle arrays were fitted with molecular sensors that, when placed on the skin, detect neuroinflammatory biomarkers such as interleukin-6 in as little as 6 minutes.

The literature suggests that these biomarkers of neurodegenerative disease are present years before patients become symptomatic, said study investigator Sanjiv Sharma, PhD.

“Neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease are [characterized by] progressive loss in nerve cell and brain cells, which leads to memory problems and a loss of mental ability. That is why early diagnosis is key to preventing the loss of brain tissue in dementia, which can go undetected for years,” added Dr. Sharma, who is a lecturer in medical engineering at Swansea (Wales) University.

Dr. Sharma developed the patch with scientists at the Polytechnic of Porto (Portugal) School of Engineering in Portugal. In 2022, they designed, and are currently testing, a microneedle patch that will deliver the COVID vaccine.

The investigators describe their research on the patch’s ability to detect IL-6 in an article published in ACS Omega.
 

At-home diagnosis?

“The skin is the largest organ in the body – it contains more skin interstitial fluid than the total blood volume,” Dr. Sharma noted. “This fluid is an ultrafiltrate of blood and holds biomarkers that complement other biofluids, such as sweat, saliva, and urine. It can be sampled in a minimally invasive manner and used either for point-of-care testing or real-time using microneedle devices.”

Dr. Sharma and associates tested the microneedle patch in artificial ISF that contained the inflammatory cytokine IL-6. They found that the patch accurately detected IL-6 concentrations as low as 1 pg/mL in the fabricated ISF solution.

“In general, the transdermal sensor presented here showed simplicity in designing, short measuring time, high accuracy, and low detection limit. This approach seems a successful tool for the screening of inflammatory biomarkers in point of care testing wherein the skin acts as a window to the body,” the investigators reported.

Dr. Sharma noted that early detection of neurodegenerative diseases is crucial, as once symptoms appear, the disease may have already progressed significantly, and meaningful intervention is challenging.

The device has yet to be tested in humans, which is the next step, said Dr. Sharma.

“We will have to test the hypothesis through extensive preclinical and clinical studies to determine if bloodless, transdermal (skin) diagnostics can offer a cost-effective device that could allow testing in simpler settings such as a clinician’s practice or even home settings,” he noted.
 

Early days

Commenting on the research, David K. Simon, MD, PhD, professor of neurology at Harvard Medical School, Boston, said it is “a promising step regarding validation of a potentially beneficial method for rapidly and accurately measuring IL-6.”

However, he added, “many additional steps are needed to validate the method in actual human skin and to determine whether or not measuring these biomarkers in skin will be useful in studies of neurodegenerative diseases.”

He noted that one study limitation is that inflammatory cytokines such as IL-6 are highly nonspecific, and levels are elevated in various diseases associated with inflammation.

“It is highly unlikely that measuring IL-6 will be useful as a diagnostic tool. However, it does have potential as a biomarker for measuring the impact of treatments aimed at reducing inflammation. As the authors point out, it’s more likely that clinicians will require a panel of biomarkers rather than only measuring IL-6,” he said.

The study was funded by Fundação para a Ciência e Tecnologia. The investigators disclosed no relevant financial relationships.

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

A new “smart patch” composed of microneedles that can detect proinflammatory markers via simulated skin interstitial fluid (ISF) may help diagnose neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease very early on.

Originally developed to deliver medications and vaccines via the skin in a minimally invasive manner, the microneedle arrays were fitted with molecular sensors that, when placed on the skin, detect neuroinflammatory biomarkers such as interleukin-6 in as little as 6 minutes.

The literature suggests that these biomarkers of neurodegenerative disease are present years before patients become symptomatic, said study investigator Sanjiv Sharma, PhD.

“Neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease are [characterized by] progressive loss in nerve cell and brain cells, which leads to memory problems and a loss of mental ability. That is why early diagnosis is key to preventing the loss of brain tissue in dementia, which can go undetected for years,” added Dr. Sharma, who is a lecturer in medical engineering at Swansea (Wales) University.

Dr. Sharma developed the patch with scientists at the Polytechnic of Porto (Portugal) School of Engineering in Portugal. In 2022, they designed, and are currently testing, a microneedle patch that will deliver the COVID vaccine.

The investigators describe their research on the patch’s ability to detect IL-6 in an article published in ACS Omega.
 

At-home diagnosis?

“The skin is the largest organ in the body – it contains more skin interstitial fluid than the total blood volume,” Dr. Sharma noted. “This fluid is an ultrafiltrate of blood and holds biomarkers that complement other biofluids, such as sweat, saliva, and urine. It can be sampled in a minimally invasive manner and used either for point-of-care testing or real-time using microneedle devices.”

Dr. Sharma and associates tested the microneedle patch in artificial ISF that contained the inflammatory cytokine IL-6. They found that the patch accurately detected IL-6 concentrations as low as 1 pg/mL in the fabricated ISF solution.

“In general, the transdermal sensor presented here showed simplicity in designing, short measuring time, high accuracy, and low detection limit. This approach seems a successful tool for the screening of inflammatory biomarkers in point of care testing wherein the skin acts as a window to the body,” the investigators reported.

Dr. Sharma noted that early detection of neurodegenerative diseases is crucial, as once symptoms appear, the disease may have already progressed significantly, and meaningful intervention is challenging.

The device has yet to be tested in humans, which is the next step, said Dr. Sharma.

“We will have to test the hypothesis through extensive preclinical and clinical studies to determine if bloodless, transdermal (skin) diagnostics can offer a cost-effective device that could allow testing in simpler settings such as a clinician’s practice or even home settings,” he noted.
 

Early days

Commenting on the research, David K. Simon, MD, PhD, professor of neurology at Harvard Medical School, Boston, said it is “a promising step regarding validation of a potentially beneficial method for rapidly and accurately measuring IL-6.”

However, he added, “many additional steps are needed to validate the method in actual human skin and to determine whether or not measuring these biomarkers in skin will be useful in studies of neurodegenerative diseases.”

He noted that one study limitation is that inflammatory cytokines such as IL-6 are highly nonspecific, and levels are elevated in various diseases associated with inflammation.

“It is highly unlikely that measuring IL-6 will be useful as a diagnostic tool. However, it does have potential as a biomarker for measuring the impact of treatments aimed at reducing inflammation. As the authors point out, it’s more likely that clinicians will require a panel of biomarkers rather than only measuring IL-6,” he said.

The study was funded by Fundação para a Ciência e Tecnologia. The investigators disclosed no relevant financial relationships.

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

A new “smart patch” composed of microneedles that can detect proinflammatory markers via simulated skin interstitial fluid (ISF) may help diagnose neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease very early on.

Originally developed to deliver medications and vaccines via the skin in a minimally invasive manner, the microneedle arrays were fitted with molecular sensors that, when placed on the skin, detect neuroinflammatory biomarkers such as interleukin-6 in as little as 6 minutes.

The literature suggests that these biomarkers of neurodegenerative disease are present years before patients become symptomatic, said study investigator Sanjiv Sharma, PhD.

“Neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease are [characterized by] progressive loss in nerve cell and brain cells, which leads to memory problems and a loss of mental ability. That is why early diagnosis is key to preventing the loss of brain tissue in dementia, which can go undetected for years,” added Dr. Sharma, who is a lecturer in medical engineering at Swansea (Wales) University.

Dr. Sharma developed the patch with scientists at the Polytechnic of Porto (Portugal) School of Engineering in Portugal. In 2022, they designed, and are currently testing, a microneedle patch that will deliver the COVID vaccine.

The investigators describe their research on the patch’s ability to detect IL-6 in an article published in ACS Omega.
 

At-home diagnosis?

“The skin is the largest organ in the body – it contains more skin interstitial fluid than the total blood volume,” Dr. Sharma noted. “This fluid is an ultrafiltrate of blood and holds biomarkers that complement other biofluids, such as sweat, saliva, and urine. It can be sampled in a minimally invasive manner and used either for point-of-care testing or real-time using microneedle devices.”

Dr. Sharma and associates tested the microneedle patch in artificial ISF that contained the inflammatory cytokine IL-6. They found that the patch accurately detected IL-6 concentrations as low as 1 pg/mL in the fabricated ISF solution.

“In general, the transdermal sensor presented here showed simplicity in designing, short measuring time, high accuracy, and low detection limit. This approach seems a successful tool for the screening of inflammatory biomarkers in point of care testing wherein the skin acts as a window to the body,” the investigators reported.

Dr. Sharma noted that early detection of neurodegenerative diseases is crucial, as once symptoms appear, the disease may have already progressed significantly, and meaningful intervention is challenging.

The device has yet to be tested in humans, which is the next step, said Dr. Sharma.

“We will have to test the hypothesis through extensive preclinical and clinical studies to determine if bloodless, transdermal (skin) diagnostics can offer a cost-effective device that could allow testing in simpler settings such as a clinician’s practice or even home settings,” he noted.
 

Early days

Commenting on the research, David K. Simon, MD, PhD, professor of neurology at Harvard Medical School, Boston, said it is “a promising step regarding validation of a potentially beneficial method for rapidly and accurately measuring IL-6.”

However, he added, “many additional steps are needed to validate the method in actual human skin and to determine whether or not measuring these biomarkers in skin will be useful in studies of neurodegenerative diseases.”

He noted that one study limitation is that inflammatory cytokines such as IL-6 are highly nonspecific, and levels are elevated in various diseases associated with inflammation.

“It is highly unlikely that measuring IL-6 will be useful as a diagnostic tool. However, it does have potential as a biomarker for measuring the impact of treatments aimed at reducing inflammation. As the authors point out, it’s more likely that clinicians will require a panel of biomarkers rather than only measuring IL-6,” he said.

The study was funded by Fundação para a Ciência e Tecnologia. The investigators disclosed no relevant financial relationships.

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

Two forms of short-term exposure therapy may help reduce symptoms of posttraumatic stress disorder, new research suggests.

In a randomized clinical trial comparing an abbreviated form of prolonged exposure (PE) therapy against an intensive outpatient program (IOP) form of PE, military veterans with combat-related PTSD in both groups experienced significant improvements in PTSD symptoms.

In addition, remission rates of around 50% were sustained in both groups up to the 6-month mark.

“With about two-thirds of study participants reporting clinically meaningful symptom improvement and more than half losing their PTSD diagnosis, this study provides important new evidence that combat-related PTSD can be effectively treated – in as little as 3 weeks,” lead investigator Alan Peterson, PhD, told this news organization.

Dr. Peterson, professor of psychiatry and behavioral sciences at the University of Texas Health Science Center, San Antonio, and director of the Consortium to Alleviate PTSD, noted that while condensed treatments may not be feasible for everyone, “results show that compressed formats adapted to the military context resulted in significant, meaningful, and lasting improvements in PTSD, disability, and functional impairments for most participants.”

The findings were published online in JAMA Network Open.
 

Breathing, direct exposure, education

The investigators randomly recruited 234 military personnel and veterans from two military treatment facilities and two Veterans Affairs facilities in south and central Texas.

Participants (78% men; mean age, 39 years) were active-duty service members or veterans who had deployed post Sept. 11 and met diagnostic criteria for PTSD. They could receive psychotropic medications at stable doses and were excluded if they had mania, substance abuse, psychosis, or suicidality.

The sample included 44% White participants, 26% Black participants, and 25% Hispanic participants.

The researchers randomly assigned the participants to receive either massed-PE (n = 117) or IOP-PE (n = 117).

PE, the foundation of both protocols, includes psychoeducation about trauma, diaphragmatic breathing, direct and imaginal exposure, and processing of the trauma.

The massed-PE protocol was delivered in 15 daily 90-minute sessions over 3 consecutive weeks, as was the IOP-PE. However, the IOP-PE also included eight additional multiple daily feedback sessions, homework, social support from friends or family, and three booster sessions post treatment.

The investigators conducted baseline assessments and follow-up assessments at 1 month, 3 months, and 6 months. At the 6-month follow-up, there were 57 participants left to analyze in the massed-PE group and 57 in the IOP-PE group.
 

Significantly decreased symptoms

As measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), PTSD symptoms decreased significantly from baseline to the 1-month follow-up in both groups (massed-PE mean change, –14.13; P < .001; IOP-PE mean change, –13.85; P < .001).

Both groups also failed to meet PTSD diagnostic criteria at 1-, 3-, and 6-month follow-ups.

At the 1-month follow-up, 62% of participants who received massed-PE and 48% of those who received IOP-PE no longer met diagnostic criteria on the CAPS-5. Diagnostic remission was maintained in more than half of the massed-PE group (52%) and the IOP-PE group (53%) at the 6-month follow-up.

Disability scores as measured by the Sheehan Disability Scale also decreased significantly in both groups (P < .001) from baseline to the 1-month follow-up mark; as did psychosocial functioning scores, as reflected by the Brief Inventory of Psychosocial Functioning (P < .001).

Dr. Peterson noted that the condensed treatment format could be an essential option to consider even in other countries, such as Ukraine, where there are concerns about PTSD in military personnel.

Study limitations included the lack of a placebo or inactive comparison group, and the lack of generalizability of the results to the entire population of U.S. service members and veterans outside of Texas.

Dr. Peterson said he plans to continue his research and that the compressed treatment formats studied “are well-suited for the evaluation of alternative modes of therapy combining cognitive-behavioral treatments with medications and medical devices.”
 

Generalizability limited?

Commenting on the research, Joshua Morganstein, MD, chair of the American Psychiatric Association’s committee on the psychiatric dimensions of disaster, said he was reassured to see participants achieve and keep improvements throughout the study.

“One of the biggest challenges we have, particularly with trauma and stress disorders, is keeping people in therapy” because of the difficult nature of the exposure therapy, said Dr. Morganstein, who was not involved with the research.

“The number of people assigned to each group and who ultimately completed the last follow-up gives a good idea of the utility of the intervention,” he added.

However, Dr. Morganstein noted that some of the exclusion criteria, particularly suicidality and substance abuse, affected the study’s relevance to real-world populations.

“The people in the study become less representative of those who are actually in clinical care,” he said, noting that these two conditions are often comorbid with PTSD.

The study was funded by the Department of Defense, the Defense Health Program, the Psychological Health and Traumatic Brain Injury Research Program, the Department of Veterans Affairs, the Office of Research and Development, and the Clinical Science Research & Development Service. The investigators and Dr. Morganstein have reported no relevant financial relationships.

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

Two forms of short-term exposure therapy may help reduce symptoms of posttraumatic stress disorder, new research suggests.

In a randomized clinical trial comparing an abbreviated form of prolonged exposure (PE) therapy against an intensive outpatient program (IOP) form of PE, military veterans with combat-related PTSD in both groups experienced significant improvements in PTSD symptoms.

In addition, remission rates of around 50% were sustained in both groups up to the 6-month mark.

“With about two-thirds of study participants reporting clinically meaningful symptom improvement and more than half losing their PTSD diagnosis, this study provides important new evidence that combat-related PTSD can be effectively treated – in as little as 3 weeks,” lead investigator Alan Peterson, PhD, told this news organization.

Dr. Peterson, professor of psychiatry and behavioral sciences at the University of Texas Health Science Center, San Antonio, and director of the Consortium to Alleviate PTSD, noted that while condensed treatments may not be feasible for everyone, “results show that compressed formats adapted to the military context resulted in significant, meaningful, and lasting improvements in PTSD, disability, and functional impairments for most participants.”

The findings were published online in JAMA Network Open.
 

Breathing, direct exposure, education

The investigators randomly recruited 234 military personnel and veterans from two military treatment facilities and two Veterans Affairs facilities in south and central Texas.

Participants (78% men; mean age, 39 years) were active-duty service members or veterans who had deployed post Sept. 11 and met diagnostic criteria for PTSD. They could receive psychotropic medications at stable doses and were excluded if they had mania, substance abuse, psychosis, or suicidality.

The sample included 44% White participants, 26% Black participants, and 25% Hispanic participants.

The researchers randomly assigned the participants to receive either massed-PE (n = 117) or IOP-PE (n = 117).

PE, the foundation of both protocols, includes psychoeducation about trauma, diaphragmatic breathing, direct and imaginal exposure, and processing of the trauma.

The massed-PE protocol was delivered in 15 daily 90-minute sessions over 3 consecutive weeks, as was the IOP-PE. However, the IOP-PE also included eight additional multiple daily feedback sessions, homework, social support from friends or family, and three booster sessions post treatment.

The investigators conducted baseline assessments and follow-up assessments at 1 month, 3 months, and 6 months. At the 6-month follow-up, there were 57 participants left to analyze in the massed-PE group and 57 in the IOP-PE group.
 

Significantly decreased symptoms

As measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), PTSD symptoms decreased significantly from baseline to the 1-month follow-up in both groups (massed-PE mean change, –14.13; P < .001; IOP-PE mean change, –13.85; P < .001).

Both groups also failed to meet PTSD diagnostic criteria at 1-, 3-, and 6-month follow-ups.

At the 1-month follow-up, 62% of participants who received massed-PE and 48% of those who received IOP-PE no longer met diagnostic criteria on the CAPS-5. Diagnostic remission was maintained in more than half of the massed-PE group (52%) and the IOP-PE group (53%) at the 6-month follow-up.

Disability scores as measured by the Sheehan Disability Scale also decreased significantly in both groups (P < .001) from baseline to the 1-month follow-up mark; as did psychosocial functioning scores, as reflected by the Brief Inventory of Psychosocial Functioning (P < .001).

Dr. Peterson noted that the condensed treatment format could be an essential option to consider even in other countries, such as Ukraine, where there are concerns about PTSD in military personnel.

Study limitations included the lack of a placebo or inactive comparison group, and the lack of generalizability of the results to the entire population of U.S. service members and veterans outside of Texas.

Dr. Peterson said he plans to continue his research and that the compressed treatment formats studied “are well-suited for the evaluation of alternative modes of therapy combining cognitive-behavioral treatments with medications and medical devices.”
 

Generalizability limited?

Commenting on the research, Joshua Morganstein, MD, chair of the American Psychiatric Association’s committee on the psychiatric dimensions of disaster, said he was reassured to see participants achieve and keep improvements throughout the study.

“One of the biggest challenges we have, particularly with trauma and stress disorders, is keeping people in therapy” because of the difficult nature of the exposure therapy, said Dr. Morganstein, who was not involved with the research.

“The number of people assigned to each group and who ultimately completed the last follow-up gives a good idea of the utility of the intervention,” he added.

However, Dr. Morganstein noted that some of the exclusion criteria, particularly suicidality and substance abuse, affected the study’s relevance to real-world populations.

“The people in the study become less representative of those who are actually in clinical care,” he said, noting that these two conditions are often comorbid with PTSD.

The study was funded by the Department of Defense, the Defense Health Program, the Psychological Health and Traumatic Brain Injury Research Program, the Department of Veterans Affairs, the Office of Research and Development, and the Clinical Science Research & Development Service. The investigators and Dr. Morganstein have reported no relevant financial relationships.

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

Two forms of short-term exposure therapy may help reduce symptoms of posttraumatic stress disorder, new research suggests.

In a randomized clinical trial comparing an abbreviated form of prolonged exposure (PE) therapy against an intensive outpatient program (IOP) form of PE, military veterans with combat-related PTSD in both groups experienced significant improvements in PTSD symptoms.

In addition, remission rates of around 50% were sustained in both groups up to the 6-month mark.

“With about two-thirds of study participants reporting clinically meaningful symptom improvement and more than half losing their PTSD diagnosis, this study provides important new evidence that combat-related PTSD can be effectively treated – in as little as 3 weeks,” lead investigator Alan Peterson, PhD, told this news organization.

Dr. Peterson, professor of psychiatry and behavioral sciences at the University of Texas Health Science Center, San Antonio, and director of the Consortium to Alleviate PTSD, noted that while condensed treatments may not be feasible for everyone, “results show that compressed formats adapted to the military context resulted in significant, meaningful, and lasting improvements in PTSD, disability, and functional impairments for most participants.”

The findings were published online in JAMA Network Open.
 

Breathing, direct exposure, education

The investigators randomly recruited 234 military personnel and veterans from two military treatment facilities and two Veterans Affairs facilities in south and central Texas.

Participants (78% men; mean age, 39 years) were active-duty service members or veterans who had deployed post Sept. 11 and met diagnostic criteria for PTSD. They could receive psychotropic medications at stable doses and were excluded if they had mania, substance abuse, psychosis, or suicidality.

The sample included 44% White participants, 26% Black participants, and 25% Hispanic participants.

The researchers randomly assigned the participants to receive either massed-PE (n = 117) or IOP-PE (n = 117).

PE, the foundation of both protocols, includes psychoeducation about trauma, diaphragmatic breathing, direct and imaginal exposure, and processing of the trauma.

The massed-PE protocol was delivered in 15 daily 90-minute sessions over 3 consecutive weeks, as was the IOP-PE. However, the IOP-PE also included eight additional multiple daily feedback sessions, homework, social support from friends or family, and three booster sessions post treatment.

The investigators conducted baseline assessments and follow-up assessments at 1 month, 3 months, and 6 months. At the 6-month follow-up, there were 57 participants left to analyze in the massed-PE group and 57 in the IOP-PE group.
 

Significantly decreased symptoms

As measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), PTSD symptoms decreased significantly from baseline to the 1-month follow-up in both groups (massed-PE mean change, –14.13; P < .001; IOP-PE mean change, –13.85; P < .001).

Both groups also failed to meet PTSD diagnostic criteria at 1-, 3-, and 6-month follow-ups.

At the 1-month follow-up, 62% of participants who received massed-PE and 48% of those who received IOP-PE no longer met diagnostic criteria on the CAPS-5. Diagnostic remission was maintained in more than half of the massed-PE group (52%) and the IOP-PE group (53%) at the 6-month follow-up.

Disability scores as measured by the Sheehan Disability Scale also decreased significantly in both groups (P < .001) from baseline to the 1-month follow-up mark; as did psychosocial functioning scores, as reflected by the Brief Inventory of Psychosocial Functioning (P < .001).

Dr. Peterson noted that the condensed treatment format could be an essential option to consider even in other countries, such as Ukraine, where there are concerns about PTSD in military personnel.

Study limitations included the lack of a placebo or inactive comparison group, and the lack of generalizability of the results to the entire population of U.S. service members and veterans outside of Texas.

Dr. Peterson said he plans to continue his research and that the compressed treatment formats studied “are well-suited for the evaluation of alternative modes of therapy combining cognitive-behavioral treatments with medications and medical devices.”
 

Generalizability limited?

Commenting on the research, Joshua Morganstein, MD, chair of the American Psychiatric Association’s committee on the psychiatric dimensions of disaster, said he was reassured to see participants achieve and keep improvements throughout the study.

“One of the biggest challenges we have, particularly with trauma and stress disorders, is keeping people in therapy” because of the difficult nature of the exposure therapy, said Dr. Morganstein, who was not involved with the research.

“The number of people assigned to each group and who ultimately completed the last follow-up gives a good idea of the utility of the intervention,” he added.

However, Dr. Morganstein noted that some of the exclusion criteria, particularly suicidality and substance abuse, affected the study’s relevance to real-world populations.

“The people in the study become less representative of those who are actually in clinical care,” he said, noting that these two conditions are often comorbid with PTSD.

The study was funded by the Department of Defense, the Defense Health Program, the Psychological Health and Traumatic Brain Injury Research Program, the Department of Veterans Affairs, the Office of Research and Development, and the Clinical Science Research & Development Service. The investigators and Dr. Morganstein have reported no relevant financial relationships.

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

A smartphone-based self-management intervention developed for patients with bipolar disorder (BD) can help decrease depressive symptoms and improve quality of life, new research suggests.

In a randomized clinical trial of usual care plus the experimental smartphone-based intervention known as LiveWell vs. usual care alone, participants in the smartphone group who were categorized as low-risk or in asymptomatic recovery at baseline also showed reduced manic symptom severity.

The results suggest that “apps for individuals with bipolar disorder will likely be useful for some people in managing medication use, sleep duration, routine, and monitoring for and managing signs and symptoms” of the disorder, coinvestigator Evan H. Goulding, MD, PhD, assistant professor of psychiatry and behavioral sciences, Northwestern University, Chicago, told this news organization.

Use of the app may also “lead to decreased recurrence of mood episodes, impact overall depressive and manic symptom levels, and improve some aspects of quality of life,” Dr. Goulding added.

The findings were published online in JAMA Psychiatry.
 

Daily check-ins

The researchers randomly assigned 205 patients with BD to receive either usual care (n = 81; 56% women; mean age, 39 years) or usual care plus the smartphone-based self-management intervention LiveWell (n = 124; 65% women; mean age, 43 years) between March 2017 and April 2020. To be included, participants could not be experiencing a current mood episode or suicidal ideation.

The smartphone intervention included a daily check-in to monitor medication adherence, sleep, and wellness levels; coach visits to support adherence to the app; six phone calls over 16 weeks; and support from mental health professionals whenever needed. Participants in this group were asked to engage their mental health providers in the intervention as well.

Each participant in the control group had a visit with a coach who facilitated self-management support.

Investigators assessed all participants every 8 weeks until week 48 to gather information on mood symptoms and severity over the past 2 weeks and on quality of life.

The patients were also stratified into high- and low-risk relapse groups. The low-risk group was in asymptomatic recovery, meaning that they experienced two or fewer moderate symptoms of mania or depression in the previous 8 weeks. In addition, they had no moderate symptoms of mania or depression at study enrollment.

Patients in the high-risk group were recovering from an episode of mania or depression. They also had two or fewer moderate symptoms, but for 8 weeks or less.
 

Low-risk group fares better

Results showed that the smartphone intervention was significantly associated with a reduction in depressive symptoms vs. usual care (P = .02), as well as improvement in one aspect of the World Health Organization Quality of Life Assessment that measures social relationships (P = .02).

When the investigators stratified participants into risk groups, they found that for those in the low-risk group the smartphone-based intervention was associated with lower episode-relapse rates, lower mean percentage time symptomatic, and decreased manic symptom severity.

Mean estimated relapse rates by 48 weeks for the low-risk group were 12% for those in the intervention group and 37.2% for those in the control group. No differences were noted for the high-risk group.

Low-risk patients in the intervention group also had lower mean percentage-time symptomatic (17.9%) than those in the control group (26.1%) (Cohen d = .31).

“Our results are consistent with literature emphasizing the identification and facilitation of management plans for early warning signs of mood episodes and using these plans as an important self-management technique for avoiding relapse,” Dr. Goulding said.

Study limitations included low engagement by mental health professionals and low data generalizability to other populations, as the sample was mostly White (84% of the app group and 81% of the control group).

“There is a fairly large literature on risk factors, longitudinal trajectories, and stages of diseases that suggest we should already be able to predict relapse risk for individuals,” Dr. Goulding said.

“However, moving from overall risk to individual risk is trickier and will require larger datasets with longer follow-up to better understand what types of help should be delivered when and to whom,” he added.
 

‘Requires commitment’

John Torous, MD, director of the division of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, noted that mental health apps such as LiveWell require “time and energy devoted by both the patient and their clinician for maximal efficacy, which requires commitment from and training for both parties as well.

“But with such an investment in people, there is good evidence apps can help people with bipolar disorder even during the more severe periods of the illness,” added Dr. Torous, who was not involved with the research.

The study was funded by the National Institute of Mental Health.

Dr. Goulding reports having received honoraria from Otsuka. Dr. Torous has reported no relevant financial relationships.

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

A smartphone-based self-management intervention developed for patients with bipolar disorder (BD) can help decrease depressive symptoms and improve quality of life, new research suggests.

In a randomized clinical trial of usual care plus the experimental smartphone-based intervention known as LiveWell vs. usual care alone, participants in the smartphone group who were categorized as low-risk or in asymptomatic recovery at baseline also showed reduced manic symptom severity.

The results suggest that “apps for individuals with bipolar disorder will likely be useful for some people in managing medication use, sleep duration, routine, and monitoring for and managing signs and symptoms” of the disorder, coinvestigator Evan H. Goulding, MD, PhD, assistant professor of psychiatry and behavioral sciences, Northwestern University, Chicago, told this news organization.

Use of the app may also “lead to decreased recurrence of mood episodes, impact overall depressive and manic symptom levels, and improve some aspects of quality of life,” Dr. Goulding added.

The findings were published online in JAMA Psychiatry.
 

Daily check-ins

The researchers randomly assigned 205 patients with BD to receive either usual care (n = 81; 56% women; mean age, 39 years) or usual care plus the smartphone-based self-management intervention LiveWell (n = 124; 65% women; mean age, 43 years) between March 2017 and April 2020. To be included, participants could not be experiencing a current mood episode or suicidal ideation.

The smartphone intervention included a daily check-in to monitor medication adherence, sleep, and wellness levels; coach visits to support adherence to the app; six phone calls over 16 weeks; and support from mental health professionals whenever needed. Participants in this group were asked to engage their mental health providers in the intervention as well.

Each participant in the control group had a visit with a coach who facilitated self-management support.

Investigators assessed all participants every 8 weeks until week 48 to gather information on mood symptoms and severity over the past 2 weeks and on quality of life.

The patients were also stratified into high- and low-risk relapse groups. The low-risk group was in asymptomatic recovery, meaning that they experienced two or fewer moderate symptoms of mania or depression in the previous 8 weeks. In addition, they had no moderate symptoms of mania or depression at study enrollment.

Patients in the high-risk group were recovering from an episode of mania or depression. They also had two or fewer moderate symptoms, but for 8 weeks or less.
 

Low-risk group fares better

Results showed that the smartphone intervention was significantly associated with a reduction in depressive symptoms vs. usual care (P = .02), as well as improvement in one aspect of the World Health Organization Quality of Life Assessment that measures social relationships (P = .02).

When the investigators stratified participants into risk groups, they found that for those in the low-risk group the smartphone-based intervention was associated with lower episode-relapse rates, lower mean percentage time symptomatic, and decreased manic symptom severity.

Mean estimated relapse rates by 48 weeks for the low-risk group were 12% for those in the intervention group and 37.2% for those in the control group. No differences were noted for the high-risk group.

Low-risk patients in the intervention group also had lower mean percentage-time symptomatic (17.9%) than those in the control group (26.1%) (Cohen d = .31).

“Our results are consistent with literature emphasizing the identification and facilitation of management plans for early warning signs of mood episodes and using these plans as an important self-management technique for avoiding relapse,” Dr. Goulding said.

Study limitations included low engagement by mental health professionals and low data generalizability to other populations, as the sample was mostly White (84% of the app group and 81% of the control group).

“There is a fairly large literature on risk factors, longitudinal trajectories, and stages of diseases that suggest we should already be able to predict relapse risk for individuals,” Dr. Goulding said.

“However, moving from overall risk to individual risk is trickier and will require larger datasets with longer follow-up to better understand what types of help should be delivered when and to whom,” he added.
 

‘Requires commitment’

John Torous, MD, director of the division of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, noted that mental health apps such as LiveWell require “time and energy devoted by both the patient and their clinician for maximal efficacy, which requires commitment from and training for both parties as well.

“But with such an investment in people, there is good evidence apps can help people with bipolar disorder even during the more severe periods of the illness,” added Dr. Torous, who was not involved with the research.

The study was funded by the National Institute of Mental Health.

Dr. Goulding reports having received honoraria from Otsuka. Dr. Torous has reported no relevant financial relationships.

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

A smartphone-based self-management intervention developed for patients with bipolar disorder (BD) can help decrease depressive symptoms and improve quality of life, new research suggests.

In a randomized clinical trial of usual care plus the experimental smartphone-based intervention known as LiveWell vs. usual care alone, participants in the smartphone group who were categorized as low-risk or in asymptomatic recovery at baseline also showed reduced manic symptom severity.

The results suggest that “apps for individuals with bipolar disorder will likely be useful for some people in managing medication use, sleep duration, routine, and monitoring for and managing signs and symptoms” of the disorder, coinvestigator Evan H. Goulding, MD, PhD, assistant professor of psychiatry and behavioral sciences, Northwestern University, Chicago, told this news organization.

Use of the app may also “lead to decreased recurrence of mood episodes, impact overall depressive and manic symptom levels, and improve some aspects of quality of life,” Dr. Goulding added.

The findings were published online in JAMA Psychiatry.
 

Daily check-ins

The researchers randomly assigned 205 patients with BD to receive either usual care (n = 81; 56% women; mean age, 39 years) or usual care plus the smartphone-based self-management intervention LiveWell (n = 124; 65% women; mean age, 43 years) between March 2017 and April 2020. To be included, participants could not be experiencing a current mood episode or suicidal ideation.

The smartphone intervention included a daily check-in to monitor medication adherence, sleep, and wellness levels; coach visits to support adherence to the app; six phone calls over 16 weeks; and support from mental health professionals whenever needed. Participants in this group were asked to engage their mental health providers in the intervention as well.

Each participant in the control group had a visit with a coach who facilitated self-management support.

Investigators assessed all participants every 8 weeks until week 48 to gather information on mood symptoms and severity over the past 2 weeks and on quality of life.

The patients were also stratified into high- and low-risk relapse groups. The low-risk group was in asymptomatic recovery, meaning that they experienced two or fewer moderate symptoms of mania or depression in the previous 8 weeks. In addition, they had no moderate symptoms of mania or depression at study enrollment.

Patients in the high-risk group were recovering from an episode of mania or depression. They also had two or fewer moderate symptoms, but for 8 weeks or less.
 

Low-risk group fares better

Results showed that the smartphone intervention was significantly associated with a reduction in depressive symptoms vs. usual care (P = .02), as well as improvement in one aspect of the World Health Organization Quality of Life Assessment that measures social relationships (P = .02).

When the investigators stratified participants into risk groups, they found that for those in the low-risk group the smartphone-based intervention was associated with lower episode-relapse rates, lower mean percentage time symptomatic, and decreased manic symptom severity.

Mean estimated relapse rates by 48 weeks for the low-risk group were 12% for those in the intervention group and 37.2% for those in the control group. No differences were noted for the high-risk group.

Low-risk patients in the intervention group also had lower mean percentage-time symptomatic (17.9%) than those in the control group (26.1%) (Cohen d = .31).

“Our results are consistent with literature emphasizing the identification and facilitation of management plans for early warning signs of mood episodes and using these plans as an important self-management technique for avoiding relapse,” Dr. Goulding said.

Study limitations included low engagement by mental health professionals and low data generalizability to other populations, as the sample was mostly White (84% of the app group and 81% of the control group).

“There is a fairly large literature on risk factors, longitudinal trajectories, and stages of diseases that suggest we should already be able to predict relapse risk for individuals,” Dr. Goulding said.

“However, moving from overall risk to individual risk is trickier and will require larger datasets with longer follow-up to better understand what types of help should be delivered when and to whom,” he added.
 

‘Requires commitment’

John Torous, MD, director of the division of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, noted that mental health apps such as LiveWell require “time and energy devoted by both the patient and their clinician for maximal efficacy, which requires commitment from and training for both parties as well.

“But with such an investment in people, there is good evidence apps can help people with bipolar disorder even during the more severe periods of the illness,” added Dr. Torous, who was not involved with the research.

The study was funded by the National Institute of Mental Health.

Dr. Goulding reports having received honoraria from Otsuka. Dr. Torous has reported no relevant financial relationships.

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

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

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

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

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

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

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

Treatment-resistant depression (TRD) is significantly linked to comorbid psychiatric conditions and a higher risk for mortality and can take more than a year to be diagnosed, new research shows.

In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.

Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.

In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.

“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.

“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.

The findings were published online in JAMA Psychiatry.
 

More anxiety, sleep disorders, substance use

Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.

Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.

Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.

Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.

This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).

Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.

The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
 

Not generalizable?

Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).

Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.

“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.

Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.

“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.

“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
 

Quality over quantity

In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”

Dr. Zisook has independently researched TRD but was not involved with the current study.

He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”

However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.

“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.

Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.

“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.

The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.

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

Treatment-resistant depression (TRD) is significantly linked to comorbid psychiatric conditions and a higher risk for mortality and can take more than a year to be diagnosed, new research shows.

In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.

Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.

In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.

“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.

“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.

The findings were published online in JAMA Psychiatry.
 

More anxiety, sleep disorders, substance use

Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.

Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.

Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.

Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.

This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).

Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.

The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
 

Not generalizable?

Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).

Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.

“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.

Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.

“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.

“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
 

Quality over quantity

In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”

Dr. Zisook has independently researched TRD but was not involved with the current study.

He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”

However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.

“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.

Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.

“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.

The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.

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

Treatment-resistant depression (TRD) is significantly linked to comorbid psychiatric conditions and a higher risk for mortality and can take more than a year to be diagnosed, new research shows.

In a population study of more than 145,000 patients, participants with TRD used outpatient resources and missed work at twice the rate as patients with treatment-responsive depression. They also had a threefold higher number of days spent in hospital.

Patients with TRD also had a 23% higher risk of dying during the time they were observed, compared with their matched counterparts with non-TRD depression, and their self-harm rates were twice as high.

In addition, it took an average of 1.5 years for patients with TRD to undergo two unsuccessful treatment attempts and reach their third treatment trial, which is several months longer than is recommended for assessing the efficacy of a treatment for depression.

“It seemed like ineffective treatments were allowed to continue for longer than should be needed and what is recommended in current guidelines,” lead investigator Johan Lundberg, MD, PhD, adjunct professor of psychiatry in the department of clinical neuroscience and head of the mood disorder section at the Northern Stockholm Psychiatry Clinic, told this news organization.

“If this is true, patients would most likely benefit from a more frequent evaluation of treatment effect and, when needed, optimization of ineffective treatments,” Dr. Lundberg said.

The findings were published online in JAMA Psychiatry.
 

More anxiety, sleep disorders, substance use

Using data from the Region Stockholm’s administrative health care database and the Swedish social insurance agency, the investigators identified nearly 160,000 unipolar major depressive disorder (MDD) episodes in 145,577 patients who sought treatment between January 2012 and December 2017.

Of those episodes, 12,800 fulfilled criteria for TRD, which meant there were three or more treatment trials with antidepressants, add-on medication (aripiprazole, lithium, olanzapine, quetiapine, and/or risperidone), electroshock therapy, or repetitive transcranial magnetic stimulation.

Each new treatment had to be initiated within the MDD episode more than 28 days after previous treatment initiation.

Investigators matched each TRD episode with up to five non-TRD episodes and found that patients with TRD were more likely to have comorbid psychiatric conditions than were their non-TRD counterparts.

This included anxiety (60% vs. 44%, respectively), sleep disorders (28% vs. 19%), substance use (15% vs. 11%) or alcohol use (10% vs. 7%) disorders, and personality disorders (6% vs. 3%). Rates of intentional self-harm were also higher in the TRD group (5% vs. 2%).

Perhaps in part because of the comorbid problems, patients with TRD had a more than 50% higher mean number of outpatient physician visits 1 year before and after the index date, defined as the date of the initiation of the third treatment trial.

The most important predictor of TRD depression was the severity of depression at diagnosis on the self-rated Montgomery Åsberg Depression Rating Scale, the researchers report.
 

Not generalizable?

Patients with TRD also had three times the number of inpatient bed days as did those with depression that responded to treatment (mean, 3.9 days vs. 1.3 days, respectively) and significantly more lost workdays (132.3 days vs. 58.7 days).

Most notably, patients with TRD episodes had a 23% higher risk of dying during the time they were observed than did their non-TRD counterparts.

“This finding in itself could be a reason to focus on how to avoid putting a patient on the TRD path. This could be done through prospective studies comparing different treatment options and their risk of leading to TRD,” Dr. Lundberg said.

Interestingly, he noted that the study results may not be generalizable to other populations, such as the United States.

“The biggest difference between Stockholm and the U.S. may not be the demographics, but the access to health care,” Dr. Lundberg said.

“In Stockholm, there is a universal access health care system, meaning that these results are what you can expect if you are able to get care. In the U.S., this is not the case, meaning that people outside the health care system may fare worse than what our study suggests,” he added.
 

Quality over quantity

In a comment, Sidney Zisook, MD, distinguished professor of psychiatry at the University of California, San Diego, said that the findings “highlight the need for our field to develop better-tolerated, more effective, and sustainable treatments for major depressive disorder and for better education of clinicians so they can employ up-to-date, evidence-based treatments and integrate sound clinical guidelines into clinical practice.”

Dr. Zisook has independently researched TRD but was not involved with the current study.

He noted that it was “striking how long patients remained on the same antidepressant, apparently despite suboptimal outcomes, without taking next steps.”

However, Dr. Zisook expressed concern that the diagnosis of TRD in the study was solely on the basis of the number of treatment trials for an episode.

“Somebody might have had three different antidepressant trials because they had had three episodes with interepisode periods of recovery followed by recurrent episodes. That would not be considered treatment-resistant depression,” he said.

Dr. Zisook also noted that patients might be given a new antidepressant for reasons other than treatment resistance. “For example, they lost an initial good response – this used to be called Prozac poop out, were nonadherent, or had troublesome side effects,” he said.

“We usually define treatment-resistant depression not only on the basis of number of trials but also the quality of the trial, taking both dose and duration into account,” Dr. Zisook added.

The study was funded by Region Stockholm. Dr. Zisook reports receiving research funding from COMPASS Pathways.

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

Intermittent fasting (IF), defined as fasting for more than eight hours at a time, is a trend that is growing in popularity. Yet new research shows it may be linked to eating disorder (ED) behaviors.

Researchers from the University of Toronto analyzed data from more than 2700 adolescents and young adults from the Canadian Study of Adolescent Health Behaviors, and found that for women, IF was significantly associated with overeating, binge eating, vomiting, laxative use, and compulsive exercise.

IF in women was also associated with higher scores on the Eating Disorder Examination Questionnaire (EDE-Q), which was used to determine ED psychopathology.

Study investigator Kyle Ganson, PhD, assistant professor in the Factor-Inwentash Faculty of Social Work at the University of Toronto, said in an interview that evidence on the effectiveness of IF for weight loss and disease prevention is mixed, and that it’s important to understand the potential harms of IF – even if there are benefits for some.

“If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors, requiring health care professionals to be very aware of this contemporary and popular dietary trend, despite proponents on social media touting the effectiveness and benefits,” he said.

The study was published online in Eating Behaviors.
 

Touted for health benefits

The practice of IF has been gaining popularity partly because of reputable medical experts touting its health benefits. Johns Hopkins Medicine, for instance, cited evidence that IF boosts working memory, improves blood pressure, enhances physical performance, and prevents obesity. Yet there has been little research on its harms.

As part of the Canadian Study of Adolescent Health Behaviors, Dr. Ganson and associates analyzed data on 2,700 adolescents and young adults aged 16-30 recruited from social media ads in November and December 2021. The sample included women, men, and transgender or gender-nonconforming individuals.

Study participants answered questions about weight perception, current weight change behavior, engagement in IF, and participation in eating disorder behaviors. They were also administered the EDE-Q, which measures eating disorder psychopathology.

In total, 47% of women (n = 1,470), 38% of men (n = 1,060), and 52% transgender or gender-nonconforming individuals (n = 225) reported engaging in IF during the past year.

Dr. Ganson and associates found that, for women, IF in the past 12 months and past 30 days were significantly associated with all eating disorder behaviors, including overeating, loss of control, binge eating, vomiting, laxative use, compulsive exercise, and fasting – as well as higher overall EDE-Q global scores.

For men, IF in the past 12 months was significantly associated with compulsive exercise, and higher overall EDE-Q global scores.

The team found that for TGNC participants, IF was positively associated with higher EDE-Q global scores.

The investigators acknowledged some limitations with the study – the method of recruiting, which involved ads placed on social media, could cause selection bias. In addition to this, data collection methods relied heavily on participants’ self-reporting, which could also be susceptible to bias.

“Certainly, there needs to be more investigation on this dietary practice,” said Dr. Ganson. “If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors requiring healthcare professionals to be very aware of this contemporary and popular dietary trend – despite proponents on social media touting the effectiveness and benefits.”
 

Screening warranted

Dr. Ganson noted that additional research is needed to support the findings from his study, and to further illuminate the potential harms of IF.

Health care professionals “need to be aware of common, contemporary dietary trends that young people engage in and are commonly discussed on social media, such as IF,” he noted. In addition, he’d like to see health care professionals assess their patients for IF who are dieting and to follow-up with assessments for ED-related attitudes and behaviors.

“Additionally, there are likely bidirectional relationships between IF and ED attitudes and behaviors, so professionals should be aware the ways in which ED behaviors are masked as IF engagement,” Dr. Ganson said.
 

More research needed

Commenting on the findings, Angela Guarda, MD, professor of eating disorders at Johns Hopkins University and director of the eating disorders program at Johns Hopkins Hospital, both in Baltimore, said more research is needed on outcomes for IF.

“We lack a definitive answer. The reality is that IF may help some and harm others and is most likely not healthy for all,” she said, noting that the study results “support what many in the eating disorders field believe, namely that IF for someone who is at risk for an eating disorder is likely to be ill advised.”

She added that “continued research is needed to establish its safety, and for whom it may be a therapeutic versus an iatrogenic recommendation.”

The study was funded by the Connaught New Researcher Award. The authors reported no relevant financial relationships.

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

Intermittent fasting (IF), defined as fasting for more than eight hours at a time, is a trend that is growing in popularity. Yet new research shows it may be linked to eating disorder (ED) behaviors.

Researchers from the University of Toronto analyzed data from more than 2700 adolescents and young adults from the Canadian Study of Adolescent Health Behaviors, and found that for women, IF was significantly associated with overeating, binge eating, vomiting, laxative use, and compulsive exercise.

IF in women was also associated with higher scores on the Eating Disorder Examination Questionnaire (EDE-Q), which was used to determine ED psychopathology.

Study investigator Kyle Ganson, PhD, assistant professor in the Factor-Inwentash Faculty of Social Work at the University of Toronto, said in an interview that evidence on the effectiveness of IF for weight loss and disease prevention is mixed, and that it’s important to understand the potential harms of IF – even if there are benefits for some.

“If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors, requiring health care professionals to be very aware of this contemporary and popular dietary trend, despite proponents on social media touting the effectiveness and benefits,” he said.

The study was published online in Eating Behaviors.
 

Touted for health benefits

The practice of IF has been gaining popularity partly because of reputable medical experts touting its health benefits. Johns Hopkins Medicine, for instance, cited evidence that IF boosts working memory, improves blood pressure, enhances physical performance, and prevents obesity. Yet there has been little research on its harms.

As part of the Canadian Study of Adolescent Health Behaviors, Dr. Ganson and associates analyzed data on 2,700 adolescents and young adults aged 16-30 recruited from social media ads in November and December 2021. The sample included women, men, and transgender or gender-nonconforming individuals.

Study participants answered questions about weight perception, current weight change behavior, engagement in IF, and participation in eating disorder behaviors. They were also administered the EDE-Q, which measures eating disorder psychopathology.

In total, 47% of women (n = 1,470), 38% of men (n = 1,060), and 52% transgender or gender-nonconforming individuals (n = 225) reported engaging in IF during the past year.

Dr. Ganson and associates found that, for women, IF in the past 12 months and past 30 days were significantly associated with all eating disorder behaviors, including overeating, loss of control, binge eating, vomiting, laxative use, compulsive exercise, and fasting – as well as higher overall EDE-Q global scores.

For men, IF in the past 12 months was significantly associated with compulsive exercise, and higher overall EDE-Q global scores.

The team found that for TGNC participants, IF was positively associated with higher EDE-Q global scores.

The investigators acknowledged some limitations with the study – the method of recruiting, which involved ads placed on social media, could cause selection bias. In addition to this, data collection methods relied heavily on participants’ self-reporting, which could also be susceptible to bias.

“Certainly, there needs to be more investigation on this dietary practice,” said Dr. Ganson. “If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors requiring healthcare professionals to be very aware of this contemporary and popular dietary trend – despite proponents on social media touting the effectiveness and benefits.”
 

Screening warranted

Dr. Ganson noted that additional research is needed to support the findings from his study, and to further illuminate the potential harms of IF.

Health care professionals “need to be aware of common, contemporary dietary trends that young people engage in and are commonly discussed on social media, such as IF,” he noted. In addition, he’d like to see health care professionals assess their patients for IF who are dieting and to follow-up with assessments for ED-related attitudes and behaviors.

“Additionally, there are likely bidirectional relationships between IF and ED attitudes and behaviors, so professionals should be aware the ways in which ED behaviors are masked as IF engagement,” Dr. Ganson said.
 

More research needed

Commenting on the findings, Angela Guarda, MD, professor of eating disorders at Johns Hopkins University and director of the eating disorders program at Johns Hopkins Hospital, both in Baltimore, said more research is needed on outcomes for IF.

“We lack a definitive answer. The reality is that IF may help some and harm others and is most likely not healthy for all,” she said, noting that the study results “support what many in the eating disorders field believe, namely that IF for someone who is at risk for an eating disorder is likely to be ill advised.”

She added that “continued research is needed to establish its safety, and for whom it may be a therapeutic versus an iatrogenic recommendation.”

The study was funded by the Connaught New Researcher Award. The authors reported no relevant financial relationships.

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

Intermittent fasting (IF), defined as fasting for more than eight hours at a time, is a trend that is growing in popularity. Yet new research shows it may be linked to eating disorder (ED) behaviors.

Researchers from the University of Toronto analyzed data from more than 2700 adolescents and young adults from the Canadian Study of Adolescent Health Behaviors, and found that for women, IF was significantly associated with overeating, binge eating, vomiting, laxative use, and compulsive exercise.

IF in women was also associated with higher scores on the Eating Disorder Examination Questionnaire (EDE-Q), which was used to determine ED psychopathology.

Study investigator Kyle Ganson, PhD, assistant professor in the Factor-Inwentash Faculty of Social Work at the University of Toronto, said in an interview that evidence on the effectiveness of IF for weight loss and disease prevention is mixed, and that it’s important to understand the potential harms of IF – even if there are benefits for some.

“If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors, requiring health care professionals to be very aware of this contemporary and popular dietary trend, despite proponents on social media touting the effectiveness and benefits,” he said.

The study was published online in Eating Behaviors.
 

Touted for health benefits

The practice of IF has been gaining popularity partly because of reputable medical experts touting its health benefits. Johns Hopkins Medicine, for instance, cited evidence that IF boosts working memory, improves blood pressure, enhances physical performance, and prevents obesity. Yet there has been little research on its harms.

As part of the Canadian Study of Adolescent Health Behaviors, Dr. Ganson and associates analyzed data on 2,700 adolescents and young adults aged 16-30 recruited from social media ads in November and December 2021. The sample included women, men, and transgender or gender-nonconforming individuals.

Study participants answered questions about weight perception, current weight change behavior, engagement in IF, and participation in eating disorder behaviors. They were also administered the EDE-Q, which measures eating disorder psychopathology.

In total, 47% of women (n = 1,470), 38% of men (n = 1,060), and 52% transgender or gender-nonconforming individuals (n = 225) reported engaging in IF during the past year.

Dr. Ganson and associates found that, for women, IF in the past 12 months and past 30 days were significantly associated with all eating disorder behaviors, including overeating, loss of control, binge eating, vomiting, laxative use, compulsive exercise, and fasting – as well as higher overall EDE-Q global scores.

For men, IF in the past 12 months was significantly associated with compulsive exercise, and higher overall EDE-Q global scores.

The team found that for TGNC participants, IF was positively associated with higher EDE-Q global scores.

The investigators acknowledged some limitations with the study – the method of recruiting, which involved ads placed on social media, could cause selection bias. In addition to this, data collection methods relied heavily on participants’ self-reporting, which could also be susceptible to bias.

“Certainly, there needs to be more investigation on this dietary practice,” said Dr. Ganson. “If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors requiring healthcare professionals to be very aware of this contemporary and popular dietary trend – despite proponents on social media touting the effectiveness and benefits.”
 

Screening warranted

Dr. Ganson noted that additional research is needed to support the findings from his study, and to further illuminate the potential harms of IF.

Health care professionals “need to be aware of common, contemporary dietary trends that young people engage in and are commonly discussed on social media, such as IF,” he noted. In addition, he’d like to see health care professionals assess their patients for IF who are dieting and to follow-up with assessments for ED-related attitudes and behaviors.

“Additionally, there are likely bidirectional relationships between IF and ED attitudes and behaviors, so professionals should be aware the ways in which ED behaviors are masked as IF engagement,” Dr. Ganson said.
 

More research needed

Commenting on the findings, Angela Guarda, MD, professor of eating disorders at Johns Hopkins University and director of the eating disorders program at Johns Hopkins Hospital, both in Baltimore, said more research is needed on outcomes for IF.

“We lack a definitive answer. The reality is that IF may help some and harm others and is most likely not healthy for all,” she said, noting that the study results “support what many in the eating disorders field believe, namely that IF for someone who is at risk for an eating disorder is likely to be ill advised.”

She added that “continued research is needed to establish its safety, and for whom it may be a therapeutic versus an iatrogenic recommendation.”

The study was funded by the Connaught New Researcher Award. The authors reported no relevant financial relationships.

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

Among older adults who use the U.S. Supplemental Nutrition Assistance Program (SNAP), rates of memory decline appear to be slower than among those who don’t use the program, new research shows. Researchers assessed the memory function of more than 3,500 persons who used SNAP or did not use SNAP over a period of 20 years. They found that those who didn’t use the food benefits program experienced 2 more years of cognitive aging compared with program users.

Of the 3,555 individuals included in the study, all were eligible to use the benefits, but only 559 did, leaving 2,996 participants who did not take advantage of the program.

Low program participation levels translate into a missed opportunity to prevent dementia, said study investigator Adina Zeki Al Hazzouri, PhD, assistant professor of epidemiology at the Columbia Aging Center at Columbia University Mailman School of Public Health in New York.

She said that prior research has shown that stigma may prevent older Americans from using SNAP. “Educational programs are needed to reduce the stigma that the public holds towards SNAP use,” she said.

Policy change could increase usage among older individuals, Dr. Zeki Al Hazzouri noted. Such changes could include simplifying enrollment and reporting procedures, shortening recertification periods, and increasing benefit levels.

The study was published online in Neurology.
 

Memory preservation

Dr. Zeki Al Hazzouri and her team assessed respondents from the Health and Retirement Study (HRS), a representative sample of Americans aged 50 and older. All respondents who were eligible to participate in SNAP in 1996 were followed every 2 years until 2016.

At each assessment, HRS respondents completed memory tests, including immediate and delayed word recall. For those who were too impaired to complete the interview, proxy informants – typically, their spouses or family members – assessed the memory and cognition of their family members using validated instruments, such as the 16-item Informant Questionnaire for Cognitive Decline.

Investigators used a validated memory function composite score, which is benchmarked against the memory assessments and evaluations of the Aging, Demographics, and Memory Study (ADAMS) cohort.

The team found that compared with nonusers, SNAP users were more likely to be women, Black, and born in the southern United States. They were less likely to be married and had more chronic conditions, such as high blood pressure, diabetes, cancer, heart problems, psychiatric problems, and arthritis.

One important study limitation was that SNAP use was measured only once during the study, the investigators noted. Ideally, Dr. Zeki Al Hazzouri said, future research would examine cumulative SNAP use history and explore the pathways that might account for the association between SNAP use and memory decline.

While findings suggest that there were no significant differences in baseline memory function between SNAP users and nonusers, users experienced approximately 2 fewer years of cognitive aging over a 10-year period than those who didn’t use the program.

Dr. Zeki Al Hazzouri speculated that SNAP benefits may slow cognitive aging by contributing to overall brain health and that, in comparison with nonusers, SNAP users absorb more nutrients, which promote neuronal integrity.

The investigators theorized that SNAP benefits may reduce stress from financial hardship, which has been linked to premature cognitive aging in other research.

“SNAP may also increase the purchasing power and investment in other health preserving behaviors, but also resulting in better access to care, which may in turn result in better disease management and management of risk factors for cognitive function,” the investigators wrote.
 

An underutilized program

In an accompanying editorial, Steven Albert, PhD, Philip B. Hallen Endowed Chair in Community Health and Social Justice at the University of Pittsburgh, noted that in 2020, among households with people aged 50 and older in the United States, more than 9 million Americans experienced food insecurity.

Furthermore, he pointed out, research from 2018 showed that 71% of people aged 60 and older who met income eligibility for SNAP did not participate in the program. “SNAP is an underutilized food security program involving substantial income supplements for older people with low incomes.

“Against the backdrop of so many failures of pharmacotherapy for dementia and the so far inexorable increase in the prevalence of dementia due to population aging, are we missing an opportunity to support cognitive health by failing to enroll the 14 million Americans who are over age 60 and eligible for SNAP but who do not participate?” Dr. Albert asked. He suggested that it would be helpful to determine this through a randomized promotion trial.

The study was funded by the National Institute on Aging. The authors reported no relevant financial relationships.

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

Among older adults who use the U.S. Supplemental Nutrition Assistance Program (SNAP), rates of memory decline appear to be slower than among those who don’t use the program, new research shows. Researchers assessed the memory function of more than 3,500 persons who used SNAP or did not use SNAP over a period of 20 years. They found that those who didn’t use the food benefits program experienced 2 more years of cognitive aging compared with program users.

Of the 3,555 individuals included in the study, all were eligible to use the benefits, but only 559 did, leaving 2,996 participants who did not take advantage of the program.

Low program participation levels translate into a missed opportunity to prevent dementia, said study investigator Adina Zeki Al Hazzouri, PhD, assistant professor of epidemiology at the Columbia Aging Center at Columbia University Mailman School of Public Health in New York.

She said that prior research has shown that stigma may prevent older Americans from using SNAP. “Educational programs are needed to reduce the stigma that the public holds towards SNAP use,” she said.

Policy change could increase usage among older individuals, Dr. Zeki Al Hazzouri noted. Such changes could include simplifying enrollment and reporting procedures, shortening recertification periods, and increasing benefit levels.

The study was published online in Neurology.
 

Memory preservation

Dr. Zeki Al Hazzouri and her team assessed respondents from the Health and Retirement Study (HRS), a representative sample of Americans aged 50 and older. All respondents who were eligible to participate in SNAP in 1996 were followed every 2 years until 2016.

At each assessment, HRS respondents completed memory tests, including immediate and delayed word recall. For those who were too impaired to complete the interview, proxy informants – typically, their spouses or family members – assessed the memory and cognition of their family members using validated instruments, such as the 16-item Informant Questionnaire for Cognitive Decline.

Investigators used a validated memory function composite score, which is benchmarked against the memory assessments and evaluations of the Aging, Demographics, and Memory Study (ADAMS) cohort.

The team found that compared with nonusers, SNAP users were more likely to be women, Black, and born in the southern United States. They were less likely to be married and had more chronic conditions, such as high blood pressure, diabetes, cancer, heart problems, psychiatric problems, and arthritis.

One important study limitation was that SNAP use was measured only once during the study, the investigators noted. Ideally, Dr. Zeki Al Hazzouri said, future research would examine cumulative SNAP use history and explore the pathways that might account for the association between SNAP use and memory decline.

While findings suggest that there were no significant differences in baseline memory function between SNAP users and nonusers, users experienced approximately 2 fewer years of cognitive aging over a 10-year period than those who didn’t use the program.

Dr. Zeki Al Hazzouri speculated that SNAP benefits may slow cognitive aging by contributing to overall brain health and that, in comparison with nonusers, SNAP users absorb more nutrients, which promote neuronal integrity.

The investigators theorized that SNAP benefits may reduce stress from financial hardship, which has been linked to premature cognitive aging in other research.

“SNAP may also increase the purchasing power and investment in other health preserving behaviors, but also resulting in better access to care, which may in turn result in better disease management and management of risk factors for cognitive function,” the investigators wrote.
 

An underutilized program

In an accompanying editorial, Steven Albert, PhD, Philip B. Hallen Endowed Chair in Community Health and Social Justice at the University of Pittsburgh, noted that in 2020, among households with people aged 50 and older in the United States, more than 9 million Americans experienced food insecurity.

Furthermore, he pointed out, research from 2018 showed that 71% of people aged 60 and older who met income eligibility for SNAP did not participate in the program. “SNAP is an underutilized food security program involving substantial income supplements for older people with low incomes.

“Against the backdrop of so many failures of pharmacotherapy for dementia and the so far inexorable increase in the prevalence of dementia due to population aging, are we missing an opportunity to support cognitive health by failing to enroll the 14 million Americans who are over age 60 and eligible for SNAP but who do not participate?” Dr. Albert asked. He suggested that it would be helpful to determine this through a randomized promotion trial.

The study was funded by the National Institute on Aging. The authors reported no relevant financial relationships.

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

Among older adults who use the U.S. Supplemental Nutrition Assistance Program (SNAP), rates of memory decline appear to be slower than among those who don’t use the program, new research shows. Researchers assessed the memory function of more than 3,500 persons who used SNAP or did not use SNAP over a period of 20 years. They found that those who didn’t use the food benefits program experienced 2 more years of cognitive aging compared with program users.

Of the 3,555 individuals included in the study, all were eligible to use the benefits, but only 559 did, leaving 2,996 participants who did not take advantage of the program.

Low program participation levels translate into a missed opportunity to prevent dementia, said study investigator Adina Zeki Al Hazzouri, PhD, assistant professor of epidemiology at the Columbia Aging Center at Columbia University Mailman School of Public Health in New York.

She said that prior research has shown that stigma may prevent older Americans from using SNAP. “Educational programs are needed to reduce the stigma that the public holds towards SNAP use,” she said.

Policy change could increase usage among older individuals, Dr. Zeki Al Hazzouri noted. Such changes could include simplifying enrollment and reporting procedures, shortening recertification periods, and increasing benefit levels.

The study was published online in Neurology.
 

Memory preservation

Dr. Zeki Al Hazzouri and her team assessed respondents from the Health and Retirement Study (HRS), a representative sample of Americans aged 50 and older. All respondents who were eligible to participate in SNAP in 1996 were followed every 2 years until 2016.

At each assessment, HRS respondents completed memory tests, including immediate and delayed word recall. For those who were too impaired to complete the interview, proxy informants – typically, their spouses or family members – assessed the memory and cognition of their family members using validated instruments, such as the 16-item Informant Questionnaire for Cognitive Decline.

Investigators used a validated memory function composite score, which is benchmarked against the memory assessments and evaluations of the Aging, Demographics, and Memory Study (ADAMS) cohort.

The team found that compared with nonusers, SNAP users were more likely to be women, Black, and born in the southern United States. They were less likely to be married and had more chronic conditions, such as high blood pressure, diabetes, cancer, heart problems, psychiatric problems, and arthritis.

One important study limitation was that SNAP use was measured only once during the study, the investigators noted. Ideally, Dr. Zeki Al Hazzouri said, future research would examine cumulative SNAP use history and explore the pathways that might account for the association between SNAP use and memory decline.

While findings suggest that there were no significant differences in baseline memory function between SNAP users and nonusers, users experienced approximately 2 fewer years of cognitive aging over a 10-year period than those who didn’t use the program.

Dr. Zeki Al Hazzouri speculated that SNAP benefits may slow cognitive aging by contributing to overall brain health and that, in comparison with nonusers, SNAP users absorb more nutrients, which promote neuronal integrity.

The investigators theorized that SNAP benefits may reduce stress from financial hardship, which has been linked to premature cognitive aging in other research.

“SNAP may also increase the purchasing power and investment in other health preserving behaviors, but also resulting in better access to care, which may in turn result in better disease management and management of risk factors for cognitive function,” the investigators wrote.
 

An underutilized program

In an accompanying editorial, Steven Albert, PhD, Philip B. Hallen Endowed Chair in Community Health and Social Justice at the University of Pittsburgh, noted that in 2020, among households with people aged 50 and older in the United States, more than 9 million Americans experienced food insecurity.

Furthermore, he pointed out, research from 2018 showed that 71% of people aged 60 and older who met income eligibility for SNAP did not participate in the program. “SNAP is an underutilized food security program involving substantial income supplements for older people with low incomes.

“Against the backdrop of so many failures of pharmacotherapy for dementia and the so far inexorable increase in the prevalence of dementia due to population aging, are we missing an opportunity to support cognitive health by failing to enroll the 14 million Americans who are over age 60 and eligible for SNAP but who do not participate?” Dr. Albert asked. He suggested that it would be helpful to determine this through a randomized promotion trial.

The study was funded by the National Institute on Aging. The authors reported no relevant financial relationships.

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

A single 25-mg dose of synthetic psilocybin in combination with psychotherapy appears to effectively ease symptoms of treatment-resistant depression (TRD) – at least in the short term, new research shows.

In the largest study of psilocybin for TRD to date, results of the phase 2b randomized, double-blind trial show participants in the 25-mg dose group experienced a significant reduction in depressive symptoms for at least 3 weeks vs. patients in the 10-mg or 1-mg group, which served as the control group.

Investigators found that 29% of participants who received the 25-mg dose were in remission 3 weeks after the treatment and 37% had at least a 50% drop in depression scores. However, at the 3-month mark, only 20% of those on the 25-mg dose experienced significant improvement.

The change from baseline to week 3 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was significantly better with a 25-mg dose than with a 1-mg dose; there was no significant difference between the 10-mg dose and the 1-mg dose, the investigators reported.

The response rate was high for those receiving the 25-mg dose, lead  investigator Guy Goodwin, MD, DPhil, told reporters attending a press briefing.

“It’s important to understand that response rates in these patients are usually somewhere between 10% and 20%, and we are seeing remission rates at three weeks of 30%,” he said.

Dr. Goodwin is chief medical officer of COMPASS Pathways, the company that funded the trial and created COMP360, the synthetic formulation of psilocybin used in the trial, and professor emeritus of psychiatry at the University of Oxford, England.

Based on the results of the trial it was announced that a phase 3 trial will launch in December.

The study was published online in the New England Journal of Medicine.
 

Further research planned

Psilocybin has been under investigation for TRD for some time, including one study that compared it with the antidepressant escitalopram (Lexapro) with promising results.

In the current study the researchers sought to find an acceptable, efficacious dose and the safety of a synthetic formulation of the drug administered in combination with psychological support.

The multicenter study was conducted at 22 sites in 10 countries and included 233 participants with TRD and evaluated the safety and efficacy of one of three doses. The study’s primary endpoint was change from baseline to 3 weeks in MADRS scores in patients with TRD. The scale runs from 0 to 60 with higher scores indicating more severe depression.

Participants were randomly assigned to receive 25 mg of psilocybin (n = 79), 10 mg (n = 75) or 1 mg (n = 79). Those taking medications discontinued them at least 2 weeks before the baseline visit. The mean MADRS score was 32 or 33 in each study group.

There was a 3- to 6-week run-up period to the study in which each participant met with a study therapist about three times to build trust and prepare for the psychedelic experience.

On the day of psilocybin administration, each participant listened to a tailored music playlist and wore eye shades while reclining in a comfortable chair to direct attention inwardly.

The psychotherapy sessions lasted 6-8 hours, and two therapists were always present. The following day, participants returned for an “integration” session with the therapists that was designed to help the participants explore insights from their session.

MADRS scores were measured at baseline, the day following psilocybin administration, and at weeks 1, 3, 6, 9, and 12.

Participants were asked to stay off standard antidepressant treatment during the first 3 weeks of the trial but could be restarted at any time if deemed necessary by a trial investigator.

Mean changes from baseline to week 3 in MADRS scores were −12.0 for 25-mg, −7.9 for 10-mg, and −5.4 for 1-mg groups. The difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P < .001 and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P = .18).

The investigators reported that in the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results.

Up to 84% of those who received the 25-mg dosage reported adverse events, with the occurrence dropping slightly with each dosage group. The most frequent adverse events included headache, nausea, dizziness, and fatigue, and occurred only on administration day.

Among those who received the 25-mg dose of psilocybin, two participants reported suicidal thoughts during the 3 weeks following treatment, and 3 months post treatment, three patients exhibited suicidal behavior.

Dr. Goodwin noted that these participants had a prior history of suicidal behavior. Two participants in the 10-mg group also had suicidal thoughts. However, the investigators also noted that suicidal ideation, behavior, or self-injury occurred in all dose groups.

The researchers noted that longer and larger trials, including comparisons with existing depression treatments, are needed to determine the safety and efficacy of psilocybin for TRD.
 

Intriguing, sobering

In an accompanying editorial, Bertha Madras, PhD, McLean Hospital, Belmont, Mass., and Harvard Medical School, Boston, noted “the findings are both intriguing and sobering. The highest dose (25 mg), but not the intermediate dose (10 mg), resulted in significantly lower levels of depressive symptoms after 3 weeks than the lowest dose (1 mg, which served as a control), but the 37% incidence of response with the 25-mg dose was numerically lower than that in large trials of conventional antidepressants and less robust than in a trial showing similar efficacies of psilocybin and a selective serotonin reuptake inhibitor.”

Also sobering, she noted, were the high percentages of adverse events in the 25-mg group and suicidal ideation and behavior. Dr. Madras also wondered if “legalization and commercialization [of psychedelics] are allied with the medical movement, psychedelic shops and ‘clinics’ could proliferate even for vulnerable populations, and rigorously designed medical protocols will be compromised.

“Nevertheless,” she concluded, “it is provocative that these agents show some short-term benefit for depression in selected populations.”

Dr. Goodwin is CMO of Compass Pathways, which funded the study. He and several coauthors disclosed relationships with industry. Dr. Madras reports no relevant financial relationships.

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

A single 25-mg dose of synthetic psilocybin in combination with psychotherapy appears to effectively ease symptoms of treatment-resistant depression (TRD) – at least in the short term, new research shows.

In the largest study of psilocybin for TRD to date, results of the phase 2b randomized, double-blind trial show participants in the 25-mg dose group experienced a significant reduction in depressive symptoms for at least 3 weeks vs. patients in the 10-mg or 1-mg group, which served as the control group.

Investigators found that 29% of participants who received the 25-mg dose were in remission 3 weeks after the treatment and 37% had at least a 50% drop in depression scores. However, at the 3-month mark, only 20% of those on the 25-mg dose experienced significant improvement.

The change from baseline to week 3 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was significantly better with a 25-mg dose than with a 1-mg dose; there was no significant difference between the 10-mg dose and the 1-mg dose, the investigators reported.

The response rate was high for those receiving the 25-mg dose, lead  investigator Guy Goodwin, MD, DPhil, told reporters attending a press briefing.

“It’s important to understand that response rates in these patients are usually somewhere between 10% and 20%, and we are seeing remission rates at three weeks of 30%,” he said.

Dr. Goodwin is chief medical officer of COMPASS Pathways, the company that funded the trial and created COMP360, the synthetic formulation of psilocybin used in the trial, and professor emeritus of psychiatry at the University of Oxford, England.

Based on the results of the trial it was announced that a phase 3 trial will launch in December.

The study was published online in the New England Journal of Medicine.
 

Further research planned

Psilocybin has been under investigation for TRD for some time, including one study that compared it with the antidepressant escitalopram (Lexapro) with promising results.

In the current study the researchers sought to find an acceptable, efficacious dose and the safety of a synthetic formulation of the drug administered in combination with psychological support.

The multicenter study was conducted at 22 sites in 10 countries and included 233 participants with TRD and evaluated the safety and efficacy of one of three doses. The study’s primary endpoint was change from baseline to 3 weeks in MADRS scores in patients with TRD. The scale runs from 0 to 60 with higher scores indicating more severe depression.

Participants were randomly assigned to receive 25 mg of psilocybin (n = 79), 10 mg (n = 75) or 1 mg (n = 79). Those taking medications discontinued them at least 2 weeks before the baseline visit. The mean MADRS score was 32 or 33 in each study group.

There was a 3- to 6-week run-up period to the study in which each participant met with a study therapist about three times to build trust and prepare for the psychedelic experience.

On the day of psilocybin administration, each participant listened to a tailored music playlist and wore eye shades while reclining in a comfortable chair to direct attention inwardly.

The psychotherapy sessions lasted 6-8 hours, and two therapists were always present. The following day, participants returned for an “integration” session with the therapists that was designed to help the participants explore insights from their session.

MADRS scores were measured at baseline, the day following psilocybin administration, and at weeks 1, 3, 6, 9, and 12.

Participants were asked to stay off standard antidepressant treatment during the first 3 weeks of the trial but could be restarted at any time if deemed necessary by a trial investigator.

Mean changes from baseline to week 3 in MADRS scores were −12.0 for 25-mg, −7.9 for 10-mg, and −5.4 for 1-mg groups. The difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P < .001 and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P = .18).

The investigators reported that in the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results.

Up to 84% of those who received the 25-mg dosage reported adverse events, with the occurrence dropping slightly with each dosage group. The most frequent adverse events included headache, nausea, dizziness, and fatigue, and occurred only on administration day.

Among those who received the 25-mg dose of psilocybin, two participants reported suicidal thoughts during the 3 weeks following treatment, and 3 months post treatment, three patients exhibited suicidal behavior.

Dr. Goodwin noted that these participants had a prior history of suicidal behavior. Two participants in the 10-mg group also had suicidal thoughts. However, the investigators also noted that suicidal ideation, behavior, or self-injury occurred in all dose groups.

The researchers noted that longer and larger trials, including comparisons with existing depression treatments, are needed to determine the safety and efficacy of psilocybin for TRD.
 

Intriguing, sobering

In an accompanying editorial, Bertha Madras, PhD, McLean Hospital, Belmont, Mass., and Harvard Medical School, Boston, noted “the findings are both intriguing and sobering. The highest dose (25 mg), but not the intermediate dose (10 mg), resulted in significantly lower levels of depressive symptoms after 3 weeks than the lowest dose (1 mg, which served as a control), but the 37% incidence of response with the 25-mg dose was numerically lower than that in large trials of conventional antidepressants and less robust than in a trial showing similar efficacies of psilocybin and a selective serotonin reuptake inhibitor.”

Also sobering, she noted, were the high percentages of adverse events in the 25-mg group and suicidal ideation and behavior. Dr. Madras also wondered if “legalization and commercialization [of psychedelics] are allied with the medical movement, psychedelic shops and ‘clinics’ could proliferate even for vulnerable populations, and rigorously designed medical protocols will be compromised.

“Nevertheless,” she concluded, “it is provocative that these agents show some short-term benefit for depression in selected populations.”

Dr. Goodwin is CMO of Compass Pathways, which funded the study. He and several coauthors disclosed relationships with industry. Dr. Madras reports no relevant financial relationships.

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

A single 25-mg dose of synthetic psilocybin in combination with psychotherapy appears to effectively ease symptoms of treatment-resistant depression (TRD) – at least in the short term, new research shows.

In the largest study of psilocybin for TRD to date, results of the phase 2b randomized, double-blind trial show participants in the 25-mg dose group experienced a significant reduction in depressive symptoms for at least 3 weeks vs. patients in the 10-mg or 1-mg group, which served as the control group.

Investigators found that 29% of participants who received the 25-mg dose were in remission 3 weeks after the treatment and 37% had at least a 50% drop in depression scores. However, at the 3-month mark, only 20% of those on the 25-mg dose experienced significant improvement.

The change from baseline to week 3 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was significantly better with a 25-mg dose than with a 1-mg dose; there was no significant difference between the 10-mg dose and the 1-mg dose, the investigators reported.

The response rate was high for those receiving the 25-mg dose, lead  investigator Guy Goodwin, MD, DPhil, told reporters attending a press briefing.

“It’s important to understand that response rates in these patients are usually somewhere between 10% and 20%, and we are seeing remission rates at three weeks of 30%,” he said.

Dr. Goodwin is chief medical officer of COMPASS Pathways, the company that funded the trial and created COMP360, the synthetic formulation of psilocybin used in the trial, and professor emeritus of psychiatry at the University of Oxford, England.

Based on the results of the trial it was announced that a phase 3 trial will launch in December.

The study was published online in the New England Journal of Medicine.
 

Further research planned

Psilocybin has been under investigation for TRD for some time, including one study that compared it with the antidepressant escitalopram (Lexapro) with promising results.

In the current study the researchers sought to find an acceptable, efficacious dose and the safety of a synthetic formulation of the drug administered in combination with psychological support.

The multicenter study was conducted at 22 sites in 10 countries and included 233 participants with TRD and evaluated the safety and efficacy of one of three doses. The study’s primary endpoint was change from baseline to 3 weeks in MADRS scores in patients with TRD. The scale runs from 0 to 60 with higher scores indicating more severe depression.

Participants were randomly assigned to receive 25 mg of psilocybin (n = 79), 10 mg (n = 75) or 1 mg (n = 79). Those taking medications discontinued them at least 2 weeks before the baseline visit. The mean MADRS score was 32 or 33 in each study group.

There was a 3- to 6-week run-up period to the study in which each participant met with a study therapist about three times to build trust and prepare for the psychedelic experience.

On the day of psilocybin administration, each participant listened to a tailored music playlist and wore eye shades while reclining in a comfortable chair to direct attention inwardly.

The psychotherapy sessions lasted 6-8 hours, and two therapists were always present. The following day, participants returned for an “integration” session with the therapists that was designed to help the participants explore insights from their session.

MADRS scores were measured at baseline, the day following psilocybin administration, and at weeks 1, 3, 6, 9, and 12.

Participants were asked to stay off standard antidepressant treatment during the first 3 weeks of the trial but could be restarted at any time if deemed necessary by a trial investigator.

Mean changes from baseline to week 3 in MADRS scores were −12.0 for 25-mg, −7.9 for 10-mg, and −5.4 for 1-mg groups. The difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P < .001 and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P = .18).

The investigators reported that in the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results.

Up to 84% of those who received the 25-mg dosage reported adverse events, with the occurrence dropping slightly with each dosage group. The most frequent adverse events included headache, nausea, dizziness, and fatigue, and occurred only on administration day.

Among those who received the 25-mg dose of psilocybin, two participants reported suicidal thoughts during the 3 weeks following treatment, and 3 months post treatment, three patients exhibited suicidal behavior.

Dr. Goodwin noted that these participants had a prior history of suicidal behavior. Two participants in the 10-mg group also had suicidal thoughts. However, the investigators also noted that suicidal ideation, behavior, or self-injury occurred in all dose groups.

The researchers noted that longer and larger trials, including comparisons with existing depression treatments, are needed to determine the safety and efficacy of psilocybin for TRD.
 

Intriguing, sobering

In an accompanying editorial, Bertha Madras, PhD, McLean Hospital, Belmont, Mass., and Harvard Medical School, Boston, noted “the findings are both intriguing and sobering. The highest dose (25 mg), but not the intermediate dose (10 mg), resulted in significantly lower levels of depressive symptoms after 3 weeks than the lowest dose (1 mg, which served as a control), but the 37% incidence of response with the 25-mg dose was numerically lower than that in large trials of conventional antidepressants and less robust than in a trial showing similar efficacies of psilocybin and a selective serotonin reuptake inhibitor.”

Also sobering, she noted, were the high percentages of adverse events in the 25-mg group and suicidal ideation and behavior. Dr. Madras also wondered if “legalization and commercialization [of psychedelics] are allied with the medical movement, psychedelic shops and ‘clinics’ could proliferate even for vulnerable populations, and rigorously designed medical protocols will be compromised.

“Nevertheless,” she concluded, “it is provocative that these agents show some short-term benefit for depression in selected populations.”

Dr. Goodwin is CMO of Compass Pathways, which funded the study. He and several coauthors disclosed relationships with industry. Dr. Madras reports no relevant financial relationships.

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