Depression

TOPLINE:

Treatment-resistant major depression (TRD) is associated with a 17% higher risk for all-cause mortality than non-TRD major depressive disorder (MDD), a new study shows. The increased mortality risk was driven largely by suicide and accidental overdose, which were nearly twice as high among people whose depression didn’t improve after two treatments. 

METHODOLOGY:

• Data on 176,942 individuals diagnosed with MDD and treated with an antidepressant (median age at diagnosis, 40 years; 63% women) were obtained from Finnish nationwide registers.
• About 11% of the participants had TRD, defined as having more than two adequate treatment trials of at least 28 days, each within 2 years from the index antidepressant prescription.
• The outcomes were all-cause and cause-specific mortality, with demographic characteristics, psychiatric comorbidities, and treatment history included as covariates.
• The median follow-up period was 8.9 years.

TAKEAWAY:

• Median time to TRD was 8 months, and 959 and 7662 deaths were observed in the TRD and non-TRD groups, respectively.
• All-cause mortality was 17% higher among patients with TRD than among those with non-TRD (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.09-1.25) because of higher mortality to external causes.
• Mortalities because of suicides (aHR, 1.90; 95% CI, 1.64-2.20) and accidental poisonings (aHR, 1.81; 95% CI, 1.48-2.22) were almost double in the TRD group, compared with the non-TRD group.
• No significant difference in mortality due to natural causes was observed between the TRD and non-TRD groups.

IN PRACTICE:

“The markedly increased mortality due to suicides and accidental overdoses suggests that persons with TRD may experience higher-intensity symptoms and more severe suicidal ideation than persons with non-TRD major depression,” the study authors wrote.

SOURCE:

The study was led by Tapio T. Gustafsson, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. It was published online on September 11, 2024, in The Journal of Affective Disorders.

LIMITATIONS:

The definition of TRD lacked consensus. The study used routine data to define TRD, which may not have captured all relevant clinical nuances. Additionally, the reasons for medication changes were unavailable.

DISCLOSURES:

This study was funded by Johnson & Johnson Innovative Medicine and Niuvanniemi Hospital, with support from the Finnish Ministry of Social Affairs and Health. Several authors disclosed financial relationships with various pharmaceutical companies, and two are employees of Johnson & Johnson Innovative Medicine.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Treatment-resistant major depression (TRD) is associated with a 17% higher risk for all-cause mortality than non-TRD major depressive disorder (MDD), a new study shows. The increased mortality risk was driven largely by suicide and accidental overdose, which were nearly twice as high among people whose depression didn’t improve after two treatments. 

METHODOLOGY:

• Data on 176,942 individuals diagnosed with MDD and treated with an antidepressant (median age at diagnosis, 40 years; 63% women) were obtained from Finnish nationwide registers.
• About 11% of the participants had TRD, defined as having more than two adequate treatment trials of at least 28 days, each within 2 years from the index antidepressant prescription.
• The outcomes were all-cause and cause-specific mortality, with demographic characteristics, psychiatric comorbidities, and treatment history included as covariates.
• The median follow-up period was 8.9 years.

TAKEAWAY:

• Median time to TRD was 8 months, and 959 and 7662 deaths were observed in the TRD and non-TRD groups, respectively.
• All-cause mortality was 17% higher among patients with TRD than among those with non-TRD (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.09-1.25) because of higher mortality to external causes.
• Mortalities because of suicides (aHR, 1.90; 95% CI, 1.64-2.20) and accidental poisonings (aHR, 1.81; 95% CI, 1.48-2.22) were almost double in the TRD group, compared with the non-TRD group.
• No significant difference in mortality due to natural causes was observed between the TRD and non-TRD groups.

IN PRACTICE:

“The markedly increased mortality due to suicides and accidental overdoses suggests that persons with TRD may experience higher-intensity symptoms and more severe suicidal ideation than persons with non-TRD major depression,” the study authors wrote.

SOURCE:

The study was led by Tapio T. Gustafsson, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. It was published online on September 11, 2024, in The Journal of Affective Disorders.

LIMITATIONS:

The definition of TRD lacked consensus. The study used routine data to define TRD, which may not have captured all relevant clinical nuances. Additionally, the reasons for medication changes were unavailable.

DISCLOSURES:

This study was funded by Johnson & Johnson Innovative Medicine and Niuvanniemi Hospital, with support from the Finnish Ministry of Social Affairs and Health. Several authors disclosed financial relationships with various pharmaceutical companies, and two are employees of Johnson & Johnson Innovative Medicine.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Treatment-resistant major depression (TRD) is associated with a 17% higher risk for all-cause mortality than non-TRD major depressive disorder (MDD), a new study shows. The increased mortality risk was driven largely by suicide and accidental overdose, which were nearly twice as high among people whose depression didn’t improve after two treatments. 

METHODOLOGY:

• Data on 176,942 individuals diagnosed with MDD and treated with an antidepressant (median age at diagnosis, 40 years; 63% women) were obtained from Finnish nationwide registers.
• About 11% of the participants had TRD, defined as having more than two adequate treatment trials of at least 28 days, each within 2 years from the index antidepressant prescription.
• The outcomes were all-cause and cause-specific mortality, with demographic characteristics, psychiatric comorbidities, and treatment history included as covariates.
• The median follow-up period was 8.9 years.

TAKEAWAY:

• Median time to TRD was 8 months, and 959 and 7662 deaths were observed in the TRD and non-TRD groups, respectively.
• All-cause mortality was 17% higher among patients with TRD than among those with non-TRD (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.09-1.25) because of higher mortality to external causes.
• Mortalities because of suicides (aHR, 1.90; 95% CI, 1.64-2.20) and accidental poisonings (aHR, 1.81; 95% CI, 1.48-2.22) were almost double in the TRD group, compared with the non-TRD group.
• No significant difference in mortality due to natural causes was observed between the TRD and non-TRD groups.

IN PRACTICE:

“The markedly increased mortality due to suicides and accidental overdoses suggests that persons with TRD may experience higher-intensity symptoms and more severe suicidal ideation than persons with non-TRD major depression,” the study authors wrote.

SOURCE:

The study was led by Tapio T. Gustafsson, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. It was published online on September 11, 2024, in The Journal of Affective Disorders.

LIMITATIONS:

The definition of TRD lacked consensus. The study used routine data to define TRD, which may not have captured all relevant clinical nuances. Additionally, the reasons for medication changes were unavailable.

DISCLOSURES:

This study was funded by Johnson & Johnson Innovative Medicine and Niuvanniemi Hospital, with support from the Finnish Ministry of Social Affairs and Health. Several authors disclosed financial relationships with various pharmaceutical companies, and two are employees of Johnson & Johnson Innovative Medicine.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

COPENHAGEN — A higher cumulative genetic burden for depression is associated with an increased risk for relapse and worsening disability in people with multiple sclerosis (MS), early results of a new study showed.

Unlike the previous research, the current analysis used polygenic risk scores for depression, which summarize the estimated effect of genetic variants to determine the potential association with MS disease activity, so results are less likely to be explained by reverse causality.

This study increases awareness of the link between depression and MS, said study investigator Kaarina Kowalec, PhD, assistant professor, College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. “We’re starting to understand how depression affects relapses and disability progression in MS,” she said.

The findings were presented at the 2024 ECTRIMS annual meeting.
 

Common Comorbidity

Depression is a common comorbidity in patients with MS and is associated with increased relapse and disability progression. Depression risk is partly polygenic in nature, involving numerous common genetic variants, said Dr. Kowalec.

The case-control study included 3420 relapsing-onset MS cases of European ancestry from four existing cohorts in three countries.

The Canadian cohort included those enrolled in a prospective longitudinal study of psychiatric comorbidity in chronic immune-mediated inflammatory disease (IMID), including MS; the Swedish cohort was an MS registry (SSReg) that encompasses 64 MS clinics (the cohort was split into two groups); and the US cohort was enrolled in a clinical trial of combined therapy with interferon and glatiramer acetate (CombiRx) in patients with MS.

The median follow-up in these cohorts ranged from 3 to 5 years.

Not surprisingly, most participants were women (from 71% in one of the Swedish cohorts to 83% in the Canadian cohort), and the age at MS onset ranged from 29 years in the Canadian cohort to 35 years in one of the Swedish cohorts.

The median baseline Expanded Disability Status Scale (EDSS) score was higher in the Canadian cohort (3.5) than in the Swedish (1.5) and US (2.0) cohorts, “reflective of the Canadian cohort being slightly more progressed,” said Dr. Kowalec.
 

Inherited Variants

To measure depression heritability, researchers generated a polygenic risk score in whole-genome imputed genotypes. The score reflects the number of inherited common genetic variants, weighted by effect sizes.

Researchers investigated the association between depression polygenic risk scores (top 20% vs. bottom 80%) with annualized relapse rate and worsening disability in MS measured by the rate of change in EDSS score. In the US cohort, they also explored the association between depression polygenic risk scores and time to relapse and confirmed EDSS worsening.

Covariates included use of disease-modifying therapy, age, sex, and the first five genetic ancestry principal components. The latter was done to capture residual stratification by genetic ancestry, although Dr. Kowalec stressed analyses were done only in those of European ancestry.

Investigators found a higher depression polygenic risk score was associated with relapse risk (incident rate ratio, 1.23; 95% CI, 1.01-1.49).

“Essentially, for every one standard deviation increase in the depression polygenic score, we found a significant increased hazard of 23% for experiencing a relapse over the follow-up period,” said Dr. Kowalec, who is also affiliated with the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

She noted the Canadian cohort did not have many relapses, while the US and Swedish cohorts “had an increased rate.”

Other analyses examined the risk of having a relapse or worsening disability. Every one SD increase in the depression polygenic risk score was significantly associated with a 2.2 greater risk of experiencing relapse (hazard ratio [HR], 2.20; 95% CI, 1.35-3.60) and a 51% increased risk for confirmed EDSS progression (HR, 1.51; 95% CI, 1.03-2.22).
 

‘An Ideal Marker’

Use of polygenetic risk scores reduces the possibility of reverse causation, noted Dr. Kowalec. “These markers are fixed at birth and don’t change over your lifespan, so they’re really an ideal marker.”

The results suggest polygenetic risk scores represent a potential biomarker for risk stratification in people with MS, said Dr. Kowalec. Although depression polygenic risk scores are not currently available in clinical practice, “I would hope this would change in the next 3-4 years,” she said.

Asked by a delegate if confounding by a third variable is possible, Dr. Kowalec said because genetic markers don’t change over time, there is a hint that the direction is causal and that depression is driving the outcome. However, she added, further confirmation is needed.

Dr. Kowalec noted that there were no data on antidepressant use but noted that about half of the Canadian and US cohorts — and likely the same number in the Swedish cohorts — self-reported depression.

A limitation of the study was that it included only participants of European ancestry.
 

Clinical Implications Unclear

Commenting on the research, Lauren Gluck, MD, program director, Montefiore Multiple Sclerosis Center, Bronx, New York, described the study as “fascinating” but noted that it’s unclear how to use this new information in clinical practice.

“Clinicians frequently ask people with MS about mood symptoms and offer interventions like antidepressants and referrals to therapists. However, genetic testing is not routine, so we don’t yet know who to target based on these data.”

Preexisting depression or more severe depression could be viewed as a “red flag” for risk for more disease activity in the future, she said.

“This could encourage clinicians to use more highly effective therapy in these patients, similar to our strategies for people with MS with frequent attacks and more disease burden on MRIs.”

The study received support from the Consortium of Multiple Sclerosis Centers and the Congressionally Directed Medical Research Programs, Department of Defense.

Dr. Kowalec reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

COPENHAGEN — A higher cumulative genetic burden for depression is associated with an increased risk for relapse and worsening disability in people with multiple sclerosis (MS), early results of a new study showed.

Unlike the previous research, the current analysis used polygenic risk scores for depression, which summarize the estimated effect of genetic variants to determine the potential association with MS disease activity, so results are less likely to be explained by reverse causality.

This study increases awareness of the link between depression and MS, said study investigator Kaarina Kowalec, PhD, assistant professor, College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. “We’re starting to understand how depression affects relapses and disability progression in MS,” she said.

The findings were presented at the 2024 ECTRIMS annual meeting.
 

Common Comorbidity

Depression is a common comorbidity in patients with MS and is associated with increased relapse and disability progression. Depression risk is partly polygenic in nature, involving numerous common genetic variants, said Dr. Kowalec.

The case-control study included 3420 relapsing-onset MS cases of European ancestry from four existing cohorts in three countries.

The Canadian cohort included those enrolled in a prospective longitudinal study of psychiatric comorbidity in chronic immune-mediated inflammatory disease (IMID), including MS; the Swedish cohort was an MS registry (SSReg) that encompasses 64 MS clinics (the cohort was split into two groups); and the US cohort was enrolled in a clinical trial of combined therapy with interferon and glatiramer acetate (CombiRx) in patients with MS.

The median follow-up in these cohorts ranged from 3 to 5 years.

Not surprisingly, most participants were women (from 71% in one of the Swedish cohorts to 83% in the Canadian cohort), and the age at MS onset ranged from 29 years in the Canadian cohort to 35 years in one of the Swedish cohorts.

The median baseline Expanded Disability Status Scale (EDSS) score was higher in the Canadian cohort (3.5) than in the Swedish (1.5) and US (2.0) cohorts, “reflective of the Canadian cohort being slightly more progressed,” said Dr. Kowalec.
 

Inherited Variants

To measure depression heritability, researchers generated a polygenic risk score in whole-genome imputed genotypes. The score reflects the number of inherited common genetic variants, weighted by effect sizes.

Researchers investigated the association between depression polygenic risk scores (top 20% vs. bottom 80%) with annualized relapse rate and worsening disability in MS measured by the rate of change in EDSS score. In the US cohort, they also explored the association between depression polygenic risk scores and time to relapse and confirmed EDSS worsening.

Covariates included use of disease-modifying therapy, age, sex, and the first five genetic ancestry principal components. The latter was done to capture residual stratification by genetic ancestry, although Dr. Kowalec stressed analyses were done only in those of European ancestry.

Investigators found a higher depression polygenic risk score was associated with relapse risk (incident rate ratio, 1.23; 95% CI, 1.01-1.49).

“Essentially, for every one standard deviation increase in the depression polygenic score, we found a significant increased hazard of 23% for experiencing a relapse over the follow-up period,” said Dr. Kowalec, who is also affiliated with the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

She noted the Canadian cohort did not have many relapses, while the US and Swedish cohorts “had an increased rate.”

Other analyses examined the risk of having a relapse or worsening disability. Every one SD increase in the depression polygenic risk score was significantly associated with a 2.2 greater risk of experiencing relapse (hazard ratio [HR], 2.20; 95% CI, 1.35-3.60) and a 51% increased risk for confirmed EDSS progression (HR, 1.51; 95% CI, 1.03-2.22).
 

‘An Ideal Marker’

Use of polygenetic risk scores reduces the possibility of reverse causation, noted Dr. Kowalec. “These markers are fixed at birth and don’t change over your lifespan, so they’re really an ideal marker.”

The results suggest polygenetic risk scores represent a potential biomarker for risk stratification in people with MS, said Dr. Kowalec. Although depression polygenic risk scores are not currently available in clinical practice, “I would hope this would change in the next 3-4 years,” she said.

Asked by a delegate if confounding by a third variable is possible, Dr. Kowalec said because genetic markers don’t change over time, there is a hint that the direction is causal and that depression is driving the outcome. However, she added, further confirmation is needed.

Dr. Kowalec noted that there were no data on antidepressant use but noted that about half of the Canadian and US cohorts — and likely the same number in the Swedish cohorts — self-reported depression.

A limitation of the study was that it included only participants of European ancestry.
 

Clinical Implications Unclear

Commenting on the research, Lauren Gluck, MD, program director, Montefiore Multiple Sclerosis Center, Bronx, New York, described the study as “fascinating” but noted that it’s unclear how to use this new information in clinical practice.

“Clinicians frequently ask people with MS about mood symptoms and offer interventions like antidepressants and referrals to therapists. However, genetic testing is not routine, so we don’t yet know who to target based on these data.”

Preexisting depression or more severe depression could be viewed as a “red flag” for risk for more disease activity in the future, she said.

“This could encourage clinicians to use more highly effective therapy in these patients, similar to our strategies for people with MS with frequent attacks and more disease burden on MRIs.”

The study received support from the Consortium of Multiple Sclerosis Centers and the Congressionally Directed Medical Research Programs, Department of Defense.

Dr. Kowalec reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

COPENHAGEN — A higher cumulative genetic burden for depression is associated with an increased risk for relapse and worsening disability in people with multiple sclerosis (MS), early results of a new study showed.

Unlike the previous research, the current analysis used polygenic risk scores for depression, which summarize the estimated effect of genetic variants to determine the potential association with MS disease activity, so results are less likely to be explained by reverse causality.

This study increases awareness of the link between depression and MS, said study investigator Kaarina Kowalec, PhD, assistant professor, College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. “We’re starting to understand how depression affects relapses and disability progression in MS,” she said.

The findings were presented at the 2024 ECTRIMS annual meeting.
 

Common Comorbidity

Depression is a common comorbidity in patients with MS and is associated with increased relapse and disability progression. Depression risk is partly polygenic in nature, involving numerous common genetic variants, said Dr. Kowalec.

The case-control study included 3420 relapsing-onset MS cases of European ancestry from four existing cohorts in three countries.

The Canadian cohort included those enrolled in a prospective longitudinal study of psychiatric comorbidity in chronic immune-mediated inflammatory disease (IMID), including MS; the Swedish cohort was an MS registry (SSReg) that encompasses 64 MS clinics (the cohort was split into two groups); and the US cohort was enrolled in a clinical trial of combined therapy with interferon and glatiramer acetate (CombiRx) in patients with MS.

The median follow-up in these cohorts ranged from 3 to 5 years.

Not surprisingly, most participants were women (from 71% in one of the Swedish cohorts to 83% in the Canadian cohort), and the age at MS onset ranged from 29 years in the Canadian cohort to 35 years in one of the Swedish cohorts.

The median baseline Expanded Disability Status Scale (EDSS) score was higher in the Canadian cohort (3.5) than in the Swedish (1.5) and US (2.0) cohorts, “reflective of the Canadian cohort being slightly more progressed,” said Dr. Kowalec.
 

Inherited Variants

To measure depression heritability, researchers generated a polygenic risk score in whole-genome imputed genotypes. The score reflects the number of inherited common genetic variants, weighted by effect sizes.

Researchers investigated the association between depression polygenic risk scores (top 20% vs. bottom 80%) with annualized relapse rate and worsening disability in MS measured by the rate of change in EDSS score. In the US cohort, they also explored the association between depression polygenic risk scores and time to relapse and confirmed EDSS worsening.

Covariates included use of disease-modifying therapy, age, sex, and the first five genetic ancestry principal components. The latter was done to capture residual stratification by genetic ancestry, although Dr. Kowalec stressed analyses were done only in those of European ancestry.

Investigators found a higher depression polygenic risk score was associated with relapse risk (incident rate ratio, 1.23; 95% CI, 1.01-1.49).

“Essentially, for every one standard deviation increase in the depression polygenic score, we found a significant increased hazard of 23% for experiencing a relapse over the follow-up period,” said Dr. Kowalec, who is also affiliated with the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

She noted the Canadian cohort did not have many relapses, while the US and Swedish cohorts “had an increased rate.”

Other analyses examined the risk of having a relapse or worsening disability. Every one SD increase in the depression polygenic risk score was significantly associated with a 2.2 greater risk of experiencing relapse (hazard ratio [HR], 2.20; 95% CI, 1.35-3.60) and a 51% increased risk for confirmed EDSS progression (HR, 1.51; 95% CI, 1.03-2.22).
 

‘An Ideal Marker’

Use of polygenetic risk scores reduces the possibility of reverse causation, noted Dr. Kowalec. “These markers are fixed at birth and don’t change over your lifespan, so they’re really an ideal marker.”

The results suggest polygenetic risk scores represent a potential biomarker for risk stratification in people with MS, said Dr. Kowalec. Although depression polygenic risk scores are not currently available in clinical practice, “I would hope this would change in the next 3-4 years,” she said.

Asked by a delegate if confounding by a third variable is possible, Dr. Kowalec said because genetic markers don’t change over time, there is a hint that the direction is causal and that depression is driving the outcome. However, she added, further confirmation is needed.

Dr. Kowalec noted that there were no data on antidepressant use but noted that about half of the Canadian and US cohorts — and likely the same number in the Swedish cohorts — self-reported depression.

A limitation of the study was that it included only participants of European ancestry.
 

Clinical Implications Unclear

Commenting on the research, Lauren Gluck, MD, program director, Montefiore Multiple Sclerosis Center, Bronx, New York, described the study as “fascinating” but noted that it’s unclear how to use this new information in clinical practice.

“Clinicians frequently ask people with MS about mood symptoms and offer interventions like antidepressants and referrals to therapists. However, genetic testing is not routine, so we don’t yet know who to target based on these data.”

Preexisting depression or more severe depression could be viewed as a “red flag” for risk for more disease activity in the future, she said.

“This could encourage clinicians to use more highly effective therapy in these patients, similar to our strategies for people with MS with frequent attacks and more disease burden on MRIs.”

The study received support from the Consortium of Multiple Sclerosis Centers and the Congressionally Directed Medical Research Programs, Department of Defense.

Dr. Kowalec reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

MILAN — Psilocybin leads to a better overall outcome in the treatment of moderate to severe major depressive disorder (MDD) than the selective serotonin reuptake inhibitor (SSRI) escitalopram, results of the first long-term comparison of the two treatments suggest.

“This is the first work to compare the long-term effects of these two drugs in the context of overall well-being, not just freedom from depression,” study investigator Tommaso Barba, PhD candidate at Imperial College London in England, said in a press release. “Psilocybin outperformed escitalopram in several measures of well-being, meaning in life, work, and social functioning.”

Findings from the 6-month follow-up study of a phase 2 double-blind, randomized, controlled trial were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and published simultaneously in The Lancet eClinicalMedicine

Addressing a Treatment ‘Mismatch’

The findings are important because they address “a mismatch” between what psychiatrists and what patients think is important, Mr. Barba said in an interview.

“Psychiatrists really focus on negative symptoms of depression. So, if you are not sad anymore, if your sleep or appetite is not impaired, they think you’re better. But if you look at what patients define as important, they say it’s the degree in which their life is meaningful, in which they can connect with people around them, in which they can function in everyday life,” Mr. Barba said.

“The study suggests that psilocybin therapy might be a more holistic treatment option for depression,” added co–first author David Erritzoe, MD, PhD, clinical director and deputy head of the Centre for Psychedelic Research, Imperial College London. “This could make a substantial difference in the overall happiness and daily activities of those suffering from depression, providing a more joined-up approach to mental health treatment.”

The initial single-center study included 59 adults with MDD (mean age, 41 years) who were randomized to receive either psilocybin or escitalopram over a 6-week period. The psilocybin arm (n = 30) received two 25-mg oral doses of psilocybin therapy (PT), and the escitalopram arm (n = 29) received 10-20 mg of daily escitalopram plus two (placebo-like) 1-mg doses of psilocybin (ET). Both groups received psychological support.

Based on change in depression scores on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) at week 6, the initial study results suggested noninferiority between the two treatments in terms of depressive symptoms (primary outcome), but superiority of PT for secondary outcomes including “well-being, anhedonia, social functioning, sexual functioning, and related variables, with fewer side effects compared to ET,” the researchers noted.

The new 6-month follow-up findings, with monthly questionnaires and no additional study treatment or psychiatric treatment restrictions, measured the QIDS-SR-16, plus Work and Social Adjustment Scale (WSAS), Meaning in Life Questionnaire, Flourishing Scale (FS), and Watts Connectedness Scale (WCS).

Again, both groups maintained similar results on the QIDS-SR-16, with slightly greater reductions in depressive symptoms for PT in the first month (positive false discovery rate [pFDR] = 0.021), but not thereafter.

At both 3 and 6 months, there were greater improvements in WSAS scores for the PT group (pFDR < 0.001 and pFDR = 0.01, respectively), and also greater improvements in meaning in life across all follow-up timepoints (pFDR < 0.001).

There was also greater improvement in the PT group regarding WCS at both 3 and 6 months (pFDR = 0.02, and pFDR = 0.04) and comparable FS improvements for both groups across all timepoints.

Confounding follow-up interventions may have muddied the results, with 30.7% of PT participants and 43.5% of ET participants receiving an additional intervention during this period.

The researchers conclude that while a short course of SSRIs combined with intensive therapeutic support (around 20 hours) “might be enough to induce sustained antidepressant effects,” patients treated with psilocybin showed greater improvements in general functioning, connectedness, and meaning in life.

Although not reassessed in the follow-up, the initial study showed that adverse events, particularly sexual functioning, favored psilocybin, said Mr. Barba. “The two treatments seemed to go in opposite directions with psilocybin seeming to improve it and the antidepressant to suppress it. Other side effects associated with psilocybin were less diverse — mainly headaches at the end of the day — but with escitalopram they were way more diverse and more impairing.”

Although many therapists may be unfamiliar with psilocybin-assisted psychotherapy, “it’s not a difficult skill to master. It might require some specialization, but I think if you’re a good psychotherapist, you can learn how to implement psilocybin into your practice,” he said.

“Normally the journey is quite inward, so patients do not require active support during the psychedelic experience [around 6 hours]. Sometimes they do require some hand-holding, or helping them to ‘let go’, or breathing exercises. The important part is the integration work that comes afterwards,” Mr. Barba added.

He said he envisions a therapy program that involves “psychiatrists working together with psychotherapists. The psychotherapists would be more in charge of the active guiding, and the psychiatrist would do the prescribing, with the follow-up psychological support on Zoom.”

He added a word of caution for therapists that “psilocybin requires active confrontation of painful, negative emotions and people who take this drug need to be open and prepared for the idea that they are going into a state where they may probably end up crying and confronting whatever they are maybe running away from in their lives. Not everyone may want to do this.”
 

A New Treatment Paradigm?

In a comment, Johan Lundberg, MD, PhD, adjunct professor of psychiatry at the Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden, said the study addresses a key outstanding question about the long-term effects of one or two doses of psilocybin.

“It’s a 6-month follow-up of a short treatment intervention, so in that sense, it’s of high interest. It has been talked about that psilocybin might have a long-term effect, but this is the first study that has followed this for a longer term.”

But Dr. Lundberg also pointed out that one shortcoming of the study is the diversity of treatments following the intervention.

“They didn’t have control over whether patients received other treatments or when they started. So, that is a key concern. But they transparently reported that, and we do know there was a difference in reported ability to perform activities of daily life, and that is important.”

He added that if psilocybin is eventually approved, it would likely come with an education package for providers — “which is already the case with other treatments like ECT [electroconvulsive therapy] or TMS [transcranial magnetic stimulation] — you have to learn how to do it.”

James Rucker, MD, PhD, psychiatrist and senior clinical lecturer at King’s College London, who was not involved in the research, also noted that they have tended to attribute differences observed in this study to comparative differences between the drugs themselves.

However, he noted, it is also possible that the results reflect biased reporting between groups. This is more likely here because studies involving psilocybin tend to attract those with positive preconceptions about psilocybin and negative preconceptions about conventional antidepressants, and study participants were unblinded during the long-term follow-up phase, so knew which condition they were allocated to.

“This said, the nature of depression varies hugely between individuals, and this calls for the development of a similarly varied suite of treatment paradigms. Psilocybin therapy is certainly a different paradigm of treatment to escitalopram. The observation of similar levels of effectiveness to antidepressants here is encouraging to see alongside the much larger trials of psilocybin currently underway here in the UK, Europe, and the US,” Dr. Rucker added.

This work was supported by The Alexander Mosley Charitable Trust and by the founding partners of Imperial College London’s Centre for Psychedelic Research.

Mr. Barba reported having received consulting fees from Adamo Bioscience. Both Dr. Lundberg and Dr. Rucker are involved in psilocybin research, but neither reported financial links.

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

MILAN — Psilocybin leads to a better overall outcome in the treatment of moderate to severe major depressive disorder (MDD) than the selective serotonin reuptake inhibitor (SSRI) escitalopram, results of the first long-term comparison of the two treatments suggest.

“This is the first work to compare the long-term effects of these two drugs in the context of overall well-being, not just freedom from depression,” study investigator Tommaso Barba, PhD candidate at Imperial College London in England, said in a press release. “Psilocybin outperformed escitalopram in several measures of well-being, meaning in life, work, and social functioning.”

Findings from the 6-month follow-up study of a phase 2 double-blind, randomized, controlled trial were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and published simultaneously in The Lancet eClinicalMedicine

Addressing a Treatment ‘Mismatch’

The findings are important because they address “a mismatch” between what psychiatrists and what patients think is important, Mr. Barba said in an interview.

“Psychiatrists really focus on negative symptoms of depression. So, if you are not sad anymore, if your sleep or appetite is not impaired, they think you’re better. But if you look at what patients define as important, they say it’s the degree in which their life is meaningful, in which they can connect with people around them, in which they can function in everyday life,” Mr. Barba said.

“The study suggests that psilocybin therapy might be a more holistic treatment option for depression,” added co–first author David Erritzoe, MD, PhD, clinical director and deputy head of the Centre for Psychedelic Research, Imperial College London. “This could make a substantial difference in the overall happiness and daily activities of those suffering from depression, providing a more joined-up approach to mental health treatment.”

The initial single-center study included 59 adults with MDD (mean age, 41 years) who were randomized to receive either psilocybin or escitalopram over a 6-week period. The psilocybin arm (n = 30) received two 25-mg oral doses of psilocybin therapy (PT), and the escitalopram arm (n = 29) received 10-20 mg of daily escitalopram plus two (placebo-like) 1-mg doses of psilocybin (ET). Both groups received psychological support.

Based on change in depression scores on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) at week 6, the initial study results suggested noninferiority between the two treatments in terms of depressive symptoms (primary outcome), but superiority of PT for secondary outcomes including “well-being, anhedonia, social functioning, sexual functioning, and related variables, with fewer side effects compared to ET,” the researchers noted.

The new 6-month follow-up findings, with monthly questionnaires and no additional study treatment or psychiatric treatment restrictions, measured the QIDS-SR-16, plus Work and Social Adjustment Scale (WSAS), Meaning in Life Questionnaire, Flourishing Scale (FS), and Watts Connectedness Scale (WCS).

Again, both groups maintained similar results on the QIDS-SR-16, with slightly greater reductions in depressive symptoms for PT in the first month (positive false discovery rate [pFDR] = 0.021), but not thereafter.

At both 3 and 6 months, there were greater improvements in WSAS scores for the PT group (pFDR < 0.001 and pFDR = 0.01, respectively), and also greater improvements in meaning in life across all follow-up timepoints (pFDR < 0.001).

There was also greater improvement in the PT group regarding WCS at both 3 and 6 months (pFDR = 0.02, and pFDR = 0.04) and comparable FS improvements for both groups across all timepoints.

Confounding follow-up interventions may have muddied the results, with 30.7% of PT participants and 43.5% of ET participants receiving an additional intervention during this period.

The researchers conclude that while a short course of SSRIs combined with intensive therapeutic support (around 20 hours) “might be enough to induce sustained antidepressant effects,” patients treated with psilocybin showed greater improvements in general functioning, connectedness, and meaning in life.

Although not reassessed in the follow-up, the initial study showed that adverse events, particularly sexual functioning, favored psilocybin, said Mr. Barba. “The two treatments seemed to go in opposite directions with psilocybin seeming to improve it and the antidepressant to suppress it. Other side effects associated with psilocybin were less diverse — mainly headaches at the end of the day — but with escitalopram they were way more diverse and more impairing.”

Although many therapists may be unfamiliar with psilocybin-assisted psychotherapy, “it’s not a difficult skill to master. It might require some specialization, but I think if you’re a good psychotherapist, you can learn how to implement psilocybin into your practice,” he said.

“Normally the journey is quite inward, so patients do not require active support during the psychedelic experience [around 6 hours]. Sometimes they do require some hand-holding, or helping them to ‘let go’, or breathing exercises. The important part is the integration work that comes afterwards,” Mr. Barba added.

He said he envisions a therapy program that involves “psychiatrists working together with psychotherapists. The psychotherapists would be more in charge of the active guiding, and the psychiatrist would do the prescribing, with the follow-up psychological support on Zoom.”

He added a word of caution for therapists that “psilocybin requires active confrontation of painful, negative emotions and people who take this drug need to be open and prepared for the idea that they are going into a state where they may probably end up crying and confronting whatever they are maybe running away from in their lives. Not everyone may want to do this.”
 

A New Treatment Paradigm?

In a comment, Johan Lundberg, MD, PhD, adjunct professor of psychiatry at the Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden, said the study addresses a key outstanding question about the long-term effects of one or two doses of psilocybin.

“It’s a 6-month follow-up of a short treatment intervention, so in that sense, it’s of high interest. It has been talked about that psilocybin might have a long-term effect, but this is the first study that has followed this for a longer term.”

But Dr. Lundberg also pointed out that one shortcoming of the study is the diversity of treatments following the intervention.

“They didn’t have control over whether patients received other treatments or when they started. So, that is a key concern. But they transparently reported that, and we do know there was a difference in reported ability to perform activities of daily life, and that is important.”

He added that if psilocybin is eventually approved, it would likely come with an education package for providers — “which is already the case with other treatments like ECT [electroconvulsive therapy] or TMS [transcranial magnetic stimulation] — you have to learn how to do it.”

James Rucker, MD, PhD, psychiatrist and senior clinical lecturer at King’s College London, who was not involved in the research, also noted that they have tended to attribute differences observed in this study to comparative differences between the drugs themselves.

However, he noted, it is also possible that the results reflect biased reporting between groups. This is more likely here because studies involving psilocybin tend to attract those with positive preconceptions about psilocybin and negative preconceptions about conventional antidepressants, and study participants were unblinded during the long-term follow-up phase, so knew which condition they were allocated to.

“This said, the nature of depression varies hugely between individuals, and this calls for the development of a similarly varied suite of treatment paradigms. Psilocybin therapy is certainly a different paradigm of treatment to escitalopram. The observation of similar levels of effectiveness to antidepressants here is encouraging to see alongside the much larger trials of psilocybin currently underway here in the UK, Europe, and the US,” Dr. Rucker added.

This work was supported by The Alexander Mosley Charitable Trust and by the founding partners of Imperial College London’s Centre for Psychedelic Research.

Mr. Barba reported having received consulting fees from Adamo Bioscience. Both Dr. Lundberg and Dr. Rucker are involved in psilocybin research, but neither reported financial links.

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

MILAN — Psilocybin leads to a better overall outcome in the treatment of moderate to severe major depressive disorder (MDD) than the selective serotonin reuptake inhibitor (SSRI) escitalopram, results of the first long-term comparison of the two treatments suggest.

“This is the first work to compare the long-term effects of these two drugs in the context of overall well-being, not just freedom from depression,” study investigator Tommaso Barba, PhD candidate at Imperial College London in England, said in a press release. “Psilocybin outperformed escitalopram in several measures of well-being, meaning in life, work, and social functioning.”

Findings from the 6-month follow-up study of a phase 2 double-blind, randomized, controlled trial were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and published simultaneously in The Lancet eClinicalMedicine

Addressing a Treatment ‘Mismatch’

The findings are important because they address “a mismatch” between what psychiatrists and what patients think is important, Mr. Barba said in an interview.

“Psychiatrists really focus on negative symptoms of depression. So, if you are not sad anymore, if your sleep or appetite is not impaired, they think you’re better. But if you look at what patients define as important, they say it’s the degree in which their life is meaningful, in which they can connect with people around them, in which they can function in everyday life,” Mr. Barba said.

“The study suggests that psilocybin therapy might be a more holistic treatment option for depression,” added co–first author David Erritzoe, MD, PhD, clinical director and deputy head of the Centre for Psychedelic Research, Imperial College London. “This could make a substantial difference in the overall happiness and daily activities of those suffering from depression, providing a more joined-up approach to mental health treatment.”

The initial single-center study included 59 adults with MDD (mean age, 41 years) who were randomized to receive either psilocybin or escitalopram over a 6-week period. The psilocybin arm (n = 30) received two 25-mg oral doses of psilocybin therapy (PT), and the escitalopram arm (n = 29) received 10-20 mg of daily escitalopram plus two (placebo-like) 1-mg doses of psilocybin (ET). Both groups received psychological support.

Based on change in depression scores on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) at week 6, the initial study results suggested noninferiority between the two treatments in terms of depressive symptoms (primary outcome), but superiority of PT for secondary outcomes including “well-being, anhedonia, social functioning, sexual functioning, and related variables, with fewer side effects compared to ET,” the researchers noted.

The new 6-month follow-up findings, with monthly questionnaires and no additional study treatment or psychiatric treatment restrictions, measured the QIDS-SR-16, plus Work and Social Adjustment Scale (WSAS), Meaning in Life Questionnaire, Flourishing Scale (FS), and Watts Connectedness Scale (WCS).

Again, both groups maintained similar results on the QIDS-SR-16, with slightly greater reductions in depressive symptoms for PT in the first month (positive false discovery rate [pFDR] = 0.021), but not thereafter.

At both 3 and 6 months, there were greater improvements in WSAS scores for the PT group (pFDR < 0.001 and pFDR = 0.01, respectively), and also greater improvements in meaning in life across all follow-up timepoints (pFDR < 0.001).

There was also greater improvement in the PT group regarding WCS at both 3 and 6 months (pFDR = 0.02, and pFDR = 0.04) and comparable FS improvements for both groups across all timepoints.

Confounding follow-up interventions may have muddied the results, with 30.7% of PT participants and 43.5% of ET participants receiving an additional intervention during this period.

The researchers conclude that while a short course of SSRIs combined with intensive therapeutic support (around 20 hours) “might be enough to induce sustained antidepressant effects,” patients treated with psilocybin showed greater improvements in general functioning, connectedness, and meaning in life.

Although not reassessed in the follow-up, the initial study showed that adverse events, particularly sexual functioning, favored psilocybin, said Mr. Barba. “The two treatments seemed to go in opposite directions with psilocybin seeming to improve it and the antidepressant to suppress it. Other side effects associated with psilocybin were less diverse — mainly headaches at the end of the day — but with escitalopram they were way more diverse and more impairing.”

Although many therapists may be unfamiliar with psilocybin-assisted psychotherapy, “it’s not a difficult skill to master. It might require some specialization, but I think if you’re a good psychotherapist, you can learn how to implement psilocybin into your practice,” he said.

“Normally the journey is quite inward, so patients do not require active support during the psychedelic experience [around 6 hours]. Sometimes they do require some hand-holding, or helping them to ‘let go’, or breathing exercises. The important part is the integration work that comes afterwards,” Mr. Barba added.

He said he envisions a therapy program that involves “psychiatrists working together with psychotherapists. The psychotherapists would be more in charge of the active guiding, and the psychiatrist would do the prescribing, with the follow-up psychological support on Zoom.”

He added a word of caution for therapists that “psilocybin requires active confrontation of painful, negative emotions and people who take this drug need to be open and prepared for the idea that they are going into a state where they may probably end up crying and confronting whatever they are maybe running away from in their lives. Not everyone may want to do this.”
 

A New Treatment Paradigm?

In a comment, Johan Lundberg, MD, PhD, adjunct professor of psychiatry at the Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden, said the study addresses a key outstanding question about the long-term effects of one or two doses of psilocybin.

“It’s a 6-month follow-up of a short treatment intervention, so in that sense, it’s of high interest. It has been talked about that psilocybin might have a long-term effect, but this is the first study that has followed this for a longer term.”

But Dr. Lundberg also pointed out that one shortcoming of the study is the diversity of treatments following the intervention.

“They didn’t have control over whether patients received other treatments or when they started. So, that is a key concern. But they transparently reported that, and we do know there was a difference in reported ability to perform activities of daily life, and that is important.”

He added that if psilocybin is eventually approved, it would likely come with an education package for providers — “which is already the case with other treatments like ECT [electroconvulsive therapy] or TMS [transcranial magnetic stimulation] — you have to learn how to do it.”

James Rucker, MD, PhD, psychiatrist and senior clinical lecturer at King’s College London, who was not involved in the research, also noted that they have tended to attribute differences observed in this study to comparative differences between the drugs themselves.

However, he noted, it is also possible that the results reflect biased reporting between groups. This is more likely here because studies involving psilocybin tend to attract those with positive preconceptions about psilocybin and negative preconceptions about conventional antidepressants, and study participants were unblinded during the long-term follow-up phase, so knew which condition they were allocated to.

“This said, the nature of depression varies hugely between individuals, and this calls for the development of a similarly varied suite of treatment paradigms. Psilocybin therapy is certainly a different paradigm of treatment to escitalopram. The observation of similar levels of effectiveness to antidepressants here is encouraging to see alongside the much larger trials of psilocybin currently underway here in the UK, Europe, and the US,” Dr. Rucker added.

This work was supported by The Alexander Mosley Charitable Trust and by the founding partners of Imperial College London’s Centre for Psychedelic Research.

Mr. Barba reported having received consulting fees from Adamo Bioscience. Both Dr. Lundberg and Dr. Rucker are involved in psilocybin research, but neither reported financial links.

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

US suicide rates have reached alarming levels, with data from Centers for Disease Control and Prevention (CDC) showing a 37% increase from 2000 to 2022. Nearly 49,000 people died by suicide in 2022 alone, translating to one death every 11 minutes. 

The increase in suicide rates has prompted calls for expansion of universal suicide screening, in which all individuals in medical or mental health care settings are screened for suicide risk, regardless of the purpose for their visit. But the psychiatric field is split on the issue, with some experts citing false positives and a lack of mental health care resources for those deemed at risk.

In 2022, when the US Preventative Services Task Force released its recommendations on suicide prevention, first in children and adolescents, and then in adults, the authors said there was insufficient evidence to support universal suicide screening. 

Proponents of the practice pushed back on that finding, arguing that universal suicide screening could help identify those at high risk who might otherwise go undiagnosed, leading to earlier, potentially lifesaving, intervention.

So, what is the case for — and against — universal screening?
 

Sounding an Alert

The introduction of universal screening was driven by a confluence of factors that began with a 1999 report by then-US Surgeon General David Satcher, MD. This was followed by a report in 2016 from the Joint Commission on Detecting and Treating Suicidal Ideation that called for healthcare organizations to improve detection and treatment of suicidal ideation in all healthcare care settings. 

Data from the alert showed that a significant number of people who died by suicide had a healthcare visit before their death. Half had seen a clinician a month before their death; nearly 30% had a medical visit just the week before — all with no detection of increased suicide risk. 

It was that sort of finding that led Parkland Health and Hospital System in Dallas to become the first US hospital to implement universal suicide screening. Since the program launched in 2015, the system has screened more than 4.3 million patients in its emergency department, inpatient units, and 20 primary care clinics.

“Since the program began, we’ve completed between 40,000 to 50,000 screenings per month,” said Kimberly Roaten, PhD, associate chief quality and safety officer for behavioral health at Parkland Health. 

Clinicians at Parkland use the five-item Ask Suicide-Screening Questions to assess suicidal intent, a commonly used tool that was originally developed for use in pediatric emergency rooms (ERs). The tool, which takes about 20 seconds to administer, has since been validated in both children and adults. 

Based on a patient’s response, a clinical decision support system integrated into the electronic health record classifies suicide risk as none, moderate, or high.

Patients identified as moderate risk are offered a more in-depth assessment with a mental health clinician, though participation is not mandatory, said Dr. Roaten. Those at high risk receive a more thorough evaluation.

The proportion of ER patients at Parkland who screen positive for any suicidal intent has consistently remained at about 7%, and at 2% in the primary care clinics, she said.

To better understand what the program may have had on suicide prevention, Dr. Roaten is leading a National Institute of Mental Health–funded study to link a decade of mortality data from the state of Texas to patient data from Parkland Health. Investigators will analyze information about patients identified at risk for suicide, those patients’ characteristics, and who dies by suicide.
 

Universal Screening Expands

Other health systems have adopted universal suicide screening including the Indian Health Service and the US Veterans Health Administration. Universal suicide screening is also in place in a growing number of primary care practices and hospitals throughout the United States and will be mandatory for patients aged 12 years and older in all acute care hospitals in California beginning in 2025.

There is also a push for universal screening to be coordinated through local, state, and federal government, nonprofit, and private sectors. The National Action Alliance for Suicide Prevention is charged with advancing the White House’s 2024 National Strategy for Suicide Prevention, a 10-year plan to address gaps in suicide prevention in the United States. 

Sarah Brummett, JD, director of the National Action Alliance for Suicide Prevention’s executive committee, said that universal suicide screening is part of the 2024 strategy. “We know there are barriers to universal screening, and so it’s important to recognize what they are so we can address them,” said Ms. Brummett. 

Barriers may include adequate staffing, or a system in place to triage patients who screen positive. 

At Parkland, cost and workload have been minimal, Dr. Roaten said. “We built a model that only dedicates our highest-value resources to the most at-risk patients.”

She also noted that relief may be on the horizon for health systems where cost is an obstacle to universal screening and subsequent intervention. “There are efforts at the federal level to increase funding for suicide assessment and crisis response,” she said. 
 

Pushback on Universal Screening

Universal suicide screening has its detractors, including critics who say expansion is unlikely to reduce suicide rates.

“The issue with suicidal ideation is that it is very dynamic. Suicidal ideation changes very quickly — sometimes within hours,” said Craig Bryan, PsyD, professor of psychiatry and behavioral health at Ohio State University in Columbus, Ohio. 

Universal screening can also lead to false positives, where a patient who screens positive for suicidal ideation has no actual intention of attempting suicide, potentially creating unnecessary concern and burden on health care resources, Dr. Bryan noted. 

“What do you do with everyone who screens positive?” Dr. Bryan said. “I’ve spoken with leaders of many health systems in the United States, and there is pushback against universal screening because they don’t have enough mental health resources to handle all of the referrals.”

Suicide screening also doesn’t predict who will die by suicide, Dr. Bryan added. It only identifies those willing to disclose suicidal thoughts. There is a significant number of people without mental illness who may never seek medical care, so “the warning signs we’re teaching people to recognize — depression, anxiety, and substance abuse — might not be evident in these individuals,” he said.

“Life sideswipes them suddenly, and they go from 0 to 60 ... and they may have access to a highly lethal method [of suicide] which weaponizes that moment of despair,” said Dr. Bryan. No amount of screening could possibly predict those types of suicides, he added. 

Paul Nestadt, MD, associate professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, agrees with Dr. Bryan and noted there isn’t a strong correlation between suicidal ideation and death by suicide.

“Suicidal thoughts are very common, but suicide is a rare event,” he said. 

He cited a study that showed that two thirds of individuals who died by suicide had denied experiencing suicidal thoughts when asked, and half of them died within 2 days of this denial. Other research suggests that as many as 98% of people who express suicidal ideation do not die by suicide, Dr. Nestadt said. 
 

A Public Health Issue

If universal screening is not the answer to predicting and preventing suicide, what is? One way would be to approach suicide as a public health issue, Dr. Nestadt said. 

“How did we reduce the rate of motor vehicle deaths? We didn’t test each driver’s reaction time behind the wheel,” he said. “Instead, we passed seatbelt and airbag legislation, implemented federal speed limits, and as a result, the number of motor vehicle fatalities decreased.”

Dr. Nestadt is an advocate for stronger gun safety legislation, which has proven effective in reducing suicide rates. A study published this year showed that states with child access prevention laws, negligent storage laws, and mandatory waiting periods for gun purchases reported fewer suicide deaths than those without that legislation.

Other measures might be applied in cases of extreme individual suicide risk, including extreme risk protection orders, also known as “red flag” laws, he added. This type of legislation provides a pathway for law enforcement to temporarily remove firearms from individuals who pose a risk to themselves or others. 

“These have been shown to be very effective in saving lives,” Dr. Nestadt said.

Dr. Nestadt and others are also using machine learning models to predict suicide risk. Those identified as high-risk may be flagged on their electronic medical record. Ideally, when the algorithm becomes more accurate at predicting suicide, anyone treating this patient can then decide if action is needed, said Dr. Nestadt. 

In his work with suicidal military personnel, Dr. Bryan and his colleagues established a brief form of cognitive behavioral therapy (BCBT) to help participants challenge cognitive distortions and build coping strategies to deal with feel with intense feelings of distress. Data show that BCBT reduced suicide attempts among active-duty soldiers by 60% compared with standard mental health treatment. It has since been shown to work in civilians as well. 

Dr. Bryan is also researching fluctuations in the wish to live versus the wish to die relative to one another and mapping the trajectory of risk states along the way. 

The goal is that these and other suicide prevention strategies currently under study by his team and others will help stem the rise in suicide deaths.

“Overall, we need to train mental health providers to implement suicide prevention therapies and establish suicide risk programs,” Dr. Bryan said. “But until we build one of these suicide prevention interventions to scale, we’re putting the cart before the horse.”

Dr. Roaten, Ms. Brummett, Dr. Bryan, and Dr. Nestadt reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

US suicide rates have reached alarming levels, with data from Centers for Disease Control and Prevention (CDC) showing a 37% increase from 2000 to 2022. Nearly 49,000 people died by suicide in 2022 alone, translating to one death every 11 minutes. 

The increase in suicide rates has prompted calls for expansion of universal suicide screening, in which all individuals in medical or mental health care settings are screened for suicide risk, regardless of the purpose for their visit. But the psychiatric field is split on the issue, with some experts citing false positives and a lack of mental health care resources for those deemed at risk.

In 2022, when the US Preventative Services Task Force released its recommendations on suicide prevention, first in children and adolescents, and then in adults, the authors said there was insufficient evidence to support universal suicide screening. 

Proponents of the practice pushed back on that finding, arguing that universal suicide screening could help identify those at high risk who might otherwise go undiagnosed, leading to earlier, potentially lifesaving, intervention.

So, what is the case for — and against — universal screening?
 

Sounding an Alert

The introduction of universal screening was driven by a confluence of factors that began with a 1999 report by then-US Surgeon General David Satcher, MD. This was followed by a report in 2016 from the Joint Commission on Detecting and Treating Suicidal Ideation that called for healthcare organizations to improve detection and treatment of suicidal ideation in all healthcare care settings. 

Data from the alert showed that a significant number of people who died by suicide had a healthcare visit before their death. Half had seen a clinician a month before their death; nearly 30% had a medical visit just the week before — all with no detection of increased suicide risk. 

It was that sort of finding that led Parkland Health and Hospital System in Dallas to become the first US hospital to implement universal suicide screening. Since the program launched in 2015, the system has screened more than 4.3 million patients in its emergency department, inpatient units, and 20 primary care clinics.

“Since the program began, we’ve completed between 40,000 to 50,000 screenings per month,” said Kimberly Roaten, PhD, associate chief quality and safety officer for behavioral health at Parkland Health. 

Clinicians at Parkland use the five-item Ask Suicide-Screening Questions to assess suicidal intent, a commonly used tool that was originally developed for use in pediatric emergency rooms (ERs). The tool, which takes about 20 seconds to administer, has since been validated in both children and adults. 

Based on a patient’s response, a clinical decision support system integrated into the electronic health record classifies suicide risk as none, moderate, or high.

Patients identified as moderate risk are offered a more in-depth assessment with a mental health clinician, though participation is not mandatory, said Dr. Roaten. Those at high risk receive a more thorough evaluation.

The proportion of ER patients at Parkland who screen positive for any suicidal intent has consistently remained at about 7%, and at 2% in the primary care clinics, she said.

To better understand what the program may have had on suicide prevention, Dr. Roaten is leading a National Institute of Mental Health–funded study to link a decade of mortality data from the state of Texas to patient data from Parkland Health. Investigators will analyze information about patients identified at risk for suicide, those patients’ characteristics, and who dies by suicide.
 

Universal Screening Expands

Other health systems have adopted universal suicide screening including the Indian Health Service and the US Veterans Health Administration. Universal suicide screening is also in place in a growing number of primary care practices and hospitals throughout the United States and will be mandatory for patients aged 12 years and older in all acute care hospitals in California beginning in 2025.

There is also a push for universal screening to be coordinated through local, state, and federal government, nonprofit, and private sectors. The National Action Alliance for Suicide Prevention is charged with advancing the White House’s 2024 National Strategy for Suicide Prevention, a 10-year plan to address gaps in suicide prevention in the United States. 

Sarah Brummett, JD, director of the National Action Alliance for Suicide Prevention’s executive committee, said that universal suicide screening is part of the 2024 strategy. “We know there are barriers to universal screening, and so it’s important to recognize what they are so we can address them,” said Ms. Brummett. 

Barriers may include adequate staffing, or a system in place to triage patients who screen positive. 

At Parkland, cost and workload have been minimal, Dr. Roaten said. “We built a model that only dedicates our highest-value resources to the most at-risk patients.”

She also noted that relief may be on the horizon for health systems where cost is an obstacle to universal screening and subsequent intervention. “There are efforts at the federal level to increase funding for suicide assessment and crisis response,” she said. 
 

Pushback on Universal Screening

Universal suicide screening has its detractors, including critics who say expansion is unlikely to reduce suicide rates.

“The issue with suicidal ideation is that it is very dynamic. Suicidal ideation changes very quickly — sometimes within hours,” said Craig Bryan, PsyD, professor of psychiatry and behavioral health at Ohio State University in Columbus, Ohio. 

Universal screening can also lead to false positives, where a patient who screens positive for suicidal ideation has no actual intention of attempting suicide, potentially creating unnecessary concern and burden on health care resources, Dr. Bryan noted. 

“What do you do with everyone who screens positive?” Dr. Bryan said. “I’ve spoken with leaders of many health systems in the United States, and there is pushback against universal screening because they don’t have enough mental health resources to handle all of the referrals.”

Suicide screening also doesn’t predict who will die by suicide, Dr. Bryan added. It only identifies those willing to disclose suicidal thoughts. There is a significant number of people without mental illness who may never seek medical care, so “the warning signs we’re teaching people to recognize — depression, anxiety, and substance abuse — might not be evident in these individuals,” he said.

“Life sideswipes them suddenly, and they go from 0 to 60 ... and they may have access to a highly lethal method [of suicide] which weaponizes that moment of despair,” said Dr. Bryan. No amount of screening could possibly predict those types of suicides, he added. 

Paul Nestadt, MD, associate professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, agrees with Dr. Bryan and noted there isn’t a strong correlation between suicidal ideation and death by suicide.

“Suicidal thoughts are very common, but suicide is a rare event,” he said. 

He cited a study that showed that two thirds of individuals who died by suicide had denied experiencing suicidal thoughts when asked, and half of them died within 2 days of this denial. Other research suggests that as many as 98% of people who express suicidal ideation do not die by suicide, Dr. Nestadt said. 
 

A Public Health Issue

If universal screening is not the answer to predicting and preventing suicide, what is? One way would be to approach suicide as a public health issue, Dr. Nestadt said. 

“How did we reduce the rate of motor vehicle deaths? We didn’t test each driver’s reaction time behind the wheel,” he said. “Instead, we passed seatbelt and airbag legislation, implemented federal speed limits, and as a result, the number of motor vehicle fatalities decreased.”

Dr. Nestadt is an advocate for stronger gun safety legislation, which has proven effective in reducing suicide rates. A study published this year showed that states with child access prevention laws, negligent storage laws, and mandatory waiting periods for gun purchases reported fewer suicide deaths than those without that legislation.

Other measures might be applied in cases of extreme individual suicide risk, including extreme risk protection orders, also known as “red flag” laws, he added. This type of legislation provides a pathway for law enforcement to temporarily remove firearms from individuals who pose a risk to themselves or others. 

“These have been shown to be very effective in saving lives,” Dr. Nestadt said.

Dr. Nestadt and others are also using machine learning models to predict suicide risk. Those identified as high-risk may be flagged on their electronic medical record. Ideally, when the algorithm becomes more accurate at predicting suicide, anyone treating this patient can then decide if action is needed, said Dr. Nestadt. 

In his work with suicidal military personnel, Dr. Bryan and his colleagues established a brief form of cognitive behavioral therapy (BCBT) to help participants challenge cognitive distortions and build coping strategies to deal with feel with intense feelings of distress. Data show that BCBT reduced suicide attempts among active-duty soldiers by 60% compared with standard mental health treatment. It has since been shown to work in civilians as well. 

Dr. Bryan is also researching fluctuations in the wish to live versus the wish to die relative to one another and mapping the trajectory of risk states along the way. 

The goal is that these and other suicide prevention strategies currently under study by his team and others will help stem the rise in suicide deaths.

“Overall, we need to train mental health providers to implement suicide prevention therapies and establish suicide risk programs,” Dr. Bryan said. “But until we build one of these suicide prevention interventions to scale, we’re putting the cart before the horse.”

Dr. Roaten, Ms. Brummett, Dr. Bryan, and Dr. Nestadt reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

US suicide rates have reached alarming levels, with data from Centers for Disease Control and Prevention (CDC) showing a 37% increase from 2000 to 2022. Nearly 49,000 people died by suicide in 2022 alone, translating to one death every 11 minutes. 

The increase in suicide rates has prompted calls for expansion of universal suicide screening, in which all individuals in medical or mental health care settings are screened for suicide risk, regardless of the purpose for their visit. But the psychiatric field is split on the issue, with some experts citing false positives and a lack of mental health care resources for those deemed at risk.

In 2022, when the US Preventative Services Task Force released its recommendations on suicide prevention, first in children and adolescents, and then in adults, the authors said there was insufficient evidence to support universal suicide screening. 

Proponents of the practice pushed back on that finding, arguing that universal suicide screening could help identify those at high risk who might otherwise go undiagnosed, leading to earlier, potentially lifesaving, intervention.

So, what is the case for — and against — universal screening?
 

Sounding an Alert

The introduction of universal screening was driven by a confluence of factors that began with a 1999 report by then-US Surgeon General David Satcher, MD. This was followed by a report in 2016 from the Joint Commission on Detecting and Treating Suicidal Ideation that called for healthcare organizations to improve detection and treatment of suicidal ideation in all healthcare care settings. 

Data from the alert showed that a significant number of people who died by suicide had a healthcare visit before their death. Half had seen a clinician a month before their death; nearly 30% had a medical visit just the week before — all with no detection of increased suicide risk. 

It was that sort of finding that led Parkland Health and Hospital System in Dallas to become the first US hospital to implement universal suicide screening. Since the program launched in 2015, the system has screened more than 4.3 million patients in its emergency department, inpatient units, and 20 primary care clinics.

“Since the program began, we’ve completed between 40,000 to 50,000 screenings per month,” said Kimberly Roaten, PhD, associate chief quality and safety officer for behavioral health at Parkland Health. 

Clinicians at Parkland use the five-item Ask Suicide-Screening Questions to assess suicidal intent, a commonly used tool that was originally developed for use in pediatric emergency rooms (ERs). The tool, which takes about 20 seconds to administer, has since been validated in both children and adults. 

Based on a patient’s response, a clinical decision support system integrated into the electronic health record classifies suicide risk as none, moderate, or high.

Patients identified as moderate risk are offered a more in-depth assessment with a mental health clinician, though participation is not mandatory, said Dr. Roaten. Those at high risk receive a more thorough evaluation.

The proportion of ER patients at Parkland who screen positive for any suicidal intent has consistently remained at about 7%, and at 2% in the primary care clinics, she said.

To better understand what the program may have had on suicide prevention, Dr. Roaten is leading a National Institute of Mental Health–funded study to link a decade of mortality data from the state of Texas to patient data from Parkland Health. Investigators will analyze information about patients identified at risk for suicide, those patients’ characteristics, and who dies by suicide.
 

Universal Screening Expands

Other health systems have adopted universal suicide screening including the Indian Health Service and the US Veterans Health Administration. Universal suicide screening is also in place in a growing number of primary care practices and hospitals throughout the United States and will be mandatory for patients aged 12 years and older in all acute care hospitals in California beginning in 2025.

There is also a push for universal screening to be coordinated through local, state, and federal government, nonprofit, and private sectors. The National Action Alliance for Suicide Prevention is charged with advancing the White House’s 2024 National Strategy for Suicide Prevention, a 10-year plan to address gaps in suicide prevention in the United States. 

Sarah Brummett, JD, director of the National Action Alliance for Suicide Prevention’s executive committee, said that universal suicide screening is part of the 2024 strategy. “We know there are barriers to universal screening, and so it’s important to recognize what they are so we can address them,” said Ms. Brummett. 

Barriers may include adequate staffing, or a system in place to triage patients who screen positive. 

At Parkland, cost and workload have been minimal, Dr. Roaten said. “We built a model that only dedicates our highest-value resources to the most at-risk patients.”

She also noted that relief may be on the horizon for health systems where cost is an obstacle to universal screening and subsequent intervention. “There are efforts at the federal level to increase funding for suicide assessment and crisis response,” she said. 
 

Pushback on Universal Screening

Universal suicide screening has its detractors, including critics who say expansion is unlikely to reduce suicide rates.

“The issue with suicidal ideation is that it is very dynamic. Suicidal ideation changes very quickly — sometimes within hours,” said Craig Bryan, PsyD, professor of psychiatry and behavioral health at Ohio State University in Columbus, Ohio. 

Universal screening can also lead to false positives, where a patient who screens positive for suicidal ideation has no actual intention of attempting suicide, potentially creating unnecessary concern and burden on health care resources, Dr. Bryan noted. 

“What do you do with everyone who screens positive?” Dr. Bryan said. “I’ve spoken with leaders of many health systems in the United States, and there is pushback against universal screening because they don’t have enough mental health resources to handle all of the referrals.”

Suicide screening also doesn’t predict who will die by suicide, Dr. Bryan added. It only identifies those willing to disclose suicidal thoughts. There is a significant number of people without mental illness who may never seek medical care, so “the warning signs we’re teaching people to recognize — depression, anxiety, and substance abuse — might not be evident in these individuals,” he said.

“Life sideswipes them suddenly, and they go from 0 to 60 ... and they may have access to a highly lethal method [of suicide] which weaponizes that moment of despair,” said Dr. Bryan. No amount of screening could possibly predict those types of suicides, he added. 

Paul Nestadt, MD, associate professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, agrees with Dr. Bryan and noted there isn’t a strong correlation between suicidal ideation and death by suicide.

“Suicidal thoughts are very common, but suicide is a rare event,” he said. 

He cited a study that showed that two thirds of individuals who died by suicide had denied experiencing suicidal thoughts when asked, and half of them died within 2 days of this denial. Other research suggests that as many as 98% of people who express suicidal ideation do not die by suicide, Dr. Nestadt said. 
 

A Public Health Issue

If universal screening is not the answer to predicting and preventing suicide, what is? One way would be to approach suicide as a public health issue, Dr. Nestadt said. 

“How did we reduce the rate of motor vehicle deaths? We didn’t test each driver’s reaction time behind the wheel,” he said. “Instead, we passed seatbelt and airbag legislation, implemented federal speed limits, and as a result, the number of motor vehicle fatalities decreased.”

Dr. Nestadt is an advocate for stronger gun safety legislation, which has proven effective in reducing suicide rates. A study published this year showed that states with child access prevention laws, negligent storage laws, and mandatory waiting periods for gun purchases reported fewer suicide deaths than those without that legislation.

Other measures might be applied in cases of extreme individual suicide risk, including extreme risk protection orders, also known as “red flag” laws, he added. This type of legislation provides a pathway for law enforcement to temporarily remove firearms from individuals who pose a risk to themselves or others. 

“These have been shown to be very effective in saving lives,” Dr. Nestadt said.

Dr. Nestadt and others are also using machine learning models to predict suicide risk. Those identified as high-risk may be flagged on their electronic medical record. Ideally, when the algorithm becomes more accurate at predicting suicide, anyone treating this patient can then decide if action is needed, said Dr. Nestadt. 

In his work with suicidal military personnel, Dr. Bryan and his colleagues established a brief form of cognitive behavioral therapy (BCBT) to help participants challenge cognitive distortions and build coping strategies to deal with feel with intense feelings of distress. Data show that BCBT reduced suicide attempts among active-duty soldiers by 60% compared with standard mental health treatment. It has since been shown to work in civilians as well. 

Dr. Bryan is also researching fluctuations in the wish to live versus the wish to die relative to one another and mapping the trajectory of risk states along the way. 

The goal is that these and other suicide prevention strategies currently under study by his team and others will help stem the rise in suicide deaths.

“Overall, we need to train mental health providers to implement suicide prevention therapies and establish suicide risk programs,” Dr. Bryan said. “But until we build one of these suicide prevention interventions to scale, we’re putting the cart before the horse.”

Dr. Roaten, Ms. Brummett, Dr. Bryan, and Dr. Nestadt reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

In 2022, nearly 22% of people who died of drug overdose had a non–substance-related mental health disorder (MHD), new data from the Centers for Disease Control and Prevention (CDC) show. Investigators say the findings point to the need for incorporating mental health care in overdose prevention efforts.

METHODOLOGY:

• The study analyzed data from the CDC’s State Unintentional Drug Overdose Reporting System for 2022, covering 43 states and the District of Columbia.
• A total of 63,424 unintentional and undetermined intent drug overdose deaths during 2022 were included; 92.3% had medical examiner or coroner reports.
• MHDs were identified using source documents such as medical records and categorized according to the DSM-5 criteria.
• Potential intervention opportunities within 1 month of death, such as release from institutional settings or emergency department visits, were also analyzed.

TAKEAWAY:

• In 2022, 21.9% of drug overdose deaths involved people with non–substance-related MHDs, most commonly depression (12.9%), anxiety (9.4%), and bipolar disorder (5.9%).
• Opioids were involved in 82.2% of overdose deaths, with fentanyl or its analogs present in 75.2% of cases.
• Decedents with MHDs had higher usage rates of antidepressants (9.7% vs 3.3%), benzodiazepines (15.3% vs 8.5%), and prescription opioids (16% vs 11.6%) compared with those without MHDs.
• About 24.5% of decedents with MHDs had at least one potential intervention opportunity within 1 month of death, compared with 14.6% of those without MHDs, most commonly release from an institutional setting, treatment for substance use disorder, emergency department or urgent care visit, and nonfatal overdose.

IN PRACTICE:

“This finding suggests the need to screen for SUDs [ substance use disorders] and other MHDs, which is consistent with US Preventive Services Task Force recommendations for adults in primary care settings, and the need to link and integrate treatments to prevent overdose and improve mental health,” the authors wrote.

SOURCE:

The study was led by Amanda T. Dinwiddie, MPH, Division of Overdose Prevention, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia. It was published online on August 29, 2024, in Morbidity and Mortality Weekly Report.

LIMITATIONS:

The findings might not be applicable to the entire US population. MHDs could have been undiagnosed or underreported, possibly leading to underestimation. Additionally, variations in the completeness of source documents could have affected the accuracy of identifying MHDs. Data on current or recent mental health treatment were also unavailable. Lastly, substance use disorders may have been recorded as MHDs when not specified.

DISCLOSURES:

The study funding source was not reported. The authors did not disclose any conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In 2022, nearly 22% of people who died of drug overdose had a non–substance-related mental health disorder (MHD), new data from the Centers for Disease Control and Prevention (CDC) show. Investigators say the findings point to the need for incorporating mental health care in overdose prevention efforts.

METHODOLOGY:

• The study analyzed data from the CDC’s State Unintentional Drug Overdose Reporting System for 2022, covering 43 states and the District of Columbia.
• A total of 63,424 unintentional and undetermined intent drug overdose deaths during 2022 were included; 92.3% had medical examiner or coroner reports.
• MHDs were identified using source documents such as medical records and categorized according to the DSM-5 criteria.
• Potential intervention opportunities within 1 month of death, such as release from institutional settings or emergency department visits, were also analyzed.

TAKEAWAY:

• In 2022, 21.9% of drug overdose deaths involved people with non–substance-related MHDs, most commonly depression (12.9%), anxiety (9.4%), and bipolar disorder (5.9%).
• Opioids were involved in 82.2% of overdose deaths, with fentanyl or its analogs present in 75.2% of cases.
• Decedents with MHDs had higher usage rates of antidepressants (9.7% vs 3.3%), benzodiazepines (15.3% vs 8.5%), and prescription opioids (16% vs 11.6%) compared with those without MHDs.
• About 24.5% of decedents with MHDs had at least one potential intervention opportunity within 1 month of death, compared with 14.6% of those without MHDs, most commonly release from an institutional setting, treatment for substance use disorder, emergency department or urgent care visit, and nonfatal overdose.

IN PRACTICE:

“This finding suggests the need to screen for SUDs [ substance use disorders] and other MHDs, which is consistent with US Preventive Services Task Force recommendations for adults in primary care settings, and the need to link and integrate treatments to prevent overdose and improve mental health,” the authors wrote.

SOURCE:

The study was led by Amanda T. Dinwiddie, MPH, Division of Overdose Prevention, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia. It was published online on August 29, 2024, in Morbidity and Mortality Weekly Report.

LIMITATIONS:

The findings might not be applicable to the entire US population. MHDs could have been undiagnosed or underreported, possibly leading to underestimation. Additionally, variations in the completeness of source documents could have affected the accuracy of identifying MHDs. Data on current or recent mental health treatment were also unavailable. Lastly, substance use disorders may have been recorded as MHDs when not specified.

DISCLOSURES:

The study funding source was not reported. The authors did not disclose any conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In 2022, nearly 22% of people who died of drug overdose had a non–substance-related mental health disorder (MHD), new data from the Centers for Disease Control and Prevention (CDC) show. Investigators say the findings point to the need for incorporating mental health care in overdose prevention efforts.

METHODOLOGY:

• The study analyzed data from the CDC’s State Unintentional Drug Overdose Reporting System for 2022, covering 43 states and the District of Columbia.
• A total of 63,424 unintentional and undetermined intent drug overdose deaths during 2022 were included; 92.3% had medical examiner or coroner reports.
• MHDs were identified using source documents such as medical records and categorized according to the DSM-5 criteria.
• Potential intervention opportunities within 1 month of death, such as release from institutional settings or emergency department visits, were also analyzed.

TAKEAWAY:

• In 2022, 21.9% of drug overdose deaths involved people with non–substance-related MHDs, most commonly depression (12.9%), anxiety (9.4%), and bipolar disorder (5.9%).
• Opioids were involved in 82.2% of overdose deaths, with fentanyl or its analogs present in 75.2% of cases.
• Decedents with MHDs had higher usage rates of antidepressants (9.7% vs 3.3%), benzodiazepines (15.3% vs 8.5%), and prescription opioids (16% vs 11.6%) compared with those without MHDs.
• About 24.5% of decedents with MHDs had at least one potential intervention opportunity within 1 month of death, compared with 14.6% of those without MHDs, most commonly release from an institutional setting, treatment for substance use disorder, emergency department or urgent care visit, and nonfatal overdose.

IN PRACTICE:

“This finding suggests the need to screen for SUDs [ substance use disorders] and other MHDs, which is consistent with US Preventive Services Task Force recommendations for adults in primary care settings, and the need to link and integrate treatments to prevent overdose and improve mental health,” the authors wrote.

SOURCE:

The study was led by Amanda T. Dinwiddie, MPH, Division of Overdose Prevention, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia. It was published online on August 29, 2024, in Morbidity and Mortality Weekly Report.

LIMITATIONS:

The findings might not be applicable to the entire US population. MHDs could have been undiagnosed or underreported, possibly leading to underestimation. Additionally, variations in the completeness of source documents could have affected the accuracy of identifying MHDs. Data on current or recent mental health treatment were also unavailable. Lastly, substance use disorders may have been recorded as MHDs when not specified.

DISCLOSURES:

The study funding source was not reported. The authors did not disclose any conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

A growing amount of data is demonstrating that new fathers are likely to develop depression in the perinatal period. Anxiety and stress during fatherhood receive less research attention than do anxiety and stress during motherhood. 

Longitudinal data tracking the evolution of men’s mental health following the birth of the first child are even rarer, especially in the French population. Only two studies of the subject have been conducted. They were dedicated solely to paternal depression and limited to the first 4 months post partum. Better understanding of the risk in the population can not only help identify public health issues, but also aid in defining targeted preventive approaches.

French researchers in epidemiology and public health sought to expand our knowledge of the mental health trajectories of new fathers using 9 years of data from the CONSTANCES cohort. Within this cohort, participants filled out self-administered questionnaires annually. They declared their parental status and the presence of mental illnesses. They also completed questionnaires to assess mental health, such as the Center for Epidemiologic Studies Depression Scale for depression and the General Health Questionnaire for depressive, anxious, and somatic disorders. Thresholds for each score were established to characterize the severity of symptoms. In addition, the researchers analyzed all factors (eg, sociodemographic, psychosocial, lifestyle, professional, family, or cultural) that potentially are associated with poor mental health and were available within the questionnaires. 

The study included 6299 men who had their first child and for whom at least one mental health measure was collected during the follow-up period. These men had an average age of 38 years at inclusion, 88% lived with a partner, and 85% were employed. Overall, 7.9% of this male cohort self-reported a mental illness during the study, with 5.6% of illnesses occurring before the child’s birth and 9.7% after. Anxiety affected 6.5% of the cohort, and it was more pronounced after the birth than before (7.8% after vs 4.9% before). 

The rate of clinically significant symptoms averaged 23.2% during the study period, increasing from 18.3% to 25.2% after the birth. The discrepancy between the self-declared diagnosis by new fathers and the symptom-related score highlights underreporting or insufficient awareness among men. 

After conducting a latent class analysis, the researchers identified three homogeneous subgroups of men who had comparable mental health trajectories over time. The first group (90.3% of the cohort) maintained a constant and low risk for mental illnesses. The second (4.1%) presented a high and generally constant risk over time. Finally, 5.6% of the cohort had a temporarily high risk in the 2-4 years surrounding the birth.

The risk factors associated with being at a transiently high risk for mental illness were, in order of descending significance, not having a job, having had at least one negative experience during childhood, forgoing healthcare for financial reasons, and being aged 35-39 years (adjusted odds ratio [AOR] between 3.01 and 1.61). The risk factors associated with a high and constant mental illness risk were, in order of descending significance, being aged 60 years or older, not having a job, not living with a partner, being aged 40-44 years, and having other children in the following years (AOR between 3.79 and 1.85). 

The authors noted that the risk factors for mental health challenges associated with fatherhood do not imply causality, the meaning of which would also need further study. They contended that French fathers, who on average are entitled to 2 weeks of paid paternity leave, may struggle to manage their time, professional responsibilities, and parenting duties. Consequently, they may experience dissatisfaction and difficulty seeking support, assistance, or a mental health diagnosis, especially in the face of a mental health risk to which they are less attuned than women.

This story was translated from Univadis France, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A growing amount of data is demonstrating that new fathers are likely to develop depression in the perinatal period. Anxiety and stress during fatherhood receive less research attention than do anxiety and stress during motherhood. 

Longitudinal data tracking the evolution of men’s mental health following the birth of the first child are even rarer, especially in the French population. Only two studies of the subject have been conducted. They were dedicated solely to paternal depression and limited to the first 4 months post partum. Better understanding of the risk in the population can not only help identify public health issues, but also aid in defining targeted preventive approaches.

French researchers in epidemiology and public health sought to expand our knowledge of the mental health trajectories of new fathers using 9 years of data from the CONSTANCES cohort. Within this cohort, participants filled out self-administered questionnaires annually. They declared their parental status and the presence of mental illnesses. They also completed questionnaires to assess mental health, such as the Center for Epidemiologic Studies Depression Scale for depression and the General Health Questionnaire for depressive, anxious, and somatic disorders. Thresholds for each score were established to characterize the severity of symptoms. In addition, the researchers analyzed all factors (eg, sociodemographic, psychosocial, lifestyle, professional, family, or cultural) that potentially are associated with poor mental health and were available within the questionnaires. 

The study included 6299 men who had their first child and for whom at least one mental health measure was collected during the follow-up period. These men had an average age of 38 years at inclusion, 88% lived with a partner, and 85% were employed. Overall, 7.9% of this male cohort self-reported a mental illness during the study, with 5.6% of illnesses occurring before the child’s birth and 9.7% after. Anxiety affected 6.5% of the cohort, and it was more pronounced after the birth than before (7.8% after vs 4.9% before). 

The rate of clinically significant symptoms averaged 23.2% during the study period, increasing from 18.3% to 25.2% after the birth. The discrepancy between the self-declared diagnosis by new fathers and the symptom-related score highlights underreporting or insufficient awareness among men. 

After conducting a latent class analysis, the researchers identified three homogeneous subgroups of men who had comparable mental health trajectories over time. The first group (90.3% of the cohort) maintained a constant and low risk for mental illnesses. The second (4.1%) presented a high and generally constant risk over time. Finally, 5.6% of the cohort had a temporarily high risk in the 2-4 years surrounding the birth.

The risk factors associated with being at a transiently high risk for mental illness were, in order of descending significance, not having a job, having had at least one negative experience during childhood, forgoing healthcare for financial reasons, and being aged 35-39 years (adjusted odds ratio [AOR] between 3.01 and 1.61). The risk factors associated with a high and constant mental illness risk were, in order of descending significance, being aged 60 years or older, not having a job, not living with a partner, being aged 40-44 years, and having other children in the following years (AOR between 3.79 and 1.85). 

The authors noted that the risk factors for mental health challenges associated with fatherhood do not imply causality, the meaning of which would also need further study. They contended that French fathers, who on average are entitled to 2 weeks of paid paternity leave, may struggle to manage their time, professional responsibilities, and parenting duties. Consequently, they may experience dissatisfaction and difficulty seeking support, assistance, or a mental health diagnosis, especially in the face of a mental health risk to which they are less attuned than women.

This story was translated from Univadis France, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A growing amount of data is demonstrating that new fathers are likely to develop depression in the perinatal period. Anxiety and stress during fatherhood receive less research attention than do anxiety and stress during motherhood. 

Longitudinal data tracking the evolution of men’s mental health following the birth of the first child are even rarer, especially in the French population. Only two studies of the subject have been conducted. They were dedicated solely to paternal depression and limited to the first 4 months post partum. Better understanding of the risk in the population can not only help identify public health issues, but also aid in defining targeted preventive approaches.

French researchers in epidemiology and public health sought to expand our knowledge of the mental health trajectories of new fathers using 9 years of data from the CONSTANCES cohort. Within this cohort, participants filled out self-administered questionnaires annually. They declared their parental status and the presence of mental illnesses. They also completed questionnaires to assess mental health, such as the Center for Epidemiologic Studies Depression Scale for depression and the General Health Questionnaire for depressive, anxious, and somatic disorders. Thresholds for each score were established to characterize the severity of symptoms. In addition, the researchers analyzed all factors (eg, sociodemographic, psychosocial, lifestyle, professional, family, or cultural) that potentially are associated with poor mental health and were available within the questionnaires. 

The study included 6299 men who had their first child and for whom at least one mental health measure was collected during the follow-up period. These men had an average age of 38 years at inclusion, 88% lived with a partner, and 85% were employed. Overall, 7.9% of this male cohort self-reported a mental illness during the study, with 5.6% of illnesses occurring before the child’s birth and 9.7% after. Anxiety affected 6.5% of the cohort, and it was more pronounced after the birth than before (7.8% after vs 4.9% before). 

The rate of clinically significant symptoms averaged 23.2% during the study period, increasing from 18.3% to 25.2% after the birth. The discrepancy between the self-declared diagnosis by new fathers and the symptom-related score highlights underreporting or insufficient awareness among men. 

After conducting a latent class analysis, the researchers identified three homogeneous subgroups of men who had comparable mental health trajectories over time. The first group (90.3% of the cohort) maintained a constant and low risk for mental illnesses. The second (4.1%) presented a high and generally constant risk over time. Finally, 5.6% of the cohort had a temporarily high risk in the 2-4 years surrounding the birth.

The risk factors associated with being at a transiently high risk for mental illness were, in order of descending significance, not having a job, having had at least one negative experience during childhood, forgoing healthcare for financial reasons, and being aged 35-39 years (adjusted odds ratio [AOR] between 3.01 and 1.61). The risk factors associated with a high and constant mental illness risk were, in order of descending significance, being aged 60 years or older, not having a job, not living with a partner, being aged 40-44 years, and having other children in the following years (AOR between 3.79 and 1.85). 

The authors noted that the risk factors for mental health challenges associated with fatherhood do not imply causality, the meaning of which would also need further study. They contended that French fathers, who on average are entitled to 2 weeks of paid paternity leave, may struggle to manage their time, professional responsibilities, and parenting duties. Consequently, they may experience dissatisfaction and difficulty seeking support, assistance, or a mental health diagnosis, especially in the face of a mental health risk to which they are less attuned than women.

This story was translated from Univadis France, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

High-dose psilocybin is associated with greater relief from depressive symptoms than placebo or escitalopram, with no increased risk for severe adverse events, a new meta-analysis suggests.
 

METHODOLOGY:

• Researchers conducted a network meta-analysis to evaluate the comparative effectiveness of oral monotherapy with psychedelics versus escitalopram in patients with clinically diagnosed depression.
• The meta-analysis included 811 participants (mean age, 42.49 years; 54.2% women) with clinically diagnosed depression across 15 psychedelic trials and 1968 participants (mean age, 39.35 years; 62.5% women) across five escitalopram trials.
• Trials evaluated oral monotherapy with psychedelics (psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine [MDMA], and ayahuasca), fixed-dose escitalopram (up to 20 mg/d) versus placebo, and psychedelic versus escitalopram monotherapy.
• The primary outcome was a change in depressive symptoms from baseline.

TAKEAWAY:

• Placebo responses in antidepressant trials (mean difference, 3.79; 95% CI, 0.77-6.80) and extremely low-dose psilocybin (mean difference, 3.96; 95% CI, 0.61-7.17) were better than those in psychedelic trials.
• High-dose psilocybin (20 mg or more) performed better than placebo in the antidepressant trials (mean difference, > 3). However, when comparing high-dose psilocybin with the placebo used in antidepressant trials, the effect size was smaller. The standardized mean difference dropped from 0.88 to 0.31, indicating that the effect of high-dose psilocybin was similar to that of current antidepressants.
• High-dose psilocybin was associated with a greater response than escitalopram at 10 mg (4.66; 95% CI, 1.36-7.74) and 20 mg (4.69; 95% CI, 1.64-7.54).
• No interventions were associated with an increased risk for all-cause discontinuation or severe adverse events.

IN PRACTICE:

“Taken together, our study findings suggest that among psychedelic treatments, high-dose psilocybin is more likely to reach the minimal important difference for depressive symptoms in studies with adequate blinding design, while the effect size of psilocybin was similar to that of current antidepressant drugs, showing a mean standardized mean difference of 0.3,” the authors wrote.

SOURCE:

The study was led by Tien-Wei Hsu, MD, I-Shou University and Kaohsiung Medical University, Kaohsiung City, Taiwan. It was published online in The BMJ. 

LIMITATIONS:

The study did not assess long-term effects of the interventions. Participants in the MDMA trials were primarily diagnosed with posttraumatic stress disorder, which may not be representative of the general population with depressive symptoms. Moreover, the sample size of the psychedelic trials was small. Using extremely low-dose psychedelics as a reference group may have eliminated some pharmacologic effects as these doses cannot be considered a placebo.

DISCLOSURES:

The study was supported by grants from the National Science and Technology Council. The authors declared no financial relationships with any organizations outside the submitted work in the past 3 years. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

High-dose psilocybin is associated with greater relief from depressive symptoms than placebo or escitalopram, with no increased risk for severe adverse events, a new meta-analysis suggests.
 

METHODOLOGY:

• Researchers conducted a network meta-analysis to evaluate the comparative effectiveness of oral monotherapy with psychedelics versus escitalopram in patients with clinically diagnosed depression.
• The meta-analysis included 811 participants (mean age, 42.49 years; 54.2% women) with clinically diagnosed depression across 15 psychedelic trials and 1968 participants (mean age, 39.35 years; 62.5% women) across five escitalopram trials.
• Trials evaluated oral monotherapy with psychedelics (psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine [MDMA], and ayahuasca), fixed-dose escitalopram (up to 20 mg/d) versus placebo, and psychedelic versus escitalopram monotherapy.
• The primary outcome was a change in depressive symptoms from baseline.

TAKEAWAY:

• Placebo responses in antidepressant trials (mean difference, 3.79; 95% CI, 0.77-6.80) and extremely low-dose psilocybin (mean difference, 3.96; 95% CI, 0.61-7.17) were better than those in psychedelic trials.
• High-dose psilocybin (20 mg or more) performed better than placebo in the antidepressant trials (mean difference, > 3). However, when comparing high-dose psilocybin with the placebo used in antidepressant trials, the effect size was smaller. The standardized mean difference dropped from 0.88 to 0.31, indicating that the effect of high-dose psilocybin was similar to that of current antidepressants.
• High-dose psilocybin was associated with a greater response than escitalopram at 10 mg (4.66; 95% CI, 1.36-7.74) and 20 mg (4.69; 95% CI, 1.64-7.54).
• No interventions were associated with an increased risk for all-cause discontinuation or severe adverse events.

IN PRACTICE:

“Taken together, our study findings suggest that among psychedelic treatments, high-dose psilocybin is more likely to reach the minimal important difference for depressive symptoms in studies with adequate blinding design, while the effect size of psilocybin was similar to that of current antidepressant drugs, showing a mean standardized mean difference of 0.3,” the authors wrote.

SOURCE:

The study was led by Tien-Wei Hsu, MD, I-Shou University and Kaohsiung Medical University, Kaohsiung City, Taiwan. It was published online in The BMJ. 

LIMITATIONS:

The study did not assess long-term effects of the interventions. Participants in the MDMA trials were primarily diagnosed with posttraumatic stress disorder, which may not be representative of the general population with depressive symptoms. Moreover, the sample size of the psychedelic trials was small. Using extremely low-dose psychedelics as a reference group may have eliminated some pharmacologic effects as these doses cannot be considered a placebo.

DISCLOSURES:

The study was supported by grants from the National Science and Technology Council. The authors declared no financial relationships with any organizations outside the submitted work in the past 3 years. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

High-dose psilocybin is associated with greater relief from depressive symptoms than placebo or escitalopram, with no increased risk for severe adverse events, a new meta-analysis suggests.
 

METHODOLOGY:

• Researchers conducted a network meta-analysis to evaluate the comparative effectiveness of oral monotherapy with psychedelics versus escitalopram in patients with clinically diagnosed depression.
• The meta-analysis included 811 participants (mean age, 42.49 years; 54.2% women) with clinically diagnosed depression across 15 psychedelic trials and 1968 participants (mean age, 39.35 years; 62.5% women) across five escitalopram trials.
• Trials evaluated oral monotherapy with psychedelics (psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine [MDMA], and ayahuasca), fixed-dose escitalopram (up to 20 mg/d) versus placebo, and psychedelic versus escitalopram monotherapy.
• The primary outcome was a change in depressive symptoms from baseline.

TAKEAWAY:

• Placebo responses in antidepressant trials (mean difference, 3.79; 95% CI, 0.77-6.80) and extremely low-dose psilocybin (mean difference, 3.96; 95% CI, 0.61-7.17) were better than those in psychedelic trials.
• High-dose psilocybin (20 mg or more) performed better than placebo in the antidepressant trials (mean difference, > 3). However, when comparing high-dose psilocybin with the placebo used in antidepressant trials, the effect size was smaller. The standardized mean difference dropped from 0.88 to 0.31, indicating that the effect of high-dose psilocybin was similar to that of current antidepressants.
• High-dose psilocybin was associated with a greater response than escitalopram at 10 mg (4.66; 95% CI, 1.36-7.74) and 20 mg (4.69; 95% CI, 1.64-7.54).
• No interventions were associated with an increased risk for all-cause discontinuation or severe adverse events.

IN PRACTICE:

“Taken together, our study findings suggest that among psychedelic treatments, high-dose psilocybin is more likely to reach the minimal important difference for depressive symptoms in studies with adequate blinding design, while the effect size of psilocybin was similar to that of current antidepressant drugs, showing a mean standardized mean difference of 0.3,” the authors wrote.

SOURCE:

The study was led by Tien-Wei Hsu, MD, I-Shou University and Kaohsiung Medical University, Kaohsiung City, Taiwan. It was published online in The BMJ. 

LIMITATIONS:

The study did not assess long-term effects of the interventions. Participants in the MDMA trials were primarily diagnosed with posttraumatic stress disorder, which may not be representative of the general population with depressive symptoms. Moreover, the sample size of the psychedelic trials was small. Using extremely low-dose psychedelics as a reference group may have eliminated some pharmacologic effects as these doses cannot be considered a placebo.

DISCLOSURES:

The study was supported by grants from the National Science and Technology Council. The authors declared no financial relationships with any organizations outside the submitted work in the past 3 years. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

The field of psychiatry is experiencing a transformative shift toward precision medicine, a paradigm that tailors treatment to the unique characteristics of individual patients. This approach echoes advances in fields like oncology and cardiology, where precision tools have already revolutionized patient care.

But what exactly is precision psychiatry? How does it differ from traditional psychiatry? What will it look like in clinical practice? And are we there yet?
 

Beyond One-Size-Fits-All

The prevailing “one-size-fits-all” approach in psychiatry, which relies heavily on subjective symptom reporting, often proves ineffective due to the broad heterogeneity of diagnostic categories. This can lead to a “trial-and-error” cycle in treatment, which is time-consuming, costly, and frustrating for both doctors and patients.

In contrast, precision psychiatry has the potential to identify subtypes of psychiatric disorders and tailor treatments using measurable, objective data.

“The data supporting the use of precision psychiatry are very promising, particularly for treatment-resistant depression,” Leanne Williams, PhD, professor in the Department of Psychiatry and Behavioral Sciences at Stanford University, Stanford, and director of the Stanford Center for Precision Mental Health and Wellness, Palo Alto, California, said in an interview with this news organization.

Using functional MRI (fMRI), Dr. Williams and her team have mapped and measured patients’ brain circuitry to identify eight “biotypes” of depression that reflect combinations of dysfunction in six different circuits of the brain.

They are using these biotypes to guide treatment decisions in the clinic, matching individual patients to more targeted and effective therapies.

“We’re offering functional MRI to directly assess brain function along with other measures, so precision psychiatry is happening, and it’s really wanted by patients and their families. And the data suggest that we can double the rate of good outcomes,” said Dr. Williams.

“Neuroimaging techniques, particularly fMRI, have revolutionized our ability to map and quantify circuit abnormalities. Neural circuit measurements potentially offer the most direct window into the neural bases of psychiatric symptoms and, crucially, their modulation by treatment,” Teddy Akiki, MD, clinical scholar, Department of Psychiatry and Behavioral Sciences at Stanford, California, who works with Dr. Williams, told this news organization.

Blood-based biomarkers can complement brain imaging by providing additional information to better target treatment, help predict side effects, and guide dosage adjustments.
 

Precision Tools

A team led by Alexander B. Niculescu, III, MD, PhD, has found that a panel of blood-based biomarkers can distinguish between depression and bipolar disorder, predict a person’s future risk for these disorders, and inform more tailored medication choices.

Dr. Niculescu is currently a professor of psychiatry and medical neuroscience at the Indiana University School of Medicine, Indianapolis. He will head west in September to direct the newly created Center for Precision Psychiatry at the University of Arizona College of Medicine–Phoenix.

MindX Sciences, the start-up company Dr. Niculescu cofounded, has been providing blood biomarker reports to “early adopting” doctors and patients.

“We are in the process of collecting and writing up the outcome data on the first 100 cases. The feedback we have received so far from the doctors and patients who have used it, as well as biopharma companies who have used it, has been very positive,” Dr. Niculescu told this news organization.

Another benefit of precision psychiatry lies in its potential to significantly accelerate drug development.

“By identifying specific neural circuits involved in subtypes of psychiatric conditions, we can repurpose or develop drugs that target these circuits more precisely. This approach allows for smaller, more focused trials with potentially higher success rates, which could speed up the typically slow and costly process of psychiatric drug development,” said Dr. Akiki.

Dr. Niculescu agreed. With precision psychiatry tools, “psychiatric drug development will become faster, cheaper, and more successful with the use of biomarkers and other precision tools,” he said.
 

The Future Is Already Here

The implementation and widespread adoption of precision psychiatry have several challenges.

It requires sophisticated technology and expertise, which may not be readily available in all clinical settings. Moreover, while evidence supports its use in conditions like major depression, there are fewer data on its efficacy in other psychiatric disorders, like schizophrenia.

Dr. Williams said future research should focus on expanding the evidence base for precision psychiatry across a broader range of psychiatric conditions.

Efforts to make precision tools more accessible and scalable, such as developing portable imaging technologies or more readily available biomarker tests, are also critical.

Integrating these precision tools into routine psychiatric practice will also require training and education for clinicians, as well as cost-effective solutions to make these approaches widely available.

“Mental health clinicians throughout the country are starting to employ semi-objective and objective measures in their practices, particularly self-report symptom questionnaires and pharmacogenomic assessment,” Laura Hack, MD, PhD, assistant professor, Department of Psychiatry and Behavioral Sciences, Stanford University, told this news organization.

“For precision psychiatry measures to be widely implemented, it is essential to demonstrate their reliability, clinical validity, clinical utility, and cost-effectiveness. Additionally, there is a need to develop clinical guidelines for their use, ensure that measurement tools are accessible, and educate all relevant stakeholders,” said Dr. Hack.

Right now, functional neuroimaging is used “only on a very limited basis in current clinical psychiatric practice,” Dr. Hack noted.

“We are developing standardized systems that will require less specialized expertise in functional neuroimaging and can be readily integrated into routine clinical care,” Dr. Akiki added.

Quoting William Gibson, “The future [of precision psychiatry] is already here; it’s just not evenly distributed,” said Dr. Niculescu.

Dr. Williams has disclosed relationships with One Mind PsyberGuide, Laureate Institute for Brain Research, and Et Cere Inc. Dr. Niculescu is a cofounder of MindX Sciences and is listed as inventor on a patent application filed by Indiana University. Dr. Akiki and Dr. Hack had no relevant disclosures.
 

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

The field of psychiatry is experiencing a transformative shift toward precision medicine, a paradigm that tailors treatment to the unique characteristics of individual patients. This approach echoes advances in fields like oncology and cardiology, where precision tools have already revolutionized patient care.

But what exactly is precision psychiatry? How does it differ from traditional psychiatry? What will it look like in clinical practice? And are we there yet?
 

Beyond One-Size-Fits-All

The prevailing “one-size-fits-all” approach in psychiatry, which relies heavily on subjective symptom reporting, often proves ineffective due to the broad heterogeneity of diagnostic categories. This can lead to a “trial-and-error” cycle in treatment, which is time-consuming, costly, and frustrating for both doctors and patients.

In contrast, precision psychiatry has the potential to identify subtypes of psychiatric disorders and tailor treatments using measurable, objective data.

“The data supporting the use of precision psychiatry are very promising, particularly for treatment-resistant depression,” Leanne Williams, PhD, professor in the Department of Psychiatry and Behavioral Sciences at Stanford University, Stanford, and director of the Stanford Center for Precision Mental Health and Wellness, Palo Alto, California, said in an interview with this news organization.

Using functional MRI (fMRI), Dr. Williams and her team have mapped and measured patients’ brain circuitry to identify eight “biotypes” of depression that reflect combinations of dysfunction in six different circuits of the brain.

They are using these biotypes to guide treatment decisions in the clinic, matching individual patients to more targeted and effective therapies.

“We’re offering functional MRI to directly assess brain function along with other measures, so precision psychiatry is happening, and it’s really wanted by patients and their families. And the data suggest that we can double the rate of good outcomes,” said Dr. Williams.

“Neuroimaging techniques, particularly fMRI, have revolutionized our ability to map and quantify circuit abnormalities. Neural circuit measurements potentially offer the most direct window into the neural bases of psychiatric symptoms and, crucially, their modulation by treatment,” Teddy Akiki, MD, clinical scholar, Department of Psychiatry and Behavioral Sciences at Stanford, California, who works with Dr. Williams, told this news organization.

Blood-based biomarkers can complement brain imaging by providing additional information to better target treatment, help predict side effects, and guide dosage adjustments.
 

Precision Tools

A team led by Alexander B. Niculescu, III, MD, PhD, has found that a panel of blood-based biomarkers can distinguish between depression and bipolar disorder, predict a person’s future risk for these disorders, and inform more tailored medication choices.

Dr. Niculescu is currently a professor of psychiatry and medical neuroscience at the Indiana University School of Medicine, Indianapolis. He will head west in September to direct the newly created Center for Precision Psychiatry at the University of Arizona College of Medicine–Phoenix.

MindX Sciences, the start-up company Dr. Niculescu cofounded, has been providing blood biomarker reports to “early adopting” doctors and patients.

“We are in the process of collecting and writing up the outcome data on the first 100 cases. The feedback we have received so far from the doctors and patients who have used it, as well as biopharma companies who have used it, has been very positive,” Dr. Niculescu told this news organization.

Another benefit of precision psychiatry lies in its potential to significantly accelerate drug development.

“By identifying specific neural circuits involved in subtypes of psychiatric conditions, we can repurpose or develop drugs that target these circuits more precisely. This approach allows for smaller, more focused trials with potentially higher success rates, which could speed up the typically slow and costly process of psychiatric drug development,” said Dr. Akiki.

Dr. Niculescu agreed. With precision psychiatry tools, “psychiatric drug development will become faster, cheaper, and more successful with the use of biomarkers and other precision tools,” he said.
 

The Future Is Already Here

The implementation and widespread adoption of precision psychiatry have several challenges.

It requires sophisticated technology and expertise, which may not be readily available in all clinical settings. Moreover, while evidence supports its use in conditions like major depression, there are fewer data on its efficacy in other psychiatric disorders, like schizophrenia.

Dr. Williams said future research should focus on expanding the evidence base for precision psychiatry across a broader range of psychiatric conditions.

Efforts to make precision tools more accessible and scalable, such as developing portable imaging technologies or more readily available biomarker tests, are also critical.

Integrating these precision tools into routine psychiatric practice will also require training and education for clinicians, as well as cost-effective solutions to make these approaches widely available.

“Mental health clinicians throughout the country are starting to employ semi-objective and objective measures in their practices, particularly self-report symptom questionnaires and pharmacogenomic assessment,” Laura Hack, MD, PhD, assistant professor, Department of Psychiatry and Behavioral Sciences, Stanford University, told this news organization.

“For precision psychiatry measures to be widely implemented, it is essential to demonstrate their reliability, clinical validity, clinical utility, and cost-effectiveness. Additionally, there is a need to develop clinical guidelines for their use, ensure that measurement tools are accessible, and educate all relevant stakeholders,” said Dr. Hack.

Right now, functional neuroimaging is used “only on a very limited basis in current clinical psychiatric practice,” Dr. Hack noted.

“We are developing standardized systems that will require less specialized expertise in functional neuroimaging and can be readily integrated into routine clinical care,” Dr. Akiki added.

Quoting William Gibson, “The future [of precision psychiatry] is already here; it’s just not evenly distributed,” said Dr. Niculescu.

Dr. Williams has disclosed relationships with One Mind PsyberGuide, Laureate Institute for Brain Research, and Et Cere Inc. Dr. Niculescu is a cofounder of MindX Sciences and is listed as inventor on a patent application filed by Indiana University. Dr. Akiki and Dr. Hack had no relevant disclosures.
 

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

The field of psychiatry is experiencing a transformative shift toward precision medicine, a paradigm that tailors treatment to the unique characteristics of individual patients. This approach echoes advances in fields like oncology and cardiology, where precision tools have already revolutionized patient care.

But what exactly is precision psychiatry? How does it differ from traditional psychiatry? What will it look like in clinical practice? And are we there yet?
 

Beyond One-Size-Fits-All

The prevailing “one-size-fits-all” approach in psychiatry, which relies heavily on subjective symptom reporting, often proves ineffective due to the broad heterogeneity of diagnostic categories. This can lead to a “trial-and-error” cycle in treatment, which is time-consuming, costly, and frustrating for both doctors and patients.

In contrast, precision psychiatry has the potential to identify subtypes of psychiatric disorders and tailor treatments using measurable, objective data.

“The data supporting the use of precision psychiatry are very promising, particularly for treatment-resistant depression,” Leanne Williams, PhD, professor in the Department of Psychiatry and Behavioral Sciences at Stanford University, Stanford, and director of the Stanford Center for Precision Mental Health and Wellness, Palo Alto, California, said in an interview with this news organization.

Using functional MRI (fMRI), Dr. Williams and her team have mapped and measured patients’ brain circuitry to identify eight “biotypes” of depression that reflect combinations of dysfunction in six different circuits of the brain.

They are using these biotypes to guide treatment decisions in the clinic, matching individual patients to more targeted and effective therapies.

“We’re offering functional MRI to directly assess brain function along with other measures, so precision psychiatry is happening, and it’s really wanted by patients and their families. And the data suggest that we can double the rate of good outcomes,” said Dr. Williams.

“Neuroimaging techniques, particularly fMRI, have revolutionized our ability to map and quantify circuit abnormalities. Neural circuit measurements potentially offer the most direct window into the neural bases of psychiatric symptoms and, crucially, their modulation by treatment,” Teddy Akiki, MD, clinical scholar, Department of Psychiatry and Behavioral Sciences at Stanford, California, who works with Dr. Williams, told this news organization.

Blood-based biomarkers can complement brain imaging by providing additional information to better target treatment, help predict side effects, and guide dosage adjustments.
 

Precision Tools

A team led by Alexander B. Niculescu, III, MD, PhD, has found that a panel of blood-based biomarkers can distinguish between depression and bipolar disorder, predict a person’s future risk for these disorders, and inform more tailored medication choices.

Dr. Niculescu is currently a professor of psychiatry and medical neuroscience at the Indiana University School of Medicine, Indianapolis. He will head west in September to direct the newly created Center for Precision Psychiatry at the University of Arizona College of Medicine–Phoenix.

MindX Sciences, the start-up company Dr. Niculescu cofounded, has been providing blood biomarker reports to “early adopting” doctors and patients.

“We are in the process of collecting and writing up the outcome data on the first 100 cases. The feedback we have received so far from the doctors and patients who have used it, as well as biopharma companies who have used it, has been very positive,” Dr. Niculescu told this news organization.

Another benefit of precision psychiatry lies in its potential to significantly accelerate drug development.

“By identifying specific neural circuits involved in subtypes of psychiatric conditions, we can repurpose or develop drugs that target these circuits more precisely. This approach allows for smaller, more focused trials with potentially higher success rates, which could speed up the typically slow and costly process of psychiatric drug development,” said Dr. Akiki.

Dr. Niculescu agreed. With precision psychiatry tools, “psychiatric drug development will become faster, cheaper, and more successful with the use of biomarkers and other precision tools,” he said.
 

The Future Is Already Here

The implementation and widespread adoption of precision psychiatry have several challenges.

It requires sophisticated technology and expertise, which may not be readily available in all clinical settings. Moreover, while evidence supports its use in conditions like major depression, there are fewer data on its efficacy in other psychiatric disorders, like schizophrenia.

Dr. Williams said future research should focus on expanding the evidence base for precision psychiatry across a broader range of psychiatric conditions.

Efforts to make precision tools more accessible and scalable, such as developing portable imaging technologies or more readily available biomarker tests, are also critical.

Integrating these precision tools into routine psychiatric practice will also require training and education for clinicians, as well as cost-effective solutions to make these approaches widely available.

“Mental health clinicians throughout the country are starting to employ semi-objective and objective measures in their practices, particularly self-report symptom questionnaires and pharmacogenomic assessment,” Laura Hack, MD, PhD, assistant professor, Department of Psychiatry and Behavioral Sciences, Stanford University, told this news organization.

“For precision psychiatry measures to be widely implemented, it is essential to demonstrate their reliability, clinical validity, clinical utility, and cost-effectiveness. Additionally, there is a need to develop clinical guidelines for their use, ensure that measurement tools are accessible, and educate all relevant stakeholders,” said Dr. Hack.

Right now, functional neuroimaging is used “only on a very limited basis in current clinical psychiatric practice,” Dr. Hack noted.

“We are developing standardized systems that will require less specialized expertise in functional neuroimaging and can be readily integrated into routine clinical care,” Dr. Akiki added.

Quoting William Gibson, “The future [of precision psychiatry] is already here; it’s just not evenly distributed,” said Dr. Niculescu.

Dr. Williams has disclosed relationships with One Mind PsyberGuide, Laureate Institute for Brain Research, and Et Cere Inc. Dr. Niculescu is a cofounder of MindX Sciences and is listed as inventor on a patent application filed by Indiana University. Dr. Akiki and Dr. Hack had no relevant disclosures.
 

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

I have written in my first two columns of 2024 about how the obstacles for women to access perinatal mental healthcare are not well understood. This is despite an almost uniform adoption of screening practices for postpartum depression (PPD) over the last 10-15 years in the United States, the approval and off-label use of effective pharmacologic and nonpharmacologic treatments for PPD, and the growing numbers of perinatal access programs across the country in various states and hospitals.

I want to revisit this topic because I believe it is extremely important that we get to a better understanding of the obstacles postpartum patients experience so we can flatten the curve with respect to the perinatal treatment cascade. It turns out that screening is easy but accessing care for those with a positive screen with significant depressive symptoms is an entirely distinct outcome.

Recently, a group of investigators examined the barriers to identifying and treating women for PPD. In a meta-analysis that included 32 reviews, the researchers analyzed the barriers women face when they seek help, access care, and engage in treatment for mental health issues while pregnant or in the postpartum period. The researchers found women have a wide variety of barriers to seeking and accessing care related to societal, political, organizational, interpersonal, healthcare professional, and individual factors at every level of the care pathway. In total, the researchers categorized barriers into six overarching themes and 62 sub-themes, and I want to highlight a few of the biggest contributors below.

In the meta-analysis, a major contributor to deciding to consult with a healthcare professional was a lack of understanding of what constituted a perinatal mental illness. This lack of understanding led women to ignore or minimize their symptoms. Others said that the cost of travel or arranging childcare were factors that prevented them from making an appointment with a provider. Some women reported that their healthcare professionals’ normalization of their symptoms was a barrier in the early stages of the care pathway, and others were unclear about the role a healthcare professional played in involving social services and removing their child from their care, or feared being judged as a bad mom.

One of the major societal factors identified in the study is the stigma associated with PPD. It is unfortunate that for so many postpartum patients, an extraordinary stigma associated with PPD still persists despite efforts from a large number of stakeholders, including the scientific community, advocacy groups, and celebrities who have publicly come out and described their experiences with PPD. For so many postpartum patients, there is an inability to let go of the stigma, shame, humiliation, and isolation associated with the suffering that goes along with PPD.

Another factor identified in the study as being an obstacle to care was a lack of a network to help postpartum patients navigate the shifting roles associated with new parenthood, which is magnified if a patient has developed major depressive disorder. This is why a strong social support network is critical to help women navigate the novelty of being a new mom. We were aware of this as a field nearly 30 years ago when Michael W. O’Hara, PhD, published a paper in the Archives of General Psychiatry noting that social support was an important predictor for risk of PPD.

When we talk with patients in clinic, and even when we interviewed subjects for our upcoming documentary More Than Blue, which will be completed in the fall of 2024, women in the postpartum period have cited the navigation of our current healthcare system as one of the greatest obstacles to getting care. Suffering from PPD and being handed a book of potential providers, absent someone helping to navigate that referral system, is really asking a new mom to climb a very tall mountain. Additionally, moms living in rural areas likely don’t have the sort of access to perinatal mental health services that women in more urban areas do.

It becomes increasingly clear that it is not the lack of availability of effective treatments that is the problem. As I’ve mentioned in previous columns, the last 15 years has given us a much greater understanding of the effectiveness of antidepressants as well as nonpharmacologic psychotherapies for women who may not want to be on a medicine. We now have very effective psychotherapies and there’s excitement about other new treatments that may have a role in the treatment of postpartum depression, including the use of neurosteroids, ketamine or esketamine, and psychedelics or neuromodulation such as transcranial magnetic stimulation. There is also no dearth of both well-studied treatments and even new and effective treatments that, as we move toward precision reproductive psychiatry, may be useful in tailoring treatment for patients.

If we’re looking to understand the anatomy of the perinatal treatment cascade, finally systematically evaluating these barriers may lead us down a path to understand how to build the bridge to postpartum wellness for women who are suffering. While what’s on the horizon is very exciting, we still have yet to address these barriers that prevent women from accessing this expanding array of treatment options. That is, in fact, the challenge to patients, their families, advocacy groups, political organizations, and society in general. The bridging of that gap is a burden that we all share as we try to mitigate the suffering associated with such an exquisitely treatable illness while access to treatment still feels beyond reach of so many postpartum persons around us.

As we continue our research on new treatments, we should keep in mind that they will be of no value unless we understand how to facilitate access to these treatments for the greatest number of patients. This endeavor really highlights the importance of health services research and implementation science, and that we need to be partnering early and often with colleagues if we are to truly achieve this goal.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com

I have written in my first two columns of 2024 about how the obstacles for women to access perinatal mental healthcare are not well understood. This is despite an almost uniform adoption of screening practices for postpartum depression (PPD) over the last 10-15 years in the United States, the approval and off-label use of effective pharmacologic and nonpharmacologic treatments for PPD, and the growing numbers of perinatal access programs across the country in various states and hospitals.

I want to revisit this topic because I believe it is extremely important that we get to a better understanding of the obstacles postpartum patients experience so we can flatten the curve with respect to the perinatal treatment cascade. It turns out that screening is easy but accessing care for those with a positive screen with significant depressive symptoms is an entirely distinct outcome.

Recently, a group of investigators examined the barriers to identifying and treating women for PPD. In a meta-analysis that included 32 reviews, the researchers analyzed the barriers women face when they seek help, access care, and engage in treatment for mental health issues while pregnant or in the postpartum period. The researchers found women have a wide variety of barriers to seeking and accessing care related to societal, political, organizational, interpersonal, healthcare professional, and individual factors at every level of the care pathway. In total, the researchers categorized barriers into six overarching themes and 62 sub-themes, and I want to highlight a few of the biggest contributors below.

In the meta-analysis, a major contributor to deciding to consult with a healthcare professional was a lack of understanding of what constituted a perinatal mental illness. This lack of understanding led women to ignore or minimize their symptoms. Others said that the cost of travel or arranging childcare were factors that prevented them from making an appointment with a provider. Some women reported that their healthcare professionals’ normalization of their symptoms was a barrier in the early stages of the care pathway, and others were unclear about the role a healthcare professional played in involving social services and removing their child from their care, or feared being judged as a bad mom.

One of the major societal factors identified in the study is the stigma associated with PPD. It is unfortunate that for so many postpartum patients, an extraordinary stigma associated with PPD still persists despite efforts from a large number of stakeholders, including the scientific community, advocacy groups, and celebrities who have publicly come out and described their experiences with PPD. For so many postpartum patients, there is an inability to let go of the stigma, shame, humiliation, and isolation associated with the suffering that goes along with PPD.

Another factor identified in the study as being an obstacle to care was a lack of a network to help postpartum patients navigate the shifting roles associated with new parenthood, which is magnified if a patient has developed major depressive disorder. This is why a strong social support network is critical to help women navigate the novelty of being a new mom. We were aware of this as a field nearly 30 years ago when Michael W. O’Hara, PhD, published a paper in the Archives of General Psychiatry noting that social support was an important predictor for risk of PPD.

When we talk with patients in clinic, and even when we interviewed subjects for our upcoming documentary More Than Blue, which will be completed in the fall of 2024, women in the postpartum period have cited the navigation of our current healthcare system as one of the greatest obstacles to getting care. Suffering from PPD and being handed a book of potential providers, absent someone helping to navigate that referral system, is really asking a new mom to climb a very tall mountain. Additionally, moms living in rural areas likely don’t have the sort of access to perinatal mental health services that women in more urban areas do.

It becomes increasingly clear that it is not the lack of availability of effective treatments that is the problem. As I’ve mentioned in previous columns, the last 15 years has given us a much greater understanding of the effectiveness of antidepressants as well as nonpharmacologic psychotherapies for women who may not want to be on a medicine. We now have very effective psychotherapies and there’s excitement about other new treatments that may have a role in the treatment of postpartum depression, including the use of neurosteroids, ketamine or esketamine, and psychedelics or neuromodulation such as transcranial magnetic stimulation. There is also no dearth of both well-studied treatments and even new and effective treatments that, as we move toward precision reproductive psychiatry, may be useful in tailoring treatment for patients.

If we’re looking to understand the anatomy of the perinatal treatment cascade, finally systematically evaluating these barriers may lead us down a path to understand how to build the bridge to postpartum wellness for women who are suffering. While what’s on the horizon is very exciting, we still have yet to address these barriers that prevent women from accessing this expanding array of treatment options. That is, in fact, the challenge to patients, their families, advocacy groups, political organizations, and society in general. The bridging of that gap is a burden that we all share as we try to mitigate the suffering associated with such an exquisitely treatable illness while access to treatment still feels beyond reach of so many postpartum persons around us.

As we continue our research on new treatments, we should keep in mind that they will be of no value unless we understand how to facilitate access to these treatments for the greatest number of patients. This endeavor really highlights the importance of health services research and implementation science, and that we need to be partnering early and often with colleagues if we are to truly achieve this goal.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com

I have written in my first two columns of 2024 about how the obstacles for women to access perinatal mental healthcare are not well understood. This is despite an almost uniform adoption of screening practices for postpartum depression (PPD) over the last 10-15 years in the United States, the approval and off-label use of effective pharmacologic and nonpharmacologic treatments for PPD, and the growing numbers of perinatal access programs across the country in various states and hospitals.

I want to revisit this topic because I believe it is extremely important that we get to a better understanding of the obstacles postpartum patients experience so we can flatten the curve with respect to the perinatal treatment cascade. It turns out that screening is easy but accessing care for those with a positive screen with significant depressive symptoms is an entirely distinct outcome.

Recently, a group of investigators examined the barriers to identifying and treating women for PPD. In a meta-analysis that included 32 reviews, the researchers analyzed the barriers women face when they seek help, access care, and engage in treatment for mental health issues while pregnant or in the postpartum period. The researchers found women have a wide variety of barriers to seeking and accessing care related to societal, political, organizational, interpersonal, healthcare professional, and individual factors at every level of the care pathway. In total, the researchers categorized barriers into six overarching themes and 62 sub-themes, and I want to highlight a few of the biggest contributors below.

In the meta-analysis, a major contributor to deciding to consult with a healthcare professional was a lack of understanding of what constituted a perinatal mental illness. This lack of understanding led women to ignore or minimize their symptoms. Others said that the cost of travel or arranging childcare were factors that prevented them from making an appointment with a provider. Some women reported that their healthcare professionals’ normalization of their symptoms was a barrier in the early stages of the care pathway, and others were unclear about the role a healthcare professional played in involving social services and removing their child from their care, or feared being judged as a bad mom.

One of the major societal factors identified in the study is the stigma associated with PPD. It is unfortunate that for so many postpartum patients, an extraordinary stigma associated with PPD still persists despite efforts from a large number of stakeholders, including the scientific community, advocacy groups, and celebrities who have publicly come out and described their experiences with PPD. For so many postpartum patients, there is an inability to let go of the stigma, shame, humiliation, and isolation associated with the suffering that goes along with PPD.

Another factor identified in the study as being an obstacle to care was a lack of a network to help postpartum patients navigate the shifting roles associated with new parenthood, which is magnified if a patient has developed major depressive disorder. This is why a strong social support network is critical to help women navigate the novelty of being a new mom. We were aware of this as a field nearly 30 years ago when Michael W. O’Hara, PhD, published a paper in the Archives of General Psychiatry noting that social support was an important predictor for risk of PPD.

When we talk with patients in clinic, and even when we interviewed subjects for our upcoming documentary More Than Blue, which will be completed in the fall of 2024, women in the postpartum period have cited the navigation of our current healthcare system as one of the greatest obstacles to getting care. Suffering from PPD and being handed a book of potential providers, absent someone helping to navigate that referral system, is really asking a new mom to climb a very tall mountain. Additionally, moms living in rural areas likely don’t have the sort of access to perinatal mental health services that women in more urban areas do.

It becomes increasingly clear that it is not the lack of availability of effective treatments that is the problem. As I’ve mentioned in previous columns, the last 15 years has given us a much greater understanding of the effectiveness of antidepressants as well as nonpharmacologic psychotherapies for women who may not want to be on a medicine. We now have very effective psychotherapies and there’s excitement about other new treatments that may have a role in the treatment of postpartum depression, including the use of neurosteroids, ketamine or esketamine, and psychedelics or neuromodulation such as transcranial magnetic stimulation. There is also no dearth of both well-studied treatments and even new and effective treatments that, as we move toward precision reproductive psychiatry, may be useful in tailoring treatment for patients.

If we’re looking to understand the anatomy of the perinatal treatment cascade, finally systematically evaluating these barriers may lead us down a path to understand how to build the bridge to postpartum wellness for women who are suffering. While what’s on the horizon is very exciting, we still have yet to address these barriers that prevent women from accessing this expanding array of treatment options. That is, in fact, the challenge to patients, their families, advocacy groups, political organizations, and society in general. The bridging of that gap is a burden that we all share as we try to mitigate the suffering associated with such an exquisitely treatable illness while access to treatment still feels beyond reach of so many postpartum persons around us.

As we continue our research on new treatments, we should keep in mind that they will be of no value unless we understand how to facilitate access to these treatments for the greatest number of patients. This endeavor really highlights the importance of health services research and implementation science, and that we need to be partnering early and often with colleagues if we are to truly achieve this goal.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com

A new analysis has detected a signal of suicidal ideation associated with the glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide, especially among individuals concurrently using antidepressants or benzodiazepines. 

However, the investigators and outside experts urge caution in drawing any firm conclusions based on the study’s observations. 

“Clinicians should not interpret these results as proof of causal relationship between suicidal ideation and semaglutide, as our pharmacovigilance study showed an association between the use of semaglutide and reports of suicidal ideation,” study investigator Georgios Schoretsanitis, MD, PhD, Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Nonetheless, “physicians prescribing semaglutide should inform their patients about the medications’ risks and assess the psychiatric history and evaluate the mental state of patients before starting treatment with semaglutide,” Dr. Schoretsanitis said. 

“For patients with history of mental disorders or suicidal ideation/behaviors/attempts, physicians should be cautious and regularly monitor their mental state while taking semaglutide. If needed, the treating physician should involve different specialists, including a psychiatrist and/or clinical psychologists,” he added. 

The study was published online on August 20 in JAMA Network Open. 
 

Emerging Concerns

GLP-1 RAs are increasingly prescribed not only for type 2 diabetes but also for weight loss. However, concerns have emerged about a potential association with suicidality, which has prompted a closer look by regulators in the United States and Europe. 

Dr. Schoretsanitis and colleagues evaluated potential signals of suicidality related to semaglutide and liraglutide using data from global World Health Organization database of suspected adverse drug reactions (ADRs). 

They conducted sensitivity analyses including patients with co-reported use of antidepressants and benzodiazepines and using dapagliflozin, metformin, and orlistat as comparators. 

Between November 2000 and August 2023, there were 107 cases of suicidal and/or self-injurious ADRs reported with semaglutide (median age, 48 years; 55% women) and 162 reported with liraglutide (median age 47 years; 61% women). 

The researchers noted that a “significant disproportionality” signal emerged for semaglutide-associated suicidal ideation (reporting odds ratio [ROR], 1.45), when compared with comparator drugs. 

This signal remained significant in sensitivity analyses that included patients on concurrent antidepressants (ROR, 4.45) and benzodiazepines (ROR, 4.07), “suggesting that people with anxiety and depressive disorders may be at higher probability of reporting suicidal ideation when medicated with semaglutide,” the authors wrote. 

No significant disproportionality signal was detected for liraglutide regarding suicidal ideation (ROR, 1.04). 

However, the authors noted that pooled data from previous phase 2 and 3 trials on liraglutide vs placebo for weight management identified a potential risk for suicidal ideation, with nine of 3384 participants in the liraglutide group vs two of 1941 in the placebo group reporting suicidal ideation or behavior during the trial (0.27% vs 0.10%). 
 

More Research Needed 

GLP-1 RAs “should be used cautiously until further data are available on this topic,” Dr. Schoretsanitis said. 

“Further real-world studies should investigate the risk of suicidal ideation or behavior in people treated with these drugs in every-day clinical practice. We categorically discourage off-label use of GLP1-RA and without any medical supervision,” he added.

The coauthors of an invited commentary published with the study note that between 2020 and 2023, GLP-1 RA use rose 594% in younger people, particularly in women.

This “timely and well-conducted study” by Dr. Schoretsanitis and colleagues adds “an important piece to the very relevant safety issue” related to GLP-1 RAs, wrote Francesco Salvo, MD, PhD, with Université de Bordeaux, and Jean-Luc Faillie, MD, PhD, with Université de Montpellier, both in France. 

Pending further studies, the position of the US Food and Drug Administration (FDA) recommending caution “continues to be reasonable. Whatever the cause, depression or suicidality are rare but extremely severe events and need to be prevented and managed as much as possible. 

“Waiting for more precise data, GPL-1 receptor agonists, and appetite suppressants in general, should be prescribed with great caution in patients with a history of depression or suicidal attempts, while in patients with new onset of depression without other apparent precipitants, immediate discontinuation of GLP-1 receptor agonists should be considered,” wrote Dr. Salvo and Dr. Faillie. 

Outside experts also weighed in on the study in a statement from the UK nonprofit Science Media Centre. 

The paper presents, “at best, weak evidence of an association between semaglutide and suicidality,” Ian Douglas, PhD, professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, United Kingdom, said in the statement. “Signal detection studies in pharmacovigilance databases are good for generating hypotheses but are not suitable for assessing whether there is a causal association between a drug and an outcome.”

Stephen Evans, MSc, emeritus professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, cautioned that the study has “major limitations.”

“This paper is based just on spontaneous reports which are sent to regulatory authorities in the country of the person reporting a suspected adverse reaction. These are sent by health professionals and patients to authorities, but are very subject to bias, including effects of media reporting. The evidence is extremely weak for a genuine effect in this instance,” Mr. Evans said. 

The study had no specific funding. Dr. Schoretsanitis reported receiving personal fees from HLS, Dexcel, Saladax, and Thermo Fisher outside the submitted work. Dr. Salvo and Dr. Faillie have no conflicts of interest. Dr. Douglas has received research grants from GSK and AstraZeneca. Mr. Evans has no conflicts of interest. 
 

A version of this article appeared on Medscape.com.

A new analysis has detected a signal of suicidal ideation associated with the glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide, especially among individuals concurrently using antidepressants or benzodiazepines. 

However, the investigators and outside experts urge caution in drawing any firm conclusions based on the study’s observations. 

“Clinicians should not interpret these results as proof of causal relationship between suicidal ideation and semaglutide, as our pharmacovigilance study showed an association between the use of semaglutide and reports of suicidal ideation,” study investigator Georgios Schoretsanitis, MD, PhD, Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Nonetheless, “physicians prescribing semaglutide should inform their patients about the medications’ risks and assess the psychiatric history and evaluate the mental state of patients before starting treatment with semaglutide,” Dr. Schoretsanitis said. 

“For patients with history of mental disorders or suicidal ideation/behaviors/attempts, physicians should be cautious and regularly monitor their mental state while taking semaglutide. If needed, the treating physician should involve different specialists, including a psychiatrist and/or clinical psychologists,” he added. 

The study was published online on August 20 in JAMA Network Open. 
 

Emerging Concerns

GLP-1 RAs are increasingly prescribed not only for type 2 diabetes but also for weight loss. However, concerns have emerged about a potential association with suicidality, which has prompted a closer look by regulators in the United States and Europe. 

Dr. Schoretsanitis and colleagues evaluated potential signals of suicidality related to semaglutide and liraglutide using data from global World Health Organization database of suspected adverse drug reactions (ADRs). 

They conducted sensitivity analyses including patients with co-reported use of antidepressants and benzodiazepines and using dapagliflozin, metformin, and orlistat as comparators. 

Between November 2000 and August 2023, there were 107 cases of suicidal and/or self-injurious ADRs reported with semaglutide (median age, 48 years; 55% women) and 162 reported with liraglutide (median age 47 years; 61% women). 

The researchers noted that a “significant disproportionality” signal emerged for semaglutide-associated suicidal ideation (reporting odds ratio [ROR], 1.45), when compared with comparator drugs. 

This signal remained significant in sensitivity analyses that included patients on concurrent antidepressants (ROR, 4.45) and benzodiazepines (ROR, 4.07), “suggesting that people with anxiety and depressive disorders may be at higher probability of reporting suicidal ideation when medicated with semaglutide,” the authors wrote. 

No significant disproportionality signal was detected for liraglutide regarding suicidal ideation (ROR, 1.04). 

However, the authors noted that pooled data from previous phase 2 and 3 trials on liraglutide vs placebo for weight management identified a potential risk for suicidal ideation, with nine of 3384 participants in the liraglutide group vs two of 1941 in the placebo group reporting suicidal ideation or behavior during the trial (0.27% vs 0.10%). 
 

More Research Needed 

GLP-1 RAs “should be used cautiously until further data are available on this topic,” Dr. Schoretsanitis said. 

“Further real-world studies should investigate the risk of suicidal ideation or behavior in people treated with these drugs in every-day clinical practice. We categorically discourage off-label use of GLP1-RA and without any medical supervision,” he added.

The coauthors of an invited commentary published with the study note that between 2020 and 2023, GLP-1 RA use rose 594% in younger people, particularly in women.

This “timely and well-conducted study” by Dr. Schoretsanitis and colleagues adds “an important piece to the very relevant safety issue” related to GLP-1 RAs, wrote Francesco Salvo, MD, PhD, with Université de Bordeaux, and Jean-Luc Faillie, MD, PhD, with Université de Montpellier, both in France. 

Pending further studies, the position of the US Food and Drug Administration (FDA) recommending caution “continues to be reasonable. Whatever the cause, depression or suicidality are rare but extremely severe events and need to be prevented and managed as much as possible. 

“Waiting for more precise data, GPL-1 receptor agonists, and appetite suppressants in general, should be prescribed with great caution in patients with a history of depression or suicidal attempts, while in patients with new onset of depression without other apparent precipitants, immediate discontinuation of GLP-1 receptor agonists should be considered,” wrote Dr. Salvo and Dr. Faillie. 

Outside experts also weighed in on the study in a statement from the UK nonprofit Science Media Centre. 

The paper presents, “at best, weak evidence of an association between semaglutide and suicidality,” Ian Douglas, PhD, professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, United Kingdom, said in the statement. “Signal detection studies in pharmacovigilance databases are good for generating hypotheses but are not suitable for assessing whether there is a causal association between a drug and an outcome.”

Stephen Evans, MSc, emeritus professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, cautioned that the study has “major limitations.”

“This paper is based just on spontaneous reports which are sent to regulatory authorities in the country of the person reporting a suspected adverse reaction. These are sent by health professionals and patients to authorities, but are very subject to bias, including effects of media reporting. The evidence is extremely weak for a genuine effect in this instance,” Mr. Evans said. 

The study had no specific funding. Dr. Schoretsanitis reported receiving personal fees from HLS, Dexcel, Saladax, and Thermo Fisher outside the submitted work. Dr. Salvo and Dr. Faillie have no conflicts of interest. Dr. Douglas has received research grants from GSK and AstraZeneca. Mr. Evans has no conflicts of interest. 
 

A version of this article appeared on Medscape.com.

A new analysis has detected a signal of suicidal ideation associated with the glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide, especially among individuals concurrently using antidepressants or benzodiazepines. 

However, the investigators and outside experts urge caution in drawing any firm conclusions based on the study’s observations. 

“Clinicians should not interpret these results as proof of causal relationship between suicidal ideation and semaglutide, as our pharmacovigilance study showed an association between the use of semaglutide and reports of suicidal ideation,” study investigator Georgios Schoretsanitis, MD, PhD, Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Nonetheless, “physicians prescribing semaglutide should inform their patients about the medications’ risks and assess the psychiatric history and evaluate the mental state of patients before starting treatment with semaglutide,” Dr. Schoretsanitis said. 

“For patients with history of mental disorders or suicidal ideation/behaviors/attempts, physicians should be cautious and regularly monitor their mental state while taking semaglutide. If needed, the treating physician should involve different specialists, including a psychiatrist and/or clinical psychologists,” he added. 

The study was published online on August 20 in JAMA Network Open. 
 

Emerging Concerns

GLP-1 RAs are increasingly prescribed not only for type 2 diabetes but also for weight loss. However, concerns have emerged about a potential association with suicidality, which has prompted a closer look by regulators in the United States and Europe. 

Dr. Schoretsanitis and colleagues evaluated potential signals of suicidality related to semaglutide and liraglutide using data from global World Health Organization database of suspected adverse drug reactions (ADRs). 

They conducted sensitivity analyses including patients with co-reported use of antidepressants and benzodiazepines and using dapagliflozin, metformin, and orlistat as comparators. 

Between November 2000 and August 2023, there were 107 cases of suicidal and/or self-injurious ADRs reported with semaglutide (median age, 48 years; 55% women) and 162 reported with liraglutide (median age 47 years; 61% women). 

The researchers noted that a “significant disproportionality” signal emerged for semaglutide-associated suicidal ideation (reporting odds ratio [ROR], 1.45), when compared with comparator drugs. 

This signal remained significant in sensitivity analyses that included patients on concurrent antidepressants (ROR, 4.45) and benzodiazepines (ROR, 4.07), “suggesting that people with anxiety and depressive disorders may be at higher probability of reporting suicidal ideation when medicated with semaglutide,” the authors wrote. 

No significant disproportionality signal was detected for liraglutide regarding suicidal ideation (ROR, 1.04). 

However, the authors noted that pooled data from previous phase 2 and 3 trials on liraglutide vs placebo for weight management identified a potential risk for suicidal ideation, with nine of 3384 participants in the liraglutide group vs two of 1941 in the placebo group reporting suicidal ideation or behavior during the trial (0.27% vs 0.10%). 
 

More Research Needed 

GLP-1 RAs “should be used cautiously until further data are available on this topic,” Dr. Schoretsanitis said. 

“Further real-world studies should investigate the risk of suicidal ideation or behavior in people treated with these drugs in every-day clinical practice. We categorically discourage off-label use of GLP1-RA and without any medical supervision,” he added.

The coauthors of an invited commentary published with the study note that between 2020 and 2023, GLP-1 RA use rose 594% in younger people, particularly in women.

This “timely and well-conducted study” by Dr. Schoretsanitis and colleagues adds “an important piece to the very relevant safety issue” related to GLP-1 RAs, wrote Francesco Salvo, MD, PhD, with Université de Bordeaux, and Jean-Luc Faillie, MD, PhD, with Université de Montpellier, both in France. 

Pending further studies, the position of the US Food and Drug Administration (FDA) recommending caution “continues to be reasonable. Whatever the cause, depression or suicidality are rare but extremely severe events and need to be prevented and managed as much as possible. 

“Waiting for more precise data, GPL-1 receptor agonists, and appetite suppressants in general, should be prescribed with great caution in patients with a history of depression or suicidal attempts, while in patients with new onset of depression without other apparent precipitants, immediate discontinuation of GLP-1 receptor agonists should be considered,” wrote Dr. Salvo and Dr. Faillie. 

Outside experts also weighed in on the study in a statement from the UK nonprofit Science Media Centre. 

The paper presents, “at best, weak evidence of an association between semaglutide and suicidality,” Ian Douglas, PhD, professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, United Kingdom, said in the statement. “Signal detection studies in pharmacovigilance databases are good for generating hypotheses but are not suitable for assessing whether there is a causal association between a drug and an outcome.”

Stephen Evans, MSc, emeritus professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, cautioned that the study has “major limitations.”

“This paper is based just on spontaneous reports which are sent to regulatory authorities in the country of the person reporting a suspected adverse reaction. These are sent by health professionals and patients to authorities, but are very subject to bias, including effects of media reporting. The evidence is extremely weak for a genuine effect in this instance,” Mr. Evans said. 

The study had no specific funding. Dr. Schoretsanitis reported receiving personal fees from HLS, Dexcel, Saladax, and Thermo Fisher outside the submitted work. Dr. Salvo and Dr. Faillie have no conflicts of interest. Dr. Douglas has received research grants from GSK and AstraZeneca. Mr. Evans has no conflicts of interest. 
 

A version of this article appeared on Medscape.com.