MDedge Psychiatry

Despite a higher symptom burden, patients with major depressive disorder (MDD) and a history of childhood trauma (CT) can achieve significant recovery following treatment with a combination of pharmacotherapy and psychotherapy, new research suggests.
 

Results from a meta-analysis of 29 studies from 1966 to 2019, which included almost 7,000 adults with MDD, showed that more than 60% reported a history of CT. But despite having more severe depression at baseline, those with CT benefited from active treatment. Effect sizes were comparable, and dropout rates were similar to those of their counterparts without CT.

“Evidence-based psychotherapy and pharmacotherapy should be offered to depressed patients, regardless of their childhood trauma status,” lead author Erika Kuzminskaite, MSc, a PhD candidate at Amsterdam UMC department of psychiatry, the Netherlands, told this news organization.

“Screening for childhood trauma is important to identify individuals at risk for more severe course of the disorder and post-treatment residual symptoms,” she added.

The study was published online in the Lancet Psychiatry.
 

Common and potent risk factor

The researchers note that CT is common and is a potent risk factor for depression. Previous studies have “consistently indicated significantly higher severity and persistence of depressive symptoms in adult patients with depression and a history of childhood trauma.”

Previous individual and meta-analytic studies “indicated poorer response to first-line depression treatments in patients with childhood trauma, compared to those without trauma, suggesting the need for new personalized treatments for depressed patients with childhood trauma history,” Ms. Kuzminskaite said.

“However, the evidence on poorer treatment outcomes has not been definitive, and a comprehensive meta-analysis of available findings has been lacking,” she added.

The previous meta-analyses showed high between-study heterogeneity, and some primary studies reported similar or even superior improvement for patients with CT, compared with those without such history, following treatment with evidence-based psychotherapy or pharmacotherapy.

Previous studies also did not investigate the “relative contribution of different childhood trauma types.”

To address this gap, investigators in the Childhood Trauma Meta-Analysis Study Group conducted the “largest and most comprehensive study of available evidence examining the effects of childhood trauma on the efficacy and effectiveness of first-line treatments for adults with MDD.”

To be included, a study had to focus on adults over 18 years old who had received a primary diagnosis of depression. The study had to have included an available assessment of childhood trauma, and patients were required to have undergone psychotherapy and/or pharmacotherapy for depression alone or in combination with other guideline-recommended treatments. Studies were also required to have a comparator group, when applicable, and to have reported depression severity before and after the acute treatment phase.

Of 10,505 publications, 54 trials met inclusion criteria; of these, 29 (20 randomized controlled trials and 9 open trials), encompassing 6,830 participants aged 18-85 years, included data that had been made available by authors of the various studies and were included in the current analysis.

Most studies focused on MDD; 11 trials focused on patients with chronic or treatment-resistant depression.

The primary outcome was “depression severity change from baseline to the end of the acute treatment phase” (expressed as standardized effect size – Hedges’ g).
 

Greater treatment motivation?

Of the included patients, 62% reported a history of CT. They were found to have more severe depression at baseline, compared with those without CT (g = .202; 95% confidence interval, 0.145-0.258; I² = 0%).

The benefits from active treatment obtained by these patients with CT were similar to the benefits obtained by their counterparts without CT (between-group treatment effect difference: g = .016; 95% CI, –0.094-0.125; I² = 44.3%).

No significant difference in active treatment effects (in comparison with control condition) was found between individuals with and those without CT (g = .605; 95% CI, 0.294-0.916; I² = 58.0%; and g = .178; 95% CI, –0.195-0.552; I² = 67.5%, respectively; between-group difference P = .051).

Dropout rates were similar for the participants with and those without CT (risk ratio, 1.063; 95% CI, 0.945-1.195; I² = 0%).

“Findings did not significantly differ by childhood trauma type, study design, depression diagnosis, assessment method of childhood trauma, study quality, year, or treatment type or length,” the authors report.

The findings did, however, differ by country, with North American studies showing larger treatment effects for patients with CT, compared with studies conducted in Asian-Pacific countries (g = 0.150; 95% CI, 0.030-0.269; vs. g = 0.255; 95% CI, –0.508- –0.002, respectively; corrected false discovery rate, 0.0080). “However, because of limited power, these findings should be interpreted with caution,” the authors warn.

“It could be a chance finding and is certainly not causal,” Ms. Kuzminskaite suggested.

Most studies (21 of the 29) had a “moderate to high risk of bias.” But when the researchers conducted a sensitivity analysis in the low-bias studies, they found that results were similar to those of the primary analysis that included all the studies.

“Treatments were similarly effective for patients with and without childhood trauma, with slightly larger active treatment (vs. control condition – placebo, wait list, care-as-usual) effects for patients with childhood trauma history,” Ms. Kuzminskaite said.

“Some evidence suggests that patients with childhood trauma are characterized by greater treatment motivation,” she noted. Moreover, “they are also more severely depressed prior to treatment [and] thus have more room for improvement.”
 

‘Hopeful message’

Commenting for this news organization, Yvette Sheline, MD, McLure professor of psychiatry, radiology, and neurology and director of the center for neuromodulation in depression and Stress, University of Pennsylvania, Philadelphia, called it a “well-executed” and “straightforward” study “with clear-cut findings.”

Dr. Sheline, the director of the section on mood, anxiety, and trauma, who was not involved with the study, agrees with the authors’ conclusions – “to use evidence-based treatments for depression in all patients,” with or without a history of CT.

In an accompanying editorial, Antoine Yrondi, MD, PhD, of Université de Toulouse (France), called the findings “important and encouraging” but cautioned that CT could be associated with conditions other than depression, which could make MDD “more difficult to treat.”

Nevertheless, the meta-analysis “delivers a hopeful message to patients with childhood trauma that evidence-based psychotherapy and pharmacotherapy could improve depressive symptoms,” Dr. Yrondi said.

Dr. Yrondi encouraged physicians not to neglect CT in patients with MDD. “For this, it is important that physicians are trained to evaluate childhood trauma and to take it into account in their daily practice.”

No source of funding for the study was listed. The authors and Dr. Sheline have disclosed no relevant financial relationships. Dr. Yrondi has received speaker’s honoraria from AstraZeneca, Janssen, Lundbeck, Otsuka, and Jazz and has carried out clinical studies in relation to the development of a medicine for Janssen and Lundbeck that are unrelated to this work.

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

Despite a higher symptom burden, patients with major depressive disorder (MDD) and a history of childhood trauma (CT) can achieve significant recovery following treatment with a combination of pharmacotherapy and psychotherapy, new research suggests.
 

Results from a meta-analysis of 29 studies from 1966 to 2019, which included almost 7,000 adults with MDD, showed that more than 60% reported a history of CT. But despite having more severe depression at baseline, those with CT benefited from active treatment. Effect sizes were comparable, and dropout rates were similar to those of their counterparts without CT.

“Evidence-based psychotherapy and pharmacotherapy should be offered to depressed patients, regardless of their childhood trauma status,” lead author Erika Kuzminskaite, MSc, a PhD candidate at Amsterdam UMC department of psychiatry, the Netherlands, told this news organization.

“Screening for childhood trauma is important to identify individuals at risk for more severe course of the disorder and post-treatment residual symptoms,” she added.

The study was published online in the Lancet Psychiatry.
 

Common and potent risk factor

The researchers note that CT is common and is a potent risk factor for depression. Previous studies have “consistently indicated significantly higher severity and persistence of depressive symptoms in adult patients with depression and a history of childhood trauma.”

Previous individual and meta-analytic studies “indicated poorer response to first-line depression treatments in patients with childhood trauma, compared to those without trauma, suggesting the need for new personalized treatments for depressed patients with childhood trauma history,” Ms. Kuzminskaite said.

“However, the evidence on poorer treatment outcomes has not been definitive, and a comprehensive meta-analysis of available findings has been lacking,” she added.

The previous meta-analyses showed high between-study heterogeneity, and some primary studies reported similar or even superior improvement for patients with CT, compared with those without such history, following treatment with evidence-based psychotherapy or pharmacotherapy.

Previous studies also did not investigate the “relative contribution of different childhood trauma types.”

To address this gap, investigators in the Childhood Trauma Meta-Analysis Study Group conducted the “largest and most comprehensive study of available evidence examining the effects of childhood trauma on the efficacy and effectiveness of first-line treatments for adults with MDD.”

To be included, a study had to focus on adults over 18 years old who had received a primary diagnosis of depression. The study had to have included an available assessment of childhood trauma, and patients were required to have undergone psychotherapy and/or pharmacotherapy for depression alone or in combination with other guideline-recommended treatments. Studies were also required to have a comparator group, when applicable, and to have reported depression severity before and after the acute treatment phase.

Of 10,505 publications, 54 trials met inclusion criteria; of these, 29 (20 randomized controlled trials and 9 open trials), encompassing 6,830 participants aged 18-85 years, included data that had been made available by authors of the various studies and were included in the current analysis.

Most studies focused on MDD; 11 trials focused on patients with chronic or treatment-resistant depression.

The primary outcome was “depression severity change from baseline to the end of the acute treatment phase” (expressed as standardized effect size – Hedges’ g).
 

Greater treatment motivation?

Of the included patients, 62% reported a history of CT. They were found to have more severe depression at baseline, compared with those without CT (g = .202; 95% confidence interval, 0.145-0.258; I² = 0%).

The benefits from active treatment obtained by these patients with CT were similar to the benefits obtained by their counterparts without CT (between-group treatment effect difference: g = .016; 95% CI, –0.094-0.125; I² = 44.3%).

No significant difference in active treatment effects (in comparison with control condition) was found between individuals with and those without CT (g = .605; 95% CI, 0.294-0.916; I² = 58.0%; and g = .178; 95% CI, –0.195-0.552; I² = 67.5%, respectively; between-group difference P = .051).

Dropout rates were similar for the participants with and those without CT (risk ratio, 1.063; 95% CI, 0.945-1.195; I² = 0%).

“Findings did not significantly differ by childhood trauma type, study design, depression diagnosis, assessment method of childhood trauma, study quality, year, or treatment type or length,” the authors report.

The findings did, however, differ by country, with North American studies showing larger treatment effects for patients with CT, compared with studies conducted in Asian-Pacific countries (g = 0.150; 95% CI, 0.030-0.269; vs. g = 0.255; 95% CI, –0.508- –0.002, respectively; corrected false discovery rate, 0.0080). “However, because of limited power, these findings should be interpreted with caution,” the authors warn.

“It could be a chance finding and is certainly not causal,” Ms. Kuzminskaite suggested.

Most studies (21 of the 29) had a “moderate to high risk of bias.” But when the researchers conducted a sensitivity analysis in the low-bias studies, they found that results were similar to those of the primary analysis that included all the studies.

“Treatments were similarly effective for patients with and without childhood trauma, with slightly larger active treatment (vs. control condition – placebo, wait list, care-as-usual) effects for patients with childhood trauma history,” Ms. Kuzminskaite said.

“Some evidence suggests that patients with childhood trauma are characterized by greater treatment motivation,” she noted. Moreover, “they are also more severely depressed prior to treatment [and] thus have more room for improvement.”
 

‘Hopeful message’

Commenting for this news organization, Yvette Sheline, MD, McLure professor of psychiatry, radiology, and neurology and director of the center for neuromodulation in depression and Stress, University of Pennsylvania, Philadelphia, called it a “well-executed” and “straightforward” study “with clear-cut findings.”

Dr. Sheline, the director of the section on mood, anxiety, and trauma, who was not involved with the study, agrees with the authors’ conclusions – “to use evidence-based treatments for depression in all patients,” with or without a history of CT.

In an accompanying editorial, Antoine Yrondi, MD, PhD, of Université de Toulouse (France), called the findings “important and encouraging” but cautioned that CT could be associated with conditions other than depression, which could make MDD “more difficult to treat.”

Nevertheless, the meta-analysis “delivers a hopeful message to patients with childhood trauma that evidence-based psychotherapy and pharmacotherapy could improve depressive symptoms,” Dr. Yrondi said.

Dr. Yrondi encouraged physicians not to neglect CT in patients with MDD. “For this, it is important that physicians are trained to evaluate childhood trauma and to take it into account in their daily practice.”

No source of funding for the study was listed. The authors and Dr. Sheline have disclosed no relevant financial relationships. Dr. Yrondi has received speaker’s honoraria from AstraZeneca, Janssen, Lundbeck, Otsuka, and Jazz and has carried out clinical studies in relation to the development of a medicine for Janssen and Lundbeck that are unrelated to this work.

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

Despite a higher symptom burden, patients with major depressive disorder (MDD) and a history of childhood trauma (CT) can achieve significant recovery following treatment with a combination of pharmacotherapy and psychotherapy, new research suggests.
 

Results from a meta-analysis of 29 studies from 1966 to 2019, which included almost 7,000 adults with MDD, showed that more than 60% reported a history of CT. But despite having more severe depression at baseline, those with CT benefited from active treatment. Effect sizes were comparable, and dropout rates were similar to those of their counterparts without CT.

“Evidence-based psychotherapy and pharmacotherapy should be offered to depressed patients, regardless of their childhood trauma status,” lead author Erika Kuzminskaite, MSc, a PhD candidate at Amsterdam UMC department of psychiatry, the Netherlands, told this news organization.

“Screening for childhood trauma is important to identify individuals at risk for more severe course of the disorder and post-treatment residual symptoms,” she added.

The study was published online in the Lancet Psychiatry.
 

Common and potent risk factor

The researchers note that CT is common and is a potent risk factor for depression. Previous studies have “consistently indicated significantly higher severity and persistence of depressive symptoms in adult patients with depression and a history of childhood trauma.”

Previous individual and meta-analytic studies “indicated poorer response to first-line depression treatments in patients with childhood trauma, compared to those without trauma, suggesting the need for new personalized treatments for depressed patients with childhood trauma history,” Ms. Kuzminskaite said.

“However, the evidence on poorer treatment outcomes has not been definitive, and a comprehensive meta-analysis of available findings has been lacking,” she added.

The previous meta-analyses showed high between-study heterogeneity, and some primary studies reported similar or even superior improvement for patients with CT, compared with those without such history, following treatment with evidence-based psychotherapy or pharmacotherapy.

Previous studies also did not investigate the “relative contribution of different childhood trauma types.”

To address this gap, investigators in the Childhood Trauma Meta-Analysis Study Group conducted the “largest and most comprehensive study of available evidence examining the effects of childhood trauma on the efficacy and effectiveness of first-line treatments for adults with MDD.”

To be included, a study had to focus on adults over 18 years old who had received a primary diagnosis of depression. The study had to have included an available assessment of childhood trauma, and patients were required to have undergone psychotherapy and/or pharmacotherapy for depression alone or in combination with other guideline-recommended treatments. Studies were also required to have a comparator group, when applicable, and to have reported depression severity before and after the acute treatment phase.

Of 10,505 publications, 54 trials met inclusion criteria; of these, 29 (20 randomized controlled trials and 9 open trials), encompassing 6,830 participants aged 18-85 years, included data that had been made available by authors of the various studies and were included in the current analysis.

Most studies focused on MDD; 11 trials focused on patients with chronic or treatment-resistant depression.

The primary outcome was “depression severity change from baseline to the end of the acute treatment phase” (expressed as standardized effect size – Hedges’ g).
 

Greater treatment motivation?

Of the included patients, 62% reported a history of CT. They were found to have more severe depression at baseline, compared with those without CT (g = .202; 95% confidence interval, 0.145-0.258; I² = 0%).

The benefits from active treatment obtained by these patients with CT were similar to the benefits obtained by their counterparts without CT (between-group treatment effect difference: g = .016; 95% CI, –0.094-0.125; I² = 44.3%).

No significant difference in active treatment effects (in comparison with control condition) was found between individuals with and those without CT (g = .605; 95% CI, 0.294-0.916; I² = 58.0%; and g = .178; 95% CI, –0.195-0.552; I² = 67.5%, respectively; between-group difference P = .051).

Dropout rates were similar for the participants with and those without CT (risk ratio, 1.063; 95% CI, 0.945-1.195; I² = 0%).

“Findings did not significantly differ by childhood trauma type, study design, depression diagnosis, assessment method of childhood trauma, study quality, year, or treatment type or length,” the authors report.

The findings did, however, differ by country, with North American studies showing larger treatment effects for patients with CT, compared with studies conducted in Asian-Pacific countries (g = 0.150; 95% CI, 0.030-0.269; vs. g = 0.255; 95% CI, –0.508- –0.002, respectively; corrected false discovery rate, 0.0080). “However, because of limited power, these findings should be interpreted with caution,” the authors warn.

“It could be a chance finding and is certainly not causal,” Ms. Kuzminskaite suggested.

Most studies (21 of the 29) had a “moderate to high risk of bias.” But when the researchers conducted a sensitivity analysis in the low-bias studies, they found that results were similar to those of the primary analysis that included all the studies.

“Treatments were similarly effective for patients with and without childhood trauma, with slightly larger active treatment (vs. control condition – placebo, wait list, care-as-usual) effects for patients with childhood trauma history,” Ms. Kuzminskaite said.

“Some evidence suggests that patients with childhood trauma are characterized by greater treatment motivation,” she noted. Moreover, “they are also more severely depressed prior to treatment [and] thus have more room for improvement.”
 

‘Hopeful message’

Commenting for this news organization, Yvette Sheline, MD, McLure professor of psychiatry, radiology, and neurology and director of the center for neuromodulation in depression and Stress, University of Pennsylvania, Philadelphia, called it a “well-executed” and “straightforward” study “with clear-cut findings.”

Dr. Sheline, the director of the section on mood, anxiety, and trauma, who was not involved with the study, agrees with the authors’ conclusions – “to use evidence-based treatments for depression in all patients,” with or without a history of CT.

In an accompanying editorial, Antoine Yrondi, MD, PhD, of Université de Toulouse (France), called the findings “important and encouraging” but cautioned that CT could be associated with conditions other than depression, which could make MDD “more difficult to treat.”

Nevertheless, the meta-analysis “delivers a hopeful message to patients with childhood trauma that evidence-based psychotherapy and pharmacotherapy could improve depressive symptoms,” Dr. Yrondi said.

Dr. Yrondi encouraged physicians not to neglect CT in patients with MDD. “For this, it is important that physicians are trained to evaluate childhood trauma and to take it into account in their daily practice.”

No source of funding for the study was listed. The authors and Dr. Sheline have disclosed no relevant financial relationships. Dr. Yrondi has received speaker’s honoraria from AstraZeneca, Janssen, Lundbeck, Otsuka, and Jazz and has carried out clinical studies in relation to the development of a medicine for Janssen and Lundbeck that are unrelated to this work.

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

Nightmares in healthy middle-aged and older adults may be an independent risk factor for cognitive decline and dementia, particularly in men, new research suggests.

Results from a large cohort study showed that healthy middle-aged adults who had bad dreams at least once a week were four times more likely to experience cognitive decline over the following decade, and older adults were twice as likely to be diagnosed with dementia, compared with peers who never had bad dreams.

Frequent nightmares may “identify people who are at high risk of developing dementia in the future, several years or decades before the characteristic memory and thinking problems emerge,” study investigator Abidemi Otaiku, BMBS, University of Birmingham, England, said in an interview.

“This would be the optimum time for doctors to intervene to try and slow down or prevent dementia from developing,” Dr. Otaiku said.

The findings were published online in The Lancet journal eClinicalMedicine).
 

Distressing dreams

Distressing dreams have been previously associated with faster cognitive decline and increased dementia risk in patients with Parkinson’s disease (PD), but whether the same holds for individuals from the general population without PD is unknown.

To investigate, Dr. Otaiku examined data from three community-based cohorts in the United States. This included 605 middle-aged adults (aged 35-64 years) who were followed for up to 13 years and 2,600 adults aged 79 and older who were followed for up to 7 years. All were considered cognitively normal at baseline.

The prevalence of frequent distressing dreams, defined as occurring “once a week or more,” was higher in the older cohort compared with the middle-aged cohort (6.9% vs. 6.0%, respectively).

This is in line with other research that showed distressing dreams remain relatively stable throughout early adulthood and then progressively increase in prevalence from middle to older adulthood. 

After adjustment for all covariates, a higher frequency of distressing dreams was linearly and statistically significantly associated with a higher risk for cognitive decline in middle-aged adults (P = .016) and a higher risk for dementia in older adults (P = .001).

In the fully adjusted model, compared with middle-aged adults who never had bad dreams, those who reported having one or more bad dreams weekly had a fourfold risk for cognitive decline (adjusted odds ratio [aOR], 3.99; 95% confidence interval [CI], 1.07-14.85).

Older adults who had one or more bad dreams weekly had a greater than twofold increased risk for developing dementia (aOR, 2.21; 95% CI, 1.35-3.62).
 

Early days

In sex-stratified analyses, distressing dreams were strongly and statistically significantly associated with cognitive decline and dementia in men, but were only weakly and nonsignificantly associated with cognitive decline and dementia in women.

Dr. Otaiku said he suspects some individuals in the preclinical phase of dementia have “subtle neurodegeneration occurring over time in the right frontal lobe: the area of the brain that helps to downregulate negative emotions whilst we are awake, and also whilst we are dreaming.”

This could result in “depression and anxiety in the day, and nightmares and bad dreams during the night,” he said.

It is possible that treatment for frequent nightmares may help to slow cognitive decline and delay or prevent dementia, Dr. Otaiku added.

He noted that prazosin is used to treat nightmares and has been shown to prevent memory decline and reduce amyloid B generation in preclinical studies of Alzheimer’s disease.

“This is an exciting prospect [but] it is still early days and we will need research to see whether treating nightmares might help to reduce dementia risk down the line,” Dr. Otaiku said.
 

Credible research

In an interview regarding these findings, Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said: “This is credible research consistent with the idea that sleep disturbances may be a risk factor or warning sign of cognitive decline.”

She added that “what’s novel here” is the researchers examined distressing dreams – not more physical sleep disturbances and disorders such as insomnia or apnea.

“However, nightmares can disturb sleep in the same way these disorders do by waking people up in the middle of the night,” said Dr. Carrillo, who was not involved with the study.

“Previous research has pointed to nightmares being indicative of potential changes in the brain that can precede other dementias like Parkinson’s disease. More research is needed to tease out what exactly is happening in the brain during nightmares that may be contributing to this increased risk,” she said.

Dr. Carrillo noted that “getting good sleep” is important for overall health, which includes brain health.

“The good news is there are treatments – both drug and nondrug – that can help address sleep disturbances,” she added.

This study received no external funding. Dr. Otaiku and Dr. Carrillo have reported no relevant financial relationships.

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

Nightmares in healthy middle-aged and older adults may be an independent risk factor for cognitive decline and dementia, particularly in men, new research suggests.

Results from a large cohort study showed that healthy middle-aged adults who had bad dreams at least once a week were four times more likely to experience cognitive decline over the following decade, and older adults were twice as likely to be diagnosed with dementia, compared with peers who never had bad dreams.

Frequent nightmares may “identify people who are at high risk of developing dementia in the future, several years or decades before the characteristic memory and thinking problems emerge,” study investigator Abidemi Otaiku, BMBS, University of Birmingham, England, said in an interview.

“This would be the optimum time for doctors to intervene to try and slow down or prevent dementia from developing,” Dr. Otaiku said.

The findings were published online in The Lancet journal eClinicalMedicine).
 

Distressing dreams

Distressing dreams have been previously associated with faster cognitive decline and increased dementia risk in patients with Parkinson’s disease (PD), but whether the same holds for individuals from the general population without PD is unknown.

To investigate, Dr. Otaiku examined data from three community-based cohorts in the United States. This included 605 middle-aged adults (aged 35-64 years) who were followed for up to 13 years and 2,600 adults aged 79 and older who were followed for up to 7 years. All were considered cognitively normal at baseline.

The prevalence of frequent distressing dreams, defined as occurring “once a week or more,” was higher in the older cohort compared with the middle-aged cohort (6.9% vs. 6.0%, respectively).

This is in line with other research that showed distressing dreams remain relatively stable throughout early adulthood and then progressively increase in prevalence from middle to older adulthood. 

After adjustment for all covariates, a higher frequency of distressing dreams was linearly and statistically significantly associated with a higher risk for cognitive decline in middle-aged adults (P = .016) and a higher risk for dementia in older adults (P = .001).

In the fully adjusted model, compared with middle-aged adults who never had bad dreams, those who reported having one or more bad dreams weekly had a fourfold risk for cognitive decline (adjusted odds ratio [aOR], 3.99; 95% confidence interval [CI], 1.07-14.85).

Older adults who had one or more bad dreams weekly had a greater than twofold increased risk for developing dementia (aOR, 2.21; 95% CI, 1.35-3.62).
 

Early days

In sex-stratified analyses, distressing dreams were strongly and statistically significantly associated with cognitive decline and dementia in men, but were only weakly and nonsignificantly associated with cognitive decline and dementia in women.

Dr. Otaiku said he suspects some individuals in the preclinical phase of dementia have “subtle neurodegeneration occurring over time in the right frontal lobe: the area of the brain that helps to downregulate negative emotions whilst we are awake, and also whilst we are dreaming.”

This could result in “depression and anxiety in the day, and nightmares and bad dreams during the night,” he said.

It is possible that treatment for frequent nightmares may help to slow cognitive decline and delay or prevent dementia, Dr. Otaiku added.

He noted that prazosin is used to treat nightmares and has been shown to prevent memory decline and reduce amyloid B generation in preclinical studies of Alzheimer’s disease.

“This is an exciting prospect [but] it is still early days and we will need research to see whether treating nightmares might help to reduce dementia risk down the line,” Dr. Otaiku said.
 

Credible research

In an interview regarding these findings, Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said: “This is credible research consistent with the idea that sleep disturbances may be a risk factor or warning sign of cognitive decline.”

She added that “what’s novel here” is the researchers examined distressing dreams – not more physical sleep disturbances and disorders such as insomnia or apnea.

“However, nightmares can disturb sleep in the same way these disorders do by waking people up in the middle of the night,” said Dr. Carrillo, who was not involved with the study.

“Previous research has pointed to nightmares being indicative of potential changes in the brain that can precede other dementias like Parkinson’s disease. More research is needed to tease out what exactly is happening in the brain during nightmares that may be contributing to this increased risk,” she said.

Dr. Carrillo noted that “getting good sleep” is important for overall health, which includes brain health.

“The good news is there are treatments – both drug and nondrug – that can help address sleep disturbances,” she added.

This study received no external funding. Dr. Otaiku and Dr. Carrillo have reported no relevant financial relationships.

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

Nightmares in healthy middle-aged and older adults may be an independent risk factor for cognitive decline and dementia, particularly in men, new research suggests.

Results from a large cohort study showed that healthy middle-aged adults who had bad dreams at least once a week were four times more likely to experience cognitive decline over the following decade, and older adults were twice as likely to be diagnosed with dementia, compared with peers who never had bad dreams.

Frequent nightmares may “identify people who are at high risk of developing dementia in the future, several years or decades before the characteristic memory and thinking problems emerge,” study investigator Abidemi Otaiku, BMBS, University of Birmingham, England, said in an interview.

“This would be the optimum time for doctors to intervene to try and slow down or prevent dementia from developing,” Dr. Otaiku said.

The findings were published online in The Lancet journal eClinicalMedicine).
 

Distressing dreams

Distressing dreams have been previously associated with faster cognitive decline and increased dementia risk in patients with Parkinson’s disease (PD), but whether the same holds for individuals from the general population without PD is unknown.

To investigate, Dr. Otaiku examined data from three community-based cohorts in the United States. This included 605 middle-aged adults (aged 35-64 years) who were followed for up to 13 years and 2,600 adults aged 79 and older who were followed for up to 7 years. All were considered cognitively normal at baseline.

The prevalence of frequent distressing dreams, defined as occurring “once a week or more,” was higher in the older cohort compared with the middle-aged cohort (6.9% vs. 6.0%, respectively).

This is in line with other research that showed distressing dreams remain relatively stable throughout early adulthood and then progressively increase in prevalence from middle to older adulthood. 

After adjustment for all covariates, a higher frequency of distressing dreams was linearly and statistically significantly associated with a higher risk for cognitive decline in middle-aged adults (P = .016) and a higher risk for dementia in older adults (P = .001).

In the fully adjusted model, compared with middle-aged adults who never had bad dreams, those who reported having one or more bad dreams weekly had a fourfold risk for cognitive decline (adjusted odds ratio [aOR], 3.99; 95% confidence interval [CI], 1.07-14.85).

Older adults who had one or more bad dreams weekly had a greater than twofold increased risk for developing dementia (aOR, 2.21; 95% CI, 1.35-3.62).
 

Early days

In sex-stratified analyses, distressing dreams were strongly and statistically significantly associated with cognitive decline and dementia in men, but were only weakly and nonsignificantly associated with cognitive decline and dementia in women.

Dr. Otaiku said he suspects some individuals in the preclinical phase of dementia have “subtle neurodegeneration occurring over time in the right frontal lobe: the area of the brain that helps to downregulate negative emotions whilst we are awake, and also whilst we are dreaming.”

This could result in “depression and anxiety in the day, and nightmares and bad dreams during the night,” he said.

It is possible that treatment for frequent nightmares may help to slow cognitive decline and delay or prevent dementia, Dr. Otaiku added.

He noted that prazosin is used to treat nightmares and has been shown to prevent memory decline and reduce amyloid B generation in preclinical studies of Alzheimer’s disease.

“This is an exciting prospect [but] it is still early days and we will need research to see whether treating nightmares might help to reduce dementia risk down the line,” Dr. Otaiku said.
 

Credible research

In an interview regarding these findings, Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, said: “This is credible research consistent with the idea that sleep disturbances may be a risk factor or warning sign of cognitive decline.”

She added that “what’s novel here” is the researchers examined distressing dreams – not more physical sleep disturbances and disorders such as insomnia or apnea.

“However, nightmares can disturb sleep in the same way these disorders do by waking people up in the middle of the night,” said Dr. Carrillo, who was not involved with the study.

“Previous research has pointed to nightmares being indicative of potential changes in the brain that can precede other dementias like Parkinson’s disease. More research is needed to tease out what exactly is happening in the brain during nightmares that may be contributing to this increased risk,” she said.

Dr. Carrillo noted that “getting good sleep” is important for overall health, which includes brain health.

“The good news is there are treatments – both drug and nondrug – that can help address sleep disturbances,” she added.

This study received no external funding. Dr. Otaiku and Dr. Carrillo have reported no relevant financial relationships.

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

Shift workers who confine their eating to the daytime may experience fewer mood symptoms compared to those who eat both day and night, new research suggests.

Investigators at Brigham and Women’s Hospital, Boston, created a simulated nightwork schedule for 19 individuals in a laboratory setting. Participants then engaged in two different meal timing models – daytime-only meals (DMI), and meals taken during both daytime and nighttime (DNMC).

Depression- and anxiety-like mood levels increased by 26% and 16%, respectively, among the daytime and nighttime eaters, but there was no such increase in daytime-only eaters.

“Our findings provide evidence for the timing of food intake as a novel strategy to potentially minimize mood vulnerability in individuals experiencing circadian misalignment, such as people engaged in shift work, experiencing jet lag, or suffering from circadian rhythm disorders,” co–corresponding author Frank A.J.L. Scheer, PhD, director of the medical chronobiology program, Brigham and Women’s Hospital, Boston, said in a news release.

The study was published online in the Proceedings of the National Academy of Sciences.
 

Misaligned circadian clock

“Shift workers often experience a misalignment between their central circadian clock in the brain and daily behaviors, such as sleep/wake and fasting/eating cycles,” senior author Sarah Chellappa, MD, PhD, currently the Alexander Von Humboldt Experienced Fellow in the department of nuclear medicine, University of Cologne (Germany). Dr. Chellappa was a postdoctoral fellow at Brigham and Women’s Hospital when the study was conducted.

“They also have a 25%-40% higher risk of depression and anxiety,” she continued. “Since meal timing is important for physical health and diet is important for mood, we sought to find out whether meal timing can benefit mental health as well.”

Given that impaired glycemic control is a “risk factor for mood disruption,” the researchers tested the prediction that daytime eating “would prevent mood vulnerability, despite simulated night work.”

To investigate the question, they conducted a parallel-design, randomized clinical trial that included a 14-day circadian laboratory protocol with 19 healthy adults (12 men, 7 women; mean age, 26.5 ± 4.1 years) who underwent a forced desynchrony (FD) in dim light for 4 “days,” each of which consisted of 28 hours. Each 28-hour “day” resulted in an additional 4-hour misalignment between the central circadian clock and external behavioral/environmental cycles.

By the fourth day, the participants were misaligned by 12 hours, compared to baseline (that is, the first day). They were then randomly assigned to two groups.

The DNMC group – the control group – had a “typical 28-hour FD protocol,” with behavioral and environmental cycles (sleep/wake, rest/activity, supine/upright posture, dark during scheduled sleep/dim light during wakefulness) scheduled on a 28-hour cycle. Thus, they took their meals during both “daytime” and “nighttime,” which is the typical way that night workers eat.

The DMI group underwent a modified 28-hour FD protocol, with all cycles scheduled on a 28-hour basis, except for the fasting/eating cycle, which was scheduled on a 24-hour basis, resulting in meals consumed only during the “daytime.”

Depression- and anxiety-like mood (which “correspond to an amalgam of mood states typically observed in depression and anxiety) were assessed every hour during the 4 FD days, using computerized visual analogue scales.
 

Nutritional psychiatry

Participants in the DNMC group experienced an increase from baseline in depression- and anxiety-like mood levels of 26.2% (95% confidence interval, 21-31.5; P = .001; P value using false discovery rate, .01; effect-size r, 0.78) and 16.1% (95% CI, 8.5-23.6; P = .005; PFDR, .001; effect-size r, 0.47), respectively.

By contrast, a similar increase did not take place in the DMI group for either depression- or anxiety-like mood levels (95% CI, –5.7% to 7.4%, P not significant and 95% CI, –3.1% to 9.9%, P not significant, respectively).

The researchers tested “whether increase mood vulnerability during simulated night work was associated with the degree of internal circadian misalignment” — defined as “change in the phase difference between the acrophase of circadian glucose rhythms and the bathyphase of circadian body temperature rhythms.”

They found that a larger degree of internal circadian misalignment was “robustly associated” with more depression-like (r, 0.77; P = .001) and anxiety-like (r, 0.67; P = .002) mood levels during simulated night work.

The findings imply that meal timing had “moderate to large effects in depression-like and anxiety-like mood levels during night work, and that such effects were associated with the degree of internal circadian misalignment,” the authors wrote.

The laboratory protocol of both groups was identical except for the timing of meals. The authors noted that the “relevance of diet on sleep, circadian rhythms, and mental health is receiving growing awareness with the emergence of a new field, nutritional psychiatry.”

People who experience depression “often report poor-quality diets with high carbohydrate intake,” and there is evidence that adherence to the Mediterranean diet is associated “with lower odds of depression, anxiety, and psychological distress.”

They cautioned that although these emerging studies suggest an association between dietary factors and mental health, “experimental studies in individuals with depression and/or anxiety/anxiety-related disorders are required to determine causality and direction of effects.”

They described meal timing as “an emerging aspect of nutrition, with increasing research interest because of its influence on physical health.” However, they noted, “the causal role of the timing of food intake on mental health remains to be tested.”
 

Novel findings

Commenting for this article, Kathleen Merikangas, PhD, distinguished investigator and chief, genetic epidemiology research branch, intramural research program, National Institute of Mental Health, Bethesda, Md., described the research as important with novel findings.

The research “employs the elegant, carefully controlled laboratory procedures that have unraveled the influence of light and other environmental cues on sleep and circadian rhythms over the past 2 decades,” said Dr. Merikangas, who was not involved with the study.

“One of the most significant contributions of this work is its demonstration of the importance of investigating circadian rhythms of multiple systems rather than solely focusing on sleep, eating, or emotional states that have often been studied in isolation,” she pointed out.

“Growing evidence from basic research highlights the interdependence of multiple human systems that should be built into interventions that tend to focus on one or two domains.”

She recommended that this work be replicated “in more diverse samples ... in both controlled and naturalistic settings...to test both the generalizability and mechanism of these intriguing findings.”

The study was funded by the National Institutes of Health. Individual investigators were funded by the Alexander Von Humboldt Foundation and the American Diabetes Association. Dr. Chellappa disclosed no relevant financial relationships. Dr. Merikangas disclosed no relevant financial relationships.

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

Shift workers who confine their eating to the daytime may experience fewer mood symptoms compared to those who eat both day and night, new research suggests.

Investigators at Brigham and Women’s Hospital, Boston, created a simulated nightwork schedule for 19 individuals in a laboratory setting. Participants then engaged in two different meal timing models – daytime-only meals (DMI), and meals taken during both daytime and nighttime (DNMC).

Depression- and anxiety-like mood levels increased by 26% and 16%, respectively, among the daytime and nighttime eaters, but there was no such increase in daytime-only eaters.

“Our findings provide evidence for the timing of food intake as a novel strategy to potentially minimize mood vulnerability in individuals experiencing circadian misalignment, such as people engaged in shift work, experiencing jet lag, or suffering from circadian rhythm disorders,” co–corresponding author Frank A.J.L. Scheer, PhD, director of the medical chronobiology program, Brigham and Women’s Hospital, Boston, said in a news release.

The study was published online in the Proceedings of the National Academy of Sciences.
 

Misaligned circadian clock

“Shift workers often experience a misalignment between their central circadian clock in the brain and daily behaviors, such as sleep/wake and fasting/eating cycles,” senior author Sarah Chellappa, MD, PhD, currently the Alexander Von Humboldt Experienced Fellow in the department of nuclear medicine, University of Cologne (Germany). Dr. Chellappa was a postdoctoral fellow at Brigham and Women’s Hospital when the study was conducted.

“They also have a 25%-40% higher risk of depression and anxiety,” she continued. “Since meal timing is important for physical health and diet is important for mood, we sought to find out whether meal timing can benefit mental health as well.”

Given that impaired glycemic control is a “risk factor for mood disruption,” the researchers tested the prediction that daytime eating “would prevent mood vulnerability, despite simulated night work.”

To investigate the question, they conducted a parallel-design, randomized clinical trial that included a 14-day circadian laboratory protocol with 19 healthy adults (12 men, 7 women; mean age, 26.5 ± 4.1 years) who underwent a forced desynchrony (FD) in dim light for 4 “days,” each of which consisted of 28 hours. Each 28-hour “day” resulted in an additional 4-hour misalignment between the central circadian clock and external behavioral/environmental cycles.

By the fourth day, the participants were misaligned by 12 hours, compared to baseline (that is, the first day). They were then randomly assigned to two groups.

The DNMC group – the control group – had a “typical 28-hour FD protocol,” with behavioral and environmental cycles (sleep/wake, rest/activity, supine/upright posture, dark during scheduled sleep/dim light during wakefulness) scheduled on a 28-hour cycle. Thus, they took their meals during both “daytime” and “nighttime,” which is the typical way that night workers eat.

The DMI group underwent a modified 28-hour FD protocol, with all cycles scheduled on a 28-hour basis, except for the fasting/eating cycle, which was scheduled on a 24-hour basis, resulting in meals consumed only during the “daytime.”

Depression- and anxiety-like mood (which “correspond to an amalgam of mood states typically observed in depression and anxiety) were assessed every hour during the 4 FD days, using computerized visual analogue scales.
 

Nutritional psychiatry

Participants in the DNMC group experienced an increase from baseline in depression- and anxiety-like mood levels of 26.2% (95% confidence interval, 21-31.5; P = .001; P value using false discovery rate, .01; effect-size r, 0.78) and 16.1% (95% CI, 8.5-23.6; P = .005; PFDR, .001; effect-size r, 0.47), respectively.

By contrast, a similar increase did not take place in the DMI group for either depression- or anxiety-like mood levels (95% CI, –5.7% to 7.4%, P not significant and 95% CI, –3.1% to 9.9%, P not significant, respectively).

The researchers tested “whether increase mood vulnerability during simulated night work was associated with the degree of internal circadian misalignment” — defined as “change in the phase difference between the acrophase of circadian glucose rhythms and the bathyphase of circadian body temperature rhythms.”

They found that a larger degree of internal circadian misalignment was “robustly associated” with more depression-like (r, 0.77; P = .001) and anxiety-like (r, 0.67; P = .002) mood levels during simulated night work.

The findings imply that meal timing had “moderate to large effects in depression-like and anxiety-like mood levels during night work, and that such effects were associated with the degree of internal circadian misalignment,” the authors wrote.

The laboratory protocol of both groups was identical except for the timing of meals. The authors noted that the “relevance of diet on sleep, circadian rhythms, and mental health is receiving growing awareness with the emergence of a new field, nutritional psychiatry.”

People who experience depression “often report poor-quality diets with high carbohydrate intake,” and there is evidence that adherence to the Mediterranean diet is associated “with lower odds of depression, anxiety, and psychological distress.”

They cautioned that although these emerging studies suggest an association between dietary factors and mental health, “experimental studies in individuals with depression and/or anxiety/anxiety-related disorders are required to determine causality and direction of effects.”

They described meal timing as “an emerging aspect of nutrition, with increasing research interest because of its influence on physical health.” However, they noted, “the causal role of the timing of food intake on mental health remains to be tested.”
 

Novel findings

Commenting for this article, Kathleen Merikangas, PhD, distinguished investigator and chief, genetic epidemiology research branch, intramural research program, National Institute of Mental Health, Bethesda, Md., described the research as important with novel findings.

The research “employs the elegant, carefully controlled laboratory procedures that have unraveled the influence of light and other environmental cues on sleep and circadian rhythms over the past 2 decades,” said Dr. Merikangas, who was not involved with the study.

“One of the most significant contributions of this work is its demonstration of the importance of investigating circadian rhythms of multiple systems rather than solely focusing on sleep, eating, or emotional states that have often been studied in isolation,” she pointed out.

“Growing evidence from basic research highlights the interdependence of multiple human systems that should be built into interventions that tend to focus on one or two domains.”

She recommended that this work be replicated “in more diverse samples ... in both controlled and naturalistic settings...to test both the generalizability and mechanism of these intriguing findings.”

The study was funded by the National Institutes of Health. Individual investigators were funded by the Alexander Von Humboldt Foundation and the American Diabetes Association. Dr. Chellappa disclosed no relevant financial relationships. Dr. Merikangas disclosed no relevant financial relationships.

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

Shift workers who confine their eating to the daytime may experience fewer mood symptoms compared to those who eat both day and night, new research suggests.

Investigators at Brigham and Women’s Hospital, Boston, created a simulated nightwork schedule for 19 individuals in a laboratory setting. Participants then engaged in two different meal timing models – daytime-only meals (DMI), and meals taken during both daytime and nighttime (DNMC).

Depression- and anxiety-like mood levels increased by 26% and 16%, respectively, among the daytime and nighttime eaters, but there was no such increase in daytime-only eaters.

“Our findings provide evidence for the timing of food intake as a novel strategy to potentially minimize mood vulnerability in individuals experiencing circadian misalignment, such as people engaged in shift work, experiencing jet lag, or suffering from circadian rhythm disorders,” co–corresponding author Frank A.J.L. Scheer, PhD, director of the medical chronobiology program, Brigham and Women’s Hospital, Boston, said in a news release.

The study was published online in the Proceedings of the National Academy of Sciences.
 

Misaligned circadian clock

“Shift workers often experience a misalignment between their central circadian clock in the brain and daily behaviors, such as sleep/wake and fasting/eating cycles,” senior author Sarah Chellappa, MD, PhD, currently the Alexander Von Humboldt Experienced Fellow in the department of nuclear medicine, University of Cologne (Germany). Dr. Chellappa was a postdoctoral fellow at Brigham and Women’s Hospital when the study was conducted.

“They also have a 25%-40% higher risk of depression and anxiety,” she continued. “Since meal timing is important for physical health and diet is important for mood, we sought to find out whether meal timing can benefit mental health as well.”

Given that impaired glycemic control is a “risk factor for mood disruption,” the researchers tested the prediction that daytime eating “would prevent mood vulnerability, despite simulated night work.”

To investigate the question, they conducted a parallel-design, randomized clinical trial that included a 14-day circadian laboratory protocol with 19 healthy adults (12 men, 7 women; mean age, 26.5 ± 4.1 years) who underwent a forced desynchrony (FD) in dim light for 4 “days,” each of which consisted of 28 hours. Each 28-hour “day” resulted in an additional 4-hour misalignment between the central circadian clock and external behavioral/environmental cycles.

By the fourth day, the participants were misaligned by 12 hours, compared to baseline (that is, the first day). They were then randomly assigned to two groups.

The DNMC group – the control group – had a “typical 28-hour FD protocol,” with behavioral and environmental cycles (sleep/wake, rest/activity, supine/upright posture, dark during scheduled sleep/dim light during wakefulness) scheduled on a 28-hour cycle. Thus, they took their meals during both “daytime” and “nighttime,” which is the typical way that night workers eat.

The DMI group underwent a modified 28-hour FD protocol, with all cycles scheduled on a 28-hour basis, except for the fasting/eating cycle, which was scheduled on a 24-hour basis, resulting in meals consumed only during the “daytime.”

Depression- and anxiety-like mood (which “correspond to an amalgam of mood states typically observed in depression and anxiety) were assessed every hour during the 4 FD days, using computerized visual analogue scales.
 

Nutritional psychiatry

Participants in the DNMC group experienced an increase from baseline in depression- and anxiety-like mood levels of 26.2% (95% confidence interval, 21-31.5; P = .001; P value using false discovery rate, .01; effect-size r, 0.78) and 16.1% (95% CI, 8.5-23.6; P = .005; PFDR, .001; effect-size r, 0.47), respectively.

By contrast, a similar increase did not take place in the DMI group for either depression- or anxiety-like mood levels (95% CI, –5.7% to 7.4%, P not significant and 95% CI, –3.1% to 9.9%, P not significant, respectively).

The researchers tested “whether increase mood vulnerability during simulated night work was associated with the degree of internal circadian misalignment” — defined as “change in the phase difference between the acrophase of circadian glucose rhythms and the bathyphase of circadian body temperature rhythms.”

They found that a larger degree of internal circadian misalignment was “robustly associated” with more depression-like (r, 0.77; P = .001) and anxiety-like (r, 0.67; P = .002) mood levels during simulated night work.

The findings imply that meal timing had “moderate to large effects in depression-like and anxiety-like mood levels during night work, and that such effects were associated with the degree of internal circadian misalignment,” the authors wrote.

The laboratory protocol of both groups was identical except for the timing of meals. The authors noted that the “relevance of diet on sleep, circadian rhythms, and mental health is receiving growing awareness with the emergence of a new field, nutritional psychiatry.”

People who experience depression “often report poor-quality diets with high carbohydrate intake,” and there is evidence that adherence to the Mediterranean diet is associated “with lower odds of depression, anxiety, and psychological distress.”

They cautioned that although these emerging studies suggest an association between dietary factors and mental health, “experimental studies in individuals with depression and/or anxiety/anxiety-related disorders are required to determine causality and direction of effects.”

They described meal timing as “an emerging aspect of nutrition, with increasing research interest because of its influence on physical health.” However, they noted, “the causal role of the timing of food intake on mental health remains to be tested.”
 

Novel findings

Commenting for this article, Kathleen Merikangas, PhD, distinguished investigator and chief, genetic epidemiology research branch, intramural research program, National Institute of Mental Health, Bethesda, Md., described the research as important with novel findings.

The research “employs the elegant, carefully controlled laboratory procedures that have unraveled the influence of light and other environmental cues on sleep and circadian rhythms over the past 2 decades,” said Dr. Merikangas, who was not involved with the study.

“One of the most significant contributions of this work is its demonstration of the importance of investigating circadian rhythms of multiple systems rather than solely focusing on sleep, eating, or emotional states that have often been studied in isolation,” she pointed out.

“Growing evidence from basic research highlights the interdependence of multiple human systems that should be built into interventions that tend to focus on one or two domains.”

She recommended that this work be replicated “in more diverse samples ... in both controlled and naturalistic settings...to test both the generalizability and mechanism of these intriguing findings.”

The study was funded by the National Institutes of Health. Individual investigators were funded by the Alexander Von Humboldt Foundation and the American Diabetes Association. Dr. Chellappa disclosed no relevant financial relationships. Dr. Merikangas disclosed no relevant financial relationships.

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

Drug overdose deaths rose significantly during the COVID-19 pandemic, but more so among Blacks and Native American and Alaska Native people.

The results underscore the “urgency of expanding prevention, treatment, and harm reduction interventions tailored to specific populations, especially American Indian or Alaska Native and Black populations, given long-standing structural racism and inequities in accessing these services,” the researchers note.

The study was published online in JAMA Network Open.
 

‘Urgent need’ for education

From February 2020 to August 2021, drug overdose deaths in the United States rose 37%, and these deaths were largely due to synthetic opioids other than methadone – primarily fentanyl or analogs – and methamphetamine.

Yet, data are lacking regarding racial and ethnic disparities in overdose death rates.

To investigate, Beth Han, MD, PhD, with the National Institute on Drug Abuse, and colleagues analyzed federal drug overdose death data for individuals aged 15-34 and 35-64 from March 2018 to August 2021.

Among individuals aged 15-34, from March 2018 to August 2021, overdose death rates involving any drug, fentanyl, and methamphetamine with or without fentanyl, increased overall.

For the 6 months from March to August 2021, non-Hispanic Native American or Alaska Native men had the highest rates overall involving any drug, fentanyl, and methamphetamine without fentanyl, with rates of 42.0, 30.2, and 6.0 per 100,000, respectively.

The highest rates (per 100,000) of drug overdose deaths involving methamphetamine with fentanyl were for Native American or Alaska Native men (9.2) and women (8.0) and non-Hispanic White men (6.7).

Among people aged 35-64, from March to August 2021, overall drug overdose rates (per 100,000) were highest among non-Hispanic Black men (61.2) and Native American or Alaska Native men (60.0), and fentanyl-involved death rates were highest among Black men (43.3).

Rates involving methamphetamine with fentanyl were highest among Native American or Alaska Native men (12.6) and women (9.4) and White men (9.5).

Rates involving methamphetamine without fentanyl were highest among Native American or Alaska Native men (22.9).

The researchers note the findings highlight the “urgent need” for education on dangers of methamphetamine and fentanyl.

Expanding access to naloxone, fentanyl test strips, and treatments for substance use disorders to disproportionately affected populations is also critical to help curb disparities in drug overdose deaths, they add.

Limitations of the study are that overdose deaths may be underestimated because of the use of 2021 provisional data and that racial or ethnic identification may be misclassified, especially for Native American or Alaska Native people.

This study was sponsored by the National Institute on Drug Abuse of the National Institutes of Health and the Centers for Disease Control and Prevention. The authors report no relevant disclosures.

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

Drug overdose deaths rose significantly during the COVID-19 pandemic, but more so among Blacks and Native American and Alaska Native people.

The results underscore the “urgency of expanding prevention, treatment, and harm reduction interventions tailored to specific populations, especially American Indian or Alaska Native and Black populations, given long-standing structural racism and inequities in accessing these services,” the researchers note.

The study was published online in JAMA Network Open.
 

‘Urgent need’ for education

From February 2020 to August 2021, drug overdose deaths in the United States rose 37%, and these deaths were largely due to synthetic opioids other than methadone – primarily fentanyl or analogs – and methamphetamine.

Yet, data are lacking regarding racial and ethnic disparities in overdose death rates.

To investigate, Beth Han, MD, PhD, with the National Institute on Drug Abuse, and colleagues analyzed federal drug overdose death data for individuals aged 15-34 and 35-64 from March 2018 to August 2021.

Among individuals aged 15-34, from March 2018 to August 2021, overdose death rates involving any drug, fentanyl, and methamphetamine with or without fentanyl, increased overall.

For the 6 months from March to August 2021, non-Hispanic Native American or Alaska Native men had the highest rates overall involving any drug, fentanyl, and methamphetamine without fentanyl, with rates of 42.0, 30.2, and 6.0 per 100,000, respectively.

The highest rates (per 100,000) of drug overdose deaths involving methamphetamine with fentanyl were for Native American or Alaska Native men (9.2) and women (8.0) and non-Hispanic White men (6.7).

Among people aged 35-64, from March to August 2021, overall drug overdose rates (per 100,000) were highest among non-Hispanic Black men (61.2) and Native American or Alaska Native men (60.0), and fentanyl-involved death rates were highest among Black men (43.3).

Rates involving methamphetamine with fentanyl were highest among Native American or Alaska Native men (12.6) and women (9.4) and White men (9.5).

Rates involving methamphetamine without fentanyl were highest among Native American or Alaska Native men (22.9).

The researchers note the findings highlight the “urgent need” for education on dangers of methamphetamine and fentanyl.

Expanding access to naloxone, fentanyl test strips, and treatments for substance use disorders to disproportionately affected populations is also critical to help curb disparities in drug overdose deaths, they add.

Limitations of the study are that overdose deaths may be underestimated because of the use of 2021 provisional data and that racial or ethnic identification may be misclassified, especially for Native American or Alaska Native people.

This study was sponsored by the National Institute on Drug Abuse of the National Institutes of Health and the Centers for Disease Control and Prevention. The authors report no relevant disclosures.

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

Drug overdose deaths rose significantly during the COVID-19 pandemic, but more so among Blacks and Native American and Alaska Native people.

The results underscore the “urgency of expanding prevention, treatment, and harm reduction interventions tailored to specific populations, especially American Indian or Alaska Native and Black populations, given long-standing structural racism and inequities in accessing these services,” the researchers note.

The study was published online in JAMA Network Open.
 

‘Urgent need’ for education

From February 2020 to August 2021, drug overdose deaths in the United States rose 37%, and these deaths were largely due to synthetic opioids other than methadone – primarily fentanyl or analogs – and methamphetamine.

Yet, data are lacking regarding racial and ethnic disparities in overdose death rates.

To investigate, Beth Han, MD, PhD, with the National Institute on Drug Abuse, and colleagues analyzed federal drug overdose death data for individuals aged 15-34 and 35-64 from March 2018 to August 2021.

Among individuals aged 15-34, from March 2018 to August 2021, overdose death rates involving any drug, fentanyl, and methamphetamine with or without fentanyl, increased overall.

For the 6 months from March to August 2021, non-Hispanic Native American or Alaska Native men had the highest rates overall involving any drug, fentanyl, and methamphetamine without fentanyl, with rates of 42.0, 30.2, and 6.0 per 100,000, respectively.

The highest rates (per 100,000) of drug overdose deaths involving methamphetamine with fentanyl were for Native American or Alaska Native men (9.2) and women (8.0) and non-Hispanic White men (6.7).

Among people aged 35-64, from March to August 2021, overall drug overdose rates (per 100,000) were highest among non-Hispanic Black men (61.2) and Native American or Alaska Native men (60.0), and fentanyl-involved death rates were highest among Black men (43.3).

Rates involving methamphetamine with fentanyl were highest among Native American or Alaska Native men (12.6) and women (9.4) and White men (9.5).

Rates involving methamphetamine without fentanyl were highest among Native American or Alaska Native men (22.9).

The researchers note the findings highlight the “urgent need” for education on dangers of methamphetamine and fentanyl.

Expanding access to naloxone, fentanyl test strips, and treatments for substance use disorders to disproportionately affected populations is also critical to help curb disparities in drug overdose deaths, they add.

Limitations of the study are that overdose deaths may be underestimated because of the use of 2021 provisional data and that racial or ethnic identification may be misclassified, especially for Native American or Alaska Native people.

This study was sponsored by the National Institute on Drug Abuse of the National Institutes of Health and the Centers for Disease Control and Prevention. The authors report no relevant disclosures.

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

Patients with inflammatory bowel disease (IBD) are 70% more likely to use benzodiazepines and “Z-drugs” than are the general population, a large study from Canada suggests. 

Mood/anxiety disorders and sleep disorders are common in patients with IBD, but few studies have looked at use of benzodiazepines and Z-drugs (such as zolpidem, zaleplon, and eszopiclone) in this patient population.

The results are “concerning, and especially as the IBD population ages, these drugs are associated with health risks, including something as simple as falls,” first author Charles Bernstein, MD, of the IBD clinical and research centre, University of Manitoba, Winnipeg, told this news organization.

“Clinicians need to find better strategies to deal with anxiety disorders and sleep disorders in the IBD population,” Dr. Bernstein said.

The study was published online in the American Journal of Gastroenterology.
 

High burden of use

Using administrative data from Manitoba, Dr. Bernstein and colleagues identified 5,741 patients with IBD (2,381 with Crohn’s disease and 3,360 with ulcerative colitis) and matched them (1:5) to 28,661 population controls without IBD.

Over a 20-year period (1997-2017), there was a “high burden” of benzodiazepine and Z-drug use in the IBD population. In 2017, roughly 20% of Manitobans with IBD were using benzodiazepines, and 20% were using Z-drugs, the study team reports.

The benzodiazepine use rate (per 1,000) was 28.06 in the IBD cohort vs. 16.83 in the non-IBD population (adjusted rate ratio, 1.67). The use rate for Z-drugs was 21.07 in the IBD cohort vs. 11.26 in the non-IBD population (adjusted RR, 1.87).

Benzodiazepine use declined from 1997 to 2016, but it remained at least 50% higher in patients with IBD than in the general population over this period, the researchers found. The rate of Z-drug use also was higher in the IBD population than in the general population but remained stable over the 20-year study period.

Regardless of age, men and women had similarly high use rates for benzodiazepines, Z-drugs, and joint use of benzodiazepines and Z-drugs. The highest incidence rates for joint benzodiazepine and Z-drug use were in young adults (age 18-44 years), and these rates were similar among men and women.

Patients with IBD and a mood/anxiety disorder also were more likely to use benzodiazepines and Z-drugs and to be continuous users than were those without a mood/anxiety disorder.
 

Mental health and IBD go hand in hand

“The results are not very surprising, but they highlight the importance of mental health and mood disturbances in patients with IBD,” Ashwin Ananthakrishnan, MBBS, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who wasn’t involved in the study, told this news organization.

“It is important for treating physicians to be aware of the important mental health implications of IBD diagnosis and disease activity, to screen patients for these disturbances, and to institute early effective interventions,” Dr. Ananthakrishnan said.

Also offering perspective, Laurie Keefer, PhD, academic health psychologist and director of psychobehavioral research within the division of gastroenterology, Mount Sinai Health System, New York, said that she is “concerned but not surprised” by the results of this study.

“One in three patients with IBD meets criteria for an anxiety disorder,” Dr. Keefer told this news organization.

And with the ongoing mental health crisis and shortage of mental health providers, “gastroenterologists are, unfortunately, in the position where they may have to manage these issues,” she said.

Dr. Keefer noted that when patients are first diagnosed with IBD, they will likely be on prednisone, and “an antidote” for the side effects of prednisone are benzodiazepines and sleeping medications because prednisone itself causes insomnia. “However, that’s really just a band-aid,” she said.

A major concern, said Dr. Keefer, is that young men and women who are diagnosed with IBD in their 20s may start using these drugs and become reliant on them.

“People do build up a tolerance to these drugs, so they need more and more to receive the same effect,” she said.

A better approach is to figure out why patients are so anxious and teach them skills to manage their anxiety and sleep problems so that they’re not dependent on these drugs, Dr. Keefer said.

“There are behavioral strategies that can help. These are harder to do, and they’re not a quick fix. However, they are skills you can learn in your 20s and so when you have an IBD flare at 50, you have the skills to deal with it,” she said.

“We just have to be a little more proactive in really encouraging patients to learn disease management skills,” Dr. Keefer added.

The study was funded by the Canadian Institutes of Health Research and Crohn’s and Colitis Canada. Dr. Bernstein has disclosed relationships with AbbVie Canada, Amgen Canada, Bristol-Myers Squibb Canada, Roche Canada, Janssen Canada, Sandoz Canada, Takeda and Takeda Canada, Pfizer Canada, Mylan Pharmaceuticals, and Medtronic Canada. Dr. Ananthakrishnan and Dr. Keefer report no relevant financial relationships.

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

Patients with inflammatory bowel disease (IBD) are 70% more likely to use benzodiazepines and “Z-drugs” than are the general population, a large study from Canada suggests. 

Mood/anxiety disorders and sleep disorders are common in patients with IBD, but few studies have looked at use of benzodiazepines and Z-drugs (such as zolpidem, zaleplon, and eszopiclone) in this patient population.

The results are “concerning, and especially as the IBD population ages, these drugs are associated with health risks, including something as simple as falls,” first author Charles Bernstein, MD, of the IBD clinical and research centre, University of Manitoba, Winnipeg, told this news organization.

“Clinicians need to find better strategies to deal with anxiety disorders and sleep disorders in the IBD population,” Dr. Bernstein said.

The study was published online in the American Journal of Gastroenterology.
 

High burden of use

Using administrative data from Manitoba, Dr. Bernstein and colleagues identified 5,741 patients with IBD (2,381 with Crohn’s disease and 3,360 with ulcerative colitis) and matched them (1:5) to 28,661 population controls without IBD.

Over a 20-year period (1997-2017), there was a “high burden” of benzodiazepine and Z-drug use in the IBD population. In 2017, roughly 20% of Manitobans with IBD were using benzodiazepines, and 20% were using Z-drugs, the study team reports.

The benzodiazepine use rate (per 1,000) was 28.06 in the IBD cohort vs. 16.83 in the non-IBD population (adjusted rate ratio, 1.67). The use rate for Z-drugs was 21.07 in the IBD cohort vs. 11.26 in the non-IBD population (adjusted RR, 1.87).

Benzodiazepine use declined from 1997 to 2016, but it remained at least 50% higher in patients with IBD than in the general population over this period, the researchers found. The rate of Z-drug use also was higher in the IBD population than in the general population but remained stable over the 20-year study period.

Regardless of age, men and women had similarly high use rates for benzodiazepines, Z-drugs, and joint use of benzodiazepines and Z-drugs. The highest incidence rates for joint benzodiazepine and Z-drug use were in young adults (age 18-44 years), and these rates were similar among men and women.

Patients with IBD and a mood/anxiety disorder also were more likely to use benzodiazepines and Z-drugs and to be continuous users than were those without a mood/anxiety disorder.
 

Mental health and IBD go hand in hand

“The results are not very surprising, but they highlight the importance of mental health and mood disturbances in patients with IBD,” Ashwin Ananthakrishnan, MBBS, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who wasn’t involved in the study, told this news organization.

“It is important for treating physicians to be aware of the important mental health implications of IBD diagnosis and disease activity, to screen patients for these disturbances, and to institute early effective interventions,” Dr. Ananthakrishnan said.

Also offering perspective, Laurie Keefer, PhD, academic health psychologist and director of psychobehavioral research within the division of gastroenterology, Mount Sinai Health System, New York, said that she is “concerned but not surprised” by the results of this study.

“One in three patients with IBD meets criteria for an anxiety disorder,” Dr. Keefer told this news organization.

And with the ongoing mental health crisis and shortage of mental health providers, “gastroenterologists are, unfortunately, in the position where they may have to manage these issues,” she said.

Dr. Keefer noted that when patients are first diagnosed with IBD, they will likely be on prednisone, and “an antidote” for the side effects of prednisone are benzodiazepines and sleeping medications because prednisone itself causes insomnia. “However, that’s really just a band-aid,” she said.

A major concern, said Dr. Keefer, is that young men and women who are diagnosed with IBD in their 20s may start using these drugs and become reliant on them.

“People do build up a tolerance to these drugs, so they need more and more to receive the same effect,” she said.

A better approach is to figure out why patients are so anxious and teach them skills to manage their anxiety and sleep problems so that they’re not dependent on these drugs, Dr. Keefer said.

“There are behavioral strategies that can help. These are harder to do, and they’re not a quick fix. However, they are skills you can learn in your 20s and so when you have an IBD flare at 50, you have the skills to deal with it,” she said.

“We just have to be a little more proactive in really encouraging patients to learn disease management skills,” Dr. Keefer added.

The study was funded by the Canadian Institutes of Health Research and Crohn’s and Colitis Canada. Dr. Bernstein has disclosed relationships with AbbVie Canada, Amgen Canada, Bristol-Myers Squibb Canada, Roche Canada, Janssen Canada, Sandoz Canada, Takeda and Takeda Canada, Pfizer Canada, Mylan Pharmaceuticals, and Medtronic Canada. Dr. Ananthakrishnan and Dr. Keefer report no relevant financial relationships.

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

Patients with inflammatory bowel disease (IBD) are 70% more likely to use benzodiazepines and “Z-drugs” than are the general population, a large study from Canada suggests. 

Mood/anxiety disorders and sleep disorders are common in patients with IBD, but few studies have looked at use of benzodiazepines and Z-drugs (such as zolpidem, zaleplon, and eszopiclone) in this patient population.

The results are “concerning, and especially as the IBD population ages, these drugs are associated with health risks, including something as simple as falls,” first author Charles Bernstein, MD, of the IBD clinical and research centre, University of Manitoba, Winnipeg, told this news organization.

“Clinicians need to find better strategies to deal with anxiety disorders and sleep disorders in the IBD population,” Dr. Bernstein said.

The study was published online in the American Journal of Gastroenterology.
 

High burden of use

Using administrative data from Manitoba, Dr. Bernstein and colleagues identified 5,741 patients with IBD (2,381 with Crohn’s disease and 3,360 with ulcerative colitis) and matched them (1:5) to 28,661 population controls without IBD.

Over a 20-year period (1997-2017), there was a “high burden” of benzodiazepine and Z-drug use in the IBD population. In 2017, roughly 20% of Manitobans with IBD were using benzodiazepines, and 20% were using Z-drugs, the study team reports.

The benzodiazepine use rate (per 1,000) was 28.06 in the IBD cohort vs. 16.83 in the non-IBD population (adjusted rate ratio, 1.67). The use rate for Z-drugs was 21.07 in the IBD cohort vs. 11.26 in the non-IBD population (adjusted RR, 1.87).

Benzodiazepine use declined from 1997 to 2016, but it remained at least 50% higher in patients with IBD than in the general population over this period, the researchers found. The rate of Z-drug use also was higher in the IBD population than in the general population but remained stable over the 20-year study period.

Regardless of age, men and women had similarly high use rates for benzodiazepines, Z-drugs, and joint use of benzodiazepines and Z-drugs. The highest incidence rates for joint benzodiazepine and Z-drug use were in young adults (age 18-44 years), and these rates were similar among men and women.

Patients with IBD and a mood/anxiety disorder also were more likely to use benzodiazepines and Z-drugs and to be continuous users than were those without a mood/anxiety disorder.
 

Mental health and IBD go hand in hand

“The results are not very surprising, but they highlight the importance of mental health and mood disturbances in patients with IBD,” Ashwin Ananthakrishnan, MBBS, MPH, with Massachusetts General Hospital and Harvard Medical School in Boston, who wasn’t involved in the study, told this news organization.

“It is important for treating physicians to be aware of the important mental health implications of IBD diagnosis and disease activity, to screen patients for these disturbances, and to institute early effective interventions,” Dr. Ananthakrishnan said.

Also offering perspective, Laurie Keefer, PhD, academic health psychologist and director of psychobehavioral research within the division of gastroenterology, Mount Sinai Health System, New York, said that she is “concerned but not surprised” by the results of this study.

“One in three patients with IBD meets criteria for an anxiety disorder,” Dr. Keefer told this news organization.

And with the ongoing mental health crisis and shortage of mental health providers, “gastroenterologists are, unfortunately, in the position where they may have to manage these issues,” she said.

Dr. Keefer noted that when patients are first diagnosed with IBD, they will likely be on prednisone, and “an antidote” for the side effects of prednisone are benzodiazepines and sleeping medications because prednisone itself causes insomnia. “However, that’s really just a band-aid,” she said.

A major concern, said Dr. Keefer, is that young men and women who are diagnosed with IBD in their 20s may start using these drugs and become reliant on them.

“People do build up a tolerance to these drugs, so they need more and more to receive the same effect,” she said.

A better approach is to figure out why patients are so anxious and teach them skills to manage their anxiety and sleep problems so that they’re not dependent on these drugs, Dr. Keefer said.

“There are behavioral strategies that can help. These are harder to do, and they’re not a quick fix. However, they are skills you can learn in your 20s and so when you have an IBD flare at 50, you have the skills to deal with it,” she said.

“We just have to be a little more proactive in really encouraging patients to learn disease management skills,” Dr. Keefer added.

The study was funded by the Canadian Institutes of Health Research and Crohn’s and Colitis Canada. Dr. Bernstein has disclosed relationships with AbbVie Canada, Amgen Canada, Bristol-Myers Squibb Canada, Roche Canada, Janssen Canada, Sandoz Canada, Takeda and Takeda Canada, Pfizer Canada, Mylan Pharmaceuticals, and Medtronic Canada. Dr. Ananthakrishnan and Dr. Keefer report no relevant financial relationships.

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

If isolated, patients with mental disorders may end up having higher levels of social impairment. This has led several hospitals in Spain to set up open-door departments that are more accessible.

The purpose of the open-door model is to help remove the stigma from individuals who need to be admitted to a psychiatric ward because they have a mental disorder.
 

Traditional locked wards

According to the World Health Organization (WHO), in 2019, one in every eight people were living with a mental disorder. Having the least restrictive type of mental health care is one of the 10 basic principles listed in a 1996 reference document from the WHO.

Among people suffering from severe psychiatric disorders, there is a high probability of being involuntarily admitted to a psychiatry ward with locked doors (PWLD). Admission to a PWLD involves the application of a set of measures that restrict the individual’s freedom.

The main argument for keeping the doors locked is that it prevents suicides and self-harm behavior, as well as abscondment. But in recent years, efforts have been made to apply a model called open-door policy psychiatry wards (ODPWs).
 

Open wards model

Experiments were undertaken in various countries, including the United Kingdom, Australia, Switzerland, and Germany. Investigators found that the new forms of hospitalization led to a reduction in conflictive events; self-harm behavior; restrictive measures, such as seclusion, mechanical restraints, and chemical restraints; as well as forced medication. On the basis of these findings, ODPWs were launched.

According to Ignacio García Cabeza, MD, psychiatrist and coordinator of the department of psychiatry at Gregorio Marañón General University Hospital in Madrid, “The open wards model is founded on the idea of respecting the patient and their autonomy. In addition, it advocates a reduction in coercive measures.

“We wanted our department to be the same as the other departments in the hospital, with patients going in and out, receiving treatment, and being able to have family visits,” he explained. “A patient’s diagnosis should not factor into these things. People with schizophrenia, people with any type of mental disorder, should be able to enjoy this minimally restrictive environment.”

Use of open wards constitutes a paradigm shift in hospitalization toward a person-centered psychiatry. The goal of this new paradigm is to prepare the individual so that he or she can live in harmony with the usual environment and participate in it to the same extent as everyone else in the community.

This model also implies fundamental changes in the interaction between health care professionals and patients. The implementation of new nursing care models, among which the Safewards model stands out, is a key element for the success of the project.

Based on a set of tools for preventing and managing conflict, the Safewards model seeks to modify the factors that regulate the relationship between staff and patients. Use of this model brought about a 15% reduction in the rate of conflictive events and a 23% reduction in the rate of coercive interventions, in comparison with a control group.

One of the major debates is about whether every patient should be able to choose this open-door system. For Dr. García Cabeza, the answer is yes, but with one caveat. “There’s a certain group of patients who perhaps need to be in locked wards, who perhaps require greater means of control – patients whose conditions put them at a high risk of suicide or of self-harm behavior or of absconding.”

He had no hesitation in saying that an open-door ward increases the patient’s self-esteem. It helps promote autonomy and a sense of control and of normalcy with respect to a community. “The idea is to get to the point where we’ve got an atmosphere, a climate, that serves to benefit the therapeutic actions that are going to continue to influence the patient’s future progress and their treatment.”

That’s why it’s important to bring about the kind of health care activities that can prevent the patient from experiencing some of the negative psychological effects, such as distrust and feeling removed from normalcy. “In traditional locked wards, the patient feels incapable of making decisions. They feel that they have very little to do with [and have] no say in the decisions made, and a lot of times, this leads to a situation where, after discharge, the patient ends up giving up on the treatments. If we can manage to break this perception held by the patient,” Dr. García Cabeza suggested, “it’s quite likely that we’ll manage to improve the course of their disorder in general.”
 

What the literature says

The effect of ODPW has been investigated through comparative studies with PWLD and research of the transition from PWLD to ODPW, both from a therapeutic and safety a point of view.

A 15-year observational study published in The Lancet Psychiatry found that, with respect to abscondment, suicide attempts, and suicide, there were no significant differences between hospitals with open-door policies and those without.

A subsequent study that was published in 2017 found that on open wards, any aggressive behavior and restraint or seclusion were less likely than on closed wards.
 

The Spanish situation

This system is already at work in some Spanish hospitals, among them Inca Comarcal Hospital (Palma de Mallorca), Elda General University Hospital (Alicante), Germans Trias i Pujol Hospital in Badalona, and Gregorio Marañón General University Hospital in Madrid.

“At Gregorio Marañón, we started the experiment just before the pandemic hit. We’re up and running now, but still with some limitations; the patient can go in and out, but not with the flexibility we’d like,” explained Dr. García Cabeza. “An open ward plays a clinical, patient-care role and a symbolic one as well. Locking the doors has a lot to do with the fear felt toward these patients. It’s a stigma that they’ve had to deal with and that they continue to have to deal with. In terms of the symbolic role, there’s also the fear that comes with giving these patients some rights.”

While the experiment at Gregorio Marañón’s psychiatric ward “is still very much in the early stages,” there have been no recorded incidents related to its open-door policy. Dr. García Cabeza is aware of the challenges of such a policy, “starting with assistance when conflictive events arise. Challenges faced by the staff – especially the nursing staff, as they’re the ones who are with the patients 24 hours day – and challenges faced by those in charge of providing care. In all of this, there are new things to learn and be aware of, new ways of understanding and looking at the patient-physician relationship. The fears are still there – they haven’t been done away with. But the way we conduct ourselves should be adjusted, matching how we act toward other patients. Although the differences have to be taken into account, we have to try to normalize, as much as possible, the environment where patients with mental disorders receive treatment.”

Dr. García Cabeza has no doubts. “The most sensible and reasonable decisions need to be made at these sites so as to allow the broadest applicability to cases. Anyone who needs psychiatric hospitalization and who is competent to consent to admission and who voluntarily agrees to be admitted – they can and must be placed in an open ward.”

The hope is that in the future, the number of open wards will increase and the number of locked wards – which have more stigma attached to them – will go down. The involvement of the staff and appropriate institutional support are essential to making this a reality.

This article was translated from Univadis Spain.

If isolated, patients with mental disorders may end up having higher levels of social impairment. This has led several hospitals in Spain to set up open-door departments that are more accessible.

The purpose of the open-door model is to help remove the stigma from individuals who need to be admitted to a psychiatric ward because they have a mental disorder.
 

Traditional locked wards

According to the World Health Organization (WHO), in 2019, one in every eight people were living with a mental disorder. Having the least restrictive type of mental health care is one of the 10 basic principles listed in a 1996 reference document from the WHO.

Among people suffering from severe psychiatric disorders, there is a high probability of being involuntarily admitted to a psychiatry ward with locked doors (PWLD). Admission to a PWLD involves the application of a set of measures that restrict the individual’s freedom.

The main argument for keeping the doors locked is that it prevents suicides and self-harm behavior, as well as abscondment. But in recent years, efforts have been made to apply a model called open-door policy psychiatry wards (ODPWs).
 

Open wards model

Experiments were undertaken in various countries, including the United Kingdom, Australia, Switzerland, and Germany. Investigators found that the new forms of hospitalization led to a reduction in conflictive events; self-harm behavior; restrictive measures, such as seclusion, mechanical restraints, and chemical restraints; as well as forced medication. On the basis of these findings, ODPWs were launched.

According to Ignacio García Cabeza, MD, psychiatrist and coordinator of the department of psychiatry at Gregorio Marañón General University Hospital in Madrid, “The open wards model is founded on the idea of respecting the patient and their autonomy. In addition, it advocates a reduction in coercive measures.

“We wanted our department to be the same as the other departments in the hospital, with patients going in and out, receiving treatment, and being able to have family visits,” he explained. “A patient’s diagnosis should not factor into these things. People with schizophrenia, people with any type of mental disorder, should be able to enjoy this minimally restrictive environment.”

Use of open wards constitutes a paradigm shift in hospitalization toward a person-centered psychiatry. The goal of this new paradigm is to prepare the individual so that he or she can live in harmony with the usual environment and participate in it to the same extent as everyone else in the community.

This model also implies fundamental changes in the interaction between health care professionals and patients. The implementation of new nursing care models, among which the Safewards model stands out, is a key element for the success of the project.

Based on a set of tools for preventing and managing conflict, the Safewards model seeks to modify the factors that regulate the relationship between staff and patients. Use of this model brought about a 15% reduction in the rate of conflictive events and a 23% reduction in the rate of coercive interventions, in comparison with a control group.

One of the major debates is about whether every patient should be able to choose this open-door system. For Dr. García Cabeza, the answer is yes, but with one caveat. “There’s a certain group of patients who perhaps need to be in locked wards, who perhaps require greater means of control – patients whose conditions put them at a high risk of suicide or of self-harm behavior or of absconding.”

He had no hesitation in saying that an open-door ward increases the patient’s self-esteem. It helps promote autonomy and a sense of control and of normalcy with respect to a community. “The idea is to get to the point where we’ve got an atmosphere, a climate, that serves to benefit the therapeutic actions that are going to continue to influence the patient’s future progress and their treatment.”

That’s why it’s important to bring about the kind of health care activities that can prevent the patient from experiencing some of the negative psychological effects, such as distrust and feeling removed from normalcy. “In traditional locked wards, the patient feels incapable of making decisions. They feel that they have very little to do with [and have] no say in the decisions made, and a lot of times, this leads to a situation where, after discharge, the patient ends up giving up on the treatments. If we can manage to break this perception held by the patient,” Dr. García Cabeza suggested, “it’s quite likely that we’ll manage to improve the course of their disorder in general.”
 

What the literature says

The effect of ODPW has been investigated through comparative studies with PWLD and research of the transition from PWLD to ODPW, both from a therapeutic and safety a point of view.

A 15-year observational study published in The Lancet Psychiatry found that, with respect to abscondment, suicide attempts, and suicide, there were no significant differences between hospitals with open-door policies and those without.

A subsequent study that was published in 2017 found that on open wards, any aggressive behavior and restraint or seclusion were less likely than on closed wards.
 

The Spanish situation

This system is already at work in some Spanish hospitals, among them Inca Comarcal Hospital (Palma de Mallorca), Elda General University Hospital (Alicante), Germans Trias i Pujol Hospital in Badalona, and Gregorio Marañón General University Hospital in Madrid.

“At Gregorio Marañón, we started the experiment just before the pandemic hit. We’re up and running now, but still with some limitations; the patient can go in and out, but not with the flexibility we’d like,” explained Dr. García Cabeza. “An open ward plays a clinical, patient-care role and a symbolic one as well. Locking the doors has a lot to do with the fear felt toward these patients. It’s a stigma that they’ve had to deal with and that they continue to have to deal with. In terms of the symbolic role, there’s also the fear that comes with giving these patients some rights.”

While the experiment at Gregorio Marañón’s psychiatric ward “is still very much in the early stages,” there have been no recorded incidents related to its open-door policy. Dr. García Cabeza is aware of the challenges of such a policy, “starting with assistance when conflictive events arise. Challenges faced by the staff – especially the nursing staff, as they’re the ones who are with the patients 24 hours day – and challenges faced by those in charge of providing care. In all of this, there are new things to learn and be aware of, new ways of understanding and looking at the patient-physician relationship. The fears are still there – they haven’t been done away with. But the way we conduct ourselves should be adjusted, matching how we act toward other patients. Although the differences have to be taken into account, we have to try to normalize, as much as possible, the environment where patients with mental disorders receive treatment.”

Dr. García Cabeza has no doubts. “The most sensible and reasonable decisions need to be made at these sites so as to allow the broadest applicability to cases. Anyone who needs psychiatric hospitalization and who is competent to consent to admission and who voluntarily agrees to be admitted – they can and must be placed in an open ward.”

The hope is that in the future, the number of open wards will increase and the number of locked wards – which have more stigma attached to them – will go down. The involvement of the staff and appropriate institutional support are essential to making this a reality.

This article was translated from Univadis Spain.

If isolated, patients with mental disorders may end up having higher levels of social impairment. This has led several hospitals in Spain to set up open-door departments that are more accessible.

The purpose of the open-door model is to help remove the stigma from individuals who need to be admitted to a psychiatric ward because they have a mental disorder.
 

Traditional locked wards

According to the World Health Organization (WHO), in 2019, one in every eight people were living with a mental disorder. Having the least restrictive type of mental health care is one of the 10 basic principles listed in a 1996 reference document from the WHO.

Among people suffering from severe psychiatric disorders, there is a high probability of being involuntarily admitted to a psychiatry ward with locked doors (PWLD). Admission to a PWLD involves the application of a set of measures that restrict the individual’s freedom.

The main argument for keeping the doors locked is that it prevents suicides and self-harm behavior, as well as abscondment. But in recent years, efforts have been made to apply a model called open-door policy psychiatry wards (ODPWs).
 

Open wards model

Experiments were undertaken in various countries, including the United Kingdom, Australia, Switzerland, and Germany. Investigators found that the new forms of hospitalization led to a reduction in conflictive events; self-harm behavior; restrictive measures, such as seclusion, mechanical restraints, and chemical restraints; as well as forced medication. On the basis of these findings, ODPWs were launched.

According to Ignacio García Cabeza, MD, psychiatrist and coordinator of the department of psychiatry at Gregorio Marañón General University Hospital in Madrid, “The open wards model is founded on the idea of respecting the patient and their autonomy. In addition, it advocates a reduction in coercive measures.

“We wanted our department to be the same as the other departments in the hospital, with patients going in and out, receiving treatment, and being able to have family visits,” he explained. “A patient’s diagnosis should not factor into these things. People with schizophrenia, people with any type of mental disorder, should be able to enjoy this minimally restrictive environment.”

Use of open wards constitutes a paradigm shift in hospitalization toward a person-centered psychiatry. The goal of this new paradigm is to prepare the individual so that he or she can live in harmony with the usual environment and participate in it to the same extent as everyone else in the community.

This model also implies fundamental changes in the interaction between health care professionals and patients. The implementation of new nursing care models, among which the Safewards model stands out, is a key element for the success of the project.

Based on a set of tools for preventing and managing conflict, the Safewards model seeks to modify the factors that regulate the relationship between staff and patients. Use of this model brought about a 15% reduction in the rate of conflictive events and a 23% reduction in the rate of coercive interventions, in comparison with a control group.

One of the major debates is about whether every patient should be able to choose this open-door system. For Dr. García Cabeza, the answer is yes, but with one caveat. “There’s a certain group of patients who perhaps need to be in locked wards, who perhaps require greater means of control – patients whose conditions put them at a high risk of suicide or of self-harm behavior or of absconding.”

He had no hesitation in saying that an open-door ward increases the patient’s self-esteem. It helps promote autonomy and a sense of control and of normalcy with respect to a community. “The idea is to get to the point where we’ve got an atmosphere, a climate, that serves to benefit the therapeutic actions that are going to continue to influence the patient’s future progress and their treatment.”

That’s why it’s important to bring about the kind of health care activities that can prevent the patient from experiencing some of the negative psychological effects, such as distrust and feeling removed from normalcy. “In traditional locked wards, the patient feels incapable of making decisions. They feel that they have very little to do with [and have] no say in the decisions made, and a lot of times, this leads to a situation where, after discharge, the patient ends up giving up on the treatments. If we can manage to break this perception held by the patient,” Dr. García Cabeza suggested, “it’s quite likely that we’ll manage to improve the course of their disorder in general.”
 

What the literature says

The effect of ODPW has been investigated through comparative studies with PWLD and research of the transition from PWLD to ODPW, both from a therapeutic and safety a point of view.

A 15-year observational study published in The Lancet Psychiatry found that, with respect to abscondment, suicide attempts, and suicide, there were no significant differences between hospitals with open-door policies and those without.

A subsequent study that was published in 2017 found that on open wards, any aggressive behavior and restraint or seclusion were less likely than on closed wards.
 

The Spanish situation

This system is already at work in some Spanish hospitals, among them Inca Comarcal Hospital (Palma de Mallorca), Elda General University Hospital (Alicante), Germans Trias i Pujol Hospital in Badalona, and Gregorio Marañón General University Hospital in Madrid.

“At Gregorio Marañón, we started the experiment just before the pandemic hit. We’re up and running now, but still with some limitations; the patient can go in and out, but not with the flexibility we’d like,” explained Dr. García Cabeza. “An open ward plays a clinical, patient-care role and a symbolic one as well. Locking the doors has a lot to do with the fear felt toward these patients. It’s a stigma that they’ve had to deal with and that they continue to have to deal with. In terms of the symbolic role, there’s also the fear that comes with giving these patients some rights.”

While the experiment at Gregorio Marañón’s psychiatric ward “is still very much in the early stages,” there have been no recorded incidents related to its open-door policy. Dr. García Cabeza is aware of the challenges of such a policy, “starting with assistance when conflictive events arise. Challenges faced by the staff – especially the nursing staff, as they’re the ones who are with the patients 24 hours day – and challenges faced by those in charge of providing care. In all of this, there are new things to learn and be aware of, new ways of understanding and looking at the patient-physician relationship. The fears are still there – they haven’t been done away with. But the way we conduct ourselves should be adjusted, matching how we act toward other patients. Although the differences have to be taken into account, we have to try to normalize, as much as possible, the environment where patients with mental disorders receive treatment.”

Dr. García Cabeza has no doubts. “The most sensible and reasonable decisions need to be made at these sites so as to allow the broadest applicability to cases. Anyone who needs psychiatric hospitalization and who is competent to consent to admission and who voluntarily agrees to be admitted – they can and must be placed in an open ward.”

The hope is that in the future, the number of open wards will increase and the number of locked wards – which have more stigma attached to them – will go down. The involvement of the staff and appropriate institutional support are essential to making this a reality.

This article was translated from Univadis Spain.

Older age is associated with many health conditions that could potentially benefit from psychedelic-assisted therapy, yet very few older adults have been included in clinical trials of psychedelics, new research shows.

“Geriatric psychiatrists and others caring for older adults are interested in how much is known about psychedelic use in older adults,” study investigator C. Bree Johnston, MD, MPH, University of Arizona, Tucson, told this news organization.

University of Arizona

“A major concern is how safe psychedelic-assisted therapy is for patients with heart disease, hypertension, neurological disorders, and multimorbidity,” Dr. Johnston said.

The study is published online in the American Journal of Geriatric Psychiatry.
 

‘Groundswell’ of research

The past few years have brought a “groundswell” of interest and promising research into the potential therapeutic benefit of psychedelic-assisted therapy for a variety of conditions affecting adults, the researchers noted.

They include psilocybin-assisted therapy for the distress associated with a terminal diagnosis, depression, and addiction, and MDMA-assisted therapy for PTSD.

However, in most studies, psychedelic therapy has been tested in relatively young healthy adults, raising the question of how generalizable the study results are for the patients that most geropsychiatrists will be treating, the investigators noted.

They reviewed “the most important” research studies on psilocybin- and MDMA-assisted therapies published over the past 2 decades that are likely to be relevant for geriatric psychiatrists and other professionals caring for older adults.

The researchers point out that psychedelics and related compounds have shown efficacy for the treatment of a number of conditions that are common among older adults, including mood disorders, distress associated with a serious medical illness, PTSD, substance use problems, and prolonged grief.

Psychedelics also have properties that may provide for cognitive impairment and dementia and promote personal growth among healthy older adults.

Research has shown that psychedelics can be safely administered to healthy adults in controlled conditions.

However, both psilocybin and MDMA can increase blood pressure and heart rate, which could be a concern if used in older adults with cardiovascular disease, the investigators noted.

“Healthy older adults are likely to face similar risks when undergoing psychedelic-assisted therapy as healthy younger adults,” said Dr. Johnston.

“In carefully selected adults, those risks appear to be minor when psychedelics are administered in controlled conditions under the guidance of a skilled therapist,” she added.

Given the potential of psychedelic compounds to benefit older adults, the authors call for more research to establish the safety and efficacy among older adults, particularly those with multiple comorbidities.
 

Pressing knowledge gaps

The exclusion of older adults from clinical trials of novel treatments is “one of contemporary psychiatry’s more pressing problems – one that extends beyond psychedelics,” Ipsit V. Vahia, MD, associate chief of the division of geriatric psychiatry, McLean Hospital, Belmont, Mass., who wasn’t involved in the review, told this news organization.

courtesy McLean Hospital

“Currently, there is little evidence that clinicians can lean on while considering the use of psychedelics in older adults,” Dr. Vahia said.

This paper highlights “the most pressing gaps in the evidence that bear addressing in order to develop more substantial best practices around the use of these drugs,” he added.

For example, little is known about appropriate dosing, pharmacokinetics, and pharmacodynamics of psychedelics in older adults, Dr. Vahia said.

“Their risks, particularly cardiovascular risks, are barely studied, and almost nothing is known about how these drugs may impact those in their 80s or older, or those with serious medical comorbidities who use multiple medications,” Dr. Vahia said. “The majority of the existing literature has excluded older adults, and the extremely limited evidence that does exist has been collected in relatively healthy, and relatively young (aged below 75) persons.”

Dr. Vahia noted that, before psychedelics as a class can be considered viable treatment options for a broader group of older adults, “more research is needed, particularly to establish safety.”

This research had no specific funding. Dr. Johnston and Dr. Vahia have no relevant conflicts of interest.

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

Older age is associated with many health conditions that could potentially benefit from psychedelic-assisted therapy, yet very few older adults have been included in clinical trials of psychedelics, new research shows.

“Geriatric psychiatrists and others caring for older adults are interested in how much is known about psychedelic use in older adults,” study investigator C. Bree Johnston, MD, MPH, University of Arizona, Tucson, told this news organization.

University of Arizona

“A major concern is how safe psychedelic-assisted therapy is for patients with heart disease, hypertension, neurological disorders, and multimorbidity,” Dr. Johnston said.

The study is published online in the American Journal of Geriatric Psychiatry.
 

‘Groundswell’ of research

The past few years have brought a “groundswell” of interest and promising research into the potential therapeutic benefit of psychedelic-assisted therapy for a variety of conditions affecting adults, the researchers noted.

They include psilocybin-assisted therapy for the distress associated with a terminal diagnosis, depression, and addiction, and MDMA-assisted therapy for PTSD.

However, in most studies, psychedelic therapy has been tested in relatively young healthy adults, raising the question of how generalizable the study results are for the patients that most geropsychiatrists will be treating, the investigators noted.

They reviewed “the most important” research studies on psilocybin- and MDMA-assisted therapies published over the past 2 decades that are likely to be relevant for geriatric psychiatrists and other professionals caring for older adults.

The researchers point out that psychedelics and related compounds have shown efficacy for the treatment of a number of conditions that are common among older adults, including mood disorders, distress associated with a serious medical illness, PTSD, substance use problems, and prolonged grief.

Psychedelics also have properties that may provide for cognitive impairment and dementia and promote personal growth among healthy older adults.

Research has shown that psychedelics can be safely administered to healthy adults in controlled conditions.

However, both psilocybin and MDMA can increase blood pressure and heart rate, which could be a concern if used in older adults with cardiovascular disease, the investigators noted.

“Healthy older adults are likely to face similar risks when undergoing psychedelic-assisted therapy as healthy younger adults,” said Dr. Johnston.

“In carefully selected adults, those risks appear to be minor when psychedelics are administered in controlled conditions under the guidance of a skilled therapist,” she added.

Given the potential of psychedelic compounds to benefit older adults, the authors call for more research to establish the safety and efficacy among older adults, particularly those with multiple comorbidities.
 

Pressing knowledge gaps

The exclusion of older adults from clinical trials of novel treatments is “one of contemporary psychiatry’s more pressing problems – one that extends beyond psychedelics,” Ipsit V. Vahia, MD, associate chief of the division of geriatric psychiatry, McLean Hospital, Belmont, Mass., who wasn’t involved in the review, told this news organization.

courtesy McLean Hospital

“Currently, there is little evidence that clinicians can lean on while considering the use of psychedelics in older adults,” Dr. Vahia said.

This paper highlights “the most pressing gaps in the evidence that bear addressing in order to develop more substantial best practices around the use of these drugs,” he added.

For example, little is known about appropriate dosing, pharmacokinetics, and pharmacodynamics of psychedelics in older adults, Dr. Vahia said.

“Their risks, particularly cardiovascular risks, are barely studied, and almost nothing is known about how these drugs may impact those in their 80s or older, or those with serious medical comorbidities who use multiple medications,” Dr. Vahia said. “The majority of the existing literature has excluded older adults, and the extremely limited evidence that does exist has been collected in relatively healthy, and relatively young (aged below 75) persons.”

Dr. Vahia noted that, before psychedelics as a class can be considered viable treatment options for a broader group of older adults, “more research is needed, particularly to establish safety.”

This research had no specific funding. Dr. Johnston and Dr. Vahia have no relevant conflicts of interest.

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

Older age is associated with many health conditions that could potentially benefit from psychedelic-assisted therapy, yet very few older adults have been included in clinical trials of psychedelics, new research shows.

“Geriatric psychiatrists and others caring for older adults are interested in how much is known about psychedelic use in older adults,” study investigator C. Bree Johnston, MD, MPH, University of Arizona, Tucson, told this news organization.

University of Arizona

“A major concern is how safe psychedelic-assisted therapy is for patients with heart disease, hypertension, neurological disorders, and multimorbidity,” Dr. Johnston said.

The study is published online in the American Journal of Geriatric Psychiatry.
 

‘Groundswell’ of research

The past few years have brought a “groundswell” of interest and promising research into the potential therapeutic benefit of psychedelic-assisted therapy for a variety of conditions affecting adults, the researchers noted.

They include psilocybin-assisted therapy for the distress associated with a terminal diagnosis, depression, and addiction, and MDMA-assisted therapy for PTSD.

However, in most studies, psychedelic therapy has been tested in relatively young healthy adults, raising the question of how generalizable the study results are for the patients that most geropsychiatrists will be treating, the investigators noted.

They reviewed “the most important” research studies on psilocybin- and MDMA-assisted therapies published over the past 2 decades that are likely to be relevant for geriatric psychiatrists and other professionals caring for older adults.

The researchers point out that psychedelics and related compounds have shown efficacy for the treatment of a number of conditions that are common among older adults, including mood disorders, distress associated with a serious medical illness, PTSD, substance use problems, and prolonged grief.

Psychedelics also have properties that may provide for cognitive impairment and dementia and promote personal growth among healthy older adults.

Research has shown that psychedelics can be safely administered to healthy adults in controlled conditions.

However, both psilocybin and MDMA can increase blood pressure and heart rate, which could be a concern if used in older adults with cardiovascular disease, the investigators noted.

“Healthy older adults are likely to face similar risks when undergoing psychedelic-assisted therapy as healthy younger adults,” said Dr. Johnston.

“In carefully selected adults, those risks appear to be minor when psychedelics are administered in controlled conditions under the guidance of a skilled therapist,” she added.

Given the potential of psychedelic compounds to benefit older adults, the authors call for more research to establish the safety and efficacy among older adults, particularly those with multiple comorbidities.
 

Pressing knowledge gaps

The exclusion of older adults from clinical trials of novel treatments is “one of contemporary psychiatry’s more pressing problems – one that extends beyond psychedelics,” Ipsit V. Vahia, MD, associate chief of the division of geriatric psychiatry, McLean Hospital, Belmont, Mass., who wasn’t involved in the review, told this news organization.

courtesy McLean Hospital

“Currently, there is little evidence that clinicians can lean on while considering the use of psychedelics in older adults,” Dr. Vahia said.

This paper highlights “the most pressing gaps in the evidence that bear addressing in order to develop more substantial best practices around the use of these drugs,” he added.

For example, little is known about appropriate dosing, pharmacokinetics, and pharmacodynamics of psychedelics in older adults, Dr. Vahia said.

“Their risks, particularly cardiovascular risks, are barely studied, and almost nothing is known about how these drugs may impact those in their 80s or older, or those with serious medical comorbidities who use multiple medications,” Dr. Vahia said. “The majority of the existing literature has excluded older adults, and the extremely limited evidence that does exist has been collected in relatively healthy, and relatively young (aged below 75) persons.”

Dr. Vahia noted that, before psychedelics as a class can be considered viable treatment options for a broader group of older adults, “more research is needed, particularly to establish safety.”

This research had no specific funding. Dr. Johnston and Dr. Vahia have no relevant conflicts of interest.

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

When Sue W’s mother died in 2018, she struggled terribly. She was already seeing a psychotherapist and was taking duloxetine, prescribed by her primary care physician. But her grief was profound, and her depression became paralyzing. She needed to see a psychiatrist, and there were many available in or near her hometown, a Connecticut suburb of New York City, but neither Sue, her therapist, nor her primary care doctor could find a psychiatrist who participated with her insurance. Finally, she was given the name of a psychiatrist in Manhattan who practiced online, and she made an appointment on the Skypiatrist (a telepsychiatry group founded in 2016) website.

“I hesitated about it at first,” Sue said. “The doctor was nice, and I liked the convenience. Appointments were 15 minutes long, although the first session was longer. He focused on the medications, which was okay because I already have a therapist. And it was really easy. I made appointments on their website and I saw the doctor through the same site, and I really liked that I could send him messages.” The psychiatrist was responsive when Sue had trouble coming off duloxetine, and he gave her instructions for a slower taper. The treatment was affordable and accessible, and she got better.

Psychiatry has a problem: The demand for services is far greater than what we can accommodate. This has opened a door for both for nonphysician prescribers and online companies to step in and fill a need that local, office-based psychiatrists can’t meet. When you also consider that many private-practice psychiatrists do not participate with insurance panels, online companies that do accept insurance may add value, convenience, and access. 

Cerebral, the largest online psychiatric service in the country, began seeing patients in January 2020, offering medications and psychotherapy. They participate with a number of commercial insurers, and this varies by state, but not with Medicaid or Medicare. Patients pay a monthly fee, and an initial 30-minute medication evaluation session is conducted, often with a nurse practitioner. They advertise wait times of less than 7 days.

Another company, Done, offers treatment specifically for ADHD. They don’t accept insurance for appointments; patients must submit their own claims for reimbursement. Their pricing structure involves a fee of $199 for the first month, then $79 a month thereafter, which does not include medications. Hims – another online company – targets men with a variety of health issues, including mental health problems.

Some of these internet companies have been in the news recently for concerns related to quality of care and prescribing practices. A The Wall Street Journal article of March 26, 2022, quoted clinicians who had previously worked for Cerebral and Done who left because they felt pressured to see patients quickly and to prescribe stimulants. Not all of the prescribers were unhappy, however. Yina Cruz-Harris, a nurse practitioner at Done who has a doctorate in nursing practice, said that she manages 2,300 patients with ADHD for Done. Virtually all are on stimulants. She renews each patient’s monthly prescription from her New Jersey home, based mostly on online forms filled out by the patients. She’s fast, doing two renewals per minute, and Done pays her almost $10 per patient, working out to around $20,000 in monthly earnings.

In May, the Department of Justice began looking into Cerebral’s practices around controlled substances and more recently, Cerebral has been in the news for complaints from patients that they have been unable to reach their prescribers when problems arise. Some pharmacy chains have refused to fill prescriptions for controlled medications from online telehealth providers, and some online providers, including Cerebral, are no longer prescribing controlled substances. A front-page The Wall Street Journal article on Aug. 19, 2022, told the story of a man with a history of addiction who was prescribed stimulants after a brief appointment with a prescriber at Done. Family and friends in his sober house believe that the stimulants triggered a relapse, and he died of an opioid overdose.

During the early days of the pandemic, nonemergency psychiatric care was shut down and we all became virtual psychiatrists. Many of us saw new patients and prescribed controlled medications to people we had never met in real life.

“John Brown,” MD, PhD, spoke with me on the condition that I don’t use his real name or the name of the practice he left. He was hired by a traditional group practice with a multidisciplinary staff and several offices in his state. Most of the clinicians worked part time and were contractual employees, and Dr. Brown was hired to develop a specialty service. He soon learned that the practice – which participates with a number of insurance plans – was not financially stable, and it was acquired by an investment firm with no medical experience.

“They wanted everyone to work 40-hour weeks and see 14 patients a day, including 3-4 new patients, and suddenly everyone was overextended and exhausted. Overnight, most of the therapists left, and they hired nurse practitioners to replace many of the psychiatrists. People weren’t getting good care.” While this was not a telepsychiatry startup, it was a corporate takeover of a traditional practice that was unable to remain financially solvent while participating with insurance panels.

Like Sue W, Elizabeth K struggled to get treatment for ADHD even before the pandemic.

“I work multiple part-time jobs, don’t own a car, and don’t have insurance. Before telehealth became available, it was difficult and discouraging for me to maintain consistent treatment. It took me months to get initial appointments with a doctor and I live in one of the largest cities in the country.” She was pleased with the care she received by Done.

“I was pleasantly surprised by the authenticity and thoroughness of my first telehealth provider,” Elizabeth noted. “She remembered and considered more about me, my medical history, and details of my personal life than nearly every psychiatric doctor I’ve ever seen. They informed me of the long-term effects of medications and the importance of routine cardiovascular check-ups. Also, they wouldn’t prescribe more than 5 mg of Adderall (even though I had been prescribed 30-90 mg a day for most of my life) until I completed a medical check-up with blood pressure and blood test results.”

Corporate telepsychiatry may fill an important void and provide care to many people who have been unable to access traditional treatment. Something, however, has to account for the fact that care is more affordable through startups than through traditional psychiatric practices. Startups have expensive technological and infrastructure costs and added layers of administration. This translates to either higher volumes with shorter appointments, less compensation for prescribers, or both. How this will affect the future of psychiatric care remains to be seen.

Dr. Miller, is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

When Sue W’s mother died in 2018, she struggled terribly. She was already seeing a psychotherapist and was taking duloxetine, prescribed by her primary care physician. But her grief was profound, and her depression became paralyzing. She needed to see a psychiatrist, and there were many available in or near her hometown, a Connecticut suburb of New York City, but neither Sue, her therapist, nor her primary care doctor could find a psychiatrist who participated with her insurance. Finally, she was given the name of a psychiatrist in Manhattan who practiced online, and she made an appointment on the Skypiatrist (a telepsychiatry group founded in 2016) website.

“I hesitated about it at first,” Sue said. “The doctor was nice, and I liked the convenience. Appointments were 15 minutes long, although the first session was longer. He focused on the medications, which was okay because I already have a therapist. And it was really easy. I made appointments on their website and I saw the doctor through the same site, and I really liked that I could send him messages.” The psychiatrist was responsive when Sue had trouble coming off duloxetine, and he gave her instructions for a slower taper. The treatment was affordable and accessible, and she got better.

Psychiatry has a problem: The demand for services is far greater than what we can accommodate. This has opened a door for both for nonphysician prescribers and online companies to step in and fill a need that local, office-based psychiatrists can’t meet. When you also consider that many private-practice psychiatrists do not participate with insurance panels, online companies that do accept insurance may add value, convenience, and access. 

Cerebral, the largest online psychiatric service in the country, began seeing patients in January 2020, offering medications and psychotherapy. They participate with a number of commercial insurers, and this varies by state, but not with Medicaid or Medicare. Patients pay a monthly fee, and an initial 30-minute medication evaluation session is conducted, often with a nurse practitioner. They advertise wait times of less than 7 days.

Another company, Done, offers treatment specifically for ADHD. They don’t accept insurance for appointments; patients must submit their own claims for reimbursement. Their pricing structure involves a fee of $199 for the first month, then $79 a month thereafter, which does not include medications. Hims – another online company – targets men with a variety of health issues, including mental health problems.

Some of these internet companies have been in the news recently for concerns related to quality of care and prescribing practices. A The Wall Street Journal article of March 26, 2022, quoted clinicians who had previously worked for Cerebral and Done who left because they felt pressured to see patients quickly and to prescribe stimulants. Not all of the prescribers were unhappy, however. Yina Cruz-Harris, a nurse practitioner at Done who has a doctorate in nursing practice, said that she manages 2,300 patients with ADHD for Done. Virtually all are on stimulants. She renews each patient’s monthly prescription from her New Jersey home, based mostly on online forms filled out by the patients. She’s fast, doing two renewals per minute, and Done pays her almost $10 per patient, working out to around $20,000 in monthly earnings.

In May, the Department of Justice began looking into Cerebral’s practices around controlled substances and more recently, Cerebral has been in the news for complaints from patients that they have been unable to reach their prescribers when problems arise. Some pharmacy chains have refused to fill prescriptions for controlled medications from online telehealth providers, and some online providers, including Cerebral, are no longer prescribing controlled substances. A front-page The Wall Street Journal article on Aug. 19, 2022, told the story of a man with a history of addiction who was prescribed stimulants after a brief appointment with a prescriber at Done. Family and friends in his sober house believe that the stimulants triggered a relapse, and he died of an opioid overdose.

During the early days of the pandemic, nonemergency psychiatric care was shut down and we all became virtual psychiatrists. Many of us saw new patients and prescribed controlled medications to people we had never met in real life.

“John Brown,” MD, PhD, spoke with me on the condition that I don’t use his real name or the name of the practice he left. He was hired by a traditional group practice with a multidisciplinary staff and several offices in his state. Most of the clinicians worked part time and were contractual employees, and Dr. Brown was hired to develop a specialty service. He soon learned that the practice – which participates with a number of insurance plans – was not financially stable, and it was acquired by an investment firm with no medical experience.

“They wanted everyone to work 40-hour weeks and see 14 patients a day, including 3-4 new patients, and suddenly everyone was overextended and exhausted. Overnight, most of the therapists left, and they hired nurse practitioners to replace many of the psychiatrists. People weren’t getting good care.” While this was not a telepsychiatry startup, it was a corporate takeover of a traditional practice that was unable to remain financially solvent while participating with insurance panels.

Like Sue W, Elizabeth K struggled to get treatment for ADHD even before the pandemic.

“I work multiple part-time jobs, don’t own a car, and don’t have insurance. Before telehealth became available, it was difficult and discouraging for me to maintain consistent treatment. It took me months to get initial appointments with a doctor and I live in one of the largest cities in the country.” She was pleased with the care she received by Done.

“I was pleasantly surprised by the authenticity and thoroughness of my first telehealth provider,” Elizabeth noted. “She remembered and considered more about me, my medical history, and details of my personal life than nearly every psychiatric doctor I’ve ever seen. They informed me of the long-term effects of medications and the importance of routine cardiovascular check-ups. Also, they wouldn’t prescribe more than 5 mg of Adderall (even though I had been prescribed 30-90 mg a day for most of my life) until I completed a medical check-up with blood pressure and blood test results.”

Corporate telepsychiatry may fill an important void and provide care to many people who have been unable to access traditional treatment. Something, however, has to account for the fact that care is more affordable through startups than through traditional psychiatric practices. Startups have expensive technological and infrastructure costs and added layers of administration. This translates to either higher volumes with shorter appointments, less compensation for prescribers, or both. How this will affect the future of psychiatric care remains to be seen.

Dr. Miller, is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

When Sue W’s mother died in 2018, she struggled terribly. She was already seeing a psychotherapist and was taking duloxetine, prescribed by her primary care physician. But her grief was profound, and her depression became paralyzing. She needed to see a psychiatrist, and there were many available in or near her hometown, a Connecticut suburb of New York City, but neither Sue, her therapist, nor her primary care doctor could find a psychiatrist who participated with her insurance. Finally, she was given the name of a psychiatrist in Manhattan who practiced online, and she made an appointment on the Skypiatrist (a telepsychiatry group founded in 2016) website.

“I hesitated about it at first,” Sue said. “The doctor was nice, and I liked the convenience. Appointments were 15 minutes long, although the first session was longer. He focused on the medications, which was okay because I already have a therapist. And it was really easy. I made appointments on their website and I saw the doctor through the same site, and I really liked that I could send him messages.” The psychiatrist was responsive when Sue had trouble coming off duloxetine, and he gave her instructions for a slower taper. The treatment was affordable and accessible, and she got better.

Psychiatry has a problem: The demand for services is far greater than what we can accommodate. This has opened a door for both for nonphysician prescribers and online companies to step in and fill a need that local, office-based psychiatrists can’t meet. When you also consider that many private-practice psychiatrists do not participate with insurance panels, online companies that do accept insurance may add value, convenience, and access. 

Cerebral, the largest online psychiatric service in the country, began seeing patients in January 2020, offering medications and psychotherapy. They participate with a number of commercial insurers, and this varies by state, but not with Medicaid or Medicare. Patients pay a monthly fee, and an initial 30-minute medication evaluation session is conducted, often with a nurse practitioner. They advertise wait times of less than 7 days.

Another company, Done, offers treatment specifically for ADHD. They don’t accept insurance for appointments; patients must submit their own claims for reimbursement. Their pricing structure involves a fee of $199 for the first month, then $79 a month thereafter, which does not include medications. Hims – another online company – targets men with a variety of health issues, including mental health problems.

Some of these internet companies have been in the news recently for concerns related to quality of care and prescribing practices. A The Wall Street Journal article of March 26, 2022, quoted clinicians who had previously worked for Cerebral and Done who left because they felt pressured to see patients quickly and to prescribe stimulants. Not all of the prescribers were unhappy, however. Yina Cruz-Harris, a nurse practitioner at Done who has a doctorate in nursing practice, said that she manages 2,300 patients with ADHD for Done. Virtually all are on stimulants. She renews each patient’s monthly prescription from her New Jersey home, based mostly on online forms filled out by the patients. She’s fast, doing two renewals per minute, and Done pays her almost $10 per patient, working out to around $20,000 in monthly earnings.

In May, the Department of Justice began looking into Cerebral’s practices around controlled substances and more recently, Cerebral has been in the news for complaints from patients that they have been unable to reach their prescribers when problems arise. Some pharmacy chains have refused to fill prescriptions for controlled medications from online telehealth providers, and some online providers, including Cerebral, are no longer prescribing controlled substances. A front-page The Wall Street Journal article on Aug. 19, 2022, told the story of a man with a history of addiction who was prescribed stimulants after a brief appointment with a prescriber at Done. Family and friends in his sober house believe that the stimulants triggered a relapse, and he died of an opioid overdose.

During the early days of the pandemic, nonemergency psychiatric care was shut down and we all became virtual psychiatrists. Many of us saw new patients and prescribed controlled medications to people we had never met in real life.

“John Brown,” MD, PhD, spoke with me on the condition that I don’t use his real name or the name of the practice he left. He was hired by a traditional group practice with a multidisciplinary staff and several offices in his state. Most of the clinicians worked part time and were contractual employees, and Dr. Brown was hired to develop a specialty service. He soon learned that the practice – which participates with a number of insurance plans – was not financially stable, and it was acquired by an investment firm with no medical experience.

“They wanted everyone to work 40-hour weeks and see 14 patients a day, including 3-4 new patients, and suddenly everyone was overextended and exhausted. Overnight, most of the therapists left, and they hired nurse practitioners to replace many of the psychiatrists. People weren’t getting good care.” While this was not a telepsychiatry startup, it was a corporate takeover of a traditional practice that was unable to remain financially solvent while participating with insurance panels.

Like Sue W, Elizabeth K struggled to get treatment for ADHD even before the pandemic.

“I work multiple part-time jobs, don’t own a car, and don’t have insurance. Before telehealth became available, it was difficult and discouraging for me to maintain consistent treatment. It took me months to get initial appointments with a doctor and I live in one of the largest cities in the country.” She was pleased with the care she received by Done.

“I was pleasantly surprised by the authenticity and thoroughness of my first telehealth provider,” Elizabeth noted. “She remembered and considered more about me, my medical history, and details of my personal life than nearly every psychiatric doctor I’ve ever seen. They informed me of the long-term effects of medications and the importance of routine cardiovascular check-ups. Also, they wouldn’t prescribe more than 5 mg of Adderall (even though I had been prescribed 30-90 mg a day for most of my life) until I completed a medical check-up with blood pressure and blood test results.”

Corporate telepsychiatry may fill an important void and provide care to many people who have been unable to access traditional treatment. Something, however, has to account for the fact that care is more affordable through startups than through traditional psychiatric practices. Startups have expensive technological and infrastructure costs and added layers of administration. This translates to either higher volumes with shorter appointments, less compensation for prescribers, or both. How this will affect the future of psychiatric care remains to be seen.

Dr. Miller, is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Individuals with depression who had high levels of C-reactive protein responded poorly to selected serotonin reuptake inhibitors compared to those with lower CRP levels, based on data from more than 900 patients.

C-reactive protein (CRP) has been shown to predict antidepressant treatment outcomes in depressed patients, but previous studies have been small and under restricted conditions, and data from large, real-world studies are lacking, wrote Yuqian Pan of First Affiliated Hospital of Zhengzhou University, Henan, China, and colleagues.

In a study published in the Journal of Affective Disorders , the researchers identified depressed patients aged 12-60 years who had tested CRP levels. The participants were followed through outpatient visits or telephone interviews to collect information on medication use and assess efficacy based on the Clinical Global Impressions–Improvement scale.

CRP was separated into the low CRP group of 709 patients (CRP < 1 mg/L) and a high CRP group of 209 patients (CRP ≥ 1 mg/L). The primary outcome was efficacy defined as effective and ineffective for high and low CRP levels in patients using different medications: Selected serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, (SNRIs), melatonin receptor agonists (MTs), and norepinephrinergic and specific serotonergic antidepressants (NaSSAs).

The researchers compared efficacy in different groups according to CRP levels.

Overall, patients with low CRP showed significantly greater efficacy with SSRIs than did those with high CRP (hazard ratio [HR], 1.257, P = .047). SNRIs were more effective than SSRIs for treating patients with high CRP levels (HR, 1.652, P = .037).

A possible reason for the difference in efficacy is the correlation between CRP and body mass index; previous studies have shown that SSRIs may be less effective in obese individuals, the researchers said.

“Another possible explanation is that at high levels of inflammation, neurons, microglia, and macrophages respond to inflammatory challenges at the cellular level by activating metabolic pathways,” they said.

No significant changes in CRP levels were observed before and after starting medication use, which supports the stability of CRP as a biomarker under normal circumstances.

No difference in efficacy appeared between SSRIs and SNRIs in patients with low CRP, “which may indicate that SNRIs have stronger anti-inflammatory effects than SSRIs,” a finding consistent with previous studies, they said.

The study findings were limited by several factors including the small number of patients taking MT and NaSSA, the irregular time intervals for before and after SSRI treatment in 90 patients, the lack of classification by antidepressant type, and the potential for recall bias, the researchers noted.

However, the results suggest that CRP could predict the efficacy of SSRIs in depressed patients in a real-world setting, which may inform treatment decisions, they said.

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

Individuals with depression who had high levels of C-reactive protein responded poorly to selected serotonin reuptake inhibitors compared to those with lower CRP levels, based on data from more than 900 patients.

C-reactive protein (CRP) has been shown to predict antidepressant treatment outcomes in depressed patients, but previous studies have been small and under restricted conditions, and data from large, real-world studies are lacking, wrote Yuqian Pan of First Affiliated Hospital of Zhengzhou University, Henan, China, and colleagues.

In a study published in the Journal of Affective Disorders , the researchers identified depressed patients aged 12-60 years who had tested CRP levels. The participants were followed through outpatient visits or telephone interviews to collect information on medication use and assess efficacy based on the Clinical Global Impressions–Improvement scale.

CRP was separated into the low CRP group of 709 patients (CRP < 1 mg/L) and a high CRP group of 209 patients (CRP ≥ 1 mg/L). The primary outcome was efficacy defined as effective and ineffective for high and low CRP levels in patients using different medications: Selected serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, (SNRIs), melatonin receptor agonists (MTs), and norepinephrinergic and specific serotonergic antidepressants (NaSSAs).

The researchers compared efficacy in different groups according to CRP levels.

Overall, patients with low CRP showed significantly greater efficacy with SSRIs than did those with high CRP (hazard ratio [HR], 1.257, P = .047). SNRIs were more effective than SSRIs for treating patients with high CRP levels (HR, 1.652, P = .037).

A possible reason for the difference in efficacy is the correlation between CRP and body mass index; previous studies have shown that SSRIs may be less effective in obese individuals, the researchers said.

“Another possible explanation is that at high levels of inflammation, neurons, microglia, and macrophages respond to inflammatory challenges at the cellular level by activating metabolic pathways,” they said.

No significant changes in CRP levels were observed before and after starting medication use, which supports the stability of CRP as a biomarker under normal circumstances.

No difference in efficacy appeared between SSRIs and SNRIs in patients with low CRP, “which may indicate that SNRIs have stronger anti-inflammatory effects than SSRIs,” a finding consistent with previous studies, they said.

The study findings were limited by several factors including the small number of patients taking MT and NaSSA, the irregular time intervals for before and after SSRI treatment in 90 patients, the lack of classification by antidepressant type, and the potential for recall bias, the researchers noted.

However, the results suggest that CRP could predict the efficacy of SSRIs in depressed patients in a real-world setting, which may inform treatment decisions, they said.

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

Individuals with depression who had high levels of C-reactive protein responded poorly to selected serotonin reuptake inhibitors compared to those with lower CRP levels, based on data from more than 900 patients.

C-reactive protein (CRP) has been shown to predict antidepressant treatment outcomes in depressed patients, but previous studies have been small and under restricted conditions, and data from large, real-world studies are lacking, wrote Yuqian Pan of First Affiliated Hospital of Zhengzhou University, Henan, China, and colleagues.

In a study published in the Journal of Affective Disorders , the researchers identified depressed patients aged 12-60 years who had tested CRP levels. The participants were followed through outpatient visits or telephone interviews to collect information on medication use and assess efficacy based on the Clinical Global Impressions–Improvement scale.

CRP was separated into the low CRP group of 709 patients (CRP < 1 mg/L) and a high CRP group of 209 patients (CRP ≥ 1 mg/L). The primary outcome was efficacy defined as effective and ineffective for high and low CRP levels in patients using different medications: Selected serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, (SNRIs), melatonin receptor agonists (MTs), and norepinephrinergic and specific serotonergic antidepressants (NaSSAs).

The researchers compared efficacy in different groups according to CRP levels.

Overall, patients with low CRP showed significantly greater efficacy with SSRIs than did those with high CRP (hazard ratio [HR], 1.257, P = .047). SNRIs were more effective than SSRIs for treating patients with high CRP levels (HR, 1.652, P = .037).

A possible reason for the difference in efficacy is the correlation between CRP and body mass index; previous studies have shown that SSRIs may be less effective in obese individuals, the researchers said.

“Another possible explanation is that at high levels of inflammation, neurons, microglia, and macrophages respond to inflammatory challenges at the cellular level by activating metabolic pathways,” they said.

No significant changes in CRP levels were observed before and after starting medication use, which supports the stability of CRP as a biomarker under normal circumstances.

No difference in efficacy appeared between SSRIs and SNRIs in patients with low CRP, “which may indicate that SNRIs have stronger anti-inflammatory effects than SSRIs,” a finding consistent with previous studies, they said.

The study findings were limited by several factors including the small number of patients taking MT and NaSSA, the irregular time intervals for before and after SSRI treatment in 90 patients, the lack of classification by antidepressant type, and the potential for recall bias, the researchers noted.

However, the results suggest that CRP could predict the efficacy of SSRIs in depressed patients in a real-world setting, which may inform treatment decisions, they said.

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

The broad-spectrum antibiotic minocycline (multiple brands) is not effective when added to standard antidepressant therapy, the largest randomized, controlled trial of minocycline in treatment-resistant depression (TRD) shows.

In the MinoTRD trial, 6 weeks of minocycline 200 mg daily added to stable antidepressant therapy did not show a statistically significant advantage over placebo on the overall course of depressive symptoms.

“The failure of minocycline treatment to reduce depressive symptoms in a naturalistic sample of patients with TRD is a setback for anti-inflammatory treatment strategies in this clinical population,” Julian Hellmann-Regen, MD, department of psychiatry and neurosciences, Charité – Universitätsmedizin Berlin, and colleagues wrote.  

The findings were published online in JAMA Network Open.
 

No additional benefit

The “inflammatory hypothesis” of depression maintains that depression arises from increased immune activation and neurotrophic mechanisms.

This view is supported by observations that depression is accompanied by increased levels of proinflammatory cytokines. In addition, low-grade inflammatory processes may interfere with response to typical antidepressant medications. 

Minocycline has been put forth as a novel antidepressant, and a few small trials have hinted at a benefit.

In the MinoTRD trial, 168 patients (mean age, 46 years; 53% men) with TRD were randomly allocated minocycline 200 mg/day or matching placebo in addition to usual antidepressant treatment for 6 weeks.

Results showed minocycline was well tolerated but was not superior to placebo in reducing depressive symptoms, the researchers report.

Overall, the mean Montgomery-Åsberg Depression Rating Scale (MADRS) score at baseline was 26.5. There was no significant between-group difference in mean change in MADRS score from baseline to 6 weeks, the primary outcome.

After 6 weeks of treatment, the mean reduction in MADRS score was 8.46 points in the minocycline group versus 8.01 points in the placebo group, and the difference of 1.46 points was not significant (P = .25).

Six weeks of minocycline treatment did not alter the course of depression severity, compared with placebo, the investigators noted.

Minocycline treatment also showed no statistically significant effect on secondary outcomes of response, remission, and various other clinical rating scales.
 

Caveats and cautionary notes

The researchers noted that one explanation for the null result of the MinoTRD trial could be that the 6-week treatment duration was not long enough to reveal detectable differences. They point to a small study that showed a strong effect of minocycline, compared with placebo by and after 8 weeks of treatment.

However, a closer look at that study suggests the overall effect in the minocycline group was caused by an almost-complete lack of improvement in the placebo group, “which is very unusual,” the investigators wrote.

In the MinoTRD trial, the magnitude of improvement for placebo was as expected from similar trials in TRD, they pointed out.

They also noted that, unlike some other trials, the MinoTRD trial purposely recruited a naturalistic population of TRD, assuming (but not confirming) elevated baseline inflammation as a potential underlying cause in at least a subgroup of the patients.

Post hoc stratification by baseline CRP levels in MinoTRD participants did not yield any results supporting the hypothesis of minocycline treatment possibly being more effective in participants with higher-grade baseline inflammation, the researchers reported.

“Our results from this large randomized controlled trial of a pleiotropic anti-inflammatory drug in this difficult-to-treat patient population are of great clinical importance, robustly demonstrating that minocycline add-on treatment does not outperform placebo, not even in those participants with elevated levels of CRP prior to treatment initiation,” they wrote.

The trial was funded by a grant from the German Federal Ministry of Education and Research within the Consortium Optimizing Treatment of Depression, as part of the Research Network for Psychiatric Disorders. Dr. Hellmann-Regen reported no relevant financial relationship.

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

The broad-spectrum antibiotic minocycline (multiple brands) is not effective when added to standard antidepressant therapy, the largest randomized, controlled trial of minocycline in treatment-resistant depression (TRD) shows.

In the MinoTRD trial, 6 weeks of minocycline 200 mg daily added to stable antidepressant therapy did not show a statistically significant advantage over placebo on the overall course of depressive symptoms.

“The failure of minocycline treatment to reduce depressive symptoms in a naturalistic sample of patients with TRD is a setback for anti-inflammatory treatment strategies in this clinical population,” Julian Hellmann-Regen, MD, department of psychiatry and neurosciences, Charité – Universitätsmedizin Berlin, and colleagues wrote.  

The findings were published online in JAMA Network Open.
 

No additional benefit

The “inflammatory hypothesis” of depression maintains that depression arises from increased immune activation and neurotrophic mechanisms.

This view is supported by observations that depression is accompanied by increased levels of proinflammatory cytokines. In addition, low-grade inflammatory processes may interfere with response to typical antidepressant medications. 

Minocycline has been put forth as a novel antidepressant, and a few small trials have hinted at a benefit.

In the MinoTRD trial, 168 patients (mean age, 46 years; 53% men) with TRD were randomly allocated minocycline 200 mg/day or matching placebo in addition to usual antidepressant treatment for 6 weeks.

Results showed minocycline was well tolerated but was not superior to placebo in reducing depressive symptoms, the researchers report.

Overall, the mean Montgomery-Åsberg Depression Rating Scale (MADRS) score at baseline was 26.5. There was no significant between-group difference in mean change in MADRS score from baseline to 6 weeks, the primary outcome.

After 6 weeks of treatment, the mean reduction in MADRS score was 8.46 points in the minocycline group versus 8.01 points in the placebo group, and the difference of 1.46 points was not significant (P = .25).

Six weeks of minocycline treatment did not alter the course of depression severity, compared with placebo, the investigators noted.

Minocycline treatment also showed no statistically significant effect on secondary outcomes of response, remission, and various other clinical rating scales.
 

Caveats and cautionary notes

The researchers noted that one explanation for the null result of the MinoTRD trial could be that the 6-week treatment duration was not long enough to reveal detectable differences. They point to a small study that showed a strong effect of minocycline, compared with placebo by and after 8 weeks of treatment.

However, a closer look at that study suggests the overall effect in the minocycline group was caused by an almost-complete lack of improvement in the placebo group, “which is very unusual,” the investigators wrote.

In the MinoTRD trial, the magnitude of improvement for placebo was as expected from similar trials in TRD, they pointed out.

They also noted that, unlike some other trials, the MinoTRD trial purposely recruited a naturalistic population of TRD, assuming (but not confirming) elevated baseline inflammation as a potential underlying cause in at least a subgroup of the patients.

Post hoc stratification by baseline CRP levels in MinoTRD participants did not yield any results supporting the hypothesis of minocycline treatment possibly being more effective in participants with higher-grade baseline inflammation, the researchers reported.

“Our results from this large randomized controlled trial of a pleiotropic anti-inflammatory drug in this difficult-to-treat patient population are of great clinical importance, robustly demonstrating that minocycline add-on treatment does not outperform placebo, not even in those participants with elevated levels of CRP prior to treatment initiation,” they wrote.

The trial was funded by a grant from the German Federal Ministry of Education and Research within the Consortium Optimizing Treatment of Depression, as part of the Research Network for Psychiatric Disorders. Dr. Hellmann-Regen reported no relevant financial relationship.

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

The broad-spectrum antibiotic minocycline (multiple brands) is not effective when added to standard antidepressant therapy, the largest randomized, controlled trial of minocycline in treatment-resistant depression (TRD) shows.

In the MinoTRD trial, 6 weeks of minocycline 200 mg daily added to stable antidepressant therapy did not show a statistically significant advantage over placebo on the overall course of depressive symptoms.

“The failure of minocycline treatment to reduce depressive symptoms in a naturalistic sample of patients with TRD is a setback for anti-inflammatory treatment strategies in this clinical population,” Julian Hellmann-Regen, MD, department of psychiatry and neurosciences, Charité – Universitätsmedizin Berlin, and colleagues wrote.  

The findings were published online in JAMA Network Open.
 

No additional benefit

The “inflammatory hypothesis” of depression maintains that depression arises from increased immune activation and neurotrophic mechanisms.

This view is supported by observations that depression is accompanied by increased levels of proinflammatory cytokines. In addition, low-grade inflammatory processes may interfere with response to typical antidepressant medications. 

Minocycline has been put forth as a novel antidepressant, and a few small trials have hinted at a benefit.

In the MinoTRD trial, 168 patients (mean age, 46 years; 53% men) with TRD were randomly allocated minocycline 200 mg/day or matching placebo in addition to usual antidepressant treatment for 6 weeks.

Results showed minocycline was well tolerated but was not superior to placebo in reducing depressive symptoms, the researchers report.

Overall, the mean Montgomery-Åsberg Depression Rating Scale (MADRS) score at baseline was 26.5. There was no significant between-group difference in mean change in MADRS score from baseline to 6 weeks, the primary outcome.

After 6 weeks of treatment, the mean reduction in MADRS score was 8.46 points in the minocycline group versus 8.01 points in the placebo group, and the difference of 1.46 points was not significant (P = .25).

Six weeks of minocycline treatment did not alter the course of depression severity, compared with placebo, the investigators noted.

Minocycline treatment also showed no statistically significant effect on secondary outcomes of response, remission, and various other clinical rating scales.
 

Caveats and cautionary notes

The researchers noted that one explanation for the null result of the MinoTRD trial could be that the 6-week treatment duration was not long enough to reveal detectable differences. They point to a small study that showed a strong effect of minocycline, compared with placebo by and after 8 weeks of treatment.

However, a closer look at that study suggests the overall effect in the minocycline group was caused by an almost-complete lack of improvement in the placebo group, “which is very unusual,” the investigators wrote.

In the MinoTRD trial, the magnitude of improvement for placebo was as expected from similar trials in TRD, they pointed out.

They also noted that, unlike some other trials, the MinoTRD trial purposely recruited a naturalistic population of TRD, assuming (but not confirming) elevated baseline inflammation as a potential underlying cause in at least a subgroup of the patients.

Post hoc stratification by baseline CRP levels in MinoTRD participants did not yield any results supporting the hypothesis of minocycline treatment possibly being more effective in participants with higher-grade baseline inflammation, the researchers reported.

“Our results from this large randomized controlled trial of a pleiotropic anti-inflammatory drug in this difficult-to-treat patient population are of great clinical importance, robustly demonstrating that minocycline add-on treatment does not outperform placebo, not even in those participants with elevated levels of CRP prior to treatment initiation,” they wrote.

The trial was funded by a grant from the German Federal Ministry of Education and Research within the Consortium Optimizing Treatment of Depression, as part of the Research Network for Psychiatric Disorders. Dr. Hellmann-Regen reported no relevant financial relationship.

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