Mental Health

A novel antidepressant (AXS-05, Axsome Therapeutics) appears to have a rapid and durable effect in patients with major depressive disorder (MDD), results of an open label, phase 3 trial, show. Yet, its new drug application (NDA) remains in limbo with the U.S. Food and Drug Administration for reasons that are unclear.

In the study, which included 876 patients with MDD, results showed the drug, a combination of dextromethorphan and bupropion, had a clinical response rate of 80% and a remission rate of almost 70%. In addition, functional improvements were “substantial” and AXS-05 was determined to be “generally safe and well-tolerated.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

The study

The COMET trial was a phase 3, multicenter, U.S. trial, in which patients with MDD were treated with AXS-05 twice daily for up to 12 months. Patients had to have a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 25. They could have completed a prior AXS-05 study or be newly enrolled.

Of 876 patients included in the study, 611 were newly enrolled. The mean age was 42.4 years, and 62.4% were women. Just over half (58.1%) were White, with 35.6% Black, and 2.0% Asian. The mean body mass index was 31.4 kg/m².

The mean MADRS total score at baseline was 32.7 and the Sheehan Disability Scale (SDS) score was 20.0.

Presenting efficacy data in 609 newly enrolled patients, the team showed that MADRS total scores fell sharply on starting AXS-05, by 9.1 points at week 1, 14.0 points at week 2, and 21.2 points at week 6.

By 6 months, the reduction over baseline was 23.9 points, which was maintained out to 12 months, at a mean reduction of 23.0 points.

The proportion of patients achieving a clinical response, defined as a greater than or equal to 50% improvement in MADRS scores, was 18.8% at week 1, 39.7% at week 2, and 73.2% at week 6. There was a clinical response in 84.6% of patients at 6 months and in 82.8% at 12 months.

Clinical remission, defined as a MADRS score less than or equal to 10, was achieved in 8.3% of patients at week 1, rising to 21.5% at week 2, and 52.5% at week 6. At 6 months, 68.7% of patients were in clinical remission, reaching 69.0% at 12 months.

These benefits were accompanied by substantial improvements in depressive symptoms on the Clinical Global Impression of Improvement scale, with a marked or moderate improvement seen in 86.7% of patients at 6 months and 93.1% at 12 months.

Moreover, a clinical response in functioning on the SDS was achieved by 80.6% of patients at 6 months and 75.9% at 12 months.

The safety analysis of AXS-05 in the entire cohort suggested it was well-tolerated, with dizziness seen in 12.7% of patients, along with nausea in 11.9%, headache in 8.8%, dry mouth in 7.1%, and decreased appetite in 6.1%.

The rate of discontinuation due to adverse events was 8.4%, and there were no signs of psychotomimetic effects, cognitive impairment, weight gain, or increased sexual dysfunction.

Other research presented at the meeting also showed that the drug was associated with a reduction in suicidal ideation and increased rates of suicidal ideation resolution, and was also effective for treatment-resistant depression.

Results from an analysis of the ASCEND phase 2 and GEMINI phase 3 trials also suggested that AXS-05 was superior to both bupropion and placebo in achieving rapid and sustained improvements in depression symptoms.

FDA delay

Yet despite these seemingly positive findings, the FDA appears to have issues with the agent’s new drug application.

As reported in August, the agency reviewed the NDA for AXS-05 for the treatment of MDD, but at that time the drug’s manufacturer revealed that the agency had identified “deficiencies that preclude labeling discussions at this time.”

With the latest results presented at ECNP 2021, this news organization asked Axsome about the status of the NDA and whether there had been any further discussions and/or movement with the FDA.

Instead of a direct reply from the drug company, this news organization was directed to a statement released by Axsome in August announcing that the FDA had informed the company that its NDA review “would not be completed by the Prescription Drug User Fee Act target action date of August 22, 2021.”

“The FDA did not request additional information from the company, and the review of the application is ongoing,” the statement said. Axsome did not respond to further questions.
 

‘Impressive’ remission rate

Commenting on the research, Marin Jukic, PhD, department of physiology and pharmacology, Karolinska Institutet, Stockholm, who was not involved in the research, said AXS-05 “looks promising in relation to the efficacy and tolerability results” with a remission rate that is “truly impressive.”

However, Dr. Jukic cautioned that it was an open-label trial and therefore had no placebo or active comparator arms.

He noted that it would be “interesting to compare the efficacy with placebo and escitalopram, for example, to evaluate the potential for the benefits and efficacy better.”

The research was funded by Axsome Therapeutics, and, except for one, the researchers for the four studies are employees of Axsome Therapeutics.

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

A novel antidepressant (AXS-05, Axsome Therapeutics) appears to have a rapid and durable effect in patients with major depressive disorder (MDD), results of an open label, phase 3 trial, show. Yet, its new drug application (NDA) remains in limbo with the U.S. Food and Drug Administration for reasons that are unclear.

In the study, which included 876 patients with MDD, results showed the drug, a combination of dextromethorphan and bupropion, had a clinical response rate of 80% and a remission rate of almost 70%. In addition, functional improvements were “substantial” and AXS-05 was determined to be “generally safe and well-tolerated.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

The study

The COMET trial was a phase 3, multicenter, U.S. trial, in which patients with MDD were treated with AXS-05 twice daily for up to 12 months. Patients had to have a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 25. They could have completed a prior AXS-05 study or be newly enrolled.

Of 876 patients included in the study, 611 were newly enrolled. The mean age was 42.4 years, and 62.4% were women. Just over half (58.1%) were White, with 35.6% Black, and 2.0% Asian. The mean body mass index was 31.4 kg/m².

The mean MADRS total score at baseline was 32.7 and the Sheehan Disability Scale (SDS) score was 20.0.

Presenting efficacy data in 609 newly enrolled patients, the team showed that MADRS total scores fell sharply on starting AXS-05, by 9.1 points at week 1, 14.0 points at week 2, and 21.2 points at week 6.

By 6 months, the reduction over baseline was 23.9 points, which was maintained out to 12 months, at a mean reduction of 23.0 points.

The proportion of patients achieving a clinical response, defined as a greater than or equal to 50% improvement in MADRS scores, was 18.8% at week 1, 39.7% at week 2, and 73.2% at week 6. There was a clinical response in 84.6% of patients at 6 months and in 82.8% at 12 months.

Clinical remission, defined as a MADRS score less than or equal to 10, was achieved in 8.3% of patients at week 1, rising to 21.5% at week 2, and 52.5% at week 6. At 6 months, 68.7% of patients were in clinical remission, reaching 69.0% at 12 months.

These benefits were accompanied by substantial improvements in depressive symptoms on the Clinical Global Impression of Improvement scale, with a marked or moderate improvement seen in 86.7% of patients at 6 months and 93.1% at 12 months.

Moreover, a clinical response in functioning on the SDS was achieved by 80.6% of patients at 6 months and 75.9% at 12 months.

The safety analysis of AXS-05 in the entire cohort suggested it was well-tolerated, with dizziness seen in 12.7% of patients, along with nausea in 11.9%, headache in 8.8%, dry mouth in 7.1%, and decreased appetite in 6.1%.

The rate of discontinuation due to adverse events was 8.4%, and there were no signs of psychotomimetic effects, cognitive impairment, weight gain, or increased sexual dysfunction.

Other research presented at the meeting also showed that the drug was associated with a reduction in suicidal ideation and increased rates of suicidal ideation resolution, and was also effective for treatment-resistant depression.

Results from an analysis of the ASCEND phase 2 and GEMINI phase 3 trials also suggested that AXS-05 was superior to both bupropion and placebo in achieving rapid and sustained improvements in depression symptoms.

FDA delay

Yet despite these seemingly positive findings, the FDA appears to have issues with the agent’s new drug application.

As reported in August, the agency reviewed the NDA for AXS-05 for the treatment of MDD, but at that time the drug’s manufacturer revealed that the agency had identified “deficiencies that preclude labeling discussions at this time.”

With the latest results presented at ECNP 2021, this news organization asked Axsome about the status of the NDA and whether there had been any further discussions and/or movement with the FDA.

Instead of a direct reply from the drug company, this news organization was directed to a statement released by Axsome in August announcing that the FDA had informed the company that its NDA review “would not be completed by the Prescription Drug User Fee Act target action date of August 22, 2021.”

“The FDA did not request additional information from the company, and the review of the application is ongoing,” the statement said. Axsome did not respond to further questions.
 

‘Impressive’ remission rate

Commenting on the research, Marin Jukic, PhD, department of physiology and pharmacology, Karolinska Institutet, Stockholm, who was not involved in the research, said AXS-05 “looks promising in relation to the efficacy and tolerability results” with a remission rate that is “truly impressive.”

However, Dr. Jukic cautioned that it was an open-label trial and therefore had no placebo or active comparator arms.

He noted that it would be “interesting to compare the efficacy with placebo and escitalopram, for example, to evaluate the potential for the benefits and efficacy better.”

The research was funded by Axsome Therapeutics, and, except for one, the researchers for the four studies are employees of Axsome Therapeutics.

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

A novel antidepressant (AXS-05, Axsome Therapeutics) appears to have a rapid and durable effect in patients with major depressive disorder (MDD), results of an open label, phase 3 trial, show. Yet, its new drug application (NDA) remains in limbo with the U.S. Food and Drug Administration for reasons that are unclear.

In the study, which included 876 patients with MDD, results showed the drug, a combination of dextromethorphan and bupropion, had a clinical response rate of 80% and a remission rate of almost 70%. In addition, functional improvements were “substantial” and AXS-05 was determined to be “generally safe and well-tolerated.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

The study

The COMET trial was a phase 3, multicenter, U.S. trial, in which patients with MDD were treated with AXS-05 twice daily for up to 12 months. Patients had to have a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 25. They could have completed a prior AXS-05 study or be newly enrolled.

Of 876 patients included in the study, 611 were newly enrolled. The mean age was 42.4 years, and 62.4% were women. Just over half (58.1%) were White, with 35.6% Black, and 2.0% Asian. The mean body mass index was 31.4 kg/m².

The mean MADRS total score at baseline was 32.7 and the Sheehan Disability Scale (SDS) score was 20.0.

Presenting efficacy data in 609 newly enrolled patients, the team showed that MADRS total scores fell sharply on starting AXS-05, by 9.1 points at week 1, 14.0 points at week 2, and 21.2 points at week 6.

By 6 months, the reduction over baseline was 23.9 points, which was maintained out to 12 months, at a mean reduction of 23.0 points.

The proportion of patients achieving a clinical response, defined as a greater than or equal to 50% improvement in MADRS scores, was 18.8% at week 1, 39.7% at week 2, and 73.2% at week 6. There was a clinical response in 84.6% of patients at 6 months and in 82.8% at 12 months.

Clinical remission, defined as a MADRS score less than or equal to 10, was achieved in 8.3% of patients at week 1, rising to 21.5% at week 2, and 52.5% at week 6. At 6 months, 68.7% of patients were in clinical remission, reaching 69.0% at 12 months.

These benefits were accompanied by substantial improvements in depressive symptoms on the Clinical Global Impression of Improvement scale, with a marked or moderate improvement seen in 86.7% of patients at 6 months and 93.1% at 12 months.

Moreover, a clinical response in functioning on the SDS was achieved by 80.6% of patients at 6 months and 75.9% at 12 months.

The safety analysis of AXS-05 in the entire cohort suggested it was well-tolerated, with dizziness seen in 12.7% of patients, along with nausea in 11.9%, headache in 8.8%, dry mouth in 7.1%, and decreased appetite in 6.1%.

The rate of discontinuation due to adverse events was 8.4%, and there were no signs of psychotomimetic effects, cognitive impairment, weight gain, or increased sexual dysfunction.

Other research presented at the meeting also showed that the drug was associated with a reduction in suicidal ideation and increased rates of suicidal ideation resolution, and was also effective for treatment-resistant depression.

Results from an analysis of the ASCEND phase 2 and GEMINI phase 3 trials also suggested that AXS-05 was superior to both bupropion and placebo in achieving rapid and sustained improvements in depression symptoms.

FDA delay

Yet despite these seemingly positive findings, the FDA appears to have issues with the agent’s new drug application.

As reported in August, the agency reviewed the NDA for AXS-05 for the treatment of MDD, but at that time the drug’s manufacturer revealed that the agency had identified “deficiencies that preclude labeling discussions at this time.”

With the latest results presented at ECNP 2021, this news organization asked Axsome about the status of the NDA and whether there had been any further discussions and/or movement with the FDA.

Instead of a direct reply from the drug company, this news organization was directed to a statement released by Axsome in August announcing that the FDA had informed the company that its NDA review “would not be completed by the Prescription Drug User Fee Act target action date of August 22, 2021.”

“The FDA did not request additional information from the company, and the review of the application is ongoing,” the statement said. Axsome did not respond to further questions.
 

‘Impressive’ remission rate

Commenting on the research, Marin Jukic, PhD, department of physiology and pharmacology, Karolinska Institutet, Stockholm, who was not involved in the research, said AXS-05 “looks promising in relation to the efficacy and tolerability results” with a remission rate that is “truly impressive.”

However, Dr. Jukic cautioned that it was an open-label trial and therefore had no placebo or active comparator arms.

He noted that it would be “interesting to compare the efficacy with placebo and escitalopram, for example, to evaluate the potential for the benefits and efficacy better.”

The research was funded by Axsome Therapeutics, and, except for one, the researchers for the four studies are employees of Axsome Therapeutics.

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

Patients with comorbid anxiety and mood disorders who have reduced, albeit “normal” serum levels of thyroid-stimulating hormone (TSH) may be at increased risk for suicidal ideation, new research suggests.

In a cross-sectional study, clinical data on diagnosis, medication use, and symptom scores were gathered, along with assessments of blood levels of thyroid axis hormones, in patients with both anxiety and mood disorders.

After investigators accounted for age, gender, symptoms, medication use, and other potential confounders, patients with suicidal ideation were 54% less likely to have higher TSH levels. There was no association found with other thyroid hormones.

Based on the results, the assessment of thyroid hormone levels “may be important for suicide prevention and might allow clinicians to evaluate the potential of the suicidal ideation risk in individuals with [anxiety and mood disorders],” co-investigator Vilma Liaugaudaite, PhD student, Neuroscience Institute of the Lithuanian University of Health Sciences, Palanga, and colleagues note.

The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress.
 

‘Complex mechanism’

Ms. Liaugaudaite told this news organization that thyroid hormones are known to have a “profound” effect on mood and behavior.

Recent studies show “various degrees of hypothalamic-pituitary-thyroid axis dysregulation are associated with suicidal behavior” in patients with depression, she added.

Noting that disturbances in the serotonin system “constitute the most common biochemical abnormality associated with suicidal behavior,” Ms. Liaugaudaite said it is thought thyroid hormones “are involved in a complex compensatory mechanism to correct reduced central 5-hydroxytryptamine activity” via lower TSH levels.

In addition, hypersecretion of thyrotropin-releasing hormone, which stimulates the release of TSH, “has been considered a compensatory mechanism to maintain normal thyroid hormone secretion and normalize serotonin activity in depressed patients,” she said.

To investigate associations between thyroid axis hormones and suicidality in individuals with comorbid anxiety and mood disorders, the researchers assessed consecutive patients attending a stress disorders clinic.

Sociodemographic and clinical information was gathered, and patients completed the Mini International Neuropsychiatric Interview, the Patient Health Questionnaire-9 (PHQ-9), and the General Anxiety Disorder-7 (GAD-7) scale.

Fasting blood samples were also tested for free thyroxine (FT4), free triiodothyronine (FT3), and TSH levels.

Significant association

Seventy-seven patients aged 18 to 73 years participated in the study. Of these, 59 were women. Suicidal ideation was identified in 42 participants. Serum FT4, FT3, and TSH levels were within the normal range.

Badmanproduction/Thinkstock

There were no significant differences between patients with and without suicidal ideation in terms of age, gender, education, obesity, smoking, and medication use.

Suicidal ideation was associated with higher scores on the PHQ-9 (15.5 vs. 13.3; P = .085), and with lower TSH levels (1.54 IU/L vs. 2.04 IU/L; P = .092).

The association between serum TSH levels and suicidal ideation was significant after multivariate logistic regression analysis accounted for age, gender, PHQ-9 and GAD-7 scores, education, body mass index, smoking, and use of antidepressants, tranquilizers, mood stabilizers, and neuroleptics.

Specifically, patients with suicidal ideation were significantly less likely to have higher TSH levels than those without, at an odds ratio of 0.46 (P = .027).

There were no significant associations between serum FT4 and FT3 levels and suicidal ideation.


 

Interesting, but preliminary

Commenting on the findings, Sanjeev Sockalingam, MD, vice chair and professor of psychiatry at the University of Toronto, said it is an “interesting study” because the literature on trying to identify individuals at risk for suicidal ideation or behaviors is “quite mixed, in terms of the results.”

However, it was a cross-sectional study with a relatively small sample size, and studies of this nature typically include patients with hypothyroidism “who end up having suicidal thoughts,” said Dr. Sockalingam, who was not involved with the research.

“I do wonder, given the sample size and patient population, if there may be other factors that may have been related to this,” he added.

Dr. Sockalingam noted that he would like to see more data on the medications the patients were taking, and he underlined that the thyroid levels were in the normal range, “so it’s a bit difficult to untangle what that means in terms of these subtle changes in thyroid levels.”

Robert Levitan, MD, Cameron Wilson Chair in Depression Research at the Centre for Addiction and Mental Health, Toronto, also emphasized that the thyroid levels were in the normal range.

He commented that it therefore “seems unlikely that there’s going to be some biological effect that’s going to affect the brain in a significant enough way” to influence suicidal ideation.

Dr. Levitan continued, “What’s probably happening is there’s some other clinical issue here that they just haven’t picked up on that’s leading in one direction to the suicidal ideation and perhaps affecting the TSH to some extent.”

Although the study is, therefore, “preliminary,” the findings are nevertheless “interesting,” he concluded.

The study received no funding. Ms. Liaugaudaite, Dr. Sockalingam, and Dr. Levitan have disclosed no relevant financial relationships.

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

Patients with comorbid anxiety and mood disorders who have reduced, albeit “normal” serum levels of thyroid-stimulating hormone (TSH) may be at increased risk for suicidal ideation, new research suggests.

In a cross-sectional study, clinical data on diagnosis, medication use, and symptom scores were gathered, along with assessments of blood levels of thyroid axis hormones, in patients with both anxiety and mood disorders.

After investigators accounted for age, gender, symptoms, medication use, and other potential confounders, patients with suicidal ideation were 54% less likely to have higher TSH levels. There was no association found with other thyroid hormones.

Based on the results, the assessment of thyroid hormone levels “may be important for suicide prevention and might allow clinicians to evaluate the potential of the suicidal ideation risk in individuals with [anxiety and mood disorders],” co-investigator Vilma Liaugaudaite, PhD student, Neuroscience Institute of the Lithuanian University of Health Sciences, Palanga, and colleagues note.

The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress.
 

‘Complex mechanism’

Ms. Liaugaudaite told this news organization that thyroid hormones are known to have a “profound” effect on mood and behavior.

Recent studies show “various degrees of hypothalamic-pituitary-thyroid axis dysregulation are associated with suicidal behavior” in patients with depression, she added.

Noting that disturbances in the serotonin system “constitute the most common biochemical abnormality associated with suicidal behavior,” Ms. Liaugaudaite said it is thought thyroid hormones “are involved in a complex compensatory mechanism to correct reduced central 5-hydroxytryptamine activity” via lower TSH levels.

In addition, hypersecretion of thyrotropin-releasing hormone, which stimulates the release of TSH, “has been considered a compensatory mechanism to maintain normal thyroid hormone secretion and normalize serotonin activity in depressed patients,” she said.

To investigate associations between thyroid axis hormones and suicidality in individuals with comorbid anxiety and mood disorders, the researchers assessed consecutive patients attending a stress disorders clinic.

Sociodemographic and clinical information was gathered, and patients completed the Mini International Neuropsychiatric Interview, the Patient Health Questionnaire-9 (PHQ-9), and the General Anxiety Disorder-7 (GAD-7) scale.

Fasting blood samples were also tested for free thyroxine (FT4), free triiodothyronine (FT3), and TSH levels.

Significant association

Seventy-seven patients aged 18 to 73 years participated in the study. Of these, 59 were women. Suicidal ideation was identified in 42 participants. Serum FT4, FT3, and TSH levels were within the normal range.

Badmanproduction/Thinkstock

There were no significant differences between patients with and without suicidal ideation in terms of age, gender, education, obesity, smoking, and medication use.

Suicidal ideation was associated with higher scores on the PHQ-9 (15.5 vs. 13.3; P = .085), and with lower TSH levels (1.54 IU/L vs. 2.04 IU/L; P = .092).

The association between serum TSH levels and suicidal ideation was significant after multivariate logistic regression analysis accounted for age, gender, PHQ-9 and GAD-7 scores, education, body mass index, smoking, and use of antidepressants, tranquilizers, mood stabilizers, and neuroleptics.

Specifically, patients with suicidal ideation were significantly less likely to have higher TSH levels than those without, at an odds ratio of 0.46 (P = .027).

There were no significant associations between serum FT4 and FT3 levels and suicidal ideation.


 

Interesting, but preliminary

Commenting on the findings, Sanjeev Sockalingam, MD, vice chair and professor of psychiatry at the University of Toronto, said it is an “interesting study” because the literature on trying to identify individuals at risk for suicidal ideation or behaviors is “quite mixed, in terms of the results.”

However, it was a cross-sectional study with a relatively small sample size, and studies of this nature typically include patients with hypothyroidism “who end up having suicidal thoughts,” said Dr. Sockalingam, who was not involved with the research.

“I do wonder, given the sample size and patient population, if there may be other factors that may have been related to this,” he added.

Dr. Sockalingam noted that he would like to see more data on the medications the patients were taking, and he underlined that the thyroid levels were in the normal range, “so it’s a bit difficult to untangle what that means in terms of these subtle changes in thyroid levels.”

Robert Levitan, MD, Cameron Wilson Chair in Depression Research at the Centre for Addiction and Mental Health, Toronto, also emphasized that the thyroid levels were in the normal range.

He commented that it therefore “seems unlikely that there’s going to be some biological effect that’s going to affect the brain in a significant enough way” to influence suicidal ideation.

Dr. Levitan continued, “What’s probably happening is there’s some other clinical issue here that they just haven’t picked up on that’s leading in one direction to the suicidal ideation and perhaps affecting the TSH to some extent.”

Although the study is, therefore, “preliminary,” the findings are nevertheless “interesting,” he concluded.

The study received no funding. Ms. Liaugaudaite, Dr. Sockalingam, and Dr. Levitan have disclosed no relevant financial relationships.

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

Patients with comorbid anxiety and mood disorders who have reduced, albeit “normal” serum levels of thyroid-stimulating hormone (TSH) may be at increased risk for suicidal ideation, new research suggests.

In a cross-sectional study, clinical data on diagnosis, medication use, and symptom scores were gathered, along with assessments of blood levels of thyroid axis hormones, in patients with both anxiety and mood disorders.

After investigators accounted for age, gender, symptoms, medication use, and other potential confounders, patients with suicidal ideation were 54% less likely to have higher TSH levels. There was no association found with other thyroid hormones.

Based on the results, the assessment of thyroid hormone levels “may be important for suicide prevention and might allow clinicians to evaluate the potential of the suicidal ideation risk in individuals with [anxiety and mood disorders],” co-investigator Vilma Liaugaudaite, PhD student, Neuroscience Institute of the Lithuanian University of Health Sciences, Palanga, and colleagues note.

The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress.
 

‘Complex mechanism’

Ms. Liaugaudaite told this news organization that thyroid hormones are known to have a “profound” effect on mood and behavior.

Recent studies show “various degrees of hypothalamic-pituitary-thyroid axis dysregulation are associated with suicidal behavior” in patients with depression, she added.

Noting that disturbances in the serotonin system “constitute the most common biochemical abnormality associated with suicidal behavior,” Ms. Liaugaudaite said it is thought thyroid hormones “are involved in a complex compensatory mechanism to correct reduced central 5-hydroxytryptamine activity” via lower TSH levels.

In addition, hypersecretion of thyrotropin-releasing hormone, which stimulates the release of TSH, “has been considered a compensatory mechanism to maintain normal thyroid hormone secretion and normalize serotonin activity in depressed patients,” she said.

To investigate associations between thyroid axis hormones and suicidality in individuals with comorbid anxiety and mood disorders, the researchers assessed consecutive patients attending a stress disorders clinic.

Sociodemographic and clinical information was gathered, and patients completed the Mini International Neuropsychiatric Interview, the Patient Health Questionnaire-9 (PHQ-9), and the General Anxiety Disorder-7 (GAD-7) scale.

Fasting blood samples were also tested for free thyroxine (FT4), free triiodothyronine (FT3), and TSH levels.

Significant association

Seventy-seven patients aged 18 to 73 years participated in the study. Of these, 59 were women. Suicidal ideation was identified in 42 participants. Serum FT4, FT3, and TSH levels were within the normal range.

Badmanproduction/Thinkstock

There were no significant differences between patients with and without suicidal ideation in terms of age, gender, education, obesity, smoking, and medication use.

Suicidal ideation was associated with higher scores on the PHQ-9 (15.5 vs. 13.3; P = .085), and with lower TSH levels (1.54 IU/L vs. 2.04 IU/L; P = .092).

The association between serum TSH levels and suicidal ideation was significant after multivariate logistic regression analysis accounted for age, gender, PHQ-9 and GAD-7 scores, education, body mass index, smoking, and use of antidepressants, tranquilizers, mood stabilizers, and neuroleptics.

Specifically, patients with suicidal ideation were significantly less likely to have higher TSH levels than those without, at an odds ratio of 0.46 (P = .027).

There were no significant associations between serum FT4 and FT3 levels and suicidal ideation.


 

Interesting, but preliminary

Commenting on the findings, Sanjeev Sockalingam, MD, vice chair and professor of psychiatry at the University of Toronto, said it is an “interesting study” because the literature on trying to identify individuals at risk for suicidal ideation or behaviors is “quite mixed, in terms of the results.”

However, it was a cross-sectional study with a relatively small sample size, and studies of this nature typically include patients with hypothyroidism “who end up having suicidal thoughts,” said Dr. Sockalingam, who was not involved with the research.

“I do wonder, given the sample size and patient population, if there may be other factors that may have been related to this,” he added.

Dr. Sockalingam noted that he would like to see more data on the medications the patients were taking, and he underlined that the thyroid levels were in the normal range, “so it’s a bit difficult to untangle what that means in terms of these subtle changes in thyroid levels.”

Robert Levitan, MD, Cameron Wilson Chair in Depression Research at the Centre for Addiction and Mental Health, Toronto, also emphasized that the thyroid levels were in the normal range.

He commented that it therefore “seems unlikely that there’s going to be some biological effect that’s going to affect the brain in a significant enough way” to influence suicidal ideation.

Dr. Levitan continued, “What’s probably happening is there’s some other clinical issue here that they just haven’t picked up on that’s leading in one direction to the suicidal ideation and perhaps affecting the TSH to some extent.”

Although the study is, therefore, “preliminary,” the findings are nevertheless “interesting,” he concluded.

The study received no funding. Ms. Liaugaudaite, Dr. Sockalingam, and Dr. Levitan have disclosed no relevant financial relationships.

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

With all the lockdowns and social distancing of the pandemic, millions of people have had a lot of time to themselves. Many may have filled that time with baking, long walks, or video games, but minds wandering during these periods was inevitable. Coincident with these experiences were increases in depression and anxiety, which could be linked to the same brain network that is thought to support a meandering mind, called the default mode network.

©Thinkstock

Scientists interested in this network wanted to understand how wandering thoughts can lead some people to a state of brooding in which the same negative thoughts resurface repeatedly. To gain some insight into these patterns, they recorded more than 2,000 thoughts spoken aloud by 78 study participants who did nothing but let their minds wander for 10 minutes.

Senior researcher Jessica Andrews-Hanna, PhD, assistant professor of psychology, University of Arizona, Tucson, and colleagues hoped that analyzing these stream-of-consciousness thoughts could yield insights into how people become stuck in negative mental spirals.

They found that most participants thought about the present or future in words that were neither particularly negative nor positive. Almost three-quarters of the thoughts were focused inward on the person or were imaginative.
 

Negativity breeds negativity

But the investigators found an interesting pattern with regard to negative thoughts. The more negative someone’s thoughts became, the more likely that their next idea would be related to their previous one. In other words, negative thoughts created a chain reaction of more negative thoughts.

Positive thoughts, in contrast, tended to be followed by completely unrelated ruminations, indicating true mental meandering. The pattern suggested that negativity tends to narrow the range of thoughts, whereas positivity tends to expand it during periods in which the mind wanders.

The researchers also found, unsurprisingly, that negative thoughts that were focused on the self and on the past were more likely to result in brooding and that positive thoughts were less likely to arise.

Most study participants were young and educated and may have only said things that they were comfortable allowing the researchers to hear. And because the authors didn’t ask participants about their moods, the investigators could not associate specific patterns of thought with any mental health conditions.

Although the findings, published in Scientific Reports, do not on their own point to solutions for depression or anxiety, they may offer a starting point for future research into how negative trains of thoughts begin – and perhaps how to derail them.

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

With all the lockdowns and social distancing of the pandemic, millions of people have had a lot of time to themselves. Many may have filled that time with baking, long walks, or video games, but minds wandering during these periods was inevitable. Coincident with these experiences were increases in depression and anxiety, which could be linked to the same brain network that is thought to support a meandering mind, called the default mode network.

©Thinkstock

Scientists interested in this network wanted to understand how wandering thoughts can lead some people to a state of brooding in which the same negative thoughts resurface repeatedly. To gain some insight into these patterns, they recorded more than 2,000 thoughts spoken aloud by 78 study participants who did nothing but let their minds wander for 10 minutes.

Senior researcher Jessica Andrews-Hanna, PhD, assistant professor of psychology, University of Arizona, Tucson, and colleagues hoped that analyzing these stream-of-consciousness thoughts could yield insights into how people become stuck in negative mental spirals.

They found that most participants thought about the present or future in words that were neither particularly negative nor positive. Almost three-quarters of the thoughts were focused inward on the person or were imaginative.
 

Negativity breeds negativity

But the investigators found an interesting pattern with regard to negative thoughts. The more negative someone’s thoughts became, the more likely that their next idea would be related to their previous one. In other words, negative thoughts created a chain reaction of more negative thoughts.

Positive thoughts, in contrast, tended to be followed by completely unrelated ruminations, indicating true mental meandering. The pattern suggested that negativity tends to narrow the range of thoughts, whereas positivity tends to expand it during periods in which the mind wanders.

The researchers also found, unsurprisingly, that negative thoughts that were focused on the self and on the past were more likely to result in brooding and that positive thoughts were less likely to arise.

Most study participants were young and educated and may have only said things that they were comfortable allowing the researchers to hear. And because the authors didn’t ask participants about their moods, the investigators could not associate specific patterns of thought with any mental health conditions.

Although the findings, published in Scientific Reports, do not on their own point to solutions for depression or anxiety, they may offer a starting point for future research into how negative trains of thoughts begin – and perhaps how to derail them.

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

With all the lockdowns and social distancing of the pandemic, millions of people have had a lot of time to themselves. Many may have filled that time with baking, long walks, or video games, but minds wandering during these periods was inevitable. Coincident with these experiences were increases in depression and anxiety, which could be linked to the same brain network that is thought to support a meandering mind, called the default mode network.

©Thinkstock

Scientists interested in this network wanted to understand how wandering thoughts can lead some people to a state of brooding in which the same negative thoughts resurface repeatedly. To gain some insight into these patterns, they recorded more than 2,000 thoughts spoken aloud by 78 study participants who did nothing but let their minds wander for 10 minutes.

Senior researcher Jessica Andrews-Hanna, PhD, assistant professor of psychology, University of Arizona, Tucson, and colleagues hoped that analyzing these stream-of-consciousness thoughts could yield insights into how people become stuck in negative mental spirals.

They found that most participants thought about the present or future in words that were neither particularly negative nor positive. Almost three-quarters of the thoughts were focused inward on the person or were imaginative.
 

Negativity breeds negativity

But the investigators found an interesting pattern with regard to negative thoughts. The more negative someone’s thoughts became, the more likely that their next idea would be related to their previous one. In other words, negative thoughts created a chain reaction of more negative thoughts.

Positive thoughts, in contrast, tended to be followed by completely unrelated ruminations, indicating true mental meandering. The pattern suggested that negativity tends to narrow the range of thoughts, whereas positivity tends to expand it during periods in which the mind wanders.

The researchers also found, unsurprisingly, that negative thoughts that were focused on the self and on the past were more likely to result in brooding and that positive thoughts were less likely to arise.

Most study participants were young and educated and may have only said things that they were comfortable allowing the researchers to hear. And because the authors didn’t ask participants about their moods, the investigators could not associate specific patterns of thought with any mental health conditions.

Although the findings, published in Scientific Reports, do not on their own point to solutions for depression or anxiety, they may offer a starting point for future research into how negative trains of thoughts begin – and perhaps how to derail them.

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

A simple caregiver education intervention reduced the use of psychotropic medications and associated drugs costs in long-term care facilities for the elderly in a new study.

The effect of the intervention was transient, possibly because of high staff turnover, according to the investigators in the new randomized, controlled trial.

The findings were presented by Ulla Aalto, MD, PhD, during a session at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

There was a significant reduction in the use of psychotropic agents at 6 months in long-term care wards where the nursing staff had undergone a short training session on drug therapy for older patients, but there was no improvement in wards that were randomly assigned to serve as controls, Dr. Aalto, from Helsinki Hospital, reported during the session.

“Future research would be investigating how we could maintain the positive effects that were gained at 6 months but not seen any more at 1 year, and how to implement the good practice in nursing homes by this kind of staff training,” she said.

Heavy drug use

Psychotropic medications are widely used in long-term care settings, but their indiscriminate use or use of the wrong drug for the wrong patient can be harmful. Inappropriate drug use in long-term care settings is also associated with higher costs, Dr. Aalto said.

To see whether a staff-training intervention could reduce drugs use and lower costs, the investigators conducted a randomized clinical trial in assisted living facilities in Helsinki in 2011, with a total of 227 patients 65 years and older.

Long-term care wards were randomly assigned to either an intervention for nursing staff consisting of two 4-hour sessions on good drug-therapy practice for older adults, or to serve as controls (10 wards in each group).

Drug use and costs were monitored at both 6 and 12 months after randomization. Psychotropic drugs included antipsychotics, antidepressants, anxiolytics, and hypnotics as classified by the World Health Organization. For the purposes of comparison, actual doses were counted and converted into relative proportions of defined daily doses.

The baseline characteristics of patients in each group were generally similar, with a mean age of around 83 years. In each study arm, nearly two-thirds of patients were on at least one psychotropic drug, and of this group, a third had been prescribed 2 or more psychotropic agents.

Nearly half of the patients were on at least one antipsychotic agent and/or antidepressant.
 

Short-term benefit

As noted before, in the wards randomized to staff training, there was a significant reduction in use of all psychotropics from baseline at 6 months after randomization (P = .045), but there was no change among the control wards.

By 12 months, however, the differences between the intervention and control arms narrowed, and drug use in the intervention arm was no longer significantly lower over baseline.

Drugs costs significantly decreased in the intervention group at 6 months (P = .027) and were numerically but not statistically lower over baseline at 12 months.

In contrast, drug costs in the control arm were numerically (but not statistically) higher at both 6 and 12 months of follow-up.

Annual drug costs in the intervention group decreased by mean of 12.3 euros ($14.22) whereas costs in the control group increased by a mean of 20.6 euros ($23.81).

“This quite light and feasible intervention succeeded in reducing overall defined daily doses of psychotropics in the short term,” Dr. Aalto said.

The waning of the intervention’s effect on drug use and costs may be caused partly by the high employee turnover rate in long-term care facilities and to the dilution effect, she said, referring to a form of judgment bias in which people tend to devalue diagnostic information when other, nondiagnostic information is also available.
 

Randomized design

In the question-and-answer session following her presentation, audience member Jesper Ryg, MD, PhD from Odense (Denmark) University Hospital and the University of Southern Denmark, also in Odense, commented: “It’s a great study, doing a [randomized, controlled trial] on deprescribing, we need more of those.”

“But what we know now is that a lot of studies show it is possible to deprescribe and get less drugs, but do we have any clinical data? Does this deprescribing lead to less falls, did it lead to lower mortality?” he asked.

Dr. Aalto replied that, in an earlier report from this study, investigators showed that harmful medication use was reduced and negative outcomes were reduced.

Another audience member asked why nursing staff were the target of the intervention, given that physicians do the actual drug prescribing.

Dr. Aalto responded: “It is the physician of course who prescribes, but in nursing homes and long-term care, nursing staff is there all the time, and the physicians are kind of consultants who just come there once in a while, so it’s important that the nurses also know about these harmful medications and can bring them to the doctor when he or she arrives there.”

Dr. Aalto and Dr. Ryg had no disclosures.

A simple caregiver education intervention reduced the use of psychotropic medications and associated drugs costs in long-term care facilities for the elderly in a new study.

The effect of the intervention was transient, possibly because of high staff turnover, according to the investigators in the new randomized, controlled trial.

The findings were presented by Ulla Aalto, MD, PhD, during a session at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

There was a significant reduction in the use of psychotropic agents at 6 months in long-term care wards where the nursing staff had undergone a short training session on drug therapy for older patients, but there was no improvement in wards that were randomly assigned to serve as controls, Dr. Aalto, from Helsinki Hospital, reported during the session.

“Future research would be investigating how we could maintain the positive effects that were gained at 6 months but not seen any more at 1 year, and how to implement the good practice in nursing homes by this kind of staff training,” she said.

Heavy drug use

Psychotropic medications are widely used in long-term care settings, but their indiscriminate use or use of the wrong drug for the wrong patient can be harmful. Inappropriate drug use in long-term care settings is also associated with higher costs, Dr. Aalto said.

To see whether a staff-training intervention could reduce drugs use and lower costs, the investigators conducted a randomized clinical trial in assisted living facilities in Helsinki in 2011, with a total of 227 patients 65 years and older.

Long-term care wards were randomly assigned to either an intervention for nursing staff consisting of two 4-hour sessions on good drug-therapy practice for older adults, or to serve as controls (10 wards in each group).

Drug use and costs were monitored at both 6 and 12 months after randomization. Psychotropic drugs included antipsychotics, antidepressants, anxiolytics, and hypnotics as classified by the World Health Organization. For the purposes of comparison, actual doses were counted and converted into relative proportions of defined daily doses.

The baseline characteristics of patients in each group were generally similar, with a mean age of around 83 years. In each study arm, nearly two-thirds of patients were on at least one psychotropic drug, and of this group, a third had been prescribed 2 or more psychotropic agents.

Nearly half of the patients were on at least one antipsychotic agent and/or antidepressant.
 

Short-term benefit

As noted before, in the wards randomized to staff training, there was a significant reduction in use of all psychotropics from baseline at 6 months after randomization (P = .045), but there was no change among the control wards.

By 12 months, however, the differences between the intervention and control arms narrowed, and drug use in the intervention arm was no longer significantly lower over baseline.

Drugs costs significantly decreased in the intervention group at 6 months (P = .027) and were numerically but not statistically lower over baseline at 12 months.

In contrast, drug costs in the control arm were numerically (but not statistically) higher at both 6 and 12 months of follow-up.

Annual drug costs in the intervention group decreased by mean of 12.3 euros ($14.22) whereas costs in the control group increased by a mean of 20.6 euros ($23.81).

“This quite light and feasible intervention succeeded in reducing overall defined daily doses of psychotropics in the short term,” Dr. Aalto said.

The waning of the intervention’s effect on drug use and costs may be caused partly by the high employee turnover rate in long-term care facilities and to the dilution effect, she said, referring to a form of judgment bias in which people tend to devalue diagnostic information when other, nondiagnostic information is also available.
 

Randomized design

In the question-and-answer session following her presentation, audience member Jesper Ryg, MD, PhD from Odense (Denmark) University Hospital and the University of Southern Denmark, also in Odense, commented: “It’s a great study, doing a [randomized, controlled trial] on deprescribing, we need more of those.”

“But what we know now is that a lot of studies show it is possible to deprescribe and get less drugs, but do we have any clinical data? Does this deprescribing lead to less falls, did it lead to lower mortality?” he asked.

Dr. Aalto replied that, in an earlier report from this study, investigators showed that harmful medication use was reduced and negative outcomes were reduced.

Another audience member asked why nursing staff were the target of the intervention, given that physicians do the actual drug prescribing.

Dr. Aalto responded: “It is the physician of course who prescribes, but in nursing homes and long-term care, nursing staff is there all the time, and the physicians are kind of consultants who just come there once in a while, so it’s important that the nurses also know about these harmful medications and can bring them to the doctor when he or she arrives there.”

Dr. Aalto and Dr. Ryg had no disclosures.

A simple caregiver education intervention reduced the use of psychotropic medications and associated drugs costs in long-term care facilities for the elderly in a new study.

The effect of the intervention was transient, possibly because of high staff turnover, according to the investigators in the new randomized, controlled trial.

The findings were presented by Ulla Aalto, MD, PhD, during a session at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

There was a significant reduction in the use of psychotropic agents at 6 months in long-term care wards where the nursing staff had undergone a short training session on drug therapy for older patients, but there was no improvement in wards that were randomly assigned to serve as controls, Dr. Aalto, from Helsinki Hospital, reported during the session.

“Future research would be investigating how we could maintain the positive effects that were gained at 6 months but not seen any more at 1 year, and how to implement the good practice in nursing homes by this kind of staff training,” she said.

Heavy drug use

Psychotropic medications are widely used in long-term care settings, but their indiscriminate use or use of the wrong drug for the wrong patient can be harmful. Inappropriate drug use in long-term care settings is also associated with higher costs, Dr. Aalto said.

To see whether a staff-training intervention could reduce drugs use and lower costs, the investigators conducted a randomized clinical trial in assisted living facilities in Helsinki in 2011, with a total of 227 patients 65 years and older.

Long-term care wards were randomly assigned to either an intervention for nursing staff consisting of two 4-hour sessions on good drug-therapy practice for older adults, or to serve as controls (10 wards in each group).

Drug use and costs were monitored at both 6 and 12 months after randomization. Psychotropic drugs included antipsychotics, antidepressants, anxiolytics, and hypnotics as classified by the World Health Organization. For the purposes of comparison, actual doses were counted and converted into relative proportions of defined daily doses.

The baseline characteristics of patients in each group were generally similar, with a mean age of around 83 years. In each study arm, nearly two-thirds of patients were on at least one psychotropic drug, and of this group, a third had been prescribed 2 or more psychotropic agents.

Nearly half of the patients were on at least one antipsychotic agent and/or antidepressant.
 

Short-term benefit

As noted before, in the wards randomized to staff training, there was a significant reduction in use of all psychotropics from baseline at 6 months after randomization (P = .045), but there was no change among the control wards.

By 12 months, however, the differences between the intervention and control arms narrowed, and drug use in the intervention arm was no longer significantly lower over baseline.

Drugs costs significantly decreased in the intervention group at 6 months (P = .027) and were numerically but not statistically lower over baseline at 12 months.

In contrast, drug costs in the control arm were numerically (but not statistically) higher at both 6 and 12 months of follow-up.

Annual drug costs in the intervention group decreased by mean of 12.3 euros ($14.22) whereas costs in the control group increased by a mean of 20.6 euros ($23.81).

“This quite light and feasible intervention succeeded in reducing overall defined daily doses of psychotropics in the short term,” Dr. Aalto said.

The waning of the intervention’s effect on drug use and costs may be caused partly by the high employee turnover rate in long-term care facilities and to the dilution effect, she said, referring to a form of judgment bias in which people tend to devalue diagnostic information when other, nondiagnostic information is also available.
 

Randomized design

In the question-and-answer session following her presentation, audience member Jesper Ryg, MD, PhD from Odense (Denmark) University Hospital and the University of Southern Denmark, also in Odense, commented: “It’s a great study, doing a [randomized, controlled trial] on deprescribing, we need more of those.”

“But what we know now is that a lot of studies show it is possible to deprescribe and get less drugs, but do we have any clinical data? Does this deprescribing lead to less falls, did it lead to lower mortality?” he asked.

Dr. Aalto replied that, in an earlier report from this study, investigators showed that harmful medication use was reduced and negative outcomes were reduced.

Another audience member asked why nursing staff were the target of the intervention, given that physicians do the actual drug prescribing.

Dr. Aalto responded: “It is the physician of course who prescribes, but in nursing homes and long-term care, nursing staff is there all the time, and the physicians are kind of consultants who just come there once in a while, so it’s important that the nurses also know about these harmful medications and can bring them to the doctor when he or she arrives there.”

Dr. Aalto and Dr. Ryg had no disclosures.

Study results of an experimental agent that improves symptoms of major depression and boosts quality of life in as little as 3 days suggest it may be an effective short-term treatment option.

Jupiterimages/ThinkStock

Phase 3 results of a randomized, placebo-controlled trial compared zuranolone, an neuroactive steroid that binds to both synaptic and extra-synaptic GABA-A receptors, to placebo in patients with major depressive disorder (MDD). Overall, 30% of participants were already taking antidepressants.

Investigators found the drug was associated with a significant improvement in depression scores versus placebo, with benefit observed as early as day 3. This was accompanied by improved function and well-being.

The drug was also “generally well tolerated” and had a safety profile that was “consistent” with what has been seen previously with the drug, said study presenter Colville Brown, MD, Sage Therapeutics, Cambridge, Mass.

“These data continue to support the development of zuranolone as a potential 14-day short course treatment for major depressive disorder episodes.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

High placebo response

However, despite being significant, the drug’s benefit was only slightly higher than that of placebo, raising questions about the study design and the true performance of the drug.

Dr. Brown explained that patients with MDD were randomized to oral zuranolone 50 mg or placebo once daily for 14 days, with dose reductions to 40 mg or matching placebo permitted in case of perceived intolerance.

Patients were assessed at baseline and day 15 via the 17-item Hamilton Rating Scale for Depression (HAMD-17) before entering a 28-day follow-up period off the study drug.

Among the 268 participants who received zuranolone, 90.3% completed the study, compared with 87.4% of 269 patients in the placebo group.

The mean age of participants was 40 years. Women made up 69.4% of those who received zuranolone and 61.7% assigned to placebo.

The mean HAMD-17 score at baseline was 26.8 and 26.9 in the zuranolone and placebo groups, respectively. Dr. Brown noted that 29.5% of patients in the zuranolone group and 30.1% of those assigned to placebo were taking antidepressants at baseline.

The study’s primary endpoint was met, with patients taking the study drug experiencing a significantly greater reduction in HAMD-17 scores from baseline to day 15 versus those given placebo, at 14.1 versus 12.3 points (P = .0141).

Dr. Brown highlighted that the difference in reduction in HAMD-17 scores between the zuranolone and placebo groups was already significant at day 3 (P < .0001), and again at day 8 (P < .0001) and day 12 (P < .001).

At day 3, response rates on the HAMD-17 were significantly higher among zuranolone-treated patients than among those given placebo, at 29.3% versus 16.3% (P < .001). However, the differences on day 15 and on day 42 were no longer significant.

A similar effect was seen for HAMD-17 remissions, which were seen in 7.6% of zuranolone-treated patients and 2.3% of those given placebo at day 3 (P < .01), rising to 29.8% versus 27.1% at day 15, and 30.8% versus 29.6% at day 42, and neither difference was significant.

Dr. Brown also showed that, at all time points during the treatment and follow-up periods, improvements in response rates in Global Improvement on the Clinical Global Impression scale favored zuranolone.

On the SF-36v2 quality of life questionnaire, improvements again favored zuranolone on all domains, although the difference between active treatment and placebo was significant only for vitality on day 15, at 12.8 versus 9.7 points (P < .05).

Treatment-emergent adverse events were more common with zuranolone, with 60.1% of patients experiencing at least one event of any grade versus 44.6% with placebo. However, severe events were seen in only 3.0% versus 1.1% of patients, and serious adverse events were recorded in only two patients (0.7%) in both groups.

The most common adverse events were somnolence, dizziness, headache, sedation, and diarrhea, with no increase in suicidal ideation or withdrawal. Dr. Brown noted that there was “no change in the safety signal” between patients with or without prior antidepressant therapy.

From the audience, Marie-Josée Filteau, MD, department of psychiatry, Laval University, Quebec, drew attention to the similarity in the improvement in HAMD-17 scores between the zuranolone and placebo groups, asking: “How is that compelling?”

Dr. Brown replied that “what they are excited about is that change from baseline with zuranolone,” adding: “You do see it in the placebo group as well, and ... this isn’t new to psychiatry.

“This is a heterogeneous disease, and remember this [study] was conducted during COVID, so patients were being seen with clinic visits during COVID.

“What impact did that have? The placebo is not really placebo” in this case.

More effective than results suggest?

Approached for comment by this news organization, Maurizio Fava, MD, executive vice chair, department of psychiatry, and executive director, Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, noted there are several issues with the trial.

Because of those, the drug “is likely to be much more efficacious than it looks because it achieved statistical significance despite an extremely high placebo response,” he said

“Whenever your change on placebo is greater than 10 points on the HAMD, you have an excessive response ... and a very, very low chance of detecting a signal,” he said.

Dr. Fava said that another issue was including patients who were either on or off antidepressants, which meant the population was not sufficiently homogenous.

Another “flaw” was to assume that the placebo effect would be “transient” and deteriorate over time, whereas the results showed the opposite.

Nevertheless, “it’s a positive study because of the sample size ... that provides further evidence for the antidepressant activity of zuranolone” and the drug was “well tolerated.”

Dr. Fava expects zuranolone “will make it to the market,” as an indication from the Food and Drug Administration is likely, “but if you’re asking me: Is the drug as effective as shown in their studies? It’s probably much more effective.”

The study was funded by Sage Therapeutics and Biogen. Dr. Brown is an employee of Sage Therapeutics. Lead investigator Anita Clayton, MD, University of Virginia, Charlottesville, has reported relationships with Dario Bioscience, Janssen, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Fabre-Kramer, MindCure, Ovoca Bio, PureTech Health, S1 Biopharma, Vella Bioscience, WCG MedAvante-ProPhase, Ballantine Books/Random House, Guilford Publications, Euthymics, and Mediflix.

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

Study results of an experimental agent that improves symptoms of major depression and boosts quality of life in as little as 3 days suggest it may be an effective short-term treatment option.

Jupiterimages/ThinkStock

Phase 3 results of a randomized, placebo-controlled trial compared zuranolone, an neuroactive steroid that binds to both synaptic and extra-synaptic GABA-A receptors, to placebo in patients with major depressive disorder (MDD). Overall, 30% of participants were already taking antidepressants.

Investigators found the drug was associated with a significant improvement in depression scores versus placebo, with benefit observed as early as day 3. This was accompanied by improved function and well-being.

The drug was also “generally well tolerated” and had a safety profile that was “consistent” with what has been seen previously with the drug, said study presenter Colville Brown, MD, Sage Therapeutics, Cambridge, Mass.

“These data continue to support the development of zuranolone as a potential 14-day short course treatment for major depressive disorder episodes.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

High placebo response

However, despite being significant, the drug’s benefit was only slightly higher than that of placebo, raising questions about the study design and the true performance of the drug.

Dr. Brown explained that patients with MDD were randomized to oral zuranolone 50 mg or placebo once daily for 14 days, with dose reductions to 40 mg or matching placebo permitted in case of perceived intolerance.

Patients were assessed at baseline and day 15 via the 17-item Hamilton Rating Scale for Depression (HAMD-17) before entering a 28-day follow-up period off the study drug.

Among the 268 participants who received zuranolone, 90.3% completed the study, compared with 87.4% of 269 patients in the placebo group.

The mean age of participants was 40 years. Women made up 69.4% of those who received zuranolone and 61.7% assigned to placebo.

The mean HAMD-17 score at baseline was 26.8 and 26.9 in the zuranolone and placebo groups, respectively. Dr. Brown noted that 29.5% of patients in the zuranolone group and 30.1% of those assigned to placebo were taking antidepressants at baseline.

The study’s primary endpoint was met, with patients taking the study drug experiencing a significantly greater reduction in HAMD-17 scores from baseline to day 15 versus those given placebo, at 14.1 versus 12.3 points (P = .0141).

Dr. Brown highlighted that the difference in reduction in HAMD-17 scores between the zuranolone and placebo groups was already significant at day 3 (P < .0001), and again at day 8 (P < .0001) and day 12 (P < .001).

At day 3, response rates on the HAMD-17 were significantly higher among zuranolone-treated patients than among those given placebo, at 29.3% versus 16.3% (P < .001). However, the differences on day 15 and on day 42 were no longer significant.

A similar effect was seen for HAMD-17 remissions, which were seen in 7.6% of zuranolone-treated patients and 2.3% of those given placebo at day 3 (P < .01), rising to 29.8% versus 27.1% at day 15, and 30.8% versus 29.6% at day 42, and neither difference was significant.

Dr. Brown also showed that, at all time points during the treatment and follow-up periods, improvements in response rates in Global Improvement on the Clinical Global Impression scale favored zuranolone.

On the SF-36v2 quality of life questionnaire, improvements again favored zuranolone on all domains, although the difference between active treatment and placebo was significant only for vitality on day 15, at 12.8 versus 9.7 points (P < .05).

Treatment-emergent adverse events were more common with zuranolone, with 60.1% of patients experiencing at least one event of any grade versus 44.6% with placebo. However, severe events were seen in only 3.0% versus 1.1% of patients, and serious adverse events were recorded in only two patients (0.7%) in both groups.

The most common adverse events were somnolence, dizziness, headache, sedation, and diarrhea, with no increase in suicidal ideation or withdrawal. Dr. Brown noted that there was “no change in the safety signal” between patients with or without prior antidepressant therapy.

From the audience, Marie-Josée Filteau, MD, department of psychiatry, Laval University, Quebec, drew attention to the similarity in the improvement in HAMD-17 scores between the zuranolone and placebo groups, asking: “How is that compelling?”

Dr. Brown replied that “what they are excited about is that change from baseline with zuranolone,” adding: “You do see it in the placebo group as well, and ... this isn’t new to psychiatry.

“This is a heterogeneous disease, and remember this [study] was conducted during COVID, so patients were being seen with clinic visits during COVID.

“What impact did that have? The placebo is not really placebo” in this case.

More effective than results suggest?

Approached for comment by this news organization, Maurizio Fava, MD, executive vice chair, department of psychiatry, and executive director, Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, noted there are several issues with the trial.

Because of those, the drug “is likely to be much more efficacious than it looks because it achieved statistical significance despite an extremely high placebo response,” he said

“Whenever your change on placebo is greater than 10 points on the HAMD, you have an excessive response ... and a very, very low chance of detecting a signal,” he said.

Dr. Fava said that another issue was including patients who were either on or off antidepressants, which meant the population was not sufficiently homogenous.

Another “flaw” was to assume that the placebo effect would be “transient” and deteriorate over time, whereas the results showed the opposite.

Nevertheless, “it’s a positive study because of the sample size ... that provides further evidence for the antidepressant activity of zuranolone” and the drug was “well tolerated.”

Dr. Fava expects zuranolone “will make it to the market,” as an indication from the Food and Drug Administration is likely, “but if you’re asking me: Is the drug as effective as shown in their studies? It’s probably much more effective.”

The study was funded by Sage Therapeutics and Biogen. Dr. Brown is an employee of Sage Therapeutics. Lead investigator Anita Clayton, MD, University of Virginia, Charlottesville, has reported relationships with Dario Bioscience, Janssen, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Fabre-Kramer, MindCure, Ovoca Bio, PureTech Health, S1 Biopharma, Vella Bioscience, WCG MedAvante-ProPhase, Ballantine Books/Random House, Guilford Publications, Euthymics, and Mediflix.

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

Study results of an experimental agent that improves symptoms of major depression and boosts quality of life in as little as 3 days suggest it may be an effective short-term treatment option.

Jupiterimages/ThinkStock

Phase 3 results of a randomized, placebo-controlled trial compared zuranolone, an neuroactive steroid that binds to both synaptic and extra-synaptic GABA-A receptors, to placebo in patients with major depressive disorder (MDD). Overall, 30% of participants were already taking antidepressants.

Investigators found the drug was associated with a significant improvement in depression scores versus placebo, with benefit observed as early as day 3. This was accompanied by improved function and well-being.

The drug was also “generally well tolerated” and had a safety profile that was “consistent” with what has been seen previously with the drug, said study presenter Colville Brown, MD, Sage Therapeutics, Cambridge, Mass.

“These data continue to support the development of zuranolone as a potential 14-day short course treatment for major depressive disorder episodes.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

High placebo response

However, despite being significant, the drug’s benefit was only slightly higher than that of placebo, raising questions about the study design and the true performance of the drug.

Dr. Brown explained that patients with MDD were randomized to oral zuranolone 50 mg or placebo once daily for 14 days, with dose reductions to 40 mg or matching placebo permitted in case of perceived intolerance.

Patients were assessed at baseline and day 15 via the 17-item Hamilton Rating Scale for Depression (HAMD-17) before entering a 28-day follow-up period off the study drug.

Among the 268 participants who received zuranolone, 90.3% completed the study, compared with 87.4% of 269 patients in the placebo group.

The mean age of participants was 40 years. Women made up 69.4% of those who received zuranolone and 61.7% assigned to placebo.

The mean HAMD-17 score at baseline was 26.8 and 26.9 in the zuranolone and placebo groups, respectively. Dr. Brown noted that 29.5% of patients in the zuranolone group and 30.1% of those assigned to placebo were taking antidepressants at baseline.

The study’s primary endpoint was met, with patients taking the study drug experiencing a significantly greater reduction in HAMD-17 scores from baseline to day 15 versus those given placebo, at 14.1 versus 12.3 points (P = .0141).

Dr. Brown highlighted that the difference in reduction in HAMD-17 scores between the zuranolone and placebo groups was already significant at day 3 (P < .0001), and again at day 8 (P < .0001) and day 12 (P < .001).

At day 3, response rates on the HAMD-17 were significantly higher among zuranolone-treated patients than among those given placebo, at 29.3% versus 16.3% (P < .001). However, the differences on day 15 and on day 42 were no longer significant.

A similar effect was seen for HAMD-17 remissions, which were seen in 7.6% of zuranolone-treated patients and 2.3% of those given placebo at day 3 (P < .01), rising to 29.8% versus 27.1% at day 15, and 30.8% versus 29.6% at day 42, and neither difference was significant.

Dr. Brown also showed that, at all time points during the treatment and follow-up periods, improvements in response rates in Global Improvement on the Clinical Global Impression scale favored zuranolone.

On the SF-36v2 quality of life questionnaire, improvements again favored zuranolone on all domains, although the difference between active treatment and placebo was significant only for vitality on day 15, at 12.8 versus 9.7 points (P < .05).

Treatment-emergent adverse events were more common with zuranolone, with 60.1% of patients experiencing at least one event of any grade versus 44.6% with placebo. However, severe events were seen in only 3.0% versus 1.1% of patients, and serious adverse events were recorded in only two patients (0.7%) in both groups.

The most common adverse events were somnolence, dizziness, headache, sedation, and diarrhea, with no increase in suicidal ideation or withdrawal. Dr. Brown noted that there was “no change in the safety signal” between patients with or without prior antidepressant therapy.

From the audience, Marie-Josée Filteau, MD, department of psychiatry, Laval University, Quebec, drew attention to the similarity in the improvement in HAMD-17 scores between the zuranolone and placebo groups, asking: “How is that compelling?”

Dr. Brown replied that “what they are excited about is that change from baseline with zuranolone,” adding: “You do see it in the placebo group as well, and ... this isn’t new to psychiatry.

“This is a heterogeneous disease, and remember this [study] was conducted during COVID, so patients were being seen with clinic visits during COVID.

“What impact did that have? The placebo is not really placebo” in this case.

More effective than results suggest?

Approached for comment by this news organization, Maurizio Fava, MD, executive vice chair, department of psychiatry, and executive director, Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, noted there are several issues with the trial.

Because of those, the drug “is likely to be much more efficacious than it looks because it achieved statistical significance despite an extremely high placebo response,” he said

“Whenever your change on placebo is greater than 10 points on the HAMD, you have an excessive response ... and a very, very low chance of detecting a signal,” he said.

Dr. Fava said that another issue was including patients who were either on or off antidepressants, which meant the population was not sufficiently homogenous.

Another “flaw” was to assume that the placebo effect would be “transient” and deteriorate over time, whereas the results showed the opposite.

Nevertheless, “it’s a positive study because of the sample size ... that provides further evidence for the antidepressant activity of zuranolone” and the drug was “well tolerated.”

Dr. Fava expects zuranolone “will make it to the market,” as an indication from the Food and Drug Administration is likely, “but if you’re asking me: Is the drug as effective as shown in their studies? It’s probably much more effective.”

The study was funded by Sage Therapeutics and Biogen. Dr. Brown is an employee of Sage Therapeutics. Lead investigator Anita Clayton, MD, University of Virginia, Charlottesville, has reported relationships with Dario Bioscience, Janssen, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Fabre-Kramer, MindCure, Ovoca Bio, PureTech Health, S1 Biopharma, Vella Bioscience, WCG MedAvante-ProPhase, Ballantine Books/Random House, Guilford Publications, Euthymics, and Mediflix.

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

After a concussion, resuming aerobic exercise relatively early on – at an intensity that does not worsen symptoms – may help young athletes recover sooner, compared with stretching, a randomized controlled trial (RCT) shows.

Douglas Levere/University at Buffalo

The study adds to emerging evidence that clinicians should prescribe exercise, rather than strict rest, to facilitate concussion recovery, researchers said.

Tamara McLeod, PhD, ATC, professor and director of athletic training programs at A.T. Still University in Mesa, Ariz., hopes the findings help clinicians see that “this is an approach that should be taken.”

“Too often with concussion, patients are given a laundry list of things they are NOT allowed to do,” including sports, school, and social activities, said Dr. McLeod, who was not involved in the study.

The research, published in The Lancet Child & Adolescent Health, largely replicates the findings of a prior trial while addressing limitations of the previous study’s design, researchers said.

For the trial, John J. Leddy, MD, with the State University of New York at Buffalo and colleagues recruited 118 male and female adolescent athletes aged 13-18 years who had had a sport-related concussion in the past 10 days. Investigators at three community and hospital-affiliated sports medicine concussion centers in the United States randomly assigned the athletes to individualized subsymptom-threshold aerobic exercise (61 participants) or stretching exercise (57 participants) at least 20 minutes per day for up to 4 weeks. Aerobic exercise included walking, jogging, or stationary cycling at home.

“It is important that the general clinician community appreciates that prolonged rest and avoidance of physical activity until spontaneous symptom resolution is no longer an acceptable approach to caring for adolescents with concussion,” Dr. Leddy and coauthors said.

The investigators improved on the “the scientific rigor of their previous RCT by including intention-to-treat and per-protocol analyses, daily symptom reporting, objective exercise adherence measurements, and greater heterogeneity of concussion severity,” said Carolyn A. Emery, PhD, and Jonathan Smirl, PhD, both with the University of Calgary (Alta.), in a related commentary. The new study is the first to show that early targeted heart rate subsymptom-threshold aerobic exercise, relative to stretching, shortened recovery time within 4 weeks after sport-related concussion (hazard ratio, 0.52) when controlling for sex, study site, and average daily exercise time, Dr. Emery and Dr. Smirl said.

A larger proportion of athletes assigned to stretching did not recover by 4 weeks, compared with those assigned to aerobic exercise (32% vs. 21%). The median time to full recovery was longer for the stretching group than for the aerobic exercise group (19 days vs. 14 days).

Among athletes who adhered to their assigned regimens, the differences were more pronounced: The median recovery time was 21 days for the stretching group, compared with 12 days for the aerobic exercise group. The rate of postconcussion symptoms beyond 28 days was 9% in the aerobic exercise group versus 31% in the stretching group, among adherent participants.

More research is needed to establish the efficacy of postconcussion aerobic exercise in adults and for nonsport injury, the researchers noted. Possible mechanisms underlying aerobic exercise’s benefits could include increased parasympathetic autonomic tone, improved cerebral blood flow regulation, or enhanced neuron repair, they suggested.

The right amount and timing of exercise, and doing so at an intensity that does not exacerbate symptoms, may be key. Other research has suggested that too much exercise, too soon may delay recovery, Dr. Emery said in an interview. “But there is now a lot of evidence to support low and moderate levels of physical activity to expedite recovery,” she said.

The study was funded by the American Medical Society for Sports Medicine. The study and commentary authors and Dr. McLeod had no disclosures.

jremaly@mdedge.com

After a concussion, resuming aerobic exercise relatively early on – at an intensity that does not worsen symptoms – may help young athletes recover sooner, compared with stretching, a randomized controlled trial (RCT) shows.

Douglas Levere/University at Buffalo

The study adds to emerging evidence that clinicians should prescribe exercise, rather than strict rest, to facilitate concussion recovery, researchers said.

Tamara McLeod, PhD, ATC, professor and director of athletic training programs at A.T. Still University in Mesa, Ariz., hopes the findings help clinicians see that “this is an approach that should be taken.”

“Too often with concussion, patients are given a laundry list of things they are NOT allowed to do,” including sports, school, and social activities, said Dr. McLeod, who was not involved in the study.

The research, published in The Lancet Child & Adolescent Health, largely replicates the findings of a prior trial while addressing limitations of the previous study’s design, researchers said.

For the trial, John J. Leddy, MD, with the State University of New York at Buffalo and colleagues recruited 118 male and female adolescent athletes aged 13-18 years who had had a sport-related concussion in the past 10 days. Investigators at three community and hospital-affiliated sports medicine concussion centers in the United States randomly assigned the athletes to individualized subsymptom-threshold aerobic exercise (61 participants) or stretching exercise (57 participants) at least 20 minutes per day for up to 4 weeks. Aerobic exercise included walking, jogging, or stationary cycling at home.

“It is important that the general clinician community appreciates that prolonged rest and avoidance of physical activity until spontaneous symptom resolution is no longer an acceptable approach to caring for adolescents with concussion,” Dr. Leddy and coauthors said.

The investigators improved on the “the scientific rigor of their previous RCT by including intention-to-treat and per-protocol analyses, daily symptom reporting, objective exercise adherence measurements, and greater heterogeneity of concussion severity,” said Carolyn A. Emery, PhD, and Jonathan Smirl, PhD, both with the University of Calgary (Alta.), in a related commentary. The new study is the first to show that early targeted heart rate subsymptom-threshold aerobic exercise, relative to stretching, shortened recovery time within 4 weeks after sport-related concussion (hazard ratio, 0.52) when controlling for sex, study site, and average daily exercise time, Dr. Emery and Dr. Smirl said.

A larger proportion of athletes assigned to stretching did not recover by 4 weeks, compared with those assigned to aerobic exercise (32% vs. 21%). The median time to full recovery was longer for the stretching group than for the aerobic exercise group (19 days vs. 14 days).

Among athletes who adhered to their assigned regimens, the differences were more pronounced: The median recovery time was 21 days for the stretching group, compared with 12 days for the aerobic exercise group. The rate of postconcussion symptoms beyond 28 days was 9% in the aerobic exercise group versus 31% in the stretching group, among adherent participants.

More research is needed to establish the efficacy of postconcussion aerobic exercise in adults and for nonsport injury, the researchers noted. Possible mechanisms underlying aerobic exercise’s benefits could include increased parasympathetic autonomic tone, improved cerebral blood flow regulation, or enhanced neuron repair, they suggested.

The right amount and timing of exercise, and doing so at an intensity that does not exacerbate symptoms, may be key. Other research has suggested that too much exercise, too soon may delay recovery, Dr. Emery said in an interview. “But there is now a lot of evidence to support low and moderate levels of physical activity to expedite recovery,” she said.

The study was funded by the American Medical Society for Sports Medicine. The study and commentary authors and Dr. McLeod had no disclosures.

jremaly@mdedge.com

After a concussion, resuming aerobic exercise relatively early on – at an intensity that does not worsen symptoms – may help young athletes recover sooner, compared with stretching, a randomized controlled trial (RCT) shows.

Douglas Levere/University at Buffalo

The study adds to emerging evidence that clinicians should prescribe exercise, rather than strict rest, to facilitate concussion recovery, researchers said.

Tamara McLeod, PhD, ATC, professor and director of athletic training programs at A.T. Still University in Mesa, Ariz., hopes the findings help clinicians see that “this is an approach that should be taken.”

“Too often with concussion, patients are given a laundry list of things they are NOT allowed to do,” including sports, school, and social activities, said Dr. McLeod, who was not involved in the study.

The research, published in The Lancet Child & Adolescent Health, largely replicates the findings of a prior trial while addressing limitations of the previous study’s design, researchers said.

For the trial, John J. Leddy, MD, with the State University of New York at Buffalo and colleagues recruited 118 male and female adolescent athletes aged 13-18 years who had had a sport-related concussion in the past 10 days. Investigators at three community and hospital-affiliated sports medicine concussion centers in the United States randomly assigned the athletes to individualized subsymptom-threshold aerobic exercise (61 participants) or stretching exercise (57 participants) at least 20 minutes per day for up to 4 weeks. Aerobic exercise included walking, jogging, or stationary cycling at home.

“It is important that the general clinician community appreciates that prolonged rest and avoidance of physical activity until spontaneous symptom resolution is no longer an acceptable approach to caring for adolescents with concussion,” Dr. Leddy and coauthors said.

The investigators improved on the “the scientific rigor of their previous RCT by including intention-to-treat and per-protocol analyses, daily symptom reporting, objective exercise adherence measurements, and greater heterogeneity of concussion severity,” said Carolyn A. Emery, PhD, and Jonathan Smirl, PhD, both with the University of Calgary (Alta.), in a related commentary. The new study is the first to show that early targeted heart rate subsymptom-threshold aerobic exercise, relative to stretching, shortened recovery time within 4 weeks after sport-related concussion (hazard ratio, 0.52) when controlling for sex, study site, and average daily exercise time, Dr. Emery and Dr. Smirl said.

A larger proportion of athletes assigned to stretching did not recover by 4 weeks, compared with those assigned to aerobic exercise (32% vs. 21%). The median time to full recovery was longer for the stretching group than for the aerobic exercise group (19 days vs. 14 days).

Among athletes who adhered to their assigned regimens, the differences were more pronounced: The median recovery time was 21 days for the stretching group, compared with 12 days for the aerobic exercise group. The rate of postconcussion symptoms beyond 28 days was 9% in the aerobic exercise group versus 31% in the stretching group, among adherent participants.

More research is needed to establish the efficacy of postconcussion aerobic exercise in adults and for nonsport injury, the researchers noted. Possible mechanisms underlying aerobic exercise’s benefits could include increased parasympathetic autonomic tone, improved cerebral blood flow regulation, or enhanced neuron repair, they suggested.

The right amount and timing of exercise, and doing so at an intensity that does not exacerbate symptoms, may be key. Other research has suggested that too much exercise, too soon may delay recovery, Dr. Emery said in an interview. “But there is now a lot of evidence to support low and moderate levels of physical activity to expedite recovery,” she said.

The study was funded by the American Medical Society for Sports Medicine. The study and commentary authors and Dr. McLeod had no disclosures.

jremaly@mdedge.com

In the United States, opioid use disorder (OUD) is a major public health challenge. In 2018 drug overdose deaths were 4 times higher than they were in 1999.¹ This increase highlights a critical need to expand treatment access. Medication for opioid use disorder (MOUD), including methadone, naltrexone, and buprenorphine, improves outcomes for patients retained in care.² Compared with the general population, veterans, particularly those with co-occurring posttraumatic stress disorder (PTSD) or depression, are more likely to receive higher dosages of opioid medications and experience opioid-related adverse outcomes (eg, overdose, OUD).^3,4 As a risk reduction strategy, patients receiving potentially dangerous full-dose agonist opioid medication who are unable to taper to safer dosages may be eligible to transition to buprenorphine.⁵

Buprenorphine and naltrexone can be prescribed in office-based settings or in addiction, primary care, mental health, and pain clinics. Office-based opioid treatment with buprenorphine (OBOT-B) expands access to patients who are not reached by addiction treatment programs.^6,7 This is particularly true in rural settings, where addiction care services are typically scarce.⁸ OBOT-B prevents relapse and maintains opioid-free days and may increase patient engagement by reducing stigma and providing treatment within an existing clinical care team.⁹ For many patients, OBOT-B results in good retention with just medical monitoring and minimal or no ancillary addiction counseling.^10,11

Successful implementation of OBOT-B has occurred through a variety of care models in selected community health care settings.^8,12,13 Historically in the Veterans Health Administration (VHA), MOUD has been prescribed in substance use disorder clinics by mental health practitioners. Currently, more than 44% of veterans with OUD are on MOUD.¹⁴

The VHA has invested significant resources to improve access to MOUD. In 2018, the Stepped Care for Opioid Use Disorder Train the Trainer (SCOUTT) initiative launched, with the aim to improve access within primary care, mental health, and pain clinics.¹⁵ SCOUTT emphasizes stepped-care treatment, with patients engaging in the step of care most appropriate to their needs. Step 0 is self-directed care/self-management, including mutual support groups; step-1 environments include office-based primary care, mental health, and pain clinics; and step-2 environments are specialty care settings. Through a series of remote webinars, an in-person national 2-day conference, and external facilitation, SCOUTT engaged 18 teams representing each Veterans Integrated Service Network (VISN) across the country to assist in implementing MOUD within 2 step-1 clinics. These teams have developed several models of providing step-1 care, including an interdisciplinary team-based primary care delivery model as well as a pharmacist care manager model.^{16, 17}

US Department of Veterans Affairs (VA) Connecticut Health Care System (VACHS), which delivers care to approximately 58,000 veterans, was chosen to be a phase 1 SCOUTT site. Though all patients in VACHS have access to specialty care step-2 clinics, including methadone and buprenorphine programs, there remained many patients not yet on MOUD who could benefit from it. Baseline data (fiscal year [FY] 2018 4th quarter), obtained through electronic health record (EHR) database dashboards indicated that 710 (56%) patients with an OUD diagnosis were not receiving MOUD. International Classification of Disease, 10th Revision codes are the foundation for VA population management dashboards, and based their data on codes for opioid abuse and opioid dependence. These tools are limited by the accuracy of coding in EHRs. Additionally, 366 patients receiving long-term opioid prescriptions were identified as moderate, high, or very high risk for overdose or death based on an algorithm that considered prescribed medications, sociodemographics, and comorbid conditions, as characterized in the VA EHR (Stratification Tool for Opioid Risk Mitigation [STORM] report).¹⁸

This article describes the VACHSquality-improvement effort to extend OBOT-B into step-1 primary care and general mental health clinics. Our objectives are to (1) outline the process for initiating SCOUTT within VACHS; (2) examine barriers to implementation and the SCOUTT team response; (3) review VACHS patient and prescriber data at baseline and 1 year after implementation; and (4) explore future implementation strategies.

SCOUTT Team

A VACHS interdisciplinary team was formed and attended the national SCOUTT kickoff conference in 2018.¹⁵ Similar to other SCOUTT teams, the team consisted of VISN leadership (in primary care, mental health, and addiction care), pharmacists, and a team of health care practitioners (HCPs) from step-2 clinics (including 2 addiction psychiatrists, and an advanced practice registered nurse, a registered nurse specializing in addiction care), and a team of HCPs from prospective step-1 clinics (including a clinical psychologist and 2 primary care physicians). An external facilitator was provided from outside the VISN who met remotely with the team to assist in facilitation. Our team met monthly, with the goal to identify local barriers and facilitators to OBOT-B and implement interventions to enhance prescribing in step-1 primary care and general mental health clinics.

Implementation Steps

The team identified multiple barriers to dissemination of OBOT-B in target clinics (Table). The 3 main barriers were limited leadership engagement in promoting OBOT-B in target clinics, inadequate number of HCPs with active X-waivered prescribing status in the targeted clinics, and the need for standardized processes and tools to facilitate prescribing and follow-up.

To address leadership engagement, the SCOUTT team held quarterly presentations of SCOUTT goals and progress on target clinic leadership calls (usually 15 minutes) and arranged a 90-minute multidisciplinary leadership summit with key leadership representation from primary care, general mental health, specialty addiction care, nursing, and pharmacy. To enhance X-waivered prescribers in target clinics, the SCOUTT team sent quarterly emails with brief education points on MOUD and links to waiver trainings. At the time of implementation, in order to prescribe buprenorphine and meet qualifications to treat OUD, prescribers were required to complete specialized training as necessitated by the Drug Addiction Treatment Act of 2000. X-waivered status can now be obtained without requiring training

The SCOUTT team advocated for X-waivered status to be incentivized by performance pay for primary care practitioners and held quarterly case-based education sessions during preexisting allotted time. The onboarding process for new waivered prescribers to navigate from waiver training to active prescribing within the EHR was standardized via development of a standard operating procedure (SOP).

The SCOUTT team also assisted in the development of standardized processes and tools for prescribing in target clinics, including implementation of a standard operating procedure regarding prescribing (both initiation of buprenorphine, and maintenance) in target clinics. This procedure specifies that target clinic HCPs prescribe for patients requiring less intensive management, and who are appropriate for office-based treatment based on specific criteria (eAppendix

Analysis

We examined changes in MOUD receipt and prescriber characteristics at baseline (FY 2018 4th quarter) and 1 year after implementation (FY 2019 4th quarter). Patient data were extracted from the VHA Corporate Data Warehouse (CDW), which contains data from all VHA EHRs. The VA STORM, is a CDW tool that automatically flags patients prescribed opioids who are at risk for overdose and suicide. Prescriber data were obtained from the Buprenorphine/X-Waivered Provider Report, a VA Academic Detailing Service database that provides details on HCP type, X-waivered status, and prescribing by location. χ² analyses were conducted on before and after measures when total values were available.

Results

There was a 4% increase in patients with an OUD diagnosis receiving MOUD, from 552 (44%) to 582 (48%) (P = .04), over this time. The number of waivered prescribers increased from 67 to 131, the number of prescribers of buprenorphine in a 6-month span increased from 35 to 52, and the percentage of HCPs capable of prescribing within the EHR increased from 75% to 89% (P =.01).

Initially, addiction HCPs prescribed to about 68% of patients on buprenorphine, with target clinic HCPs prescribing to 24% (with the remaining coming from other specialty HCPs). On follow-up, addiction professionals prescribed to 63%, with target clinic clincians prescribing to 32%.

Interpretation

SCOUTT team interventions succeeded in increasing the number of patients receiving MOUD, a substantial increase in waivered HCPs, an increase in the number of waivered HCPs prescribing MOUD, and an increase in the proportion of patients receiving MOUD in step-1 target clinics. It is important to note that within the quality-improvement framework and goals of our SCOUTT team that the data were not collected as part of a research study but to assess impact of our interventions. Within this framework, it is not possible to directly attribute the increase in eligible patients receiving MOUD solely to SCOUTT team interventions, as other factors may have contributed, including improved awareness of HCPs.

Summary and Future Directions

Since implementation of SCOUTT in August 2018, VACHS has identified several barriers to buprenorphine prescribing in step-1 clinics and implemented strategies to overcome them. Describing our approach will hopefully inform other large health care systems (VA or non-VA) on changes required in order to scale up implementation of OBOT-B. The VACHS SCOUTT team was successful at enhancing a ready workforce in step-1 clinics, though noted a delay in changing prescribing practice and culture.

We recommend utilizing academic detailing to work with clinics and individual HCPs to identify and overcome barriers to prescribing. Also, we recommend implementation of a nursing or clinical pharmacy collaborative care model in target step-1 clinics (rather than the HCP-driven model). A collaborative care model reflects the patient aligned care team (PACT) principle of team-based efficient care, and PACT nurses or clinical pharmacists should be able to provide the minimal quarterly follow-up of clinically stable patients on MOUD within the step-1 clinics. Templated notes for assessment, initiation, and follow-up of patients on MOUD are now available from the SCOUTT national program and should be broadly implemented to facilitate adoption of the collaborative model in target clinics. In order to accomplish a full collaborative model, the VHA would need to enhance appropriate staffing to support this model, broaden access to telehealth, and expand incentives to teams/clinicians who prescribe in these settings.

Acknowledgments/Funding

This material is based upon work supported by the US Department of Veterans Affairs (VA), Office of Mental Health and Suicide Prevention, Veterans Health Administration; the VA Health Services Research and Development (HSR&D) Quality Enhancement Research Initiative (QUERI) Partnered Evaluation Initiative (PEC) grants #19-001. Supporting organizations had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

In the United States, opioid use disorder (OUD) is a major public health challenge. In 2018 drug overdose deaths were 4 times higher than they were in 1999.¹ This increase highlights a critical need to expand treatment access. Medication for opioid use disorder (MOUD), including methadone, naltrexone, and buprenorphine, improves outcomes for patients retained in care.² Compared with the general population, veterans, particularly those with co-occurring posttraumatic stress disorder (PTSD) or depression, are more likely to receive higher dosages of opioid medications and experience opioid-related adverse outcomes (eg, overdose, OUD).^3,4 As a risk reduction strategy, patients receiving potentially dangerous full-dose agonist opioid medication who are unable to taper to safer dosages may be eligible to transition to buprenorphine.⁵

Buprenorphine and naltrexone can be prescribed in office-based settings or in addiction, primary care, mental health, and pain clinics. Office-based opioid treatment with buprenorphine (OBOT-B) expands access to patients who are not reached by addiction treatment programs.^6,7 This is particularly true in rural settings, where addiction care services are typically scarce.⁸ OBOT-B prevents relapse and maintains opioid-free days and may increase patient engagement by reducing stigma and providing treatment within an existing clinical care team.⁹ For many patients, OBOT-B results in good retention with just medical monitoring and minimal or no ancillary addiction counseling.^10,11

Successful implementation of OBOT-B has occurred through a variety of care models in selected community health care settings.^8,12,13 Historically in the Veterans Health Administration (VHA), MOUD has been prescribed in substance use disorder clinics by mental health practitioners. Currently, more than 44% of veterans with OUD are on MOUD.¹⁴

The VHA has invested significant resources to improve access to MOUD. In 2018, the Stepped Care for Opioid Use Disorder Train the Trainer (SCOUTT) initiative launched, with the aim to improve access within primary care, mental health, and pain clinics.¹⁵ SCOUTT emphasizes stepped-care treatment, with patients engaging in the step of care most appropriate to their needs. Step 0 is self-directed care/self-management, including mutual support groups; step-1 environments include office-based primary care, mental health, and pain clinics; and step-2 environments are specialty care settings. Through a series of remote webinars, an in-person national 2-day conference, and external facilitation, SCOUTT engaged 18 teams representing each Veterans Integrated Service Network (VISN) across the country to assist in implementing MOUD within 2 step-1 clinics. These teams have developed several models of providing step-1 care, including an interdisciplinary team-based primary care delivery model as well as a pharmacist care manager model.^{16, 17}

US Department of Veterans Affairs (VA) Connecticut Health Care System (VACHS), which delivers care to approximately 58,000 veterans, was chosen to be a phase 1 SCOUTT site. Though all patients in VACHS have access to specialty care step-2 clinics, including methadone and buprenorphine programs, there remained many patients not yet on MOUD who could benefit from it. Baseline data (fiscal year [FY] 2018 4th quarter), obtained through electronic health record (EHR) database dashboards indicated that 710 (56%) patients with an OUD diagnosis were not receiving MOUD. International Classification of Disease, 10th Revision codes are the foundation for VA population management dashboards, and based their data on codes for opioid abuse and opioid dependence. These tools are limited by the accuracy of coding in EHRs. Additionally, 366 patients receiving long-term opioid prescriptions were identified as moderate, high, or very high risk for overdose or death based on an algorithm that considered prescribed medications, sociodemographics, and comorbid conditions, as characterized in the VA EHR (Stratification Tool for Opioid Risk Mitigation [STORM] report).¹⁸

This article describes the VACHSquality-improvement effort to extend OBOT-B into step-1 primary care and general mental health clinics. Our objectives are to (1) outline the process for initiating SCOUTT within VACHS; (2) examine barriers to implementation and the SCOUTT team response; (3) review VACHS patient and prescriber data at baseline and 1 year after implementation; and (4) explore future implementation strategies.

SCOUTT Team

A VACHS interdisciplinary team was formed and attended the national SCOUTT kickoff conference in 2018.¹⁵ Similar to other SCOUTT teams, the team consisted of VISN leadership (in primary care, mental health, and addiction care), pharmacists, and a team of health care practitioners (HCPs) from step-2 clinics (including 2 addiction psychiatrists, and an advanced practice registered nurse, a registered nurse specializing in addiction care), and a team of HCPs from prospective step-1 clinics (including a clinical psychologist and 2 primary care physicians). An external facilitator was provided from outside the VISN who met remotely with the team to assist in facilitation. Our team met monthly, with the goal to identify local barriers and facilitators to OBOT-B and implement interventions to enhance prescribing in step-1 primary care and general mental health clinics.

Implementation Steps

The team identified multiple barriers to dissemination of OBOT-B in target clinics (Table). The 3 main barriers were limited leadership engagement in promoting OBOT-B in target clinics, inadequate number of HCPs with active X-waivered prescribing status in the targeted clinics, and the need for standardized processes and tools to facilitate prescribing and follow-up.

To address leadership engagement, the SCOUTT team held quarterly presentations of SCOUTT goals and progress on target clinic leadership calls (usually 15 minutes) and arranged a 90-minute multidisciplinary leadership summit with key leadership representation from primary care, general mental health, specialty addiction care, nursing, and pharmacy. To enhance X-waivered prescribers in target clinics, the SCOUTT team sent quarterly emails with brief education points on MOUD and links to waiver trainings. At the time of implementation, in order to prescribe buprenorphine and meet qualifications to treat OUD, prescribers were required to complete specialized training as necessitated by the Drug Addiction Treatment Act of 2000. X-waivered status can now be obtained without requiring training

The SCOUTT team advocated for X-waivered status to be incentivized by performance pay for primary care practitioners and held quarterly case-based education sessions during preexisting allotted time. The onboarding process for new waivered prescribers to navigate from waiver training to active prescribing within the EHR was standardized via development of a standard operating procedure (SOP).

The SCOUTT team also assisted in the development of standardized processes and tools for prescribing in target clinics, including implementation of a standard operating procedure regarding prescribing (both initiation of buprenorphine, and maintenance) in target clinics. This procedure specifies that target clinic HCPs prescribe for patients requiring less intensive management, and who are appropriate for office-based treatment based on specific criteria (eAppendix

Analysis

We examined changes in MOUD receipt and prescriber characteristics at baseline (FY 2018 4th quarter) and 1 year after implementation (FY 2019 4th quarter). Patient data were extracted from the VHA Corporate Data Warehouse (CDW), which contains data from all VHA EHRs. The VA STORM, is a CDW tool that automatically flags patients prescribed opioids who are at risk for overdose and suicide. Prescriber data were obtained from the Buprenorphine/X-Waivered Provider Report, a VA Academic Detailing Service database that provides details on HCP type, X-waivered status, and prescribing by location. χ² analyses were conducted on before and after measures when total values were available.

Results

There was a 4% increase in patients with an OUD diagnosis receiving MOUD, from 552 (44%) to 582 (48%) (P = .04), over this time. The number of waivered prescribers increased from 67 to 131, the number of prescribers of buprenorphine in a 6-month span increased from 35 to 52, and the percentage of HCPs capable of prescribing within the EHR increased from 75% to 89% (P =.01).

Initially, addiction HCPs prescribed to about 68% of patients on buprenorphine, with target clinic HCPs prescribing to 24% (with the remaining coming from other specialty HCPs). On follow-up, addiction professionals prescribed to 63%, with target clinic clincians prescribing to 32%.

Interpretation

SCOUTT team interventions succeeded in increasing the number of patients receiving MOUD, a substantial increase in waivered HCPs, an increase in the number of waivered HCPs prescribing MOUD, and an increase in the proportion of patients receiving MOUD in step-1 target clinics. It is important to note that within the quality-improvement framework and goals of our SCOUTT team that the data were not collected as part of a research study but to assess impact of our interventions. Within this framework, it is not possible to directly attribute the increase in eligible patients receiving MOUD solely to SCOUTT team interventions, as other factors may have contributed, including improved awareness of HCPs.

Summary and Future Directions

Since implementation of SCOUTT in August 2018, VACHS has identified several barriers to buprenorphine prescribing in step-1 clinics and implemented strategies to overcome them. Describing our approach will hopefully inform other large health care systems (VA or non-VA) on changes required in order to scale up implementation of OBOT-B. The VACHS SCOUTT team was successful at enhancing a ready workforce in step-1 clinics, though noted a delay in changing prescribing practice and culture.

We recommend utilizing academic detailing to work with clinics and individual HCPs to identify and overcome barriers to prescribing. Also, we recommend implementation of a nursing or clinical pharmacy collaborative care model in target step-1 clinics (rather than the HCP-driven model). A collaborative care model reflects the patient aligned care team (PACT) principle of team-based efficient care, and PACT nurses or clinical pharmacists should be able to provide the minimal quarterly follow-up of clinically stable patients on MOUD within the step-1 clinics. Templated notes for assessment, initiation, and follow-up of patients on MOUD are now available from the SCOUTT national program and should be broadly implemented to facilitate adoption of the collaborative model in target clinics. In order to accomplish a full collaborative model, the VHA would need to enhance appropriate staffing to support this model, broaden access to telehealth, and expand incentives to teams/clinicians who prescribe in these settings.

Acknowledgments/Funding

This material is based upon work supported by the US Department of Veterans Affairs (VA), Office of Mental Health and Suicide Prevention, Veterans Health Administration; the VA Health Services Research and Development (HSR&D) Quality Enhancement Research Initiative (QUERI) Partnered Evaluation Initiative (PEC) grants #19-001. Supporting organizations had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

In the United States, opioid use disorder (OUD) is a major public health challenge. In 2018 drug overdose deaths were 4 times higher than they were in 1999.¹ This increase highlights a critical need to expand treatment access. Medication for opioid use disorder (MOUD), including methadone, naltrexone, and buprenorphine, improves outcomes for patients retained in care.² Compared with the general population, veterans, particularly those with co-occurring posttraumatic stress disorder (PTSD) or depression, are more likely to receive higher dosages of opioid medications and experience opioid-related adverse outcomes (eg, overdose, OUD).^3,4 As a risk reduction strategy, patients receiving potentially dangerous full-dose agonist opioid medication who are unable to taper to safer dosages may be eligible to transition to buprenorphine.⁵

Buprenorphine and naltrexone can be prescribed in office-based settings or in addiction, primary care, mental health, and pain clinics. Office-based opioid treatment with buprenorphine (OBOT-B) expands access to patients who are not reached by addiction treatment programs.^6,7 This is particularly true in rural settings, where addiction care services are typically scarce.⁸ OBOT-B prevents relapse and maintains opioid-free days and may increase patient engagement by reducing stigma and providing treatment within an existing clinical care team.⁹ For many patients, OBOT-B results in good retention with just medical monitoring and minimal or no ancillary addiction counseling.^10,11

Successful implementation of OBOT-B has occurred through a variety of care models in selected community health care settings.^8,12,13 Historically in the Veterans Health Administration (VHA), MOUD has been prescribed in substance use disorder clinics by mental health practitioners. Currently, more than 44% of veterans with OUD are on MOUD.¹⁴

The VHA has invested significant resources to improve access to MOUD. In 2018, the Stepped Care for Opioid Use Disorder Train the Trainer (SCOUTT) initiative launched, with the aim to improve access within primary care, mental health, and pain clinics.¹⁵ SCOUTT emphasizes stepped-care treatment, with patients engaging in the step of care most appropriate to their needs. Step 0 is self-directed care/self-management, including mutual support groups; step-1 environments include office-based primary care, mental health, and pain clinics; and step-2 environments are specialty care settings. Through a series of remote webinars, an in-person national 2-day conference, and external facilitation, SCOUTT engaged 18 teams representing each Veterans Integrated Service Network (VISN) across the country to assist in implementing MOUD within 2 step-1 clinics. These teams have developed several models of providing step-1 care, including an interdisciplinary team-based primary care delivery model as well as a pharmacist care manager model.^{16, 17}

US Department of Veterans Affairs (VA) Connecticut Health Care System (VACHS), which delivers care to approximately 58,000 veterans, was chosen to be a phase 1 SCOUTT site. Though all patients in VACHS have access to specialty care step-2 clinics, including methadone and buprenorphine programs, there remained many patients not yet on MOUD who could benefit from it. Baseline data (fiscal year [FY] 2018 4th quarter), obtained through electronic health record (EHR) database dashboards indicated that 710 (56%) patients with an OUD diagnosis were not receiving MOUD. International Classification of Disease, 10th Revision codes are the foundation for VA population management dashboards, and based their data on codes for opioid abuse and opioid dependence. These tools are limited by the accuracy of coding in EHRs. Additionally, 366 patients receiving long-term opioid prescriptions were identified as moderate, high, or very high risk for overdose or death based on an algorithm that considered prescribed medications, sociodemographics, and comorbid conditions, as characterized in the VA EHR (Stratification Tool for Opioid Risk Mitigation [STORM] report).¹⁸

This article describes the VACHSquality-improvement effort to extend OBOT-B into step-1 primary care and general mental health clinics. Our objectives are to (1) outline the process for initiating SCOUTT within VACHS; (2) examine barriers to implementation and the SCOUTT team response; (3) review VACHS patient and prescriber data at baseline and 1 year after implementation; and (4) explore future implementation strategies.

SCOUTT Team

A VACHS interdisciplinary team was formed and attended the national SCOUTT kickoff conference in 2018.¹⁵ Similar to other SCOUTT teams, the team consisted of VISN leadership (in primary care, mental health, and addiction care), pharmacists, and a team of health care practitioners (HCPs) from step-2 clinics (including 2 addiction psychiatrists, and an advanced practice registered nurse, a registered nurse specializing in addiction care), and a team of HCPs from prospective step-1 clinics (including a clinical psychologist and 2 primary care physicians). An external facilitator was provided from outside the VISN who met remotely with the team to assist in facilitation. Our team met monthly, with the goal to identify local barriers and facilitators to OBOT-B and implement interventions to enhance prescribing in step-1 primary care and general mental health clinics.

Implementation Steps

The team identified multiple barriers to dissemination of OBOT-B in target clinics (Table). The 3 main barriers were limited leadership engagement in promoting OBOT-B in target clinics, inadequate number of HCPs with active X-waivered prescribing status in the targeted clinics, and the need for standardized processes and tools to facilitate prescribing and follow-up.

To address leadership engagement, the SCOUTT team held quarterly presentations of SCOUTT goals and progress on target clinic leadership calls (usually 15 minutes) and arranged a 90-minute multidisciplinary leadership summit with key leadership representation from primary care, general mental health, specialty addiction care, nursing, and pharmacy. To enhance X-waivered prescribers in target clinics, the SCOUTT team sent quarterly emails with brief education points on MOUD and links to waiver trainings. At the time of implementation, in order to prescribe buprenorphine and meet qualifications to treat OUD, prescribers were required to complete specialized training as necessitated by the Drug Addiction Treatment Act of 2000. X-waivered status can now be obtained without requiring training

The SCOUTT team advocated for X-waivered status to be incentivized by performance pay for primary care practitioners and held quarterly case-based education sessions during preexisting allotted time. The onboarding process for new waivered prescribers to navigate from waiver training to active prescribing within the EHR was standardized via development of a standard operating procedure (SOP).

The SCOUTT team also assisted in the development of standardized processes and tools for prescribing in target clinics, including implementation of a standard operating procedure regarding prescribing (both initiation of buprenorphine, and maintenance) in target clinics. This procedure specifies that target clinic HCPs prescribe for patients requiring less intensive management, and who are appropriate for office-based treatment based on specific criteria (eAppendix

Analysis

We examined changes in MOUD receipt and prescriber characteristics at baseline (FY 2018 4th quarter) and 1 year after implementation (FY 2019 4th quarter). Patient data were extracted from the VHA Corporate Data Warehouse (CDW), which contains data from all VHA EHRs. The VA STORM, is a CDW tool that automatically flags patients prescribed opioids who are at risk for overdose and suicide. Prescriber data were obtained from the Buprenorphine/X-Waivered Provider Report, a VA Academic Detailing Service database that provides details on HCP type, X-waivered status, and prescribing by location. χ² analyses were conducted on before and after measures when total values were available.

Results

There was a 4% increase in patients with an OUD diagnosis receiving MOUD, from 552 (44%) to 582 (48%) (P = .04), over this time. The number of waivered prescribers increased from 67 to 131, the number of prescribers of buprenorphine in a 6-month span increased from 35 to 52, and the percentage of HCPs capable of prescribing within the EHR increased from 75% to 89% (P =.01).

Initially, addiction HCPs prescribed to about 68% of patients on buprenorphine, with target clinic HCPs prescribing to 24% (with the remaining coming from other specialty HCPs). On follow-up, addiction professionals prescribed to 63%, with target clinic clincians prescribing to 32%.

Interpretation

SCOUTT team interventions succeeded in increasing the number of patients receiving MOUD, a substantial increase in waivered HCPs, an increase in the number of waivered HCPs prescribing MOUD, and an increase in the proportion of patients receiving MOUD in step-1 target clinics. It is important to note that within the quality-improvement framework and goals of our SCOUTT team that the data were not collected as part of a research study but to assess impact of our interventions. Within this framework, it is not possible to directly attribute the increase in eligible patients receiving MOUD solely to SCOUTT team interventions, as other factors may have contributed, including improved awareness of HCPs.

Summary and Future Directions

Since implementation of SCOUTT in August 2018, VACHS has identified several barriers to buprenorphine prescribing in step-1 clinics and implemented strategies to overcome them. Describing our approach will hopefully inform other large health care systems (VA or non-VA) on changes required in order to scale up implementation of OBOT-B. The VACHS SCOUTT team was successful at enhancing a ready workforce in step-1 clinics, though noted a delay in changing prescribing practice and culture.

We recommend utilizing academic detailing to work with clinics and individual HCPs to identify and overcome barriers to prescribing. Also, we recommend implementation of a nursing or clinical pharmacy collaborative care model in target step-1 clinics (rather than the HCP-driven model). A collaborative care model reflects the patient aligned care team (PACT) principle of team-based efficient care, and PACT nurses or clinical pharmacists should be able to provide the minimal quarterly follow-up of clinically stable patients on MOUD within the step-1 clinics. Templated notes for assessment, initiation, and follow-up of patients on MOUD are now available from the SCOUTT national program and should be broadly implemented to facilitate adoption of the collaborative model in target clinics. In order to accomplish a full collaborative model, the VHA would need to enhance appropriate staffing to support this model, broaden access to telehealth, and expand incentives to teams/clinicians who prescribe in these settings.

Acknowledgments/Funding

This material is based upon work supported by the US Department of Veterans Affairs (VA), Office of Mental Health and Suicide Prevention, Veterans Health Administration; the VA Health Services Research and Development (HSR&D) Quality Enhancement Research Initiative (QUERI) Partnered Evaluation Initiative (PEC) grants #19-001. Supporting organizations had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

A year into the COVID-19 pandemic, the share of the U.S. adult population reporting symptoms of elevated depression had more than tripled from prepandemic levels and worsened significantly since restrictions went into effect, a study of more than 1,000 adults surveyed at the start of the pandemic and 1 year into it has reported.

The study also found that younger adults, people with lower incomes and savings, unmarried people, and those exposed to multiple stress factors were most vulnerable to elevated levels of depression through the first year of the pandemic.

“The pandemic has been an ongoing exposure,” lead author Catherine K. Ettman, a PhD candidate at Brown University, Providence, R.I., said in an interview. “Mental health is sensitive to economic and social conditions. While living conditions have improved for some people over the last 12 months, the pandemic has been disruptive to life and economic well-being for many,” said Ms. Ettman, who is also chief of staff and director of strategic initiatives in the office of the dean at Boston University. Her study was published in Lancet Regional Health – Americas.

Ms. Ettman and coauthors reported that 32.8% (95% confidence interval, 29.1%-36.8%) of surveyed adults had elevated depressive symptoms in 2021, compared with 27.8% (95% CI, 24.9%-30.9%) in the early months of the pandemic in 2020 (P = .0016). That compares with a rate of 8.5% before the pandemic, a figure based on a prepandemic sample of 5,065 patients from the National Health and Nutrition Examination Survey reported previously by Ms. Ettman and associates.

“The COVID-19 pandemic and its economic consequences have displaced social networks, created ongoing stressors, and reduced access to the resources that protect mental health,” Ms. Ettman said.
 

Four groups most affected

In this latest research, a longitudinal panel study of a nationally representative group of U.S. adults, the researchers surveyed participants in March and April 2020 (n = 1,414) and the same group again in March and April 2021 (n = 1,161). The participants completed the Patient Health Questionnaire–9 (PHQ-9) and were enrolled in the COVID-19 and Life Stressors Impact on Mental Health and Well-Being study.

The study found that elevated depressive symptoms were most prevalent in four groups:

• Younger patients, with 43.9% of patients aged 18-39 years self-reporting elevated depressive symptoms, compared with 32.4% of those aged 40-59, and 19.1% of patients aged 60 and older.
• People with lower incomes, with 58.1% of people making $19,999 or less reporting elevated symptoms, compared with 41.3% of those making $20,000-$44,999, 31.4% of people making $45,000-$74,999, and 14.1% of those making $75,000 or more.
• People with less than $5,000 in family savings, with a rate of 51.1%, compared with 24.2% of those with more than that.
• People never married, with a rate of 39.8% versus 37.7% of those living with a partner; 31.5% widowed, divorced, or separated; and 18.3% married.

The study also found correlations between the number of self-reported stressors and elevated depression symptoms: a rate of 51.1% in people with four or more stressors; 25.8% in those with two or three stressors; and 17% in people with one or no stressors.

Among the groups reporting the lowest rates of depressive symptoms in 2021 were people making more than $75,000 a year; those with one or no COVID-19 stressors; and non-Hispanic Asian persons.

“Stressors such as difficulties finding childcare, difficulties paying for housing, and job loss were associated with greater depression 12 months into the COVID-19 pandemic,” Ms. Ettman said. “Efforts to address stressors and improve access to childcare, housing, employment, and fair wages can improve mental health.”

The duration of the pandemic is another explanation for the significant rise in depressive symptoms, senior author Sandro Galea, MD, MPH, DrPH, said in an interview. “The COVID-19 pandemic is different from other traumatic events in its ongoing length, in its widespread reach, and in its inequities,” Dr. Galea added. “Unlike acute traumatic events, the COVID-19 pandemic has been ongoing.”

He said clinicians, public health officials, and policy makers need to be aware of the impact COVID-19 has had on mental health. “We can take steps as a society to treat and prevent depression and create conditions that allow all populations to be healthy,” said Dr. Galea, who is dean and a professor of family medicine at Boston University.
 

Age of sample cited as limitation

The study builds on existing evidence linking depression trends and the COVID-19 pandemic, David Puder, MD, a medical director at Loma Linda (Calif.) University, said in an interview. However, he noted it had some limitations. “The age range is only 18 and older, so we don’t get to see what is happening with a highly impacted group of students who have not been able to go to school and be with their friends during COVID,” said Dr. Puder, who also hosts the podcast “Psychiatry & Psychotherapy.” “Further, the PHQ-9 is often a screening tool for depression and is not best used for changes in mental health over time.”

At the same time, Dr. Puder said, one of the study’s strengths was that it showed how depressive symptoms increased during the COVID lockdown. “It shows certain groups are at higher risk, including those with less financial resources and those with higher amounts of stress,” Dr. Puder said.

Ms. Ettman, Dr. Galea, and Dr. Puder reported no relevant disclosures.

A year into the COVID-19 pandemic, the share of the U.S. adult population reporting symptoms of elevated depression had more than tripled from prepandemic levels and worsened significantly since restrictions went into effect, a study of more than 1,000 adults surveyed at the start of the pandemic and 1 year into it has reported.

The study also found that younger adults, people with lower incomes and savings, unmarried people, and those exposed to multiple stress factors were most vulnerable to elevated levels of depression through the first year of the pandemic.

“The pandemic has been an ongoing exposure,” lead author Catherine K. Ettman, a PhD candidate at Brown University, Providence, R.I., said in an interview. “Mental health is sensitive to economic and social conditions. While living conditions have improved for some people over the last 12 months, the pandemic has been disruptive to life and economic well-being for many,” said Ms. Ettman, who is also chief of staff and director of strategic initiatives in the office of the dean at Boston University. Her study was published in Lancet Regional Health – Americas.

Ms. Ettman and coauthors reported that 32.8% (95% confidence interval, 29.1%-36.8%) of surveyed adults had elevated depressive symptoms in 2021, compared with 27.8% (95% CI, 24.9%-30.9%) in the early months of the pandemic in 2020 (P = .0016). That compares with a rate of 8.5% before the pandemic, a figure based on a prepandemic sample of 5,065 patients from the National Health and Nutrition Examination Survey reported previously by Ms. Ettman and associates.

“The COVID-19 pandemic and its economic consequences have displaced social networks, created ongoing stressors, and reduced access to the resources that protect mental health,” Ms. Ettman said.
 

Four groups most affected

In this latest research, a longitudinal panel study of a nationally representative group of U.S. adults, the researchers surveyed participants in March and April 2020 (n = 1,414) and the same group again in March and April 2021 (n = 1,161). The participants completed the Patient Health Questionnaire–9 (PHQ-9) and were enrolled in the COVID-19 and Life Stressors Impact on Mental Health and Well-Being study.

The study found that elevated depressive symptoms were most prevalent in four groups:

• Younger patients, with 43.9% of patients aged 18-39 years self-reporting elevated depressive symptoms, compared with 32.4% of those aged 40-59, and 19.1% of patients aged 60 and older.
• People with lower incomes, with 58.1% of people making $19,999 or less reporting elevated symptoms, compared with 41.3% of those making $20,000-$44,999, 31.4% of people making $45,000-$74,999, and 14.1% of those making $75,000 or more.
• People with less than $5,000 in family savings, with a rate of 51.1%, compared with 24.2% of those with more than that.
• People never married, with a rate of 39.8% versus 37.7% of those living with a partner; 31.5% widowed, divorced, or separated; and 18.3% married.

The study also found correlations between the number of self-reported stressors and elevated depression symptoms: a rate of 51.1% in people with four or more stressors; 25.8% in those with two or three stressors; and 17% in people with one or no stressors.

Among the groups reporting the lowest rates of depressive symptoms in 2021 were people making more than $75,000 a year; those with one or no COVID-19 stressors; and non-Hispanic Asian persons.

“Stressors such as difficulties finding childcare, difficulties paying for housing, and job loss were associated with greater depression 12 months into the COVID-19 pandemic,” Ms. Ettman said. “Efforts to address stressors and improve access to childcare, housing, employment, and fair wages can improve mental health.”

The duration of the pandemic is another explanation for the significant rise in depressive symptoms, senior author Sandro Galea, MD, MPH, DrPH, said in an interview. “The COVID-19 pandemic is different from other traumatic events in its ongoing length, in its widespread reach, and in its inequities,” Dr. Galea added. “Unlike acute traumatic events, the COVID-19 pandemic has been ongoing.”

He said clinicians, public health officials, and policy makers need to be aware of the impact COVID-19 has had on mental health. “We can take steps as a society to treat and prevent depression and create conditions that allow all populations to be healthy,” said Dr. Galea, who is dean and a professor of family medicine at Boston University.
 

Age of sample cited as limitation

The study builds on existing evidence linking depression trends and the COVID-19 pandemic, David Puder, MD, a medical director at Loma Linda (Calif.) University, said in an interview. However, he noted it had some limitations. “The age range is only 18 and older, so we don’t get to see what is happening with a highly impacted group of students who have not been able to go to school and be with their friends during COVID,” said Dr. Puder, who also hosts the podcast “Psychiatry & Psychotherapy.” “Further, the PHQ-9 is often a screening tool for depression and is not best used for changes in mental health over time.”

At the same time, Dr. Puder said, one of the study’s strengths was that it showed how depressive symptoms increased during the COVID lockdown. “It shows certain groups are at higher risk, including those with less financial resources and those with higher amounts of stress,” Dr. Puder said.

Ms. Ettman, Dr. Galea, and Dr. Puder reported no relevant disclosures.

A year into the COVID-19 pandemic, the share of the U.S. adult population reporting symptoms of elevated depression had more than tripled from prepandemic levels and worsened significantly since restrictions went into effect, a study of more than 1,000 adults surveyed at the start of the pandemic and 1 year into it has reported.

The study also found that younger adults, people with lower incomes and savings, unmarried people, and those exposed to multiple stress factors were most vulnerable to elevated levels of depression through the first year of the pandemic.

“The pandemic has been an ongoing exposure,” lead author Catherine K. Ettman, a PhD candidate at Brown University, Providence, R.I., said in an interview. “Mental health is sensitive to economic and social conditions. While living conditions have improved for some people over the last 12 months, the pandemic has been disruptive to life and economic well-being for many,” said Ms. Ettman, who is also chief of staff and director of strategic initiatives in the office of the dean at Boston University. Her study was published in Lancet Regional Health – Americas.

Ms. Ettman and coauthors reported that 32.8% (95% confidence interval, 29.1%-36.8%) of surveyed adults had elevated depressive symptoms in 2021, compared with 27.8% (95% CI, 24.9%-30.9%) in the early months of the pandemic in 2020 (P = .0016). That compares with a rate of 8.5% before the pandemic, a figure based on a prepandemic sample of 5,065 patients from the National Health and Nutrition Examination Survey reported previously by Ms. Ettman and associates.

“The COVID-19 pandemic and its economic consequences have displaced social networks, created ongoing stressors, and reduced access to the resources that protect mental health,” Ms. Ettman said.
 

Four groups most affected

In this latest research, a longitudinal panel study of a nationally representative group of U.S. adults, the researchers surveyed participants in March and April 2020 (n = 1,414) and the same group again in March and April 2021 (n = 1,161). The participants completed the Patient Health Questionnaire–9 (PHQ-9) and were enrolled in the COVID-19 and Life Stressors Impact on Mental Health and Well-Being study.

The study found that elevated depressive symptoms were most prevalent in four groups:

• Younger patients, with 43.9% of patients aged 18-39 years self-reporting elevated depressive symptoms, compared with 32.4% of those aged 40-59, and 19.1% of patients aged 60 and older.
• People with lower incomes, with 58.1% of people making $19,999 or less reporting elevated symptoms, compared with 41.3% of those making $20,000-$44,999, 31.4% of people making $45,000-$74,999, and 14.1% of those making $75,000 or more.
• People with less than $5,000 in family savings, with a rate of 51.1%, compared with 24.2% of those with more than that.
• People never married, with a rate of 39.8% versus 37.7% of those living with a partner; 31.5% widowed, divorced, or separated; and 18.3% married.

The study also found correlations between the number of self-reported stressors and elevated depression symptoms: a rate of 51.1% in people with four or more stressors; 25.8% in those with two or three stressors; and 17% in people with one or no stressors.

Among the groups reporting the lowest rates of depressive symptoms in 2021 were people making more than $75,000 a year; those with one or no COVID-19 stressors; and non-Hispanic Asian persons.

“Stressors such as difficulties finding childcare, difficulties paying for housing, and job loss were associated with greater depression 12 months into the COVID-19 pandemic,” Ms. Ettman said. “Efforts to address stressors and improve access to childcare, housing, employment, and fair wages can improve mental health.”

The duration of the pandemic is another explanation for the significant rise in depressive symptoms, senior author Sandro Galea, MD, MPH, DrPH, said in an interview. “The COVID-19 pandemic is different from other traumatic events in its ongoing length, in its widespread reach, and in its inequities,” Dr. Galea added. “Unlike acute traumatic events, the COVID-19 pandemic has been ongoing.”

He said clinicians, public health officials, and policy makers need to be aware of the impact COVID-19 has had on mental health. “We can take steps as a society to treat and prevent depression and create conditions that allow all populations to be healthy,” said Dr. Galea, who is dean and a professor of family medicine at Boston University.
 

Age of sample cited as limitation

The study builds on existing evidence linking depression trends and the COVID-19 pandemic, David Puder, MD, a medical director at Loma Linda (Calif.) University, said in an interview. However, he noted it had some limitations. “The age range is only 18 and older, so we don’t get to see what is happening with a highly impacted group of students who have not been able to go to school and be with their friends during COVID,” said Dr. Puder, who also hosts the podcast “Psychiatry & Psychotherapy.” “Further, the PHQ-9 is often a screening tool for depression and is not best used for changes in mental health over time.”

At the same time, Dr. Puder said, one of the study’s strengths was that it showed how depressive symptoms increased during the COVID lockdown. “It shows certain groups are at higher risk, including those with less financial resources and those with higher amounts of stress,” Dr. Puder said.

Ms. Ettman, Dr. Galea, and Dr. Puder reported no relevant disclosures.

Sixteen-year-old Ana and is sitting on the bench with her science teacher, Ms. Tehrani, waiting for the bus to take them back to their village after school. Ana wants to hear her science teacher’s opinion about her grandmother.

Do you respect your grandmother?

Why yes, of course, why to do you ask?

So you think my grandmother is wise when she tells me old wife tales?

Like what?

Well, she says not to take my medicine because it will have bad effects and that I should take her remedies instead.

What else does she tell you?

Well, she says that people are born how they are and that they belong to either God or the Devil, not to their parents.

What else?

She thinks I am a fay child; she has always said that about me.

What does that mean?

It means that I have my own ways, fairy ways, and that I should go out in the forest and listen.

Do you?

Yes.

What do you hear?

I hear about my destiny.

What do you hear?

I hear that I must wash in witch hazel. My grandmother taught me how to find it and how to prepare it. She said I should sit in the forest and wait for a sign.

What sign?

I don’t know.

Well, what do you think about your grandmother?

I love her but …

But what?

I think she might be wrong about all of this, you know, science and all that.

But you do it, anyway?

Yes.

Why?

Aren’t we supposed to respect our elders, and aren’t they supposed to be wise?



Ms. Tehrani is in a bind. What to say? She has no ready answer, feeling caught between two beliefs: the unscientific basis of ineffective old wives’ treatments and the purported wisdom of our elders. She knows Ana’s family and that there are women in that family going back generations who are identified as medicine women or women with the special powers of the forest.

Ana wants to study science but she is being groomed as the family wise mother. Ana is caught between the ways of the past and the ways of the future. She sees that to go with the future is to devalue her family tradition. If she chooses to study medicine, can she keep the balance between magical ways and the ways of science?

Ms. Tehrani decides to expose her class to Indigenous and preindustrial cultural practices and what science has to say. She describes how knowledge is passed down through the generations, and how some of this knowledge has now been proved correct by science, such as the use of opium for pain management and how some knowledge has been corrected by science. She asks the class: What myths have been passed down in your family that science has shown to be effective or ineffective? What does science have to say about how we live our lives?

After a baby in the village dies, Ms. Tehrani asks the local health center to think about implementing a teaching course on caring for babies, a course that will discuss tradition and science. She is well aware of the fact that Black mothers tend not to follow the advice of the pediatricians who now recommend that parents put babies to sleep on their backs. Black women trust the advice of their paternal and maternal grandmothers more than the advice of health care providers, research by Deborah Stiffler, PhD, RN, CNM, shows (J Spec Pediatr Nurs. 2018 Apr;23[2]:e12213). While new Black mothers feel that they have limited knowledge and are eager to learn about safe sleep practices, their grandmothers were skeptical – and the grandmothers often won that argument. Black mothers believed that their own mothers knew best, based on their experience raising infants.

In Dr. Stiffler’s study, one grandmother commented: “Girls today need a mother to help them take care of their babies. They don’t know how to do anything. When I was growing up, our moms helped us.”

One new mother said: I “listen more to the elderly people because like the social workers and stuff some of them don’t have kids. They just go by the book … so I feel like I listen more to like my grandparents.”
 

Integrating traditions

When Ana enters medical school she is faced with the task of integration of traditional practice and Western medicine. Ana looks to the National Center for Complementary and Integrative Health (NCCIH), the U.S. government’s lead agency for scientific research on complementary and integrative health approaches for support in her task. The NCCIH was established in 1998 with the mission of determining the usefulness and safety of complementary and integrative health approaches, and their roles in improving health and health care.

The NCCIH notes that more than 30% of adults use health care approaches that are not part of conventional medical care or that have origins outside of usual Western practice, and 17.7% of American adults had used a dietary supplement other than vitamins and minerals in the past year, most commonly fish oil. This agency notes that large rigorous research studies extend to only a few dietary supplements, with results showing that the products didn’t work for the conditions studied. The work of the NCCIH is mirrored worldwide.

The 2008 Beijing Declaration called on World Health Organization member states and other stakeholders to integrate traditional medicine and complementary alternative medicines into national health care systems. The WHO Congress on Traditional Medicine recognizes that traditional medicine (TM) may be more affordable and accessible than Western medicine, and that it plays an important role in meeting the demands of primary health care in many developing countries. From 70% to 80% of the population in India and Ethiopia depend on TM for primary health care, and 70% of the population in Canada and 80% in Germany are reported to have used TM as complementary and/or alternative medical treatment.

After graduation and residency, Ana returns to her village and helps her science teacher consider how best to shape the intergenerational transmission of knowledge, so that it is both honored by the elders and also shaped by the science of medicine.

Every village, regardless of where it is in the world, has to contend with finding the balance between the traditional medical knowledge that is passed down through the family and the discoveries of science. When it comes to practicing medicine and psychiatry, a respect for family tradition must be weighed against the application of science: this is a long conversation that is well worth its time.
 

Dr. Heru is professor of psychiatry at the University of Colorado at Denver, Aurora. She is editor of “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013). Dr. Heru has no conflicts of interest. Contact Dr. Heru at alison.heru@cuanschutz.edu.

Sixteen-year-old Ana and is sitting on the bench with her science teacher, Ms. Tehrani, waiting for the bus to take them back to their village after school. Ana wants to hear her science teacher’s opinion about her grandmother.

Do you respect your grandmother?

Why yes, of course, why to do you ask?

So you think my grandmother is wise when she tells me old wife tales?

Like what?

Well, she says not to take my medicine because it will have bad effects and that I should take her remedies instead.

What else does she tell you?

Well, she says that people are born how they are and that they belong to either God or the Devil, not to their parents.

What else?

She thinks I am a fay child; she has always said that about me.

What does that mean?

It means that I have my own ways, fairy ways, and that I should go out in the forest and listen.

Do you?

Yes.

What do you hear?

I hear about my destiny.

What do you hear?

I hear that I must wash in witch hazel. My grandmother taught me how to find it and how to prepare it. She said I should sit in the forest and wait for a sign.

What sign?

I don’t know.

Well, what do you think about your grandmother?

I love her but …

But what?

I think she might be wrong about all of this, you know, science and all that.

But you do it, anyway?

Yes.

Why?

Aren’t we supposed to respect our elders, and aren’t they supposed to be wise?



Ms. Tehrani is in a bind. What to say? She has no ready answer, feeling caught between two beliefs: the unscientific basis of ineffective old wives’ treatments and the purported wisdom of our elders. She knows Ana’s family and that there are women in that family going back generations who are identified as medicine women or women with the special powers of the forest.

Ana wants to study science but she is being groomed as the family wise mother. Ana is caught between the ways of the past and the ways of the future. She sees that to go with the future is to devalue her family tradition. If she chooses to study medicine, can she keep the balance between magical ways and the ways of science?

Ms. Tehrani decides to expose her class to Indigenous and preindustrial cultural practices and what science has to say. She describes how knowledge is passed down through the generations, and how some of this knowledge has now been proved correct by science, such as the use of opium for pain management and how some knowledge has been corrected by science. She asks the class: What myths have been passed down in your family that science has shown to be effective or ineffective? What does science have to say about how we live our lives?

After a baby in the village dies, Ms. Tehrani asks the local health center to think about implementing a teaching course on caring for babies, a course that will discuss tradition and science. She is well aware of the fact that Black mothers tend not to follow the advice of the pediatricians who now recommend that parents put babies to sleep on their backs. Black women trust the advice of their paternal and maternal grandmothers more than the advice of health care providers, research by Deborah Stiffler, PhD, RN, CNM, shows (J Spec Pediatr Nurs. 2018 Apr;23[2]:e12213). While new Black mothers feel that they have limited knowledge and are eager to learn about safe sleep practices, their grandmothers were skeptical – and the grandmothers often won that argument. Black mothers believed that their own mothers knew best, based on their experience raising infants.

In Dr. Stiffler’s study, one grandmother commented: “Girls today need a mother to help them take care of their babies. They don’t know how to do anything. When I was growing up, our moms helped us.”

One new mother said: I “listen more to the elderly people because like the social workers and stuff some of them don’t have kids. They just go by the book … so I feel like I listen more to like my grandparents.”
 

Integrating traditions

When Ana enters medical school she is faced with the task of integration of traditional practice and Western medicine. Ana looks to the National Center for Complementary and Integrative Health (NCCIH), the U.S. government’s lead agency for scientific research on complementary and integrative health approaches for support in her task. The NCCIH was established in 1998 with the mission of determining the usefulness and safety of complementary and integrative health approaches, and their roles in improving health and health care.

The NCCIH notes that more than 30% of adults use health care approaches that are not part of conventional medical care or that have origins outside of usual Western practice, and 17.7% of American adults had used a dietary supplement other than vitamins and minerals in the past year, most commonly fish oil. This agency notes that large rigorous research studies extend to only a few dietary supplements, with results showing that the products didn’t work for the conditions studied. The work of the NCCIH is mirrored worldwide.

The 2008 Beijing Declaration called on World Health Organization member states and other stakeholders to integrate traditional medicine and complementary alternative medicines into national health care systems. The WHO Congress on Traditional Medicine recognizes that traditional medicine (TM) may be more affordable and accessible than Western medicine, and that it plays an important role in meeting the demands of primary health care in many developing countries. From 70% to 80% of the population in India and Ethiopia depend on TM for primary health care, and 70% of the population in Canada and 80% in Germany are reported to have used TM as complementary and/or alternative medical treatment.

After graduation and residency, Ana returns to her village and helps her science teacher consider how best to shape the intergenerational transmission of knowledge, so that it is both honored by the elders and also shaped by the science of medicine.

Every village, regardless of where it is in the world, has to contend with finding the balance between the traditional medical knowledge that is passed down through the family and the discoveries of science. When it comes to practicing medicine and psychiatry, a respect for family tradition must be weighed against the application of science: this is a long conversation that is well worth its time.
 

Dr. Heru is professor of psychiatry at the University of Colorado at Denver, Aurora. She is editor of “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013). Dr. Heru has no conflicts of interest. Contact Dr. Heru at alison.heru@cuanschutz.edu.

Sixteen-year-old Ana and is sitting on the bench with her science teacher, Ms. Tehrani, waiting for the bus to take them back to their village after school. Ana wants to hear her science teacher’s opinion about her grandmother.

Do you respect your grandmother?

Why yes, of course, why to do you ask?

So you think my grandmother is wise when she tells me old wife tales?

Like what?

Well, she says not to take my medicine because it will have bad effects and that I should take her remedies instead.

What else does she tell you?

Well, she says that people are born how they are and that they belong to either God or the Devil, not to their parents.

What else?

She thinks I am a fay child; she has always said that about me.

What does that mean?

It means that I have my own ways, fairy ways, and that I should go out in the forest and listen.

Do you?

Yes.

What do you hear?

I hear about my destiny.

What do you hear?

I hear that I must wash in witch hazel. My grandmother taught me how to find it and how to prepare it. She said I should sit in the forest and wait for a sign.

What sign?

I don’t know.

Well, what do you think about your grandmother?

I love her but …

But what?

I think she might be wrong about all of this, you know, science and all that.

But you do it, anyway?

Yes.

Why?

Aren’t we supposed to respect our elders, and aren’t they supposed to be wise?



Ms. Tehrani is in a bind. What to say? She has no ready answer, feeling caught between two beliefs: the unscientific basis of ineffective old wives’ treatments and the purported wisdom of our elders. She knows Ana’s family and that there are women in that family going back generations who are identified as medicine women or women with the special powers of the forest.

Ana wants to study science but she is being groomed as the family wise mother. Ana is caught between the ways of the past and the ways of the future. She sees that to go with the future is to devalue her family tradition. If she chooses to study medicine, can she keep the balance between magical ways and the ways of science?

Ms. Tehrani decides to expose her class to Indigenous and preindustrial cultural practices and what science has to say. She describes how knowledge is passed down through the generations, and how some of this knowledge has now been proved correct by science, such as the use of opium for pain management and how some knowledge has been corrected by science. She asks the class: What myths have been passed down in your family that science has shown to be effective or ineffective? What does science have to say about how we live our lives?

After a baby in the village dies, Ms. Tehrani asks the local health center to think about implementing a teaching course on caring for babies, a course that will discuss tradition and science. She is well aware of the fact that Black mothers tend not to follow the advice of the pediatricians who now recommend that parents put babies to sleep on their backs. Black women trust the advice of their paternal and maternal grandmothers more than the advice of health care providers, research by Deborah Stiffler, PhD, RN, CNM, shows (J Spec Pediatr Nurs. 2018 Apr;23[2]:e12213). While new Black mothers feel that they have limited knowledge and are eager to learn about safe sleep practices, their grandmothers were skeptical – and the grandmothers often won that argument. Black mothers believed that their own mothers knew best, based on their experience raising infants.

In Dr. Stiffler’s study, one grandmother commented: “Girls today need a mother to help them take care of their babies. They don’t know how to do anything. When I was growing up, our moms helped us.”

One new mother said: I “listen more to the elderly people because like the social workers and stuff some of them don’t have kids. They just go by the book … so I feel like I listen more to like my grandparents.”
 

Integrating traditions

When Ana enters medical school she is faced with the task of integration of traditional practice and Western medicine. Ana looks to the National Center for Complementary and Integrative Health (NCCIH), the U.S. government’s lead agency for scientific research on complementary and integrative health approaches for support in her task. The NCCIH was established in 1998 with the mission of determining the usefulness and safety of complementary and integrative health approaches, and their roles in improving health and health care.

The NCCIH notes that more than 30% of adults use health care approaches that are not part of conventional medical care or that have origins outside of usual Western practice, and 17.7% of American adults had used a dietary supplement other than vitamins and minerals in the past year, most commonly fish oil. This agency notes that large rigorous research studies extend to only a few dietary supplements, with results showing that the products didn’t work for the conditions studied. The work of the NCCIH is mirrored worldwide.

The 2008 Beijing Declaration called on World Health Organization member states and other stakeholders to integrate traditional medicine and complementary alternative medicines into national health care systems. The WHO Congress on Traditional Medicine recognizes that traditional medicine (TM) may be more affordable and accessible than Western medicine, and that it plays an important role in meeting the demands of primary health care in many developing countries. From 70% to 80% of the population in India and Ethiopia depend on TM for primary health care, and 70% of the population in Canada and 80% in Germany are reported to have used TM as complementary and/or alternative medical treatment.

After graduation and residency, Ana returns to her village and helps her science teacher consider how best to shape the intergenerational transmission of knowledge, so that it is both honored by the elders and also shaped by the science of medicine.

Every village, regardless of where it is in the world, has to contend with finding the balance between the traditional medical knowledge that is passed down through the family and the discoveries of science. When it comes to practicing medicine and psychiatry, a respect for family tradition must be weighed against the application of science: this is a long conversation that is well worth its time.
 

Dr. Heru is professor of psychiatry at the University of Colorado at Denver, Aurora. She is editor of “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013). Dr. Heru has no conflicts of interest. Contact Dr. Heru at alison.heru@cuanschutz.edu.

Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.

Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.

Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.