Depression

The U.S. Preventive Services Task Force on Apr. 12 posted draft recommendations on screening for depression and anxiety in children and adolescents.

For the first time, the USPSTF is recommending screening children ages 8 and older for anxiety.

It also recommended screening children ages 12 and older for depression, which was consistent with the USPSTF’s prior recommendations on the topic.

These B-grade draft recommendations are for children and teens who are not showing signs or symptoms of these conditions. The task force emphasized that anyone who has concerns about or shows signs of these conditions should be connected to care.

Task force member Martha Kubik, PhD, RN, a professor with George Mason University, Fairfax, Va, said in a statement: “Fortunately, we found that screening older children for anxiety and depression is effective in identifying these conditions so children and teens can be connected to the support they need.”

The group cited in its recommendation on anxiety the 2018-2019 National Survey of Children’s Health, which found that 7.8% of children and adolescents ages 3-17 years had a current anxiety disorder. It also noted that the National Survey on LGBTQ Youth Mental Health found that 72% of LGBTQ youth and 77% of transgender and nonbinary youth described general anxiety disorder symptoms.

“Anxiety disorders in childhood and adolescence are associated with an increased likelihood of a future anxiety disorder or depression,” the task force authors wrote.

They highlighted that “the prevalence of anxiety in Black youth may be evolving.” Previously, studies had suggested that young Black people may have had lower rates of mental health disorders, compared with their White counterparts.

“However, recent cohorts of Black children or adolescents have reported a higher prevalence of anxiety disorders than in the past,” the authors wrote.

Joanna Quigley, MD, clinical associate professor and associate medical director for child & adolescent services at the University of Michigan, Ann Arbor, said in an interview she was not surprised the USPSTF recommended screening for anxiety starting at age 8.

That’s when parents and providers see anxiety disorders begin to present or become more problematic, she said.

“It’s also acknowledging the importance of prevention,” she said. “The sooner we can identify these challenges for kids, the sooner we can intervene and have better outcomes for that child across their lifespan.”

Screening gets providers and families in the habit of thinking about these concerns when a child or adolescent comes in for another kind of visit, Dr. Quigley said. Chest pains in a well-child check, for example, may trigger thoughts to consider anxiety later if the child is brought in for a cardiac check for chest pains.

“It creates a culture of awareness that is important as well,” Dr. Quigley said. “I think part of what the task force is trying to do is saying that identifying anxiety can be a precursor to what could turn out to be related to depression or related to ADHD and factors we think about when we think about suicide risk as well.

“We’re seeing an increase in suicide in the younger age group as well, which is a huge concern, “ she noted.

Dr. Quigley said, if these recommendations are adopted after the comment period, pediatricians and family practice providers will likely be doing most of the screening for anxiety, but there may also be a role for the screening in pediatric subspecialty care, such as those treating children with chronic illness and in specialized mental health care.

She added: “This builds on the national conversation going on about the mental health crisis, declared a national emergency in the fall. This deserves attention in continuing the momentum.”
 

Factors that may signal higher risk for depression

While the USPSTF recommends screening for major depressive disorder in all adolescents aged 12 years and older, the USPSTF notes that several risk factors might help identify those at higher risk.

Markers for higher risk include a combination of factors such as a family history of depression, prior episode of depression, and other mental health or behavioral problems.

“Other psychosocial risk factors include childhood abuse or neglect, exposure to traumatic events, bullying (either as perpetrators or as victims), adverse life events, early exposure to stress, maltreatment, and an insecure parental relationship,” the task force authors wrote.

There was limited evidence, however, on the benefits and harms of screening children younger than 8 for anxiety and screening kids younger than 12 for depression.
 

Not enough evidence for suicide risk screening

The authors of the recommendations acknowledged that, while suicide is a leading cause of death for older children and teens, evidence is still too sparse to make recommendations regarding screening for suicide risk in those without signs or symptoms at any age.

They also explained that evidence is lacking and inconsistent on the effectiveness of treatment (psychotherapy, pharmacotherapy, or collaborative care) for suicide risk in improving outcomes in children and adolescents.

Comments on the USPSTF recommendations may be submitted until May 9, 2022. The USPSTF topic leads review all comments, revise the draft recommendations, put them to a vote by the full task force, and then post the final versions to the website.

The task force authors and Dr. Quigley reported no financial disclosures.

The U.S. Preventive Services Task Force on Apr. 12 posted draft recommendations on screening for depression and anxiety in children and adolescents.

For the first time, the USPSTF is recommending screening children ages 8 and older for anxiety.

It also recommended screening children ages 12 and older for depression, which was consistent with the USPSTF’s prior recommendations on the topic.

These B-grade draft recommendations are for children and teens who are not showing signs or symptoms of these conditions. The task force emphasized that anyone who has concerns about or shows signs of these conditions should be connected to care.

Task force member Martha Kubik, PhD, RN, a professor with George Mason University, Fairfax, Va, said in a statement: “Fortunately, we found that screening older children for anxiety and depression is effective in identifying these conditions so children and teens can be connected to the support they need.”

The group cited in its recommendation on anxiety the 2018-2019 National Survey of Children’s Health, which found that 7.8% of children and adolescents ages 3-17 years had a current anxiety disorder. It also noted that the National Survey on LGBTQ Youth Mental Health found that 72% of LGBTQ youth and 77% of transgender and nonbinary youth described general anxiety disorder symptoms.

“Anxiety disorders in childhood and adolescence are associated with an increased likelihood of a future anxiety disorder or depression,” the task force authors wrote.

They highlighted that “the prevalence of anxiety in Black youth may be evolving.” Previously, studies had suggested that young Black people may have had lower rates of mental health disorders, compared with their White counterparts.

“However, recent cohorts of Black children or adolescents have reported a higher prevalence of anxiety disorders than in the past,” the authors wrote.

Joanna Quigley, MD, clinical associate professor and associate medical director for child & adolescent services at the University of Michigan, Ann Arbor, said in an interview she was not surprised the USPSTF recommended screening for anxiety starting at age 8.

That’s when parents and providers see anxiety disorders begin to present or become more problematic, she said.

“It’s also acknowledging the importance of prevention,” she said. “The sooner we can identify these challenges for kids, the sooner we can intervene and have better outcomes for that child across their lifespan.”

Screening gets providers and families in the habit of thinking about these concerns when a child or adolescent comes in for another kind of visit, Dr. Quigley said. Chest pains in a well-child check, for example, may trigger thoughts to consider anxiety later if the child is brought in for a cardiac check for chest pains.

“It creates a culture of awareness that is important as well,” Dr. Quigley said. “I think part of what the task force is trying to do is saying that identifying anxiety can be a precursor to what could turn out to be related to depression or related to ADHD and factors we think about when we think about suicide risk as well.

“We’re seeing an increase in suicide in the younger age group as well, which is a huge concern, “ she noted.

Dr. Quigley said, if these recommendations are adopted after the comment period, pediatricians and family practice providers will likely be doing most of the screening for anxiety, but there may also be a role for the screening in pediatric subspecialty care, such as those treating children with chronic illness and in specialized mental health care.

She added: “This builds on the national conversation going on about the mental health crisis, declared a national emergency in the fall. This deserves attention in continuing the momentum.”
 

Factors that may signal higher risk for depression

While the USPSTF recommends screening for major depressive disorder in all adolescents aged 12 years and older, the USPSTF notes that several risk factors might help identify those at higher risk.

Markers for higher risk include a combination of factors such as a family history of depression, prior episode of depression, and other mental health or behavioral problems.

“Other psychosocial risk factors include childhood abuse or neglect, exposure to traumatic events, bullying (either as perpetrators or as victims), adverse life events, early exposure to stress, maltreatment, and an insecure parental relationship,” the task force authors wrote.

There was limited evidence, however, on the benefits and harms of screening children younger than 8 for anxiety and screening kids younger than 12 for depression.
 

Not enough evidence for suicide risk screening

The authors of the recommendations acknowledged that, while suicide is a leading cause of death for older children and teens, evidence is still too sparse to make recommendations regarding screening for suicide risk in those without signs or symptoms at any age.

They also explained that evidence is lacking and inconsistent on the effectiveness of treatment (psychotherapy, pharmacotherapy, or collaborative care) for suicide risk in improving outcomes in children and adolescents.

Comments on the USPSTF recommendations may be submitted until May 9, 2022. The USPSTF topic leads review all comments, revise the draft recommendations, put them to a vote by the full task force, and then post the final versions to the website.

The task force authors and Dr. Quigley reported no financial disclosures.

The U.S. Preventive Services Task Force on Apr. 12 posted draft recommendations on screening for depression and anxiety in children and adolescents.

For the first time, the USPSTF is recommending screening children ages 8 and older for anxiety.

It also recommended screening children ages 12 and older for depression, which was consistent with the USPSTF’s prior recommendations on the topic.

These B-grade draft recommendations are for children and teens who are not showing signs or symptoms of these conditions. The task force emphasized that anyone who has concerns about or shows signs of these conditions should be connected to care.

Task force member Martha Kubik, PhD, RN, a professor with George Mason University, Fairfax, Va, said in a statement: “Fortunately, we found that screening older children for anxiety and depression is effective in identifying these conditions so children and teens can be connected to the support they need.”

The group cited in its recommendation on anxiety the 2018-2019 National Survey of Children’s Health, which found that 7.8% of children and adolescents ages 3-17 years had a current anxiety disorder. It also noted that the National Survey on LGBTQ Youth Mental Health found that 72% of LGBTQ youth and 77% of transgender and nonbinary youth described general anxiety disorder symptoms.

“Anxiety disorders in childhood and adolescence are associated with an increased likelihood of a future anxiety disorder or depression,” the task force authors wrote.

They highlighted that “the prevalence of anxiety in Black youth may be evolving.” Previously, studies had suggested that young Black people may have had lower rates of mental health disorders, compared with their White counterparts.

“However, recent cohorts of Black children or adolescents have reported a higher prevalence of anxiety disorders than in the past,” the authors wrote.

Joanna Quigley, MD, clinical associate professor and associate medical director for child & adolescent services at the University of Michigan, Ann Arbor, said in an interview she was not surprised the USPSTF recommended screening for anxiety starting at age 8.

That’s when parents and providers see anxiety disorders begin to present or become more problematic, she said.

“It’s also acknowledging the importance of prevention,” she said. “The sooner we can identify these challenges for kids, the sooner we can intervene and have better outcomes for that child across their lifespan.”

Screening gets providers and families in the habit of thinking about these concerns when a child or adolescent comes in for another kind of visit, Dr. Quigley said. Chest pains in a well-child check, for example, may trigger thoughts to consider anxiety later if the child is brought in for a cardiac check for chest pains.

“It creates a culture of awareness that is important as well,” Dr. Quigley said. “I think part of what the task force is trying to do is saying that identifying anxiety can be a precursor to what could turn out to be related to depression or related to ADHD and factors we think about when we think about suicide risk as well.

“We’re seeing an increase in suicide in the younger age group as well, which is a huge concern, “ she noted.

Dr. Quigley said, if these recommendations are adopted after the comment period, pediatricians and family practice providers will likely be doing most of the screening for anxiety, but there may also be a role for the screening in pediatric subspecialty care, such as those treating children with chronic illness and in specialized mental health care.

She added: “This builds on the national conversation going on about the mental health crisis, declared a national emergency in the fall. This deserves attention in continuing the momentum.”
 

Factors that may signal higher risk for depression

While the USPSTF recommends screening for major depressive disorder in all adolescents aged 12 years and older, the USPSTF notes that several risk factors might help identify those at higher risk.

Markers for higher risk include a combination of factors such as a family history of depression, prior episode of depression, and other mental health or behavioral problems.

“Other psychosocial risk factors include childhood abuse or neglect, exposure to traumatic events, bullying (either as perpetrators or as victims), adverse life events, early exposure to stress, maltreatment, and an insecure parental relationship,” the task force authors wrote.

There was limited evidence, however, on the benefits and harms of screening children younger than 8 for anxiety and screening kids younger than 12 for depression.
 

Not enough evidence for suicide risk screening

The authors of the recommendations acknowledged that, while suicide is a leading cause of death for older children and teens, evidence is still too sparse to make recommendations regarding screening for suicide risk in those without signs or symptoms at any age.

They also explained that evidence is lacking and inconsistent on the effectiveness of treatment (psychotherapy, pharmacotherapy, or collaborative care) for suicide risk in improving outcomes in children and adolescents.

Comments on the USPSTF recommendations may be submitted until May 9, 2022. The USPSTF topic leads review all comments, revise the draft recommendations, put them to a vote by the full task force, and then post the final versions to the website.

The task force authors and Dr. Quigley reported no financial disclosures.

New research points to a general mechanism that may explain how psychedelics act on the brain to alleviate depression and potentially other psychiatric conditions marked by fixed patterns of thinking, including rumination and excessive self-focus.

Led by investigators from the University of California, San Francisco, and Imperial College London’s Centre for Psychedelic Research, the findings come from a new analysis of brain scans of almost 60 patients with resistant depression treated with psilocybin.

Thomas Angus/Imperial College London

“Not much is known about the changes in brain function after psychedelic experience. There has been much more research done on the acute brain action of psychedelics, but there is very little on the postacute or subacute changes in brain function,” study investigator Robin Carhart-Harris, PhD, former head of the Imperial Centre for Psychedelic Research and now director of the Neuroscape psychedelics division at UCSF, and senior author of the study, told this news organization.

“This research is a major advance because it is showing replication across two datasets with different designs. One in which the scanning is done 1 day after intervention and the other one when the posttreatment scanning is done 3 weeks after the second of two psilocybin therapy sessions,” Dr. Carhart-Harris added.

The study was published online in Nature Medicine.
 

A disruptor?

Psilocybin is one of a number of psychedelics under investigation as a potential therapy for psychiatric disorders. In the last 15 years, at least six separate clinical trials have reported impressive improvements in depressive symptoms with psilocybin therapy. Several studies have tested a synthesized a form of the drug to treat patients with depression and anxiety – with promising results.

However, the therapeutic action of psilocybin and other serotonergic psychedelics is still not completely understood, although it is known that they affect 5-HT_2A receptors and are hypothesized to briefly disrupt these connections, allowing them to reform in new ways in the days and weeks following treatment.

This research assessed the subacute impact of psilocybin on brain function in two clinical trials of depression:

The first trial was an open-label trial of oral psilocybin in patients with treatment-resistant depression.

Patients had baseline clinical assessment and resting-state functional MRI, followed by fixed-order “low” (10 mg) and “high” (25 mg) psilocybin therapy dosing days separated by 1 week. Of the 19 patients recruited, 3 were excluded as a result of excessive fMRI head motion. The team confirmed an antidepressant effect of psilocybin in 16 patients via reduced questionnaire scores from baseline.

Brain network modularity was significantly reduced 1 day after psilocybin therapy in 10 of 16 participants (mean difference, –0.29; t₁₅, 2.87; 95% confidence interval, 0.07-0.50; P = .012; d = 0.72). This result implies an increase in functional connectivity between the brain’s main intrinsic networks. 

Pre- vs posttreatment change in modularity significantly correlated with change in Beck Depression Inventory (BDI) score at 6 months, relative to baseline (r₁₄ = 0.54, 95% CI, 0.14-0.78, P = .033). Results imply that decreased brain modularity 1 day after psilocybin therapy relates to long-term improvements in symptom severity.
 

Effective antidepressant alternative?

The second trial was a double-blind, phase 2, randomized, controlled trial comparing psilocybin with escitalopram (Lexapro). Twenty-one patients were included in the escitalopram imaging sample and 22 patients were included in the psilocybin imaging sample. 

Patients received either 2 x 25 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo (psilocybin arm) or 2 x 1 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram (10-20 mg) (escitalopram arm). Functional MRI was recorded at baseline and 3 weeks after the second psilocybin dose.

On average, BDI-measured reductions in depressive symptom severity were significantly greater under psilocybin than escitalopram, indicating superior efficacy of psilocybin therapy versus escitalopram.

Evidence indicated that the reduction in network modularity and its relationship to depression severity was specific to the psilocybin group. In the escitalopram group, network modularity did not change from baseline and there was no significant correlation between changes in modularity and changes in BDI scores. 

Post–psilocybin therapy changes in network flexibility were correlated with changes in BDI score. After false discovery rate correction, increased executive network dynamic flexibility strongly correlated with greater symptom improvement at the 6-week primary endpoint for the psilocybin arm (r20, –0.76, 95% CI, −0.90 to –0.50, P = .001).

There were no significant correlations between changes in BDI scores and changes in dynamic flexibility in the escitalopram arm.

Imperial Centre for Psychedelic Research

“These findings are important because for the first time we find that psilocybin works differently from conventional antidepressants, making the brain more flexible and fluid and less entrenched in the negative thinking patterns associated with depression. This supports our initial predictions and confirms psilocybin could be a real alternative approach to depression treatments,” study investigator David Nutt, DM, head of the Imperial Centre for Psychedelic Research, London, said in a release.

“In previous studies we had seen a similar effect in the brain when people were scanned whilst on a psychedelic, but here we’re seeing it weeks after treatment for depression, which suggests a carryover of the acute drug action,” said Dr. Carhart-Harris.
 

Durable effect?

“We don’t yet know how long the changes in brain activity seen with psilocybin therapy last, and we need to do more research to understand this,” said Dr. Carhart-Harris, who is a member of the UCSF Weill Institute for Neurosciences. “If the changes don’t last, then is it related to relapse into a depressive episode? We need to do follow-up scans to see where people’s brains are at 3 months or even 6 months after treatment.

“We do know that some people relapse, and it may be that after a while their brains revert to the rigid patterns of activity we see in depression.

“One exciting implication of our findings is that we have discovered a fundamental mechanism via which psychedelic therapy works not just for depression but other mental illnesses, such as anorexia or addiction. We now need to test if this is the case, and if it is, then we have found something important,” added Dr. Carhart-Harris.

Successful phase 3, double-blind randomized, controlled trials will be required to achieve licensing for psilocybin therapy, but pragmatic trials may better address questions regarding treatment practicability, specificity, and optimization. Given the emerging research into psychedelic therapy, it is important for large-scale trials to establish the generalizability, reliability, and specificity of the drug’s antidepressant response.

So how close are we to full federal approval for psilocybin in the treatment of depression? Dr. Carhart-Harris estimated that within 4-5 years is realistic at the federal level. At the state level, in Oregon psilocybin therapy is on track for approval in 2023, including for patients currently undergoing treatment for depressive disorders. In addition, things are opening up in Canada, with some special-access opportunities.

The researchers cautioned that, while these findings are encouraging, trials assessing psilocybin for depression have taken place under controlled, clinical conditions, using a regulated dose formulated in a laboratory, and involved extensive psychological support by a mental health professional – before, during, and after dosing. Taking psychedelics in the absence of these combined safeguards may not have a positive outcome.

The research was supported by funding from the Alex Mosley Charitable Trust and founding donors of the Imperial Centre for Psychedelic Research. One coauthor was supported by the Imperial College London EPSRC Centre London for doctoral training in neurotechnology.

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

New research points to a general mechanism that may explain how psychedelics act on the brain to alleviate depression and potentially other psychiatric conditions marked by fixed patterns of thinking, including rumination and excessive self-focus.

Led by investigators from the University of California, San Francisco, and Imperial College London’s Centre for Psychedelic Research, the findings come from a new analysis of brain scans of almost 60 patients with resistant depression treated with psilocybin.

Thomas Angus/Imperial College London

“Not much is known about the changes in brain function after psychedelic experience. There has been much more research done on the acute brain action of psychedelics, but there is very little on the postacute or subacute changes in brain function,” study investigator Robin Carhart-Harris, PhD, former head of the Imperial Centre for Psychedelic Research and now director of the Neuroscape psychedelics division at UCSF, and senior author of the study, told this news organization.

“This research is a major advance because it is showing replication across two datasets with different designs. One in which the scanning is done 1 day after intervention and the other one when the posttreatment scanning is done 3 weeks after the second of two psilocybin therapy sessions,” Dr. Carhart-Harris added.

The study was published online in Nature Medicine.
 

A disruptor?

Psilocybin is one of a number of psychedelics under investigation as a potential therapy for psychiatric disorders. In the last 15 years, at least six separate clinical trials have reported impressive improvements in depressive symptoms with psilocybin therapy. Several studies have tested a synthesized a form of the drug to treat patients with depression and anxiety – with promising results.

However, the therapeutic action of psilocybin and other serotonergic psychedelics is still not completely understood, although it is known that they affect 5-HT_2A receptors and are hypothesized to briefly disrupt these connections, allowing them to reform in new ways in the days and weeks following treatment.

This research assessed the subacute impact of psilocybin on brain function in two clinical trials of depression:

The first trial was an open-label trial of oral psilocybin in patients with treatment-resistant depression.

Patients had baseline clinical assessment and resting-state functional MRI, followed by fixed-order “low” (10 mg) and “high” (25 mg) psilocybin therapy dosing days separated by 1 week. Of the 19 patients recruited, 3 were excluded as a result of excessive fMRI head motion. The team confirmed an antidepressant effect of psilocybin in 16 patients via reduced questionnaire scores from baseline.

Brain network modularity was significantly reduced 1 day after psilocybin therapy in 10 of 16 participants (mean difference, –0.29; t₁₅, 2.87; 95% confidence interval, 0.07-0.50; P = .012; d = 0.72). This result implies an increase in functional connectivity between the brain’s main intrinsic networks. 

Pre- vs posttreatment change in modularity significantly correlated with change in Beck Depression Inventory (BDI) score at 6 months, relative to baseline (r₁₄ = 0.54, 95% CI, 0.14-0.78, P = .033). Results imply that decreased brain modularity 1 day after psilocybin therapy relates to long-term improvements in symptom severity.
 

Effective antidepressant alternative?

The second trial was a double-blind, phase 2, randomized, controlled trial comparing psilocybin with escitalopram (Lexapro). Twenty-one patients were included in the escitalopram imaging sample and 22 patients were included in the psilocybin imaging sample. 

Patients received either 2 x 25 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo (psilocybin arm) or 2 x 1 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram (10-20 mg) (escitalopram arm). Functional MRI was recorded at baseline and 3 weeks after the second psilocybin dose.

On average, BDI-measured reductions in depressive symptom severity were significantly greater under psilocybin than escitalopram, indicating superior efficacy of psilocybin therapy versus escitalopram.

Evidence indicated that the reduction in network modularity and its relationship to depression severity was specific to the psilocybin group. In the escitalopram group, network modularity did not change from baseline and there was no significant correlation between changes in modularity and changes in BDI scores. 

Post–psilocybin therapy changes in network flexibility were correlated with changes in BDI score. After false discovery rate correction, increased executive network dynamic flexibility strongly correlated with greater symptom improvement at the 6-week primary endpoint for the psilocybin arm (r20, –0.76, 95% CI, −0.90 to –0.50, P = .001).

There were no significant correlations between changes in BDI scores and changes in dynamic flexibility in the escitalopram arm.

Imperial Centre for Psychedelic Research

“These findings are important because for the first time we find that psilocybin works differently from conventional antidepressants, making the brain more flexible and fluid and less entrenched in the negative thinking patterns associated with depression. This supports our initial predictions and confirms psilocybin could be a real alternative approach to depression treatments,” study investigator David Nutt, DM, head of the Imperial Centre for Psychedelic Research, London, said in a release.

“In previous studies we had seen a similar effect in the brain when people were scanned whilst on a psychedelic, but here we’re seeing it weeks after treatment for depression, which suggests a carryover of the acute drug action,” said Dr. Carhart-Harris.
 

Durable effect?

“We don’t yet know how long the changes in brain activity seen with psilocybin therapy last, and we need to do more research to understand this,” said Dr. Carhart-Harris, who is a member of the UCSF Weill Institute for Neurosciences. “If the changes don’t last, then is it related to relapse into a depressive episode? We need to do follow-up scans to see where people’s brains are at 3 months or even 6 months after treatment.

“We do know that some people relapse, and it may be that after a while their brains revert to the rigid patterns of activity we see in depression.

“One exciting implication of our findings is that we have discovered a fundamental mechanism via which psychedelic therapy works not just for depression but other mental illnesses, such as anorexia or addiction. We now need to test if this is the case, and if it is, then we have found something important,” added Dr. Carhart-Harris.

Successful phase 3, double-blind randomized, controlled trials will be required to achieve licensing for psilocybin therapy, but pragmatic trials may better address questions regarding treatment practicability, specificity, and optimization. Given the emerging research into psychedelic therapy, it is important for large-scale trials to establish the generalizability, reliability, and specificity of the drug’s antidepressant response.

So how close are we to full federal approval for psilocybin in the treatment of depression? Dr. Carhart-Harris estimated that within 4-5 years is realistic at the federal level. At the state level, in Oregon psilocybin therapy is on track for approval in 2023, including for patients currently undergoing treatment for depressive disorders. In addition, things are opening up in Canada, with some special-access opportunities.

The researchers cautioned that, while these findings are encouraging, trials assessing psilocybin for depression have taken place under controlled, clinical conditions, using a regulated dose formulated in a laboratory, and involved extensive psychological support by a mental health professional – before, during, and after dosing. Taking psychedelics in the absence of these combined safeguards may not have a positive outcome.

The research was supported by funding from the Alex Mosley Charitable Trust and founding donors of the Imperial Centre for Psychedelic Research. One coauthor was supported by the Imperial College London EPSRC Centre London for doctoral training in neurotechnology.

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

New research points to a general mechanism that may explain how psychedelics act on the brain to alleviate depression and potentially other psychiatric conditions marked by fixed patterns of thinking, including rumination and excessive self-focus.

Led by investigators from the University of California, San Francisco, and Imperial College London’s Centre for Psychedelic Research, the findings come from a new analysis of brain scans of almost 60 patients with resistant depression treated with psilocybin.

Thomas Angus/Imperial College London

“Not much is known about the changes in brain function after psychedelic experience. There has been much more research done on the acute brain action of psychedelics, but there is very little on the postacute or subacute changes in brain function,” study investigator Robin Carhart-Harris, PhD, former head of the Imperial Centre for Psychedelic Research and now director of the Neuroscape psychedelics division at UCSF, and senior author of the study, told this news organization.

“This research is a major advance because it is showing replication across two datasets with different designs. One in which the scanning is done 1 day after intervention and the other one when the posttreatment scanning is done 3 weeks after the second of two psilocybin therapy sessions,” Dr. Carhart-Harris added.

The study was published online in Nature Medicine.
 

A disruptor?

Psilocybin is one of a number of psychedelics under investigation as a potential therapy for psychiatric disorders. In the last 15 years, at least six separate clinical trials have reported impressive improvements in depressive symptoms with psilocybin therapy. Several studies have tested a synthesized a form of the drug to treat patients with depression and anxiety – with promising results.

However, the therapeutic action of psilocybin and other serotonergic psychedelics is still not completely understood, although it is known that they affect 5-HT_2A receptors and are hypothesized to briefly disrupt these connections, allowing them to reform in new ways in the days and weeks following treatment.

This research assessed the subacute impact of psilocybin on brain function in two clinical trials of depression:

The first trial was an open-label trial of oral psilocybin in patients with treatment-resistant depression.

Patients had baseline clinical assessment and resting-state functional MRI, followed by fixed-order “low” (10 mg) and “high” (25 mg) psilocybin therapy dosing days separated by 1 week. Of the 19 patients recruited, 3 were excluded as a result of excessive fMRI head motion. The team confirmed an antidepressant effect of psilocybin in 16 patients via reduced questionnaire scores from baseline.

Brain network modularity was significantly reduced 1 day after psilocybin therapy in 10 of 16 participants (mean difference, –0.29; t₁₅, 2.87; 95% confidence interval, 0.07-0.50; P = .012; d = 0.72). This result implies an increase in functional connectivity between the brain’s main intrinsic networks. 

Pre- vs posttreatment change in modularity significantly correlated with change in Beck Depression Inventory (BDI) score at 6 months, relative to baseline (r₁₄ = 0.54, 95% CI, 0.14-0.78, P = .033). Results imply that decreased brain modularity 1 day after psilocybin therapy relates to long-term improvements in symptom severity.
 

Effective antidepressant alternative?

The second trial was a double-blind, phase 2, randomized, controlled trial comparing psilocybin with escitalopram (Lexapro). Twenty-one patients were included in the escitalopram imaging sample and 22 patients were included in the psilocybin imaging sample. 

Patients received either 2 x 25 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo (psilocybin arm) or 2 x 1 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram (10-20 mg) (escitalopram arm). Functional MRI was recorded at baseline and 3 weeks after the second psilocybin dose.

On average, BDI-measured reductions in depressive symptom severity were significantly greater under psilocybin than escitalopram, indicating superior efficacy of psilocybin therapy versus escitalopram.

Evidence indicated that the reduction in network modularity and its relationship to depression severity was specific to the psilocybin group. In the escitalopram group, network modularity did not change from baseline and there was no significant correlation between changes in modularity and changes in BDI scores. 

Post–psilocybin therapy changes in network flexibility were correlated with changes in BDI score. After false discovery rate correction, increased executive network dynamic flexibility strongly correlated with greater symptom improvement at the 6-week primary endpoint for the psilocybin arm (r20, –0.76, 95% CI, −0.90 to –0.50, P = .001).

There were no significant correlations between changes in BDI scores and changes in dynamic flexibility in the escitalopram arm.

Imperial Centre for Psychedelic Research

“These findings are important because for the first time we find that psilocybin works differently from conventional antidepressants, making the brain more flexible and fluid and less entrenched in the negative thinking patterns associated with depression. This supports our initial predictions and confirms psilocybin could be a real alternative approach to depression treatments,” study investigator David Nutt, DM, head of the Imperial Centre for Psychedelic Research, London, said in a release.

“In previous studies we had seen a similar effect in the brain when people were scanned whilst on a psychedelic, but here we’re seeing it weeks after treatment for depression, which suggests a carryover of the acute drug action,” said Dr. Carhart-Harris.
 

Durable effect?

“We don’t yet know how long the changes in brain activity seen with psilocybin therapy last, and we need to do more research to understand this,” said Dr. Carhart-Harris, who is a member of the UCSF Weill Institute for Neurosciences. “If the changes don’t last, then is it related to relapse into a depressive episode? We need to do follow-up scans to see where people’s brains are at 3 months or even 6 months after treatment.

“We do know that some people relapse, and it may be that after a while their brains revert to the rigid patterns of activity we see in depression.

“One exciting implication of our findings is that we have discovered a fundamental mechanism via which psychedelic therapy works not just for depression but other mental illnesses, such as anorexia or addiction. We now need to test if this is the case, and if it is, then we have found something important,” added Dr. Carhart-Harris.

Successful phase 3, double-blind randomized, controlled trials will be required to achieve licensing for psilocybin therapy, but pragmatic trials may better address questions regarding treatment practicability, specificity, and optimization. Given the emerging research into psychedelic therapy, it is important for large-scale trials to establish the generalizability, reliability, and specificity of the drug’s antidepressant response.

So how close are we to full federal approval for psilocybin in the treatment of depression? Dr. Carhart-Harris estimated that within 4-5 years is realistic at the federal level. At the state level, in Oregon psilocybin therapy is on track for approval in 2023, including for patients currently undergoing treatment for depressive disorders. In addition, things are opening up in Canada, with some special-access opportunities.

The researchers cautioned that, while these findings are encouraging, trials assessing psilocybin for depression have taken place under controlled, clinical conditions, using a regulated dose formulated in a laboratory, and involved extensive psychological support by a mental health professional – before, during, and after dosing. Taking psychedelics in the absence of these combined safeguards may not have a positive outcome.

The research was supported by funding from the Alex Mosley Charitable Trust and founding donors of the Imperial Centre for Psychedelic Research. One coauthor was supported by the Imperial College London EPSRC Centre London for doctoral training in neurotechnology.

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

An analysis at a large academic health system suggests that universal screening might help to reduce problematic disparities in depression treatment.  

The study began soon after the U.S. Preventive Services Task Force recommended depression screening for all adults in 2016. The task force based this recommendation on evidence that people who are screened and treated experience fewer debilitating symptoms.

In the new research, the investigators analyzed electronic health record data following a rollout of a universal depression screening program at the University of California, San Francisco. The researchers found that the overall rate of depression screening doubled at six primary care practices over a little more than 2 years, reaching nearly 90%. The investigators presented the data April 9 at the Society of General Internal Medicine 2022 Annual Meeting in Orlando.

Meanwhile, screening disparities diminished for men, older individuals, racial and ethnic minorities, and people with language barriers – all groups that are undertreated for depression.

“It shows that if a health system is really invested, it can achieve really high depression screening,” primary investigator Maria Garcia, MD, MPH, co-director of UCSF’s Multiethnic Health Equity Research Center, told this news organization.
 

Methods for identifying depression

The health system assigned medical assistants to administer annual screening using a validated tool, the Patient Health Questionnaire-2 (PHQ-2). A “yes” response to either of its two questions triggered a longer questionnaire, the PHQ-9, used to diagnose and guide treatment.

Screening forms were available in multiple languages. Medical assistants received training on the importance of identifying depression in undertreated groups, and a banner was inserted in the electronic health record to indicate a screening was due, Dr. Garcia said.

During the rollout, a committee was assigned to monitor screening rates and adjust strategies to target disparities.

Dr. Garcia and fellow researchers calculated the likelihood of a patient being screened starting in September 2017 – when a field for depression screening status was added to the system’s electronic health record – until the rollout was completed on Dec. 31, 2019.
 

Screening disparities narrowed for all groups studied

The screening rate for patients who had a primary care visit increased from 40.5% to 88.8%. Early on, patients with language barriers were less likely to be screened than English-speaking White individuals (odds ratios, 0.55-0.59). Men were less likely to be screened than women (OR, 0.82; 95% confidence interval, 0.78-0.86), and the likelihood of being screened decreased as people got older. By 2019, screening disparities had narrowed for all groups and were only statistically significant for men (OR, 0.87; 95% CI, 0.81-0.93).

Ian Kronish, MD, MPH, a general internist and associate professor of medicine at Columbia University, New York, called the increases “impressive,” adding that the data show universal depression screening is possible in a system that serves a diverse population.

Dr. Kronish, who was not involved in this study, noted that other research indicates screening does not result in a significant reduction in depressive symptoms in the overall population. He found this to be the case in a trial he led, which focused on patients with recent cardiac events, for example.

“Given all the effort that is going into depression screening and the inclusion of depression screening as a quality metric, we need definitive randomized clinical trials testing whether depression screening leads to increased treatment uptake and, importantly, improved depressive symptoms and quality of life,” he said.

Dr. Garcia acknowledged that more work needs to be done to address treatment barriers, such as language and lack of insurance, and assess whether greater recognition of depressive symptoms in underserved groups can lead to effective treatment. “But this is an important step to know that universal depression screening narrowed disparities in screening over time,” she added.

Dr. Garcia and Dr. Kronish have disclosed no relevant financial relationships.

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

An analysis at a large academic health system suggests that universal screening might help to reduce problematic disparities in depression treatment.  

The study began soon after the U.S. Preventive Services Task Force recommended depression screening for all adults in 2016. The task force based this recommendation on evidence that people who are screened and treated experience fewer debilitating symptoms.

In the new research, the investigators analyzed electronic health record data following a rollout of a universal depression screening program at the University of California, San Francisco. The researchers found that the overall rate of depression screening doubled at six primary care practices over a little more than 2 years, reaching nearly 90%. The investigators presented the data April 9 at the Society of General Internal Medicine 2022 Annual Meeting in Orlando.

Meanwhile, screening disparities diminished for men, older individuals, racial and ethnic minorities, and people with language barriers – all groups that are undertreated for depression.

“It shows that if a health system is really invested, it can achieve really high depression screening,” primary investigator Maria Garcia, MD, MPH, co-director of UCSF’s Multiethnic Health Equity Research Center, told this news organization.
 

Methods for identifying depression

The health system assigned medical assistants to administer annual screening using a validated tool, the Patient Health Questionnaire-2 (PHQ-2). A “yes” response to either of its two questions triggered a longer questionnaire, the PHQ-9, used to diagnose and guide treatment.

Screening forms were available in multiple languages. Medical assistants received training on the importance of identifying depression in undertreated groups, and a banner was inserted in the electronic health record to indicate a screening was due, Dr. Garcia said.

During the rollout, a committee was assigned to monitor screening rates and adjust strategies to target disparities.

Dr. Garcia and fellow researchers calculated the likelihood of a patient being screened starting in September 2017 – when a field for depression screening status was added to the system’s electronic health record – until the rollout was completed on Dec. 31, 2019.
 

Screening disparities narrowed for all groups studied

The screening rate for patients who had a primary care visit increased from 40.5% to 88.8%. Early on, patients with language barriers were less likely to be screened than English-speaking White individuals (odds ratios, 0.55-0.59). Men were less likely to be screened than women (OR, 0.82; 95% confidence interval, 0.78-0.86), and the likelihood of being screened decreased as people got older. By 2019, screening disparities had narrowed for all groups and were only statistically significant for men (OR, 0.87; 95% CI, 0.81-0.93).

Ian Kronish, MD, MPH, a general internist and associate professor of medicine at Columbia University, New York, called the increases “impressive,” adding that the data show universal depression screening is possible in a system that serves a diverse population.

Dr. Kronish, who was not involved in this study, noted that other research indicates screening does not result in a significant reduction in depressive symptoms in the overall population. He found this to be the case in a trial he led, which focused on patients with recent cardiac events, for example.

“Given all the effort that is going into depression screening and the inclusion of depression screening as a quality metric, we need definitive randomized clinical trials testing whether depression screening leads to increased treatment uptake and, importantly, improved depressive symptoms and quality of life,” he said.

Dr. Garcia acknowledged that more work needs to be done to address treatment barriers, such as language and lack of insurance, and assess whether greater recognition of depressive symptoms in underserved groups can lead to effective treatment. “But this is an important step to know that universal depression screening narrowed disparities in screening over time,” she added.

Dr. Garcia and Dr. Kronish have disclosed no relevant financial relationships.

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

An analysis at a large academic health system suggests that universal screening might help to reduce problematic disparities in depression treatment.  

The study began soon after the U.S. Preventive Services Task Force recommended depression screening for all adults in 2016. The task force based this recommendation on evidence that people who are screened and treated experience fewer debilitating symptoms.

In the new research, the investigators analyzed electronic health record data following a rollout of a universal depression screening program at the University of California, San Francisco. The researchers found that the overall rate of depression screening doubled at six primary care practices over a little more than 2 years, reaching nearly 90%. The investigators presented the data April 9 at the Society of General Internal Medicine 2022 Annual Meeting in Orlando.

Meanwhile, screening disparities diminished for men, older individuals, racial and ethnic minorities, and people with language barriers – all groups that are undertreated for depression.

“It shows that if a health system is really invested, it can achieve really high depression screening,” primary investigator Maria Garcia, MD, MPH, co-director of UCSF’s Multiethnic Health Equity Research Center, told this news organization.
 

Methods for identifying depression

The health system assigned medical assistants to administer annual screening using a validated tool, the Patient Health Questionnaire-2 (PHQ-2). A “yes” response to either of its two questions triggered a longer questionnaire, the PHQ-9, used to diagnose and guide treatment.

Screening forms were available in multiple languages. Medical assistants received training on the importance of identifying depression in undertreated groups, and a banner was inserted in the electronic health record to indicate a screening was due, Dr. Garcia said.

During the rollout, a committee was assigned to monitor screening rates and adjust strategies to target disparities.

Dr. Garcia and fellow researchers calculated the likelihood of a patient being screened starting in September 2017 – when a field for depression screening status was added to the system’s electronic health record – until the rollout was completed on Dec. 31, 2019.
 

Screening disparities narrowed for all groups studied

The screening rate for patients who had a primary care visit increased from 40.5% to 88.8%. Early on, patients with language barriers were less likely to be screened than English-speaking White individuals (odds ratios, 0.55-0.59). Men were less likely to be screened than women (OR, 0.82; 95% confidence interval, 0.78-0.86), and the likelihood of being screened decreased as people got older. By 2019, screening disparities had narrowed for all groups and were only statistically significant for men (OR, 0.87; 95% CI, 0.81-0.93).

Ian Kronish, MD, MPH, a general internist and associate professor of medicine at Columbia University, New York, called the increases “impressive,” adding that the data show universal depression screening is possible in a system that serves a diverse population.

Dr. Kronish, who was not involved in this study, noted that other research indicates screening does not result in a significant reduction in depressive symptoms in the overall population. He found this to be the case in a trial he led, which focused on patients with recent cardiac events, for example.

“Given all the effort that is going into depression screening and the inclusion of depression screening as a quality metric, we need definitive randomized clinical trials testing whether depression screening leads to increased treatment uptake and, importantly, improved depressive symptoms and quality of life,” he said.

Dr. Garcia acknowledged that more work needs to be done to address treatment barriers, such as language and lack of insurance, and assess whether greater recognition of depressive symptoms in underserved groups can lead to effective treatment. “But this is an important step to know that universal depression screening narrowed disparities in screening over time,” she added.

Dr. Garcia and Dr. Kronish have disclosed no relevant financial relationships.

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

There’s a strong likelihood that the antidepressant fluvoxamine (Luvox) may moderately lower rates of hospitalization caused by COVID-19 in unvaccinated patients, a new systematic review and meta-analysis has found. But outside experts differ over whether the evidence from just three studies is strong enough to warrant adding the drug to the COVID-19 armamentarium.

The report, published online in JAMA Network Open, looked at three studies and estimated that the drug could reduce the relative risk of hospitalization by around 25% (likelihood of moderate effect, 81.6%-91.8%), depending on the type of analysis used.

“This research might be valuable, but the jury remains out until several other adequately powered and designed trials are completed,” said infectious disease specialist Carl J. Fichtenbaum, MD, of the University of Cincinnati, who’s familiar with the findings. “I’m not sure how useful this is given we have several antiviral agents available. Why would we choose this over Paxlovid, remdesivir, or molnupiravir?”

According to Dr. Fichtenbaum, researchers began focusing on fluvoxamine after case reports about patients improving while on the medication. This led to further interest, he said, boosted by the drug’s known ability to dampen the immune system.

A Silicon Valley investor and antivaccine activist named Steve Kirsch has been pushing the drug along with the debunked treatment hydroxychloroquine. He’s accused the government of a cover-up of fluvoxamine’s worth, according to MIT Technology Review, and he wrote a commentary that referred to the drug as “the fast, easy, safe, simple, low-cost solution to COVID that works 100% of the time that nobody wants to talk about.”

For the new analysis, researchers examined three randomized clinical trials with a total of 2,196 participants. The most extensive trial, the TOGETHER study in Brazil (n = 1,497), focused on an unusual outcome: It linked the drug to a 32% reduction in relative risk of patients with COVID-19 being hospitalized in an ED for fewer than 6 hours or transferred to a tertiary hospital because of the disease.

Another study, the STOP COVID 2 trial in the United States and Canada (n = 547), was stopped because too few patients could be recruited to provide useful results. The initial phase of this trial, STOP COVID 1 (n = 152), was also included in the analysis.

All participants in the three studies were unvaccinated. Their median age was 46-50 years, 55%-72% were women, and 44%-56% were obese. Most were multiracial due to the high number of participants from Brazil.

“In the Bayesian analyses, the pooled risk ratio in favor of fluvoxamine was 0.78 (95% confidence interval, 0.58-1.08) for the weakly neutral prior and 0.73 (95% CI, 0.53-1.01) for the moderately optimistic prior,” the researchers reported, referring to a reduction in risk of hospitalization. “In the frequentist meta-analysis, the pooled risk ratio in favor of fluvoxamine was 0.75 (95% CI, 0.58-0.97; I², 0.2%).”

Two of the authors of the new analysis were also coauthors of the TOGETHER trial and both STOP COVID trials.

Corresponding author Emily G. McDonald, MD, division of experimental medicine at McGill University, Montreal, said in an interview that the findings show fluvoxamine “very likely reduces hospitalization in high-risk outpatient adults with COVID-19. This effect varies depending on your baseline risk of developing complications in the first place.”

Dr. McDonald added that “fluvoxamine is an option to reduce hospitalizations in high-risk adults. It is likely effective, is inexpensive, and has a long safety track record.” She also noted that “not all countries have access to Paxlovid, and some people have drug interactions that preclude its use. Existing monoclonals are not effective with newer variants.”

The drug’s apparent anti-inflammatory properties seem to be key, she said. According to her, the next steps should be “testing lower doses to see if they remain effective, following patients long term to see what impact there is on long COVID symptoms, testing related medications in the drug class to see if they also show an effect, and testing in vaccinated people and with newer variants.”

In an interview, biostatistician James Watson, PhD, of the Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand, and Nuffield department of medicine, University of Oxford, England, said the findings of the analysis are “not overwhelming data.”

He noted the TOGETHER study’s unusual focus on ED visits that latest fewer than 6 hours, which he described as “not a very objective endpoint.” The new meta-analysis focused instead on “outcome data on emergency department visits lasting more than 24 hours and used this as a more representative proxy for hospital admission than an ED visit alone.”

Dr. Fichtenbaum also highlighted the odd endpoint. “Most of us would have chosen something like use of oxygen, requirement for ventilation, or death,” he said. “There are many reasons why people go to the ED. This endpoint is not very strong.”

He also noted that the three studies “are very different in design and endpoints.”

Jeffrey S. Morris, PhD, a biostatistician at the University of Pennsylvania, Philadelphia, offered a different perspective about the findings in an interview. “There’s good evidence that it helps some,” he said, and may reduce hospitalizations by 10%. “If the pill is super cheap and toxicity is very acceptable, it’s not adding additional risk. Most clinicians would say that: ‘If I’m reducing risk by 10%, it’s worthwhile.’ ”

No funding was reported. Two authors report having a patent application filed by Washington University for methods of treating COVID-19 during the conduct of the study. Dr. Watson is an investigator for studies analyzing antiviral drugs and Prozac as COVID-19 treatments. Dr. Fichtenbaum and Dr. Morris disclosed no relevant financial relationships.

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

There’s a strong likelihood that the antidepressant fluvoxamine (Luvox) may moderately lower rates of hospitalization caused by COVID-19 in unvaccinated patients, a new systematic review and meta-analysis has found. But outside experts differ over whether the evidence from just three studies is strong enough to warrant adding the drug to the COVID-19 armamentarium.

The report, published online in JAMA Network Open, looked at three studies and estimated that the drug could reduce the relative risk of hospitalization by around 25% (likelihood of moderate effect, 81.6%-91.8%), depending on the type of analysis used.

“This research might be valuable, but the jury remains out until several other adequately powered and designed trials are completed,” said infectious disease specialist Carl J. Fichtenbaum, MD, of the University of Cincinnati, who’s familiar with the findings. “I’m not sure how useful this is given we have several antiviral agents available. Why would we choose this over Paxlovid, remdesivir, or molnupiravir?”

According to Dr. Fichtenbaum, researchers began focusing on fluvoxamine after case reports about patients improving while on the medication. This led to further interest, he said, boosted by the drug’s known ability to dampen the immune system.

A Silicon Valley investor and antivaccine activist named Steve Kirsch has been pushing the drug along with the debunked treatment hydroxychloroquine. He’s accused the government of a cover-up of fluvoxamine’s worth, according to MIT Technology Review, and he wrote a commentary that referred to the drug as “the fast, easy, safe, simple, low-cost solution to COVID that works 100% of the time that nobody wants to talk about.”

For the new analysis, researchers examined three randomized clinical trials with a total of 2,196 participants. The most extensive trial, the TOGETHER study in Brazil (n = 1,497), focused on an unusual outcome: It linked the drug to a 32% reduction in relative risk of patients with COVID-19 being hospitalized in an ED for fewer than 6 hours or transferred to a tertiary hospital because of the disease.

Another study, the STOP COVID 2 trial in the United States and Canada (n = 547), was stopped because too few patients could be recruited to provide useful results. The initial phase of this trial, STOP COVID 1 (n = 152), was also included in the analysis.

All participants in the three studies were unvaccinated. Their median age was 46-50 years, 55%-72% were women, and 44%-56% were obese. Most were multiracial due to the high number of participants from Brazil.

“In the Bayesian analyses, the pooled risk ratio in favor of fluvoxamine was 0.78 (95% confidence interval, 0.58-1.08) for the weakly neutral prior and 0.73 (95% CI, 0.53-1.01) for the moderately optimistic prior,” the researchers reported, referring to a reduction in risk of hospitalization. “In the frequentist meta-analysis, the pooled risk ratio in favor of fluvoxamine was 0.75 (95% CI, 0.58-0.97; I², 0.2%).”

Two of the authors of the new analysis were also coauthors of the TOGETHER trial and both STOP COVID trials.

Corresponding author Emily G. McDonald, MD, division of experimental medicine at McGill University, Montreal, said in an interview that the findings show fluvoxamine “very likely reduces hospitalization in high-risk outpatient adults with COVID-19. This effect varies depending on your baseline risk of developing complications in the first place.”

Dr. McDonald added that “fluvoxamine is an option to reduce hospitalizations in high-risk adults. It is likely effective, is inexpensive, and has a long safety track record.” She also noted that “not all countries have access to Paxlovid, and some people have drug interactions that preclude its use. Existing monoclonals are not effective with newer variants.”

The drug’s apparent anti-inflammatory properties seem to be key, she said. According to her, the next steps should be “testing lower doses to see if they remain effective, following patients long term to see what impact there is on long COVID symptoms, testing related medications in the drug class to see if they also show an effect, and testing in vaccinated people and with newer variants.”

In an interview, biostatistician James Watson, PhD, of the Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand, and Nuffield department of medicine, University of Oxford, England, said the findings of the analysis are “not overwhelming data.”

He noted the TOGETHER study’s unusual focus on ED visits that latest fewer than 6 hours, which he described as “not a very objective endpoint.” The new meta-analysis focused instead on “outcome data on emergency department visits lasting more than 24 hours and used this as a more representative proxy for hospital admission than an ED visit alone.”

Dr. Fichtenbaum also highlighted the odd endpoint. “Most of us would have chosen something like use of oxygen, requirement for ventilation, or death,” he said. “There are many reasons why people go to the ED. This endpoint is not very strong.”

He also noted that the three studies “are very different in design and endpoints.”

Jeffrey S. Morris, PhD, a biostatistician at the University of Pennsylvania, Philadelphia, offered a different perspective about the findings in an interview. “There’s good evidence that it helps some,” he said, and may reduce hospitalizations by 10%. “If the pill is super cheap and toxicity is very acceptable, it’s not adding additional risk. Most clinicians would say that: ‘If I’m reducing risk by 10%, it’s worthwhile.’ ”

No funding was reported. Two authors report having a patent application filed by Washington University for methods of treating COVID-19 during the conduct of the study. Dr. Watson is an investigator for studies analyzing antiviral drugs and Prozac as COVID-19 treatments. Dr. Fichtenbaum and Dr. Morris disclosed no relevant financial relationships.

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

There’s a strong likelihood that the antidepressant fluvoxamine (Luvox) may moderately lower rates of hospitalization caused by COVID-19 in unvaccinated patients, a new systematic review and meta-analysis has found. But outside experts differ over whether the evidence from just three studies is strong enough to warrant adding the drug to the COVID-19 armamentarium.

The report, published online in JAMA Network Open, looked at three studies and estimated that the drug could reduce the relative risk of hospitalization by around 25% (likelihood of moderate effect, 81.6%-91.8%), depending on the type of analysis used.

“This research might be valuable, but the jury remains out until several other adequately powered and designed trials are completed,” said infectious disease specialist Carl J. Fichtenbaum, MD, of the University of Cincinnati, who’s familiar with the findings. “I’m not sure how useful this is given we have several antiviral agents available. Why would we choose this over Paxlovid, remdesivir, or molnupiravir?”

According to Dr. Fichtenbaum, researchers began focusing on fluvoxamine after case reports about patients improving while on the medication. This led to further interest, he said, boosted by the drug’s known ability to dampen the immune system.

A Silicon Valley investor and antivaccine activist named Steve Kirsch has been pushing the drug along with the debunked treatment hydroxychloroquine. He’s accused the government of a cover-up of fluvoxamine’s worth, according to MIT Technology Review, and he wrote a commentary that referred to the drug as “the fast, easy, safe, simple, low-cost solution to COVID that works 100% of the time that nobody wants to talk about.”

For the new analysis, researchers examined three randomized clinical trials with a total of 2,196 participants. The most extensive trial, the TOGETHER study in Brazil (n = 1,497), focused on an unusual outcome: It linked the drug to a 32% reduction in relative risk of patients with COVID-19 being hospitalized in an ED for fewer than 6 hours or transferred to a tertiary hospital because of the disease.

Another study, the STOP COVID 2 trial in the United States and Canada (n = 547), was stopped because too few patients could be recruited to provide useful results. The initial phase of this trial, STOP COVID 1 (n = 152), was also included in the analysis.

All participants in the three studies were unvaccinated. Their median age was 46-50 years, 55%-72% were women, and 44%-56% were obese. Most were multiracial due to the high number of participants from Brazil.

“In the Bayesian analyses, the pooled risk ratio in favor of fluvoxamine was 0.78 (95% confidence interval, 0.58-1.08) for the weakly neutral prior and 0.73 (95% CI, 0.53-1.01) for the moderately optimistic prior,” the researchers reported, referring to a reduction in risk of hospitalization. “In the frequentist meta-analysis, the pooled risk ratio in favor of fluvoxamine was 0.75 (95% CI, 0.58-0.97; I², 0.2%).”

Two of the authors of the new analysis were also coauthors of the TOGETHER trial and both STOP COVID trials.

Corresponding author Emily G. McDonald, MD, division of experimental medicine at McGill University, Montreal, said in an interview that the findings show fluvoxamine “very likely reduces hospitalization in high-risk outpatient adults with COVID-19. This effect varies depending on your baseline risk of developing complications in the first place.”

Dr. McDonald added that “fluvoxamine is an option to reduce hospitalizations in high-risk adults. It is likely effective, is inexpensive, and has a long safety track record.” She also noted that “not all countries have access to Paxlovid, and some people have drug interactions that preclude its use. Existing monoclonals are not effective with newer variants.”

The drug’s apparent anti-inflammatory properties seem to be key, she said. According to her, the next steps should be “testing lower doses to see if they remain effective, following patients long term to see what impact there is on long COVID symptoms, testing related medications in the drug class to see if they also show an effect, and testing in vaccinated people and with newer variants.”

In an interview, biostatistician James Watson, PhD, of the Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand, and Nuffield department of medicine, University of Oxford, England, said the findings of the analysis are “not overwhelming data.”

He noted the TOGETHER study’s unusual focus on ED visits that latest fewer than 6 hours, which he described as “not a very objective endpoint.” The new meta-analysis focused instead on “outcome data on emergency department visits lasting more than 24 hours and used this as a more representative proxy for hospital admission than an ED visit alone.”

Dr. Fichtenbaum also highlighted the odd endpoint. “Most of us would have chosen something like use of oxygen, requirement for ventilation, or death,” he said. “There are many reasons why people go to the ED. This endpoint is not very strong.”

He also noted that the three studies “are very different in design and endpoints.”

Jeffrey S. Morris, PhD, a biostatistician at the University of Pennsylvania, Philadelphia, offered a different perspective about the findings in an interview. “There’s good evidence that it helps some,” he said, and may reduce hospitalizations by 10%. “If the pill is super cheap and toxicity is very acceptable, it’s not adding additional risk. Most clinicians would say that: ‘If I’m reducing risk by 10%, it’s worthwhile.’ ”

No funding was reported. Two authors report having a patent application filed by Washington University for methods of treating COVID-19 during the conduct of the study. Dr. Watson is an investigator for studies analyzing antiviral drugs and Prozac as COVID-19 treatments. Dr. Fichtenbaum and Dr. Morris disclosed no relevant financial relationships.

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

DENVER – An investigational once-daily oral neuroactive steroid is linked to significant improvement in quality of life (QoL) and well-being in patients with major depressive disorder (MDD), new research shows.

In a phase 3 trial that included more than 500 adult patients with MDD, those who received zuranolone for 14 days showed greater improvement at day 15 across numerous QoL outcomes, compared with their counterparts in the placebo group.

In addition, combined analysis of four zuranolone clinical trials showed “mental well-being and functioning improved to near general population norm levels” for the active-treatment group, reported the researchers, led by Anita H. Clayton, MD, chair and professor of psychiatry, University of Virginia, Charlottesville.

“Based on these integrated analyses, the benefit of treatment with zuranolone may extend beyond reduction in depressive symptoms to include potential improvement in quality of life and overall health, as perceived by patients,” they add.

The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

First oral formulation

Zuranolone represents the second entry in the new class of neuroactive steroid drugs, which modulate GABA-A receptor activity – but it would be the first to have an oral formulation. Brexanolone, which was approved by the Food and Drug Administration in 2019 for postpartum depression, is administered through continuous IV infusion over 60 hours.

As previously reported by this news organization, zuranolone improved depressive symptoms as early as day 3, achieving the primary endpoint of significantly greater reduction in scores on the 17-item Hamilton Rating Scale for Depression from baseline to day 15 versus placebo (P = .014).

In the new analysis, patient-reported measures of functional health and well-being were assessed in the WATERFALL trial. It included 266 patients with MDD who were treated with zuranolone 50 mg daily for 2 weeks and 268 patients with MDD who were treated with placebo.

The study used the Short Form–36 (SF-36v2), which covers a wide range of patient-reported measures, including physical function, bodily pain, general health, vitality, social function, and “role-emotional” symptoms.

Results showed that although the treatment and placebo groups had similar baseline SF-36v2 scores, those receiving zuranolone reported significantly greater improvements at day 15 in almost all of the assessment’s domains, including physical function (treatment difference, 0.8), general health (1.0), vitality (3.1), social functioning (1.1), and role-emotional symptoms (1.5; for all comparisons, P < .05). The only exceptions were in role-physical symptoms and bodily pain.

In measures that included physical function, bodily pain, and general health, the patients achieved improvements at day 15 that were consistent with normal levels, with the improvement in vitality considered clinically meaningful versus placebo.

Integrated data

In further analysis of integrated data from four zuranolone clinical trials in the NEST and LANDSCAPE programs for patients with MDD and postpartum depression, results showed similar improvements at day 15 for zuranolone in QoL and overall health across all of the SF-36v2 functioning and well-being domains (P <.05), with the exceptions of physical measure and bodily pain.

By day 42, all of the domains showed significantly greater improvement with zuranolone versus placebo (all, P <.05).

Among the strongest score improvements in the integrated trials were measures in social functioning, which improved from baseline scores of 29.66 to 42.82 on day 15 and to 43.59 on day 42.

Emotional domain scores improved from 24.43 at baseline to 39.13 on day 15 and to 39.82 on day 42. For mental health, the integrated scores for the zuranolone group improved from 27.13 at baseline to 42.40 on day 15 and 42.62 on day 42.

Of note, the baseline scores for mental health represented just 54.3% of those in the normal population; with the increase at day 15, the level was 84.8% of the normal population.

“Across four completed placebo-controlled NEST and LANDSCAPE clinical trials, patient reports of functional health and well-being as assessed by the SF-36v2 indicated substantial impairment at baseline compared to the population norm,” the researchers reported.

The improvements are especially important in light of the fact that in some patients with MDD, functional improvement is a top priority.

“Patients have often prioritized returning to their usual level of functioning over reduction in depressive symptoms, and functional recovery has been associated with better prognosis of depression,” the investigators wrote.

Zuranolone trials have shown that treatment-emergent adverse events (AEs) occur among about 60% of patients, versus about 44% with placebo. The most common AEs are somnolence, dizziness, headache, sedation, and diarrhea, with no increases in suicidal ideation or withdrawal.

The rates of severe AEs are low, and they are observed in about 3% of patients, versus 1.1% with placebo, the researchers noted.

Further, as opposed to serotonergic antidepressants such as SNRIs and SSRIs, zuranolone does not appear to have the undesirable side effects of decreased libido and sexual dysfunction, they added.
 

Clinically meaningful?

Andrew J. Cutler, MD, clinical associate professor of psychiatry at State University of New York, Syracuse, said the data are “very significant” for a number of reasons.

“We need more options to treat depression, especially ones with novel mechanisms of action and faster onset of efficacy, such as zuranolone,” said Dr. Cutler, who was not involved in the current study. He has coauthored other studies on zuranolone.

Regarding the study’s QoL outcomes, “while improvement in depressive symptoms is very important, what really matters to patients is improvement in function and quality of life,” Dr. Cutler noted.

Also commenting on the study, Jonathan E. Alpert, MD, PhD, chair of the department of psychiatry and behavioral sciences and professor of psychiatry, neuroscience, and pediatrics at Albert Einstein College of Medicine, New York, said the investigational drug could represent an important addition to the armamentarium for treating depression.

“Zuranolone has good oral bioavailability and would represent the first neuroactive steroid antidepressant available in oral form and, indeed, the first non–monoamine-based antidepressant available in oral form,” he said in an interview.

Courtesy Dr. Jonathan E. Alpert

Dr. Alpert was not involved in the research and has no relationship with the drug’s development.

He noted that although there are modest differences between the patients who received zuranolone and those who received placebo in the trials, “this may have been related to high placebo response rates, which often complicate antidepressant trials.

“Further research is needed to determine whether differences between zuranolone and placebo are clinically meaningful, though the separation between drug and placebo on the primary endpoint, as well as some other measures, such as quality of life measures, is promising,” Dr. Alpert said.

However, he added that comparisons with other active antidepressants in terms of efficacy and tolerability remain to be seen.

“Given the large number of individuals with major depressive disorder who have incomplete response to or do not tolerate monoaminergic antidepressants, the development of agents that leverage novel nonmonoaminergic mechanisms is important,” Dr. Alpert concluded.

The study was funded by Sage Therapeutics and Biogen. Dr. Cutler has been involved in research of zuranolone for Sage Therapeutics. Dr. Alpert has reported no relevant financial relationships.

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

DENVER – An investigational once-daily oral neuroactive steroid is linked to significant improvement in quality of life (QoL) and well-being in patients with major depressive disorder (MDD), new research shows.

In a phase 3 trial that included more than 500 adult patients with MDD, those who received zuranolone for 14 days showed greater improvement at day 15 across numerous QoL outcomes, compared with their counterparts in the placebo group.

In addition, combined analysis of four zuranolone clinical trials showed “mental well-being and functioning improved to near general population norm levels” for the active-treatment group, reported the researchers, led by Anita H. Clayton, MD, chair and professor of psychiatry, University of Virginia, Charlottesville.

“Based on these integrated analyses, the benefit of treatment with zuranolone may extend beyond reduction in depressive symptoms to include potential improvement in quality of life and overall health, as perceived by patients,” they add.

The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

First oral formulation

Zuranolone represents the second entry in the new class of neuroactive steroid drugs, which modulate GABA-A receptor activity – but it would be the first to have an oral formulation. Brexanolone, which was approved by the Food and Drug Administration in 2019 for postpartum depression, is administered through continuous IV infusion over 60 hours.

As previously reported by this news organization, zuranolone improved depressive symptoms as early as day 3, achieving the primary endpoint of significantly greater reduction in scores on the 17-item Hamilton Rating Scale for Depression from baseline to day 15 versus placebo (P = .014).

In the new analysis, patient-reported measures of functional health and well-being were assessed in the WATERFALL trial. It included 266 patients with MDD who were treated with zuranolone 50 mg daily for 2 weeks and 268 patients with MDD who were treated with placebo.

The study used the Short Form–36 (SF-36v2), which covers a wide range of patient-reported measures, including physical function, bodily pain, general health, vitality, social function, and “role-emotional” symptoms.

Results showed that although the treatment and placebo groups had similar baseline SF-36v2 scores, those receiving zuranolone reported significantly greater improvements at day 15 in almost all of the assessment’s domains, including physical function (treatment difference, 0.8), general health (1.0), vitality (3.1), social functioning (1.1), and role-emotional symptoms (1.5; for all comparisons, P < .05). The only exceptions were in role-physical symptoms and bodily pain.

In measures that included physical function, bodily pain, and general health, the patients achieved improvements at day 15 that were consistent with normal levels, with the improvement in vitality considered clinically meaningful versus placebo.

Integrated data

In further analysis of integrated data from four zuranolone clinical trials in the NEST and LANDSCAPE programs for patients with MDD and postpartum depression, results showed similar improvements at day 15 for zuranolone in QoL and overall health across all of the SF-36v2 functioning and well-being domains (P <.05), with the exceptions of physical measure and bodily pain.

By day 42, all of the domains showed significantly greater improvement with zuranolone versus placebo (all, P <.05).

Among the strongest score improvements in the integrated trials were measures in social functioning, which improved from baseline scores of 29.66 to 42.82 on day 15 and to 43.59 on day 42.

Emotional domain scores improved from 24.43 at baseline to 39.13 on day 15 and to 39.82 on day 42. For mental health, the integrated scores for the zuranolone group improved from 27.13 at baseline to 42.40 on day 15 and 42.62 on day 42.

Of note, the baseline scores for mental health represented just 54.3% of those in the normal population; with the increase at day 15, the level was 84.8% of the normal population.

“Across four completed placebo-controlled NEST and LANDSCAPE clinical trials, patient reports of functional health and well-being as assessed by the SF-36v2 indicated substantial impairment at baseline compared to the population norm,” the researchers reported.

The improvements are especially important in light of the fact that in some patients with MDD, functional improvement is a top priority.

“Patients have often prioritized returning to their usual level of functioning over reduction in depressive symptoms, and functional recovery has been associated with better prognosis of depression,” the investigators wrote.

Zuranolone trials have shown that treatment-emergent adverse events (AEs) occur among about 60% of patients, versus about 44% with placebo. The most common AEs are somnolence, dizziness, headache, sedation, and diarrhea, with no increases in suicidal ideation or withdrawal.

The rates of severe AEs are low, and they are observed in about 3% of patients, versus 1.1% with placebo, the researchers noted.

Further, as opposed to serotonergic antidepressants such as SNRIs and SSRIs, zuranolone does not appear to have the undesirable side effects of decreased libido and sexual dysfunction, they added.
 

Clinically meaningful?

Andrew J. Cutler, MD, clinical associate professor of psychiatry at State University of New York, Syracuse, said the data are “very significant” for a number of reasons.

“We need more options to treat depression, especially ones with novel mechanisms of action and faster onset of efficacy, such as zuranolone,” said Dr. Cutler, who was not involved in the current study. He has coauthored other studies on zuranolone.

Regarding the study’s QoL outcomes, “while improvement in depressive symptoms is very important, what really matters to patients is improvement in function and quality of life,” Dr. Cutler noted.

Also commenting on the study, Jonathan E. Alpert, MD, PhD, chair of the department of psychiatry and behavioral sciences and professor of psychiatry, neuroscience, and pediatrics at Albert Einstein College of Medicine, New York, said the investigational drug could represent an important addition to the armamentarium for treating depression.

“Zuranolone has good oral bioavailability and would represent the first neuroactive steroid antidepressant available in oral form and, indeed, the first non–monoamine-based antidepressant available in oral form,” he said in an interview.

Courtesy Dr. Jonathan E. Alpert

Dr. Alpert was not involved in the research and has no relationship with the drug’s development.

He noted that although there are modest differences between the patients who received zuranolone and those who received placebo in the trials, “this may have been related to high placebo response rates, which often complicate antidepressant trials.

“Further research is needed to determine whether differences between zuranolone and placebo are clinically meaningful, though the separation between drug and placebo on the primary endpoint, as well as some other measures, such as quality of life measures, is promising,” Dr. Alpert said.

However, he added that comparisons with other active antidepressants in terms of efficacy and tolerability remain to be seen.

“Given the large number of individuals with major depressive disorder who have incomplete response to or do not tolerate monoaminergic antidepressants, the development of agents that leverage novel nonmonoaminergic mechanisms is important,” Dr. Alpert concluded.

The study was funded by Sage Therapeutics and Biogen. Dr. Cutler has been involved in research of zuranolone for Sage Therapeutics. Dr. Alpert has reported no relevant financial relationships.

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

DENVER – An investigational once-daily oral neuroactive steroid is linked to significant improvement in quality of life (QoL) and well-being in patients with major depressive disorder (MDD), new research shows.

In a phase 3 trial that included more than 500 adult patients with MDD, those who received zuranolone for 14 days showed greater improvement at day 15 across numerous QoL outcomes, compared with their counterparts in the placebo group.

In addition, combined analysis of four zuranolone clinical trials showed “mental well-being and functioning improved to near general population norm levels” for the active-treatment group, reported the researchers, led by Anita H. Clayton, MD, chair and professor of psychiatry, University of Virginia, Charlottesville.

“Based on these integrated analyses, the benefit of treatment with zuranolone may extend beyond reduction in depressive symptoms to include potential improvement in quality of life and overall health, as perceived by patients,” they add.

The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
 

First oral formulation

Zuranolone represents the second entry in the new class of neuroactive steroid drugs, which modulate GABA-A receptor activity – but it would be the first to have an oral formulation. Brexanolone, which was approved by the Food and Drug Administration in 2019 for postpartum depression, is administered through continuous IV infusion over 60 hours.

As previously reported by this news organization, zuranolone improved depressive symptoms as early as day 3, achieving the primary endpoint of significantly greater reduction in scores on the 17-item Hamilton Rating Scale for Depression from baseline to day 15 versus placebo (P = .014).

In the new analysis, patient-reported measures of functional health and well-being were assessed in the WATERFALL trial. It included 266 patients with MDD who were treated with zuranolone 50 mg daily for 2 weeks and 268 patients with MDD who were treated with placebo.

The study used the Short Form–36 (SF-36v2), which covers a wide range of patient-reported measures, including physical function, bodily pain, general health, vitality, social function, and “role-emotional” symptoms.

Results showed that although the treatment and placebo groups had similar baseline SF-36v2 scores, those receiving zuranolone reported significantly greater improvements at day 15 in almost all of the assessment’s domains, including physical function (treatment difference, 0.8), general health (1.0), vitality (3.1), social functioning (1.1), and role-emotional symptoms (1.5; for all comparisons, P < .05). The only exceptions were in role-physical symptoms and bodily pain.

In measures that included physical function, bodily pain, and general health, the patients achieved improvements at day 15 that were consistent with normal levels, with the improvement in vitality considered clinically meaningful versus placebo.

Integrated data

In further analysis of integrated data from four zuranolone clinical trials in the NEST and LANDSCAPE programs for patients with MDD and postpartum depression, results showed similar improvements at day 15 for zuranolone in QoL and overall health across all of the SF-36v2 functioning and well-being domains (P <.05), with the exceptions of physical measure and bodily pain.

By day 42, all of the domains showed significantly greater improvement with zuranolone versus placebo (all, P <.05).

Among the strongest score improvements in the integrated trials were measures in social functioning, which improved from baseline scores of 29.66 to 42.82 on day 15 and to 43.59 on day 42.

Emotional domain scores improved from 24.43 at baseline to 39.13 on day 15 and to 39.82 on day 42. For mental health, the integrated scores for the zuranolone group improved from 27.13 at baseline to 42.40 on day 15 and 42.62 on day 42.

Of note, the baseline scores for mental health represented just 54.3% of those in the normal population; with the increase at day 15, the level was 84.8% of the normal population.

“Across four completed placebo-controlled NEST and LANDSCAPE clinical trials, patient reports of functional health and well-being as assessed by the SF-36v2 indicated substantial impairment at baseline compared to the population norm,” the researchers reported.

The improvements are especially important in light of the fact that in some patients with MDD, functional improvement is a top priority.

“Patients have often prioritized returning to their usual level of functioning over reduction in depressive symptoms, and functional recovery has been associated with better prognosis of depression,” the investigators wrote.

Zuranolone trials have shown that treatment-emergent adverse events (AEs) occur among about 60% of patients, versus about 44% with placebo. The most common AEs are somnolence, dizziness, headache, sedation, and diarrhea, with no increases in suicidal ideation or withdrawal.

The rates of severe AEs are low, and they are observed in about 3% of patients, versus 1.1% with placebo, the researchers noted.

Further, as opposed to serotonergic antidepressants such as SNRIs and SSRIs, zuranolone does not appear to have the undesirable side effects of decreased libido and sexual dysfunction, they added.
 

Clinically meaningful?

Andrew J. Cutler, MD, clinical associate professor of psychiatry at State University of New York, Syracuse, said the data are “very significant” for a number of reasons.

“We need more options to treat depression, especially ones with novel mechanisms of action and faster onset of efficacy, such as zuranolone,” said Dr. Cutler, who was not involved in the current study. He has coauthored other studies on zuranolone.

Regarding the study’s QoL outcomes, “while improvement in depressive symptoms is very important, what really matters to patients is improvement in function and quality of life,” Dr. Cutler noted.

Also commenting on the study, Jonathan E. Alpert, MD, PhD, chair of the department of psychiatry and behavioral sciences and professor of psychiatry, neuroscience, and pediatrics at Albert Einstein College of Medicine, New York, said the investigational drug could represent an important addition to the armamentarium for treating depression.

“Zuranolone has good oral bioavailability and would represent the first neuroactive steroid antidepressant available in oral form and, indeed, the first non–monoamine-based antidepressant available in oral form,” he said in an interview.

Courtesy Dr. Jonathan E. Alpert

Dr. Alpert was not involved in the research and has no relationship with the drug’s development.

He noted that although there are modest differences between the patients who received zuranolone and those who received placebo in the trials, “this may have been related to high placebo response rates, which often complicate antidepressant trials.

“Further research is needed to determine whether differences between zuranolone and placebo are clinically meaningful, though the separation between drug and placebo on the primary endpoint, as well as some other measures, such as quality of life measures, is promising,” Dr. Alpert said.

However, he added that comparisons with other active antidepressants in terms of efficacy and tolerability remain to be seen.

“Given the large number of individuals with major depressive disorder who have incomplete response to or do not tolerate monoaminergic antidepressants, the development of agents that leverage novel nonmonoaminergic mechanisms is important,” Dr. Alpert concluded.

The study was funded by Sage Therapeutics and Biogen. Dr. Cutler has been involved in research of zuranolone for Sage Therapeutics. Dr. Alpert has reported no relevant financial relationships.

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

Insomnia rates continue to rise in the setting of the pandemic,¹ contributing to increasing rates of depression and anxiety, as well as worsening symptoms of other severe mental illnesses. Data suggests this symptom, defined as chronic sleep onset and/or sleep continuity problems associated with impaired daytime functioning, is common in psychiatric illnesses, and can worsen their course.²

The incidence of psychiatric illness in patients with insomnia is estimated at near 50%, with the highest rates found in mood disorders such as depression and bipolar disorder, as well as anxiety disorders.³ In patients with diagnosed major depressive disorder, insomnia rates can approach 90%.^4-6

Courtesy Dr. Jennifer Reid

Insomnia has been identified as a risk factor for development of mental illness, including doubling the risk of major depressive disorder and tripling the risk of any depressive or anxiety disorder.^7,8 It can also significantly increase the risk of alcohol abuse and psychosis.⁸

Sleep disturbances can worsen symptoms of diagnosed mental illness, including substance abuse, mood and psychotic disorders.^9-10 In one study, nearly 75% of patients with a diagnosis of schizophrenia or bipolar spectrum disorder had at least one type of sleep disturbance (insomnia, hypersomnia, or delayed sleep phase).¹⁰ This was almost twice the rate in healthy controls. Importantly, compared with well-rested subjects with mental illness in this study, sleep-disordered participants had higher rates of negative and depressive symptoms on the Positive and Negative Syndrome Scale, as well as significantly lower function via the global assessment of functioning.^11,12

Additional data suggests simply being awake during the night (00:00-05:59) elevates risk of suicide. The mean incident rate of completed suicide in one study was a striking four times the rate noted during daytime hours (06:00-23:59 ) (P < .001).¹³

Although insomnia symptoms can resolve after relief from a particular life stressor, as many as half of patients with more severe symptoms develop a chronic course.¹⁴ This then leads to an extended use of many types of sedative-hypnotics designed and studied primarily for short-term use.¹⁵ In a survey reviewing national use of prescription drugs for insomnia, as many as 20% of individuals use a medication to target insomnia in a given month.¹⁶

Fortunately, despite the many challenges posed by COVID-19, particularly for those with psychiatric illness and limited access to care, telehealth has become more readily available. Additionally, digital versions of evidence-based treatments specifically for sleep problems, such as cognitive-behavioral therapy for insomnia (CBT-I), are regularly being developed.

The benefits of CBT-I have been demonstrated repeatedly and it is recommended as the first line treatment for insomnia by the Clinical Guidelines of the American Academy of Sleep Medicine, the Centers for Disease Control and Prevention, and the National Institutes of Health.^17-21 Studies suggest benefits persist long-term, even after completing the therapy sessions, which differ in durability from medication choices.¹⁸

One group that may be particularly suited for treatment with CBT-I is women with insomnia during pregnancy or the postpartum period. In these women, options for treatment may be limited by risk of medication during breastfeeding, as well as difficulty traveling to a physician’s or therapist’s office to receive psychotherapy. However, two recent studies evaluated the use of digital CBT-I to treat insomnia during pregnancy and in the postpartum period, respectively.^22-23

In both studies,the same group of women with insomnia diagnosed during pregnancy were given six weekly 20-minute sessions of digital CBT-I or standard treatment for insomnia, including medication and psychotherapy per their usual provider.

By study end, the pregnant women receiving the CBT-I intervention not only had significantly improved severity of insomnia, they also experienced improved depression and anxiety symptoms, and a decrease in the use of prescription or over-the-counter sleep aides, compared with the standard treatment group, lowering the fetal exposure to medication during pregnancy.²²

In the more recent study, the same group was followed for 6 months post partum.²³ Results were again notable, with the women who received CBT-I reporting significantly less insomnia, as well as significantly lower rates of probable major depression at 3 and 6 months (18% vs. 4%, 10% vs. 0%, respectively.) They also exhibited lower rates of moderate to severe anxiety (17% vs. 4%) at 3 months, compared with those receiving standard care. With as many as one in seven women suffering from postpartum depression, these findings represent a substantial public health benefit.

In summary, insomnia is a critical area of focus for any provider diagnosing and treating psychiatric illness. Attempts to optimize sleep, whether through CBT-I or other psychotherapy approaches, or evidence-based medications dosed for appropriate lengths and at safe doses, should be a part of most, if not all, clinical encounters.

Dr. Reid is a board-certified psychiatrist and award-winning medical educator with a private practice in Philadelphia, as well as a clinical faculty role at the University of Pennsylvania, also in Philadelphia. She attended medical school at Columbia University, New York, and completed her psychiatry residency at the University of California, Los Angeles. Dr. Reid is a regular contributor to Psychology Today with her blog, “Think Like a Shrink,” and writes and podcasts as The Reflective Doc.

References

1. Voitsidis P et al. Psychiatry Res. 2020 Jul;289:113076. doi: 10.1016/j.psychres.2020.113076.

2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, Va.: American Psychiatric Publishing, 2013.

3. Ford DE and Kamerow DB. JAMA. 1989;262(11):1479-84. doi: 10.1001/jama.1989.03430110069030.

4. Ohayon MM and Roth T. J Psychiatr Res. Jan-Feb 2003;37(1):9-15. doi: 10.1016/s0022-3956(02)00052-3.

5. Seow LSE et al. J Ment Health. 2016 Dec;25(6):492-9. doi: 10.3109/09638237.2015.1124390.

6. Thase ME. J Clin Psychiatry. 1999;60 Suppl 17:28-31; discussion 46-8.

7. Baglioni C et al. J Affect Disord. 2011 Dec;135(1-3):10-9. doi: 10.1016/j.jad.2011.01.011.

8. Hertenstein E et al. Sleep Med Rev. 2019 Feb;43:96-105. doi: 10.1016/j.smrv.2018.10.006.

9. Brower KJ et al. Medical Hypotheses. 2010;74(5):928-33. doi: 10.1016/j.mehy.2009.10.020.

10. Laskemoen JF et al. Compr Psychiatry. 2019 May;91:6-12. doi: 10.1016/j.comppsych.2019.02.006.

11. Kay SR et al. Schizophr Bull. 1987;13(2):261-76. doi: 10.1093/schbul/13.2.261.

12. Hall R. Psychosomatics. May-Jun 1995;36(3):267-75. doi: 10.1016/S0033-3182(95)71666-8.

13. Perlis ML et al. J Clin Psychiatry. 2016 Jun;77(6):e726-33. doi: 10.4088/JCP.15m10131.

14. Morin CM et al. Arch Intern Med. 2009 Mar 9. doi: 10.1001/archinternmed.2008.610.

15. Cheung J et al. Sleep Med Clin. 2019 Jun;14(2):253-65. doi: 10.1016/j.jsmc.2019.01.006.

16. Bertisch SM et al. Sleep. 2014 Feb 1. doi: 10.5665/sleep.3410.

17. Okajima I et al. Sleep Biol Rhythms. 2010 Nov 28. doi: 10.1111/j.1479-8425.2010.00481.x.

18. Trauer JM et al. Ann Intern Med. 2015 Aug 4. doi: 10.7326/M14-2841.

19. Edinger J et al. J Clin Sleep Med. 2021 Feb 1. doi: 10.5664/jcsm.8986.

20. U.S. Centers for Disease Control and Prevention. https://www.cdc.gov/sleep/for-clinicians.html.

21. National Institutes of Health. Sleep Health. https://www.nhlbi.nih.gov/health-topics/education-and-awareness/sleep-health.

22. Felder JN et al. JAMA Psychiatry. 2020;77(5):484-92. doi:10.1001/jamapsychiatry.2019.4491.

23. Felder JN et al. Sleep. 2022 Feb 14. doi: 10.1093/sleep/zsab280.

Insomnia rates continue to rise in the setting of the pandemic,¹ contributing to increasing rates of depression and anxiety, as well as worsening symptoms of other severe mental illnesses. Data suggests this symptom, defined as chronic sleep onset and/or sleep continuity problems associated with impaired daytime functioning, is common in psychiatric illnesses, and can worsen their course.²

The incidence of psychiatric illness in patients with insomnia is estimated at near 50%, with the highest rates found in mood disorders such as depression and bipolar disorder, as well as anxiety disorders.³ In patients with diagnosed major depressive disorder, insomnia rates can approach 90%.^4-6

Courtesy Dr. Jennifer Reid

Insomnia has been identified as a risk factor for development of mental illness, including doubling the risk of major depressive disorder and tripling the risk of any depressive or anxiety disorder.^7,8 It can also significantly increase the risk of alcohol abuse and psychosis.⁸

Sleep disturbances can worsen symptoms of diagnosed mental illness, including substance abuse, mood and psychotic disorders.^9-10 In one study, nearly 75% of patients with a diagnosis of schizophrenia or bipolar spectrum disorder had at least one type of sleep disturbance (insomnia, hypersomnia, or delayed sleep phase).¹⁰ This was almost twice the rate in healthy controls. Importantly, compared with well-rested subjects with mental illness in this study, sleep-disordered participants had higher rates of negative and depressive symptoms on the Positive and Negative Syndrome Scale, as well as significantly lower function via the global assessment of functioning.^11,12

Additional data suggests simply being awake during the night (00:00-05:59) elevates risk of suicide. The mean incident rate of completed suicide in one study was a striking four times the rate noted during daytime hours (06:00-23:59 ) (P < .001).¹³

Although insomnia symptoms can resolve after relief from a particular life stressor, as many as half of patients with more severe symptoms develop a chronic course.¹⁴ This then leads to an extended use of many types of sedative-hypnotics designed and studied primarily for short-term use.¹⁵ In a survey reviewing national use of prescription drugs for insomnia, as many as 20% of individuals use a medication to target insomnia in a given month.¹⁶

Fortunately, despite the many challenges posed by COVID-19, particularly for those with psychiatric illness and limited access to care, telehealth has become more readily available. Additionally, digital versions of evidence-based treatments specifically for sleep problems, such as cognitive-behavioral therapy for insomnia (CBT-I), are regularly being developed.

The benefits of CBT-I have been demonstrated repeatedly and it is recommended as the first line treatment for insomnia by the Clinical Guidelines of the American Academy of Sleep Medicine, the Centers for Disease Control and Prevention, and the National Institutes of Health.^17-21 Studies suggest benefits persist long-term, even after completing the therapy sessions, which differ in durability from medication choices.¹⁸

One group that may be particularly suited for treatment with CBT-I is women with insomnia during pregnancy or the postpartum period. In these women, options for treatment may be limited by risk of medication during breastfeeding, as well as difficulty traveling to a physician’s or therapist’s office to receive psychotherapy. However, two recent studies evaluated the use of digital CBT-I to treat insomnia during pregnancy and in the postpartum period, respectively.^22-23

In both studies,the same group of women with insomnia diagnosed during pregnancy were given six weekly 20-minute sessions of digital CBT-I or standard treatment for insomnia, including medication and psychotherapy per their usual provider.

By study end, the pregnant women receiving the CBT-I intervention not only had significantly improved severity of insomnia, they also experienced improved depression and anxiety symptoms, and a decrease in the use of prescription or over-the-counter sleep aides, compared with the standard treatment group, lowering the fetal exposure to medication during pregnancy.²²

In the more recent study, the same group was followed for 6 months post partum.²³ Results were again notable, with the women who received CBT-I reporting significantly less insomnia, as well as significantly lower rates of probable major depression at 3 and 6 months (18% vs. 4%, 10% vs. 0%, respectively.) They also exhibited lower rates of moderate to severe anxiety (17% vs. 4%) at 3 months, compared with those receiving standard care. With as many as one in seven women suffering from postpartum depression, these findings represent a substantial public health benefit.

In summary, insomnia is a critical area of focus for any provider diagnosing and treating psychiatric illness. Attempts to optimize sleep, whether through CBT-I or other psychotherapy approaches, or evidence-based medications dosed for appropriate lengths and at safe doses, should be a part of most, if not all, clinical encounters.

Dr. Reid is a board-certified psychiatrist and award-winning medical educator with a private practice in Philadelphia, as well as a clinical faculty role at the University of Pennsylvania, also in Philadelphia. She attended medical school at Columbia University, New York, and completed her psychiatry residency at the University of California, Los Angeles. Dr. Reid is a regular contributor to Psychology Today with her blog, “Think Like a Shrink,” and writes and podcasts as The Reflective Doc.

References

1. Voitsidis P et al. Psychiatry Res. 2020 Jul;289:113076. doi: 10.1016/j.psychres.2020.113076.

2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, Va.: American Psychiatric Publishing, 2013.

3. Ford DE and Kamerow DB. JAMA. 1989;262(11):1479-84. doi: 10.1001/jama.1989.03430110069030.

4. Ohayon MM and Roth T. J Psychiatr Res. Jan-Feb 2003;37(1):9-15. doi: 10.1016/s0022-3956(02)00052-3.

5. Seow LSE et al. J Ment Health. 2016 Dec;25(6):492-9. doi: 10.3109/09638237.2015.1124390.

6. Thase ME. J Clin Psychiatry. 1999;60 Suppl 17:28-31; discussion 46-8.

7. Baglioni C et al. J Affect Disord. 2011 Dec;135(1-3):10-9. doi: 10.1016/j.jad.2011.01.011.

8. Hertenstein E et al. Sleep Med Rev. 2019 Feb;43:96-105. doi: 10.1016/j.smrv.2018.10.006.

9. Brower KJ et al. Medical Hypotheses. 2010;74(5):928-33. doi: 10.1016/j.mehy.2009.10.020.

10. Laskemoen JF et al. Compr Psychiatry. 2019 May;91:6-12. doi: 10.1016/j.comppsych.2019.02.006.

11. Kay SR et al. Schizophr Bull. 1987;13(2):261-76. doi: 10.1093/schbul/13.2.261.

12. Hall R. Psychosomatics. May-Jun 1995;36(3):267-75. doi: 10.1016/S0033-3182(95)71666-8.

13. Perlis ML et al. J Clin Psychiatry. 2016 Jun;77(6):e726-33. doi: 10.4088/JCP.15m10131.

14. Morin CM et al. Arch Intern Med. 2009 Mar 9. doi: 10.1001/archinternmed.2008.610.

15. Cheung J et al. Sleep Med Clin. 2019 Jun;14(2):253-65. doi: 10.1016/j.jsmc.2019.01.006.

16. Bertisch SM et al. Sleep. 2014 Feb 1. doi: 10.5665/sleep.3410.

17. Okajima I et al. Sleep Biol Rhythms. 2010 Nov 28. doi: 10.1111/j.1479-8425.2010.00481.x.

18. Trauer JM et al. Ann Intern Med. 2015 Aug 4. doi: 10.7326/M14-2841.

19. Edinger J et al. J Clin Sleep Med. 2021 Feb 1. doi: 10.5664/jcsm.8986.

20. U.S. Centers for Disease Control and Prevention. https://www.cdc.gov/sleep/for-clinicians.html.

21. National Institutes of Health. Sleep Health. https://www.nhlbi.nih.gov/health-topics/education-and-awareness/sleep-health.

22. Felder JN et al. JAMA Psychiatry. 2020;77(5):484-92. doi:10.1001/jamapsychiatry.2019.4491.

23. Felder JN et al. Sleep. 2022 Feb 14. doi: 10.1093/sleep/zsab280.

Insomnia rates continue to rise in the setting of the pandemic,¹ contributing to increasing rates of depression and anxiety, as well as worsening symptoms of other severe mental illnesses. Data suggests this symptom, defined as chronic sleep onset and/or sleep continuity problems associated with impaired daytime functioning, is common in psychiatric illnesses, and can worsen their course.²

The incidence of psychiatric illness in patients with insomnia is estimated at near 50%, with the highest rates found in mood disorders such as depression and bipolar disorder, as well as anxiety disorders.³ In patients with diagnosed major depressive disorder, insomnia rates can approach 90%.^4-6

Courtesy Dr. Jennifer Reid

Insomnia has been identified as a risk factor for development of mental illness, including doubling the risk of major depressive disorder and tripling the risk of any depressive or anxiety disorder.^7,8 It can also significantly increase the risk of alcohol abuse and psychosis.⁸

Sleep disturbances can worsen symptoms of diagnosed mental illness, including substance abuse, mood and psychotic disorders.^9-10 In one study, nearly 75% of patients with a diagnosis of schizophrenia or bipolar spectrum disorder had at least one type of sleep disturbance (insomnia, hypersomnia, or delayed sleep phase).¹⁰ This was almost twice the rate in healthy controls. Importantly, compared with well-rested subjects with mental illness in this study, sleep-disordered participants had higher rates of negative and depressive symptoms on the Positive and Negative Syndrome Scale, as well as significantly lower function via the global assessment of functioning.^11,12

Additional data suggests simply being awake during the night (00:00-05:59) elevates risk of suicide. The mean incident rate of completed suicide in one study was a striking four times the rate noted during daytime hours (06:00-23:59 ) (P < .001).¹³

Although insomnia symptoms can resolve after relief from a particular life stressor, as many as half of patients with more severe symptoms develop a chronic course.¹⁴ This then leads to an extended use of many types of sedative-hypnotics designed and studied primarily for short-term use.¹⁵ In a survey reviewing national use of prescription drugs for insomnia, as many as 20% of individuals use a medication to target insomnia in a given month.¹⁶

Fortunately, despite the many challenges posed by COVID-19, particularly for those with psychiatric illness and limited access to care, telehealth has become more readily available. Additionally, digital versions of evidence-based treatments specifically for sleep problems, such as cognitive-behavioral therapy for insomnia (CBT-I), are regularly being developed.

The benefits of CBT-I have been demonstrated repeatedly and it is recommended as the first line treatment for insomnia by the Clinical Guidelines of the American Academy of Sleep Medicine, the Centers for Disease Control and Prevention, and the National Institutes of Health.^17-21 Studies suggest benefits persist long-term, even after completing the therapy sessions, which differ in durability from medication choices.¹⁸

One group that may be particularly suited for treatment with CBT-I is women with insomnia during pregnancy or the postpartum period. In these women, options for treatment may be limited by risk of medication during breastfeeding, as well as difficulty traveling to a physician’s or therapist’s office to receive psychotherapy. However, two recent studies evaluated the use of digital CBT-I to treat insomnia during pregnancy and in the postpartum period, respectively.^22-23

In both studies,the same group of women with insomnia diagnosed during pregnancy were given six weekly 20-minute sessions of digital CBT-I or standard treatment for insomnia, including medication and psychotherapy per their usual provider.

By study end, the pregnant women receiving the CBT-I intervention not only had significantly improved severity of insomnia, they also experienced improved depression and anxiety symptoms, and a decrease in the use of prescription or over-the-counter sleep aides, compared with the standard treatment group, lowering the fetal exposure to medication during pregnancy.²²

In the more recent study, the same group was followed for 6 months post partum.²³ Results were again notable, with the women who received CBT-I reporting significantly less insomnia, as well as significantly lower rates of probable major depression at 3 and 6 months (18% vs. 4%, 10% vs. 0%, respectively.) They also exhibited lower rates of moderate to severe anxiety (17% vs. 4%) at 3 months, compared with those receiving standard care. With as many as one in seven women suffering from postpartum depression, these findings represent a substantial public health benefit.

In summary, insomnia is a critical area of focus for any provider diagnosing and treating psychiatric illness. Attempts to optimize sleep, whether through CBT-I or other psychotherapy approaches, or evidence-based medications dosed for appropriate lengths and at safe doses, should be a part of most, if not all, clinical encounters.

Dr. Reid is a board-certified psychiatrist and award-winning medical educator with a private practice in Philadelphia, as well as a clinical faculty role at the University of Pennsylvania, also in Philadelphia. She attended medical school at Columbia University, New York, and completed her psychiatry residency at the University of California, Los Angeles. Dr. Reid is a regular contributor to Psychology Today with her blog, “Think Like a Shrink,” and writes and podcasts as The Reflective Doc.

References

1. Voitsidis P et al. Psychiatry Res. 2020 Jul;289:113076. doi: 10.1016/j.psychres.2020.113076.

2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, Va.: American Psychiatric Publishing, 2013.

3. Ford DE and Kamerow DB. JAMA. 1989;262(11):1479-84. doi: 10.1001/jama.1989.03430110069030.

4. Ohayon MM and Roth T. J Psychiatr Res. Jan-Feb 2003;37(1):9-15. doi: 10.1016/s0022-3956(02)00052-3.

5. Seow LSE et al. J Ment Health. 2016 Dec;25(6):492-9. doi: 10.3109/09638237.2015.1124390.

6. Thase ME. J Clin Psychiatry. 1999;60 Suppl 17:28-31; discussion 46-8.

7. Baglioni C et al. J Affect Disord. 2011 Dec;135(1-3):10-9. doi: 10.1016/j.jad.2011.01.011.

8. Hertenstein E et al. Sleep Med Rev. 2019 Feb;43:96-105. doi: 10.1016/j.smrv.2018.10.006.

9. Brower KJ et al. Medical Hypotheses. 2010;74(5):928-33. doi: 10.1016/j.mehy.2009.10.020.

10. Laskemoen JF et al. Compr Psychiatry. 2019 May;91:6-12. doi: 10.1016/j.comppsych.2019.02.006.

11. Kay SR et al. Schizophr Bull. 1987;13(2):261-76. doi: 10.1093/schbul/13.2.261.

12. Hall R. Psychosomatics. May-Jun 1995;36(3):267-75. doi: 10.1016/S0033-3182(95)71666-8.

13. Perlis ML et al. J Clin Psychiatry. 2016 Jun;77(6):e726-33. doi: 10.4088/JCP.15m10131.

14. Morin CM et al. Arch Intern Med. 2009 Mar 9. doi: 10.1001/archinternmed.2008.610.

15. Cheung J et al. Sleep Med Clin. 2019 Jun;14(2):253-65. doi: 10.1016/j.jsmc.2019.01.006.

16. Bertisch SM et al. Sleep. 2014 Feb 1. doi: 10.5665/sleep.3410.

17. Okajima I et al. Sleep Biol Rhythms. 2010 Nov 28. doi: 10.1111/j.1479-8425.2010.00481.x.

18. Trauer JM et al. Ann Intern Med. 2015 Aug 4. doi: 10.7326/M14-2841.

19. Edinger J et al. J Clin Sleep Med. 2021 Feb 1. doi: 10.5664/jcsm.8986.

20. U.S. Centers for Disease Control and Prevention. https://www.cdc.gov/sleep/for-clinicians.html.

21. National Institutes of Health. Sleep Health. https://www.nhlbi.nih.gov/health-topics/education-and-awareness/sleep-health.

22. Felder JN et al. JAMA Psychiatry. 2020;77(5):484-92. doi:10.1001/jamapsychiatry.2019.4491.

23. Felder JN et al. Sleep. 2022 Feb 14. doi: 10.1093/sleep/zsab280.

Anxiety and depression are common among individuals with inflammatory bowel disease (IBD) who are in remission, and the conditions are linked to unemployment and presenteeism, according to a prospective study.

Previous studies have found a heightened risk of anxiety and depression in IBD, as well as an association with poor treatment compliance and greater morbidity. Presenteeism, defined as reduced productivity due to a physical or mental condition, is increasingly recognized as an indirect economic cost of chronic conditions that may exact a higher cost than absenteeism.

Westend61/Getty Images

Anxiety and depression are common among individuals with inflammatory bowel disease (IBD) who are in remission, and the conditions are linked to unemployment and presenteeism, according to a prospective study.

Previous studies have found a heightened risk of anxiety and depression in IBD, as well as an association with poor treatment compliance and greater morbidity. Presenteeism, defined as reduced productivity due to a physical or mental condition, is increasingly recognized as an indirect economic cost of chronic conditions that may exact a higher cost than absenteeism.

Westend61/Getty Images

Anxiety and depression are common among individuals with inflammatory bowel disease (IBD) who are in remission, and the conditions are linked to unemployment and presenteeism, according to a prospective study.

Previous studies have found a heightened risk of anxiety and depression in IBD, as well as an association with poor treatment compliance and greater morbidity. Presenteeism, defined as reduced productivity due to a physical or mental condition, is increasingly recognized as an indirect economic cost of chronic conditions that may exact a higher cost than absenteeism.

Westend61/Getty Images

Suicidal behaviors are common in older adults – and especially older women, new research suggests.

In a meta-analysis that included 20 studies and more than 3 million total individuals living in long-term care (LTC), the prevalence rate for suicidal behavior was more than 6%. In addition, the most common of these behaviors was suicidal ideation.

The prevalence was much higher in women than in men.

These high rates underline the need for clinicians to exercise “extra caution” when assessing elderly people living in a long-term care facility, coinvestigator Syeda Beenish Bareeqa, MBBS, clinical researcher, Jinnah Medical and Dental College, Karachi, Pakistan, and research observer, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Missed diagnoses or undertreatment in this population can lead to deleterious health outcomes,” Dr. Bareeqa said.

The findings were presented at the annual meeting of the American Association for Geriatric Psychiatry.
 

Underdiagnosed, undertreated

In the United States, about 42% of adults 70 years and older will live in LTC, either in an assisted care facility or a nursing home, Dr. Bareeqa noted.

Although many LTC residents have a mood disorder, previous research shows that fewer than 25% of cases are diagnosed and treated, she said.

Dr. Bareeqa added that suicide – and its association with factors such as the COVID-19 pandemic, depression, and cyberbullying – is a topic of increasing interest to researchers. She and her colleagues wanted to investigate suicidal behaviors in the setting of LTC.

The researchers conducted a literature search for studies of suicidal behavior among LTC residents over aged 60 years. They examined general suicidal behavior and the most common subtypes: suicide ideation, suicide attempts, completed suicide, self-destructive behavior, and nonsuicidal self-injury.

The analysis included 20 studies and 3 million individuals living in LTC. The majority of the studies were conducted in the United States (n = 5) and Australia (n = 4).

Results showed an estimated suicidal behavior prevalence rate of 6.4% (.064; 95% confidence interval, .057 to .070), or 64 per 100,000 persons.

A rate this high is “alarming and unexpected,” said Dr. Bareeqa. She noted most of the studies included in the analysis were conducted in developed countries with advanced health care systems.

The World Health Organization reports the suicide rate per 100,000 older adults (aged 75 years and older) is 50 for men and 16 for women, but this is not stratified by living settings, Dr. Bareeqa noted.
 

Higher rates in women

In the current analysis, 5 of the 20 studies had low risk of bias, 14 had moderate risk, and 1 had high risk, Dr. Bareeqa reported.

In subgroup analyses, the researchers found much of the suicidal behavior was driven by studies out of Australia, where the prevalence of suicidal behaviors was 36.9% (95% CI, 9.2-64.7) vs. 1.4% in the U.S. (95% CI, 1.0-1.8).

Another surprising finding was the prevalence of suicidal behaviors among women (15.8%), which was much higher than among men (7.9%). “Male gender is a well-established risk factor for suicide in the medical literature but this is not the case in our study,” said Dr. Bareeqa.

In addition, the analysis showed suicidal ideation was the most common type of suicidal behavior. In a pooled population of around 2 million people in eight studies, the prevalence of suicidal ideation was 12%.

For psychiatric illnesses accompanying suicidal behavior, the prevalence of depression alone was 14.4%, which was much higher than the rate of 5.1% for multiple comorbidities – including depression, anxiety, obsessive-compulsive disorder, psychotic disorder, history of previous suicide attempt, delusion, delirium, and hallucination.

Although depression and other psychiatric conditions may help explain suicidal behavior in older adults, Dr. Bareeqa said physical illness also plays a major role.

“Illnesses like cancer or end-stage organ failure, which are quite common with advancing age, are debilitating and in some instances incurable. These medical problems create a breeding ground for mental health problems and can eventually lead to devastating outcomes such as suicide,” she said.

She noted the importance of a “multipronged approach” to prevent suicide among older people in LTC facilities.

In addition, her research team aims to assess the quality of care provided by LTC facilities. “Maybe we can get to the root of this problem and devise strategies to improve it,” she said.
 

‘Not uncommon’

In an interview with this news organization Rajesh R. Tampi, MBBS, professor and chairman, department of psychiatry, Creighton University and Catholic Health Initiatives Health Behavioral Health Services, Omaha, Neb., said the results suggest that, despite the risk for bias among the included studies, “suicidal behaviors are not uncommon among older adults in LTC.”

The analysis describes only associations “but does not indicate causality,” said Dr. Tampi, past president of the AAGP. He was not involved with the research.

Additional subgroup analyses should yield information on possible risk factors for suicidal behaviors in LTC, such as depression, anxiety, and chronic pain, he added.

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

Suicidal behaviors are common in older adults – and especially older women, new research suggests.

In a meta-analysis that included 20 studies and more than 3 million total individuals living in long-term care (LTC), the prevalence rate for suicidal behavior was more than 6%. In addition, the most common of these behaviors was suicidal ideation.

The prevalence was much higher in women than in men.

These high rates underline the need for clinicians to exercise “extra caution” when assessing elderly people living in a long-term care facility, coinvestigator Syeda Beenish Bareeqa, MBBS, clinical researcher, Jinnah Medical and Dental College, Karachi, Pakistan, and research observer, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Missed diagnoses or undertreatment in this population can lead to deleterious health outcomes,” Dr. Bareeqa said.

The findings were presented at the annual meeting of the American Association for Geriatric Psychiatry.
 

Underdiagnosed, undertreated

In the United States, about 42% of adults 70 years and older will live in LTC, either in an assisted care facility or a nursing home, Dr. Bareeqa noted.

Although many LTC residents have a mood disorder, previous research shows that fewer than 25% of cases are diagnosed and treated, she said.

Dr. Bareeqa added that suicide – and its association with factors such as the COVID-19 pandemic, depression, and cyberbullying – is a topic of increasing interest to researchers. She and her colleagues wanted to investigate suicidal behaviors in the setting of LTC.

The researchers conducted a literature search for studies of suicidal behavior among LTC residents over aged 60 years. They examined general suicidal behavior and the most common subtypes: suicide ideation, suicide attempts, completed suicide, self-destructive behavior, and nonsuicidal self-injury.

The analysis included 20 studies and 3 million individuals living in LTC. The majority of the studies were conducted in the United States (n = 5) and Australia (n = 4).

Results showed an estimated suicidal behavior prevalence rate of 6.4% (.064; 95% confidence interval, .057 to .070), or 64 per 100,000 persons.

A rate this high is “alarming and unexpected,” said Dr. Bareeqa. She noted most of the studies included in the analysis were conducted in developed countries with advanced health care systems.

The World Health Organization reports the suicide rate per 100,000 older adults (aged 75 years and older) is 50 for men and 16 for women, but this is not stratified by living settings, Dr. Bareeqa noted.
 

Higher rates in women

In the current analysis, 5 of the 20 studies had low risk of bias, 14 had moderate risk, and 1 had high risk, Dr. Bareeqa reported.

In subgroup analyses, the researchers found much of the suicidal behavior was driven by studies out of Australia, where the prevalence of suicidal behaviors was 36.9% (95% CI, 9.2-64.7) vs. 1.4% in the U.S. (95% CI, 1.0-1.8).

Another surprising finding was the prevalence of suicidal behaviors among women (15.8%), which was much higher than among men (7.9%). “Male gender is a well-established risk factor for suicide in the medical literature but this is not the case in our study,” said Dr. Bareeqa.

In addition, the analysis showed suicidal ideation was the most common type of suicidal behavior. In a pooled population of around 2 million people in eight studies, the prevalence of suicidal ideation was 12%.

For psychiatric illnesses accompanying suicidal behavior, the prevalence of depression alone was 14.4%, which was much higher than the rate of 5.1% for multiple comorbidities – including depression, anxiety, obsessive-compulsive disorder, psychotic disorder, history of previous suicide attempt, delusion, delirium, and hallucination.

Although depression and other psychiatric conditions may help explain suicidal behavior in older adults, Dr. Bareeqa said physical illness also plays a major role.

“Illnesses like cancer or end-stage organ failure, which are quite common with advancing age, are debilitating and in some instances incurable. These medical problems create a breeding ground for mental health problems and can eventually lead to devastating outcomes such as suicide,” she said.

She noted the importance of a “multipronged approach” to prevent suicide among older people in LTC facilities.

In addition, her research team aims to assess the quality of care provided by LTC facilities. “Maybe we can get to the root of this problem and devise strategies to improve it,” she said.
 

‘Not uncommon’

In an interview with this news organization Rajesh R. Tampi, MBBS, professor and chairman, department of psychiatry, Creighton University and Catholic Health Initiatives Health Behavioral Health Services, Omaha, Neb., said the results suggest that, despite the risk for bias among the included studies, “suicidal behaviors are not uncommon among older adults in LTC.”

The analysis describes only associations “but does not indicate causality,” said Dr. Tampi, past president of the AAGP. He was not involved with the research.

Additional subgroup analyses should yield information on possible risk factors for suicidal behaviors in LTC, such as depression, anxiety, and chronic pain, he added.

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

Suicidal behaviors are common in older adults – and especially older women, new research suggests.

In a meta-analysis that included 20 studies and more than 3 million total individuals living in long-term care (LTC), the prevalence rate for suicidal behavior was more than 6%. In addition, the most common of these behaviors was suicidal ideation.

The prevalence was much higher in women than in men.

These high rates underline the need for clinicians to exercise “extra caution” when assessing elderly people living in a long-term care facility, coinvestigator Syeda Beenish Bareeqa, MBBS, clinical researcher, Jinnah Medical and Dental College, Karachi, Pakistan, and research observer, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Missed diagnoses or undertreatment in this population can lead to deleterious health outcomes,” Dr. Bareeqa said.

The findings were presented at the annual meeting of the American Association for Geriatric Psychiatry.
 

Underdiagnosed, undertreated

In the United States, about 42% of adults 70 years and older will live in LTC, either in an assisted care facility or a nursing home, Dr. Bareeqa noted.

Although many LTC residents have a mood disorder, previous research shows that fewer than 25% of cases are diagnosed and treated, she said.

Dr. Bareeqa added that suicide – and its association with factors such as the COVID-19 pandemic, depression, and cyberbullying – is a topic of increasing interest to researchers. She and her colleagues wanted to investigate suicidal behaviors in the setting of LTC.

The researchers conducted a literature search for studies of suicidal behavior among LTC residents over aged 60 years. They examined general suicidal behavior and the most common subtypes: suicide ideation, suicide attempts, completed suicide, self-destructive behavior, and nonsuicidal self-injury.

The analysis included 20 studies and 3 million individuals living in LTC. The majority of the studies were conducted in the United States (n = 5) and Australia (n = 4).

Results showed an estimated suicidal behavior prevalence rate of 6.4% (.064; 95% confidence interval, .057 to .070), or 64 per 100,000 persons.

A rate this high is “alarming and unexpected,” said Dr. Bareeqa. She noted most of the studies included in the analysis were conducted in developed countries with advanced health care systems.

The World Health Organization reports the suicide rate per 100,000 older adults (aged 75 years and older) is 50 for men and 16 for women, but this is not stratified by living settings, Dr. Bareeqa noted.
 

Higher rates in women

In the current analysis, 5 of the 20 studies had low risk of bias, 14 had moderate risk, and 1 had high risk, Dr. Bareeqa reported.

In subgroup analyses, the researchers found much of the suicidal behavior was driven by studies out of Australia, where the prevalence of suicidal behaviors was 36.9% (95% CI, 9.2-64.7) vs. 1.4% in the U.S. (95% CI, 1.0-1.8).

Another surprising finding was the prevalence of suicidal behaviors among women (15.8%), which was much higher than among men (7.9%). “Male gender is a well-established risk factor for suicide in the medical literature but this is not the case in our study,” said Dr. Bareeqa.

In addition, the analysis showed suicidal ideation was the most common type of suicidal behavior. In a pooled population of around 2 million people in eight studies, the prevalence of suicidal ideation was 12%.

For psychiatric illnesses accompanying suicidal behavior, the prevalence of depression alone was 14.4%, which was much higher than the rate of 5.1% for multiple comorbidities – including depression, anxiety, obsessive-compulsive disorder, psychotic disorder, history of previous suicide attempt, delusion, delirium, and hallucination.

Although depression and other psychiatric conditions may help explain suicidal behavior in older adults, Dr. Bareeqa said physical illness also plays a major role.

“Illnesses like cancer or end-stage organ failure, which are quite common with advancing age, are debilitating and in some instances incurable. These medical problems create a breeding ground for mental health problems and can eventually lead to devastating outcomes such as suicide,” she said.

She noted the importance of a “multipronged approach” to prevent suicide among older people in LTC facilities.

In addition, her research team aims to assess the quality of care provided by LTC facilities. “Maybe we can get to the root of this problem and devise strategies to improve it,” she said.
 

‘Not uncommon’

In an interview with this news organization Rajesh R. Tampi, MBBS, professor and chairman, department of psychiatry, Creighton University and Catholic Health Initiatives Health Behavioral Health Services, Omaha, Neb., said the results suggest that, despite the risk for bias among the included studies, “suicidal behaviors are not uncommon among older adults in LTC.”

The analysis describes only associations “but does not indicate causality,” said Dr. Tampi, past president of the AAGP. He was not involved with the research.

Additional subgroup analyses should yield information on possible risk factors for suicidal behaviors in LTC, such as depression, anxiety, and chronic pain, he added.

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

A cross-sectional study in the United Kingdom has revealed an association between social media use and lower life satisfaction among children and adolescents aged 10-21 years.

“[Our] study provides evidence for age- and sex-specific windows of sensitivity to social media use in adolescence,” lead author Amy Orben, PhD, of the University of Cambridge (England), and colleagues wrote. The findings were published in Nature Communications.

The researchers analyzed cross-sectional and longitudinal data from the Understanding Society dataset and the Millennium Cohort Study. The cross-sectional data was used to investigate the existence of developmental windows of sensitivity to social media, while the longitudinal data was used to evaluate whether sex-specific windows of sensitivity to social media were present during the adolescence period.

These two datasets comprised 84,011 participants aged 10-80 years old. After applying the modeling framework, 17,409 participants aged 10-21 years were included in the analysis.

Longitudinal analyses revealed different developmental windows of sensitivity to social media during adolescence, with higher estimated social media use predicting lower life satisfaction scores 1 year later (regression coefficient [beta], −0.02; 95% confidence interval, −0.03 to −0.01; P = .004).

Among females, the researchers observed a window of sensitivity to social media between the ages of 11 and 13, with higher estimated social media use predicting lower life satisfaction ratings 1 year later (age 11: beta, −0.11; 95% CI, −0.21 to −0.02; P = .020; age 12: beta, −0.14; 95% CI, −0.22 to −0.07; P < .001; age 13: beta, −0.08; 95% CI, −0.15 to −0.01; P = .019).

Among males, a similar window was observed between the ages of 14 and 15 (age 14: beta, −0.10; 95% CI, −0.17 to −0.03; P = .005; age 15: beta, –0.18; 95% CI, −0.29 to −0.08; P = .001).

Furthermore, they showed that a later increase in sensitivity to social media, which was present at age 19 for both females and males, suggested a different underlying process was present in late adolescence (females: beta, −0.16; 95% CI, −0.25 to −0.07; P < .001; males: beta, −0.16; 95% CI, −0.26 to −0.07; P = .001).

“Speculatively, this might be related to changes in the social environment such as a move away from home and subsequent disruptions in social networks,” the researchers wrote.

Importantly, Dr. Orben and colleagues noted that these results should be interpreted with caution. Owing to the cross-sectional nature of the data, causality cannot be inferred from these findings.

“The findings reported here may enable investigation of potential mechanisms of interest, for example, in datasets with pubertal or additional social measurements,” they wrote. “One could also carry out more targeted investigations, for example, by examining the mental health measures only completed by select age ranges in the datasets.”
 

Digital literacy is important, expert says

“Digital literacy and education about social media use is warranted for all ages, starting young,” Yalda T. Uhls, MBA, PhD, of the department of psychology at the University of California, Los Angeles, said in an interview. “Attending to underlying issues for vulnerable ages, such as anxiety, as well as parental support is critical.”

“I would urge social media platforms to pay attention to what kinds of content they are making available to ensure the highest possible quality, and to embed things like suggestions for pauses and other ways to check in on someone who may be experiencing distress when on socials,” Dr. Uhls said. “We also need to increase access to mental health resources for young people and social media could help provide information for those experiencing issues.”

This study was supported by the University of Cambridge and the UK Medical Research Council. The authors reported no relevant disclosures. Dr. Uhls had no relevant disclosures.

A cross-sectional study in the United Kingdom has revealed an association between social media use and lower life satisfaction among children and adolescents aged 10-21 years.

“[Our] study provides evidence for age- and sex-specific windows of sensitivity to social media use in adolescence,” lead author Amy Orben, PhD, of the University of Cambridge (England), and colleagues wrote. The findings were published in Nature Communications.

The researchers analyzed cross-sectional and longitudinal data from the Understanding Society dataset and the Millennium Cohort Study. The cross-sectional data was used to investigate the existence of developmental windows of sensitivity to social media, while the longitudinal data was used to evaluate whether sex-specific windows of sensitivity to social media were present during the adolescence period.

These two datasets comprised 84,011 participants aged 10-80 years old. After applying the modeling framework, 17,409 participants aged 10-21 years were included in the analysis.

Longitudinal analyses revealed different developmental windows of sensitivity to social media during adolescence, with higher estimated social media use predicting lower life satisfaction scores 1 year later (regression coefficient [beta], −0.02; 95% confidence interval, −0.03 to −0.01; P = .004).

Among females, the researchers observed a window of sensitivity to social media between the ages of 11 and 13, with higher estimated social media use predicting lower life satisfaction ratings 1 year later (age 11: beta, −0.11; 95% CI, −0.21 to −0.02; P = .020; age 12: beta, −0.14; 95% CI, −0.22 to −0.07; P < .001; age 13: beta, −0.08; 95% CI, −0.15 to −0.01; P = .019).

Among males, a similar window was observed between the ages of 14 and 15 (age 14: beta, −0.10; 95% CI, −0.17 to −0.03; P = .005; age 15: beta, –0.18; 95% CI, −0.29 to −0.08; P = .001).

Furthermore, they showed that a later increase in sensitivity to social media, which was present at age 19 for both females and males, suggested a different underlying process was present in late adolescence (females: beta, −0.16; 95% CI, −0.25 to −0.07; P < .001; males: beta, −0.16; 95% CI, −0.26 to −0.07; P = .001).

“Speculatively, this might be related to changes in the social environment such as a move away from home and subsequent disruptions in social networks,” the researchers wrote.

Importantly, Dr. Orben and colleagues noted that these results should be interpreted with caution. Owing to the cross-sectional nature of the data, causality cannot be inferred from these findings.

“The findings reported here may enable investigation of potential mechanisms of interest, for example, in datasets with pubertal or additional social measurements,” they wrote. “One could also carry out more targeted investigations, for example, by examining the mental health measures only completed by select age ranges in the datasets.”
 

Digital literacy is important, expert says

“Digital literacy and education about social media use is warranted for all ages, starting young,” Yalda T. Uhls, MBA, PhD, of the department of psychology at the University of California, Los Angeles, said in an interview. “Attending to underlying issues for vulnerable ages, such as anxiety, as well as parental support is critical.”

“I would urge social media platforms to pay attention to what kinds of content they are making available to ensure the highest possible quality, and to embed things like suggestions for pauses and other ways to check in on someone who may be experiencing distress when on socials,” Dr. Uhls said. “We also need to increase access to mental health resources for young people and social media could help provide information for those experiencing issues.”

This study was supported by the University of Cambridge and the UK Medical Research Council. The authors reported no relevant disclosures. Dr. Uhls had no relevant disclosures.

A cross-sectional study in the United Kingdom has revealed an association between social media use and lower life satisfaction among children and adolescents aged 10-21 years.

“[Our] study provides evidence for age- and sex-specific windows of sensitivity to social media use in adolescence,” lead author Amy Orben, PhD, of the University of Cambridge (England), and colleagues wrote. The findings were published in Nature Communications.

The researchers analyzed cross-sectional and longitudinal data from the Understanding Society dataset and the Millennium Cohort Study. The cross-sectional data was used to investigate the existence of developmental windows of sensitivity to social media, while the longitudinal data was used to evaluate whether sex-specific windows of sensitivity to social media were present during the adolescence period.

These two datasets comprised 84,011 participants aged 10-80 years old. After applying the modeling framework, 17,409 participants aged 10-21 years were included in the analysis.

Longitudinal analyses revealed different developmental windows of sensitivity to social media during adolescence, with higher estimated social media use predicting lower life satisfaction scores 1 year later (regression coefficient [beta], −0.02; 95% confidence interval, −0.03 to −0.01; P = .004).

Among females, the researchers observed a window of sensitivity to social media between the ages of 11 and 13, with higher estimated social media use predicting lower life satisfaction ratings 1 year later (age 11: beta, −0.11; 95% CI, −0.21 to −0.02; P = .020; age 12: beta, −0.14; 95% CI, −0.22 to −0.07; P < .001; age 13: beta, −0.08; 95% CI, −0.15 to −0.01; P = .019).

Among males, a similar window was observed between the ages of 14 and 15 (age 14: beta, −0.10; 95% CI, −0.17 to −0.03; P = .005; age 15: beta, –0.18; 95% CI, −0.29 to −0.08; P = .001).

Furthermore, they showed that a later increase in sensitivity to social media, which was present at age 19 for both females and males, suggested a different underlying process was present in late adolescence (females: beta, −0.16; 95% CI, −0.25 to −0.07; P < .001; males: beta, −0.16; 95% CI, −0.26 to −0.07; P = .001).

“Speculatively, this might be related to changes in the social environment such as a move away from home and subsequent disruptions in social networks,” the researchers wrote.

Importantly, Dr. Orben and colleagues noted that these results should be interpreted with caution. Owing to the cross-sectional nature of the data, causality cannot be inferred from these findings.

“The findings reported here may enable investigation of potential mechanisms of interest, for example, in datasets with pubertal or additional social measurements,” they wrote. “One could also carry out more targeted investigations, for example, by examining the mental health measures only completed by select age ranges in the datasets.”
 

Digital literacy is important, expert says

“Digital literacy and education about social media use is warranted for all ages, starting young,” Yalda T. Uhls, MBA, PhD, of the department of psychology at the University of California, Los Angeles, said in an interview. “Attending to underlying issues for vulnerable ages, such as anxiety, as well as parental support is critical.”

“I would urge social media platforms to pay attention to what kinds of content they are making available to ensure the highest possible quality, and to embed things like suggestions for pauses and other ways to check in on someone who may be experiencing distress when on socials,” Dr. Uhls said. “We also need to increase access to mental health resources for young people and social media could help provide information for those experiencing issues.”

This study was supported by the University of Cambridge and the UK Medical Research Council. The authors reported no relevant disclosures. Dr. Uhls had no relevant disclosures.

In her month-long memoir, A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life (Knopf, 2017), author Ayelet Waldman turns herself into a one-woman experiment.

Over a single month she takes one-tenth of a recreational dose of LSD every third day. She plots her emotions, her productivity, and her pain along the way. Ms. Waldman obtains the LSD in a single vial, enough for 10 doses, from a researcher, who is retiring. What she’s looking for, she tells the reader, is a really good day – something that has been elusive in her turbulent life.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. Dr. Miller has no conflicts of interest.

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

In her month-long memoir, A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life (Knopf, 2017), author Ayelet Waldman turns herself into a one-woman experiment.

Over a single month she takes one-tenth of a recreational dose of LSD every third day. She plots her emotions, her productivity, and her pain along the way. Ms. Waldman obtains the LSD in a single vial, enough for 10 doses, from a researcher, who is retiring. What she’s looking for, she tells the reader, is a really good day – something that has been elusive in her turbulent life.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. Dr. Miller has no conflicts of interest.

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

In her month-long memoir, A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life (Knopf, 2017), author Ayelet Waldman turns herself into a one-woman experiment.

Over a single month she takes one-tenth of a recreational dose of LSD every third day. She plots her emotions, her productivity, and her pain along the way. Ms. Waldman obtains the LSD in a single vial, enough for 10 doses, from a researcher, who is retiring. What she’s looking for, she tells the reader, is a really good day – something that has been elusive in her turbulent life.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins in Baltimore. Dr. Miller has no conflicts of interest.

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