Mental Health

For the last 25 years, my colleagues have spent midday on Wednesdays at clinical rounds as a group – a time spent reviewing cases in perinatal psychiatry and important new scientific findings in the literature that inform patient care. At the start of the pandemic, my colleague Marlene Freeman, MD, and I started Virtual Rounds at the Center for Women’s Mental Health to open our rounds to colleagues involved in multiple aspects of perinatal psychiatric care.

In my last column of 2021, I wanted to take the opportunity to reflect on some of what we have learned from 19 months of virtual rounding as a community of clinicians during the pandemic.

Telemedicine

Telemedicine allows us to see into the homes, relationships, and environments of our pregnant and postpartum women in a way we could never have imagined. It’s an opportunity to follow patients closely and intervene sooner rather than later, which might have been constrained by pre–COVID-19 typical scheduled office appointments. Telemedicine also gives us a clearer sense of some of the issues faced by underserved and marginalized populations of patients as we look to increase outreach to those groups.

COVID-19 vaccines in pregnancy

We now know much more about the potential for COVID-19 to cause complications during pregnancy than we did earlier in the pandemic. Although there may be a variety of factors fueling whether those in the general population decide to get vaccinated or not, there is no ambiguity in the message from our colleagues in obstetrics about the importance of vaccination for pregnant and postpartum women.

Bipolar disorder

Appropriate treatment for the spectrum of subtypes of bipolar disorder during pregnancy in the postpartum period is a frequent topic of discussion that colleagues raise. The pandemic has kindled clinical worsening for women with mood and anxiety disorders presumably driven by a host of factors ranging from shifts in medication adherence to sleep dysregulation to name just a few. Bipolar II disorder is underdiagnosed, yet there’s a growing appreciation of the morbidity associated with this subtype of bipolar disorder, which probably equals that of other groups on the bipolar spectrum such as those with bipolar I disorder.

Sustaining emotional well-being for bipolar women during pregnancy has never been more important than during the pandemic since psychiatric illness during pregnancy is the strongest predictor of risk for postpartum psychiatric disorder and the literature demonstrates that bipolar women are at particular risk for postpartum mood disorder. Historically, treatment of bipolar disorder during pregnancy was particularly problematic for clinicians and patients deciding about potential use of pharmacotherapy because options were finite; some treatments were known teratogens (valproate and to a far less extent lithium) and other newer treatments for bipolar disorder had sparse reproductive safety data (second-generation antipsychotics).

The message today is we have tools to safely treat bipolar disorder during pregnancy and the postpartum period not available 10 years ago. Lithium is likely underused and can be safely used during pregnancy; we have vast data on the effectiveness of lithium in bipolar disorder. Clinicians should also know that lamotrigine is safe to use for pregnant women with bipolar disorder and the data show no increased risk for major malformations associated with first trimester exposure. In the case of atypical antipsychotics, which increasingly are used in the treatment of bipolar disorder, the take-home message is our comfort level using these medicines during pregnancy is growing given more data supporting that atypical antipsychotics are not major teratogens.

We’ve also learned polytherapy is the rule, not the exception. As my colleague Adele Viguera, MD, recently referenced in Virtual Rounds: Polytherapy is a small price to pay when the other side is sustaining euthymia in bipolar disorder.

What we’ve learned about treating perinatal mood disorder is it takes a village of clinicians and resources to treat and mitigate risk for recurrence. Nothing is more important than either ensuring or recapturing maternal euthymia. The flip side is a recent report that maternal self-harm/suicide is the leading cause of death in the first year postpartum. It is a charge to the medical community at large to screen for maternal psychiatric illness and, more importantly, to refer patients and ensure they receive adequate care during the postpartum period.
 

Anxiety

Anxiety and insomnia have been prevalent during the pandemic. Pregnancy-associated and postpartum anxiety have been underappreciated in lieu of focusing on perinatal depression, and we lack consensus regarding the most appropriate treatment of perinatal anxiety. Nonpharmacologic interventions have been extremely helpful for women whose anxiety is mild to moderate or as an adjunct to pharmacologic intervention for patients with more severe anxiety disorders.

Robust data on untreated anxiety during pregnancy suggest it leads to adverse outcomes. The reproductive safety rules above for depression also apply for anxiety. Here, we find a multimodal approach, both nonpharmacologic and pharmacologic, optimizes treatment for that population.

Clinicians have asked about other medicines many women take to treat anxiety including gabapentin, hydroxyzine, and benzodiazepines. Because of concerns about dependence and about using benzodiazepines during pregnancy, hydroxyzine is frequently used despite sparse reproductive safety data. Data on the effectiveness of hydroxyzine is even smaller and tends to be incomplete for patients with more moderate to severe anxiety.

Our comfort level in our center is greater for using benzodiazepines in patients who are clearly not at risk for substance use disorder because particularly when used with selective serotonin reuptake inhibitors, we find it optimizes treatment, mitigates symptoms, and attenuates suffering.
 

Insomnia

For insomnia, cognitive behavioral therapy for insomnia (CBTI) has the most data for effectiveness. Pharmacologic interventions such as gabapentin and benzodiazepines are also frequently used as therapies for insomnia.

Concern about treating insomnia by perinatal psychiatrists comes from the knowledge that insomnia is so often comorbid with anxiety and depression. Psychiatrists must consider the possibility that complaints of insomnia are part of an underlying mood or anxiety disorder; it would be unfortunate to miss the underlying illness and only treat just symptoms of insomnia. That being said, circumscribed insomnia is not uncommon during pregnancy and needs to be managed accordingly.
 

Postpartum psychosis

It’s been noteworthy the extent to which rare cases of postpartum psychosis have been presented in our Virtual Round meetings during the pandemic. As discussed previously, postpartum psychosis is one of the most serious illnesses we treat in reproductive psychiatry.

The debate as to whether postpartum psychosis is a discrete circumscribed illness or an illness that recurs over time won’t be answered without better longitudinal data. What we can say is there is no role, particularly during the pandemic, for outpatient management of postpartum psychosis. The waxing and waning of psychotic symptoms, while reassuring when patients are compensated, are of great concern when patients are psychotic and not in a safe environment.

While there are no consensus guidelines for postpartum psychosis treatment, the data support use of agents such as lithium. Growing data exist on the use of atypical antipsychotics to ameliorate psychotic symptoms and get patients functioning as quickly as possible. Resolution of postpartum psychosis may take a considerable amount of time. During the pandemic, it is critical that appropriate resources be managed before patients leave the hospital, including support by family, open communication with community-based providers, and support groups.

Nineteen months into the pandemic, it seems we’ve learned much: how to leverage technology like telemedicine, and the upsides of folding in our multidisciplinary colleagues to reduce barriers around collaboration and learn from one another to provide the best care for our shared patients.

*This column was updated on Jan. 11. 2022.
 

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

For the last 25 years, my colleagues have spent midday on Wednesdays at clinical rounds as a group – a time spent reviewing cases in perinatal psychiatry and important new scientific findings in the literature that inform patient care. At the start of the pandemic, my colleague Marlene Freeman, MD, and I started Virtual Rounds at the Center for Women’s Mental Health to open our rounds to colleagues involved in multiple aspects of perinatal psychiatric care.

In my last column of 2021, I wanted to take the opportunity to reflect on some of what we have learned from 19 months of virtual rounding as a community of clinicians during the pandemic.

Telemedicine

Telemedicine allows us to see into the homes, relationships, and environments of our pregnant and postpartum women in a way we could never have imagined. It’s an opportunity to follow patients closely and intervene sooner rather than later, which might have been constrained by pre–COVID-19 typical scheduled office appointments. Telemedicine also gives us a clearer sense of some of the issues faced by underserved and marginalized populations of patients as we look to increase outreach to those groups.

COVID-19 vaccines in pregnancy

We now know much more about the potential for COVID-19 to cause complications during pregnancy than we did earlier in the pandemic. Although there may be a variety of factors fueling whether those in the general population decide to get vaccinated or not, there is no ambiguity in the message from our colleagues in obstetrics about the importance of vaccination for pregnant and postpartum women.

Bipolar disorder

Appropriate treatment for the spectrum of subtypes of bipolar disorder during pregnancy in the postpartum period is a frequent topic of discussion that colleagues raise. The pandemic has kindled clinical worsening for women with mood and anxiety disorders presumably driven by a host of factors ranging from shifts in medication adherence to sleep dysregulation to name just a few. Bipolar II disorder is underdiagnosed, yet there’s a growing appreciation of the morbidity associated with this subtype of bipolar disorder, which probably equals that of other groups on the bipolar spectrum such as those with bipolar I disorder.

Sustaining emotional well-being for bipolar women during pregnancy has never been more important than during the pandemic since psychiatric illness during pregnancy is the strongest predictor of risk for postpartum psychiatric disorder and the literature demonstrates that bipolar women are at particular risk for postpartum mood disorder. Historically, treatment of bipolar disorder during pregnancy was particularly problematic for clinicians and patients deciding about potential use of pharmacotherapy because options were finite; some treatments were known teratogens (valproate and to a far less extent lithium) and other newer treatments for bipolar disorder had sparse reproductive safety data (second-generation antipsychotics).

The message today is we have tools to safely treat bipolar disorder during pregnancy and the postpartum period not available 10 years ago. Lithium is likely underused and can be safely used during pregnancy; we have vast data on the effectiveness of lithium in bipolar disorder. Clinicians should also know that lamotrigine is safe to use for pregnant women with bipolar disorder and the data show no increased risk for major malformations associated with first trimester exposure. In the case of atypical antipsychotics, which increasingly are used in the treatment of bipolar disorder, the take-home message is our comfort level using these medicines during pregnancy is growing given more data supporting that atypical antipsychotics are not major teratogens.

We’ve also learned polytherapy is the rule, not the exception. As my colleague Adele Viguera, MD, recently referenced in Virtual Rounds: Polytherapy is a small price to pay when the other side is sustaining euthymia in bipolar disorder.

What we’ve learned about treating perinatal mood disorder is it takes a village of clinicians and resources to treat and mitigate risk for recurrence. Nothing is more important than either ensuring or recapturing maternal euthymia. The flip side is a recent report that maternal self-harm/suicide is the leading cause of death in the first year postpartum. It is a charge to the medical community at large to screen for maternal psychiatric illness and, more importantly, to refer patients and ensure they receive adequate care during the postpartum period.
 

Anxiety

Anxiety and insomnia have been prevalent during the pandemic. Pregnancy-associated and postpartum anxiety have been underappreciated in lieu of focusing on perinatal depression, and we lack consensus regarding the most appropriate treatment of perinatal anxiety. Nonpharmacologic interventions have been extremely helpful for women whose anxiety is mild to moderate or as an adjunct to pharmacologic intervention for patients with more severe anxiety disorders.

Robust data on untreated anxiety during pregnancy suggest it leads to adverse outcomes. The reproductive safety rules above for depression also apply for anxiety. Here, we find a multimodal approach, both nonpharmacologic and pharmacologic, optimizes treatment for that population.

Clinicians have asked about other medicines many women take to treat anxiety including gabapentin, hydroxyzine, and benzodiazepines. Because of concerns about dependence and about using benzodiazepines during pregnancy, hydroxyzine is frequently used despite sparse reproductive safety data. Data on the effectiveness of hydroxyzine is even smaller and tends to be incomplete for patients with more moderate to severe anxiety.

Our comfort level in our center is greater for using benzodiazepines in patients who are clearly not at risk for substance use disorder because particularly when used with selective serotonin reuptake inhibitors, we find it optimizes treatment, mitigates symptoms, and attenuates suffering.
 

Insomnia

For insomnia, cognitive behavioral therapy for insomnia (CBTI) has the most data for effectiveness. Pharmacologic interventions such as gabapentin and benzodiazepines are also frequently used as therapies for insomnia.

Concern about treating insomnia by perinatal psychiatrists comes from the knowledge that insomnia is so often comorbid with anxiety and depression. Psychiatrists must consider the possibility that complaints of insomnia are part of an underlying mood or anxiety disorder; it would be unfortunate to miss the underlying illness and only treat just symptoms of insomnia. That being said, circumscribed insomnia is not uncommon during pregnancy and needs to be managed accordingly.
 

Postpartum psychosis

It’s been noteworthy the extent to which rare cases of postpartum psychosis have been presented in our Virtual Round meetings during the pandemic. As discussed previously, postpartum psychosis is one of the most serious illnesses we treat in reproductive psychiatry.

The debate as to whether postpartum psychosis is a discrete circumscribed illness or an illness that recurs over time won’t be answered without better longitudinal data. What we can say is there is no role, particularly during the pandemic, for outpatient management of postpartum psychosis. The waxing and waning of psychotic symptoms, while reassuring when patients are compensated, are of great concern when patients are psychotic and not in a safe environment.

While there are no consensus guidelines for postpartum psychosis treatment, the data support use of agents such as lithium. Growing data exist on the use of atypical antipsychotics to ameliorate psychotic symptoms and get patients functioning as quickly as possible. Resolution of postpartum psychosis may take a considerable amount of time. During the pandemic, it is critical that appropriate resources be managed before patients leave the hospital, including support by family, open communication with community-based providers, and support groups.

Nineteen months into the pandemic, it seems we’ve learned much: how to leverage technology like telemedicine, and the upsides of folding in our multidisciplinary colleagues to reduce barriers around collaboration and learn from one another to provide the best care for our shared patients.

*This column was updated on Jan. 11. 2022.
 

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

For the last 25 years, my colleagues have spent midday on Wednesdays at clinical rounds as a group – a time spent reviewing cases in perinatal psychiatry and important new scientific findings in the literature that inform patient care. At the start of the pandemic, my colleague Marlene Freeman, MD, and I started Virtual Rounds at the Center for Women’s Mental Health to open our rounds to colleagues involved in multiple aspects of perinatal psychiatric care.

In my last column of 2021, I wanted to take the opportunity to reflect on some of what we have learned from 19 months of virtual rounding as a community of clinicians during the pandemic.

Telemedicine

Telemedicine allows us to see into the homes, relationships, and environments of our pregnant and postpartum women in a way we could never have imagined. It’s an opportunity to follow patients closely and intervene sooner rather than later, which might have been constrained by pre–COVID-19 typical scheduled office appointments. Telemedicine also gives us a clearer sense of some of the issues faced by underserved and marginalized populations of patients as we look to increase outreach to those groups.

COVID-19 vaccines in pregnancy

We now know much more about the potential for COVID-19 to cause complications during pregnancy than we did earlier in the pandemic. Although there may be a variety of factors fueling whether those in the general population decide to get vaccinated or not, there is no ambiguity in the message from our colleagues in obstetrics about the importance of vaccination for pregnant and postpartum women.

Bipolar disorder

Appropriate treatment for the spectrum of subtypes of bipolar disorder during pregnancy in the postpartum period is a frequent topic of discussion that colleagues raise. The pandemic has kindled clinical worsening for women with mood and anxiety disorders presumably driven by a host of factors ranging from shifts in medication adherence to sleep dysregulation to name just a few. Bipolar II disorder is underdiagnosed, yet there’s a growing appreciation of the morbidity associated with this subtype of bipolar disorder, which probably equals that of other groups on the bipolar spectrum such as those with bipolar I disorder.

Sustaining emotional well-being for bipolar women during pregnancy has never been more important than during the pandemic since psychiatric illness during pregnancy is the strongest predictor of risk for postpartum psychiatric disorder and the literature demonstrates that bipolar women are at particular risk for postpartum mood disorder. Historically, treatment of bipolar disorder during pregnancy was particularly problematic for clinicians and patients deciding about potential use of pharmacotherapy because options were finite; some treatments were known teratogens (valproate and to a far less extent lithium) and other newer treatments for bipolar disorder had sparse reproductive safety data (second-generation antipsychotics).

The message today is we have tools to safely treat bipolar disorder during pregnancy and the postpartum period not available 10 years ago. Lithium is likely underused and can be safely used during pregnancy; we have vast data on the effectiveness of lithium in bipolar disorder. Clinicians should also know that lamotrigine is safe to use for pregnant women with bipolar disorder and the data show no increased risk for major malformations associated with first trimester exposure. In the case of atypical antipsychotics, which increasingly are used in the treatment of bipolar disorder, the take-home message is our comfort level using these medicines during pregnancy is growing given more data supporting that atypical antipsychotics are not major teratogens.

We’ve also learned polytherapy is the rule, not the exception. As my colleague Adele Viguera, MD, recently referenced in Virtual Rounds: Polytherapy is a small price to pay when the other side is sustaining euthymia in bipolar disorder.

What we’ve learned about treating perinatal mood disorder is it takes a village of clinicians and resources to treat and mitigate risk for recurrence. Nothing is more important than either ensuring or recapturing maternal euthymia. The flip side is a recent report that maternal self-harm/suicide is the leading cause of death in the first year postpartum. It is a charge to the medical community at large to screen for maternal psychiatric illness and, more importantly, to refer patients and ensure they receive adequate care during the postpartum period.
 

Anxiety

Anxiety and insomnia have been prevalent during the pandemic. Pregnancy-associated and postpartum anxiety have been underappreciated in lieu of focusing on perinatal depression, and we lack consensus regarding the most appropriate treatment of perinatal anxiety. Nonpharmacologic interventions have been extremely helpful for women whose anxiety is mild to moderate or as an adjunct to pharmacologic intervention for patients with more severe anxiety disorders.

Robust data on untreated anxiety during pregnancy suggest it leads to adverse outcomes. The reproductive safety rules above for depression also apply for anxiety. Here, we find a multimodal approach, both nonpharmacologic and pharmacologic, optimizes treatment for that population.

Clinicians have asked about other medicines many women take to treat anxiety including gabapentin, hydroxyzine, and benzodiazepines. Because of concerns about dependence and about using benzodiazepines during pregnancy, hydroxyzine is frequently used despite sparse reproductive safety data. Data on the effectiveness of hydroxyzine is even smaller and tends to be incomplete for patients with more moderate to severe anxiety.

Our comfort level in our center is greater for using benzodiazepines in patients who are clearly not at risk for substance use disorder because particularly when used with selective serotonin reuptake inhibitors, we find it optimizes treatment, mitigates symptoms, and attenuates suffering.
 

Insomnia

For insomnia, cognitive behavioral therapy for insomnia (CBTI) has the most data for effectiveness. Pharmacologic interventions such as gabapentin and benzodiazepines are also frequently used as therapies for insomnia.

Concern about treating insomnia by perinatal psychiatrists comes from the knowledge that insomnia is so often comorbid with anxiety and depression. Psychiatrists must consider the possibility that complaints of insomnia are part of an underlying mood or anxiety disorder; it would be unfortunate to miss the underlying illness and only treat just symptoms of insomnia. That being said, circumscribed insomnia is not uncommon during pregnancy and needs to be managed accordingly.
 

Postpartum psychosis

It’s been noteworthy the extent to which rare cases of postpartum psychosis have been presented in our Virtual Round meetings during the pandemic. As discussed previously, postpartum psychosis is one of the most serious illnesses we treat in reproductive psychiatry.

The debate as to whether postpartum psychosis is a discrete circumscribed illness or an illness that recurs over time won’t be answered without better longitudinal data. What we can say is there is no role, particularly during the pandemic, for outpatient management of postpartum psychosis. The waxing and waning of psychotic symptoms, while reassuring when patients are compensated, are of great concern when patients are psychotic and not in a safe environment.

While there are no consensus guidelines for postpartum psychosis treatment, the data support use of agents such as lithium. Growing data exist on the use of atypical antipsychotics to ameliorate psychotic symptoms and get patients functioning as quickly as possible. Resolution of postpartum psychosis may take a considerable amount of time. During the pandemic, it is critical that appropriate resources be managed before patients leave the hospital, including support by family, open communication with community-based providers, and support groups.

Nineteen months into the pandemic, it seems we’ve learned much: how to leverage technology like telemedicine, and the upsides of folding in our multidisciplinary colleagues to reduce barriers around collaboration and learn from one another to provide the best care for our shared patients.

*This column was updated on Jan. 11. 2022.
 

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

Adding lithium to usual care does not decrease the risk of suicide-related events in those with major depressive disorder (MDD) or bipolar disorder (BD) who have survived a recent suicidal event, new research shows.

The results of a randomized, double-blind, placebo-controlled trial in veterans showed no apparent advantage of the drug in preventing self-injury, suicide attempts, or urgent hospitalization to prevent suicide.

“Lithium is an important therapy for bipolar disorders and depression subsets. Our study indicates that, in patients who are actively followed and treated in a system of care that the VA provides, simply adding lithium to their existing management, including medications, is unlikely to be effective for preventing a broad range of suicide-related events,” study investigator Ryan Ferguson, MPH, ScD, Boston Cooperative Studies Coordinating Center, VA Boston Healthcare System, told this news organization.

The study was published online JAMA Psychiatry.
 

Surprising findings

The results were somewhat surprising, Dr. Ferguson added. “Lithium showed little or no effect in our study, compared to observational data and results from previous trials. Many clinicians and practice guidelines had assumed that lithium was an effective agent in preventing suicide,” he said.

However, the authors of an accompanying editorial urge caution in concluding that lithium has no antisuicidal effects.

This “rigorously designed and conducted trial has much to teach but cannot be taken as evidence that lithium treatment is ineffective regarding suicidal risk,” write Ross Baldessarini, MD, and Leonardo Tondo, MD, department of psychiatry, Harvard Medical School, Boston.

Study participants were veterans with MDD or BD receiving care at one of 29 Veterans Administration medical centers who survived a recent suicide-related event. In addition to usual care, they were randomly assigned to receive oral extended-release lithium carbonate starting at 600 mg/day or matching placebo for 52 weeks.

The primary outcome was time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide.

The trial was stopped for futility after 519 veterans (mean age, 42.8 years; 84% male) were randomly assigned to receive lithium (n = 255) or placebo (n = 264). At 3 months, mean lithium concentrations were 0.54 mEq/L for patients with BD and 0.46 mEq/L for those with MDD.

There was no significant difference in the primary outcome (hazard ratio, 1.10; 95% confidence interval, 0.77-1.55; P = .61).

A total of 127 participants (24.5%) had suicide-related outcomes – 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and three in the placebo group. There were no unanticipated drug-related safety concerns.
 

Caveats, cautionary notes

The researchers note that the study did not reach its original recruitment goal. “One of the barriers to recruitment was the perception of many of the clinicians caring for potential participants that the effectiveness of lithium was already established; in fact, this perception was supported by the VA/U.S. Department of Defense Clinical Practice Guideline,” they point out.

They also note that most veterans in the study had depression rather than BD, which is the most common indication for lithium use. Most also had substance use disorders, posttraumatic stress disorder, or both, which could influence outcomes.

As a result of small numbers, it wasn’t possible to evaluate outcomes for patients with BD, test whether outcomes differed among patients with BD and MDD, or assess whether comorbidities attenuated the effects of lithium.

The study’s protocol increased participants’ contacts with the VA, which also may have affected outcomes, the researchers note.

In addition, high rates of attrition and low rates of substantial adherence to lithium meant only about half (48.1%) of the study population achieved target serum lithium concentrations.

Editorial writers Dr. Baldessarini and Dr. Tondo note that the low circulating concentrations of lithium and the fact that adherence to assigned treatment was considered adequate in only 17% of participants are key limitations of the study.

“In general, controlled treatment trials aimed at detecting suicide preventive effects are difficult to design, perform, and interpret,” they point out.

Evidence supporting an antisuicidal effect of lithium treatment includes nearly three dozen observational trials that have shown fewer suicides or attempts with lithium treatment, as well as “marked, temporary” increases in suicidal behavior soon after stopping lithium treatment.

Dr. Baldessarini and Dr. Tondo note the current findings “cannot be taken as evidence that lithium lacks antisuicidal effects. An ironic final note is that recruiting participants to such trials may be made difficult by an evidently prevalent belief that the question of antisuicidal effects of lithium is already settled, which it certainly is not,” they write.

Dr. Ferguson “agrees that more work needs to be done to understand the antisuicidal effect of lithium.

The study received financial and material support from a grant from the Cooperative Studies Program, Office of Research and Development, U.S. Department of Veterans Affairs. Dr. Ferguson has disclosed no relevant financial relationships. A complete list of author disclosures is available with the original article.

Dr. Baldessarini and Dr. Tondo have disclosed no relevant financial relationships. Their editorial was supported by grants from the Bruce J. Anderson Foundation, the McLean Private Donors Fund for Psychiatric Research, and the Aretaeus Foundation of Rome.

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

Adding lithium to usual care does not decrease the risk of suicide-related events in those with major depressive disorder (MDD) or bipolar disorder (BD) who have survived a recent suicidal event, new research shows.

The results of a randomized, double-blind, placebo-controlled trial in veterans showed no apparent advantage of the drug in preventing self-injury, suicide attempts, or urgent hospitalization to prevent suicide.

“Lithium is an important therapy for bipolar disorders and depression subsets. Our study indicates that, in patients who are actively followed and treated in a system of care that the VA provides, simply adding lithium to their existing management, including medications, is unlikely to be effective for preventing a broad range of suicide-related events,” study investigator Ryan Ferguson, MPH, ScD, Boston Cooperative Studies Coordinating Center, VA Boston Healthcare System, told this news organization.

The study was published online JAMA Psychiatry.
 

Surprising findings

The results were somewhat surprising, Dr. Ferguson added. “Lithium showed little or no effect in our study, compared to observational data and results from previous trials. Many clinicians and practice guidelines had assumed that lithium was an effective agent in preventing suicide,” he said.

However, the authors of an accompanying editorial urge caution in concluding that lithium has no antisuicidal effects.

This “rigorously designed and conducted trial has much to teach but cannot be taken as evidence that lithium treatment is ineffective regarding suicidal risk,” write Ross Baldessarini, MD, and Leonardo Tondo, MD, department of psychiatry, Harvard Medical School, Boston.

Study participants were veterans with MDD or BD receiving care at one of 29 Veterans Administration medical centers who survived a recent suicide-related event. In addition to usual care, they were randomly assigned to receive oral extended-release lithium carbonate starting at 600 mg/day or matching placebo for 52 weeks.

The primary outcome was time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide.

The trial was stopped for futility after 519 veterans (mean age, 42.8 years; 84% male) were randomly assigned to receive lithium (n = 255) or placebo (n = 264). At 3 months, mean lithium concentrations were 0.54 mEq/L for patients with BD and 0.46 mEq/L for those with MDD.

There was no significant difference in the primary outcome (hazard ratio, 1.10; 95% confidence interval, 0.77-1.55; P = .61).

A total of 127 participants (24.5%) had suicide-related outcomes – 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and three in the placebo group. There were no unanticipated drug-related safety concerns.
 

Caveats, cautionary notes

The researchers note that the study did not reach its original recruitment goal. “One of the barriers to recruitment was the perception of many of the clinicians caring for potential participants that the effectiveness of lithium was already established; in fact, this perception was supported by the VA/U.S. Department of Defense Clinical Practice Guideline,” they point out.

They also note that most veterans in the study had depression rather than BD, which is the most common indication for lithium use. Most also had substance use disorders, posttraumatic stress disorder, or both, which could influence outcomes.

As a result of small numbers, it wasn’t possible to evaluate outcomes for patients with BD, test whether outcomes differed among patients with BD and MDD, or assess whether comorbidities attenuated the effects of lithium.

The study’s protocol increased participants’ contacts with the VA, which also may have affected outcomes, the researchers note.

In addition, high rates of attrition and low rates of substantial adherence to lithium meant only about half (48.1%) of the study population achieved target serum lithium concentrations.

Editorial writers Dr. Baldessarini and Dr. Tondo note that the low circulating concentrations of lithium and the fact that adherence to assigned treatment was considered adequate in only 17% of participants are key limitations of the study.

“In general, controlled treatment trials aimed at detecting suicide preventive effects are difficult to design, perform, and interpret,” they point out.

Evidence supporting an antisuicidal effect of lithium treatment includes nearly three dozen observational trials that have shown fewer suicides or attempts with lithium treatment, as well as “marked, temporary” increases in suicidal behavior soon after stopping lithium treatment.

Dr. Baldessarini and Dr. Tondo note the current findings “cannot be taken as evidence that lithium lacks antisuicidal effects. An ironic final note is that recruiting participants to such trials may be made difficult by an evidently prevalent belief that the question of antisuicidal effects of lithium is already settled, which it certainly is not,” they write.

Dr. Ferguson “agrees that more work needs to be done to understand the antisuicidal effect of lithium.

The study received financial and material support from a grant from the Cooperative Studies Program, Office of Research and Development, U.S. Department of Veterans Affairs. Dr. Ferguson has disclosed no relevant financial relationships. A complete list of author disclosures is available with the original article.

Dr. Baldessarini and Dr. Tondo have disclosed no relevant financial relationships. Their editorial was supported by grants from the Bruce J. Anderson Foundation, the McLean Private Donors Fund for Psychiatric Research, and the Aretaeus Foundation of Rome.

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

Adding lithium to usual care does not decrease the risk of suicide-related events in those with major depressive disorder (MDD) or bipolar disorder (BD) who have survived a recent suicidal event, new research shows.

The results of a randomized, double-blind, placebo-controlled trial in veterans showed no apparent advantage of the drug in preventing self-injury, suicide attempts, or urgent hospitalization to prevent suicide.

“Lithium is an important therapy for bipolar disorders and depression subsets. Our study indicates that, in patients who are actively followed and treated in a system of care that the VA provides, simply adding lithium to their existing management, including medications, is unlikely to be effective for preventing a broad range of suicide-related events,” study investigator Ryan Ferguson, MPH, ScD, Boston Cooperative Studies Coordinating Center, VA Boston Healthcare System, told this news organization.

The study was published online JAMA Psychiatry.
 

Surprising findings

The results were somewhat surprising, Dr. Ferguson added. “Lithium showed little or no effect in our study, compared to observational data and results from previous trials. Many clinicians and practice guidelines had assumed that lithium was an effective agent in preventing suicide,” he said.

However, the authors of an accompanying editorial urge caution in concluding that lithium has no antisuicidal effects.

This “rigorously designed and conducted trial has much to teach but cannot be taken as evidence that lithium treatment is ineffective regarding suicidal risk,” write Ross Baldessarini, MD, and Leonardo Tondo, MD, department of psychiatry, Harvard Medical School, Boston.

Study participants were veterans with MDD or BD receiving care at one of 29 Veterans Administration medical centers who survived a recent suicide-related event. In addition to usual care, they were randomly assigned to receive oral extended-release lithium carbonate starting at 600 mg/day or matching placebo for 52 weeks.

The primary outcome was time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide.

The trial was stopped for futility after 519 veterans (mean age, 42.8 years; 84% male) were randomly assigned to receive lithium (n = 255) or placebo (n = 264). At 3 months, mean lithium concentrations were 0.54 mEq/L for patients with BD and 0.46 mEq/L for those with MDD.

There was no significant difference in the primary outcome (hazard ratio, 1.10; 95% confidence interval, 0.77-1.55; P = .61).

A total of 127 participants (24.5%) had suicide-related outcomes – 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and three in the placebo group. There were no unanticipated drug-related safety concerns.
 

Caveats, cautionary notes

The researchers note that the study did not reach its original recruitment goal. “One of the barriers to recruitment was the perception of many of the clinicians caring for potential participants that the effectiveness of lithium was already established; in fact, this perception was supported by the VA/U.S. Department of Defense Clinical Practice Guideline,” they point out.

They also note that most veterans in the study had depression rather than BD, which is the most common indication for lithium use. Most also had substance use disorders, posttraumatic stress disorder, or both, which could influence outcomes.

As a result of small numbers, it wasn’t possible to evaluate outcomes for patients with BD, test whether outcomes differed among patients with BD and MDD, or assess whether comorbidities attenuated the effects of lithium.

The study’s protocol increased participants’ contacts with the VA, which also may have affected outcomes, the researchers note.

In addition, high rates of attrition and low rates of substantial adherence to lithium meant only about half (48.1%) of the study population achieved target serum lithium concentrations.

Editorial writers Dr. Baldessarini and Dr. Tondo note that the low circulating concentrations of lithium and the fact that adherence to assigned treatment was considered adequate in only 17% of participants are key limitations of the study.

“In general, controlled treatment trials aimed at detecting suicide preventive effects are difficult to design, perform, and interpret,” they point out.

Evidence supporting an antisuicidal effect of lithium treatment includes nearly three dozen observational trials that have shown fewer suicides or attempts with lithium treatment, as well as “marked, temporary” increases in suicidal behavior soon after stopping lithium treatment.

Dr. Baldessarini and Dr. Tondo note the current findings “cannot be taken as evidence that lithium lacks antisuicidal effects. An ironic final note is that recruiting participants to such trials may be made difficult by an evidently prevalent belief that the question of antisuicidal effects of lithium is already settled, which it certainly is not,” they write.

Dr. Ferguson “agrees that more work needs to be done to understand the antisuicidal effect of lithium.

The study received financial and material support from a grant from the Cooperative Studies Program, Office of Research and Development, U.S. Department of Veterans Affairs. Dr. Ferguson has disclosed no relevant financial relationships. A complete list of author disclosures is available with the original article.

Dr. Baldessarini and Dr. Tondo have disclosed no relevant financial relationships. Their editorial was supported by grants from the Bruce J. Anderson Foundation, the McLean Private Donors Fund for Psychiatric Research, and the Aretaeus Foundation of Rome.

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

Federal health officials have outlined a five-part plan to improve and protect the mental health and well-being of America’s health care workers (HCWs) and create sustainable change for the next generation of HCWs.

“It’s long past time for us to care for the people who care for all of us and address burnout in our health care workers,” U.S. Surgeon General Vivek H. Murthy, MD, MBA, said during a webinar hosted by the National Institute for Occupational Safety and Health, part of the U.S. Centers for Disease Control and Prevention.

“My hope is that, going forward, we will be able to embark on this journey together to create a health care system, a health care environment, a country where we can not only provide extraordinary care to all those who need it, but where we can take good care of those who have sacrificed so much and make sure that they are well,” Dr. Murthy said.
 

Burnout is not selective

There are 20 million HCWs in the United States, and no one is immune from burnout, said NIOSH Director John Howard, MD.

He noted that from June through Sept. of 2020 – the height of the COVID-19 pandemic – 93% of HCWs experienced some degree of stress, with 22% reporting moderate depression and post-traumatic stress disorder.

Looking at subsets of HCWs, a recent survey showed that one in five nurses contemplated leaving the profession because of insufficient staffing, intensity of workload, emotional and physical toll of the job, and lack of support, Dr. Howard noted.

Physician burnout was a significant issue even before the pandemic, with about 79% of physicians reporting burnout. In the fall of 2020, 69% reported depression and “a very alarming figure” of 13% reported having thoughts of suicide, Dr. Howard said.

Women in health care jobs are especially vulnerable to burnout; 76% of health care jobs are held by women and 64% of physicians that feel burned-out are women, according to federal data. 

“We have significant work to do in shoring up the safety and health of women in health care,” Dr. Howard said.

Mental health is also suffering among local and state public health workers. In a recent CDC survey of 26,000 of these workers, 53% reported symptoms of at least one mental health condition in the past 2 weeks.

“That is really an alarming proportion of public health workers who are as vital and essential as nurses and doctors are in our health care system,” Dr. Howard said.
 

Primary prevention approach

To tackle the burnout crisis, NIOSH plans to:

• Take a deep dive into understanding the personal, social, and economic burdens HCWs face on a daily basis.
• Assimilate the evidence and create a repository of best practices, resources, and interventions.
• Partner with key stakeholders, including the American Hospital Association, the American Nurses Association, National Nurses United, the Joint Commission.
• Identify and adapt tools for the health care workplace that emphasize stress reduction.

NIOSH also plans to “generate awareness through a national, multidimensional social marketing campaign to get the word out about stress so health care workers don’t feel so alone,” Dr. Howard said.

This five-part plan takes a primary prevention approach to identifying and eliminating risk factors for burnout and stress, he added.

Secondary prevention, “when damage has already been done and you’re trying to save a health care worker who is suffering from a mental health issue, that’s a lot harder than taking a good look at what you can do to organizational practices that lead to health care workers’ stress and burnout,” Dr. Howard said.

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

Federal health officials have outlined a five-part plan to improve and protect the mental health and well-being of America’s health care workers (HCWs) and create sustainable change for the next generation of HCWs.

“It’s long past time for us to care for the people who care for all of us and address burnout in our health care workers,” U.S. Surgeon General Vivek H. Murthy, MD, MBA, said during a webinar hosted by the National Institute for Occupational Safety and Health, part of the U.S. Centers for Disease Control and Prevention.

“My hope is that, going forward, we will be able to embark on this journey together to create a health care system, a health care environment, a country where we can not only provide extraordinary care to all those who need it, but where we can take good care of those who have sacrificed so much and make sure that they are well,” Dr. Murthy said.
 

Burnout is not selective

There are 20 million HCWs in the United States, and no one is immune from burnout, said NIOSH Director John Howard, MD.

He noted that from June through Sept. of 2020 – the height of the COVID-19 pandemic – 93% of HCWs experienced some degree of stress, with 22% reporting moderate depression and post-traumatic stress disorder.

Looking at subsets of HCWs, a recent survey showed that one in five nurses contemplated leaving the profession because of insufficient staffing, intensity of workload, emotional and physical toll of the job, and lack of support, Dr. Howard noted.

Physician burnout was a significant issue even before the pandemic, with about 79% of physicians reporting burnout. In the fall of 2020, 69% reported depression and “a very alarming figure” of 13% reported having thoughts of suicide, Dr. Howard said.

Women in health care jobs are especially vulnerable to burnout; 76% of health care jobs are held by women and 64% of physicians that feel burned-out are women, according to federal data. 

“We have significant work to do in shoring up the safety and health of women in health care,” Dr. Howard said.

Mental health is also suffering among local and state public health workers. In a recent CDC survey of 26,000 of these workers, 53% reported symptoms of at least one mental health condition in the past 2 weeks.

“That is really an alarming proportion of public health workers who are as vital and essential as nurses and doctors are in our health care system,” Dr. Howard said.
 

Primary prevention approach

To tackle the burnout crisis, NIOSH plans to:

• Take a deep dive into understanding the personal, social, and economic burdens HCWs face on a daily basis.
• Assimilate the evidence and create a repository of best practices, resources, and interventions.
• Partner with key stakeholders, including the American Hospital Association, the American Nurses Association, National Nurses United, the Joint Commission.
• Identify and adapt tools for the health care workplace that emphasize stress reduction.

NIOSH also plans to “generate awareness through a national, multidimensional social marketing campaign to get the word out about stress so health care workers don’t feel so alone,” Dr. Howard said.

This five-part plan takes a primary prevention approach to identifying and eliminating risk factors for burnout and stress, he added.

Secondary prevention, “when damage has already been done and you’re trying to save a health care worker who is suffering from a mental health issue, that’s a lot harder than taking a good look at what you can do to organizational practices that lead to health care workers’ stress and burnout,” Dr. Howard said.

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

Federal health officials have outlined a five-part plan to improve and protect the mental health and well-being of America’s health care workers (HCWs) and create sustainable change for the next generation of HCWs.

“It’s long past time for us to care for the people who care for all of us and address burnout in our health care workers,” U.S. Surgeon General Vivek H. Murthy, MD, MBA, said during a webinar hosted by the National Institute for Occupational Safety and Health, part of the U.S. Centers for Disease Control and Prevention.

“My hope is that, going forward, we will be able to embark on this journey together to create a health care system, a health care environment, a country where we can not only provide extraordinary care to all those who need it, but where we can take good care of those who have sacrificed so much and make sure that they are well,” Dr. Murthy said.
 

Burnout is not selective

There are 20 million HCWs in the United States, and no one is immune from burnout, said NIOSH Director John Howard, MD.

He noted that from June through Sept. of 2020 – the height of the COVID-19 pandemic – 93% of HCWs experienced some degree of stress, with 22% reporting moderate depression and post-traumatic stress disorder.

Looking at subsets of HCWs, a recent survey showed that one in five nurses contemplated leaving the profession because of insufficient staffing, intensity of workload, emotional and physical toll of the job, and lack of support, Dr. Howard noted.

Physician burnout was a significant issue even before the pandemic, with about 79% of physicians reporting burnout. In the fall of 2020, 69% reported depression and “a very alarming figure” of 13% reported having thoughts of suicide, Dr. Howard said.

Women in health care jobs are especially vulnerable to burnout; 76% of health care jobs are held by women and 64% of physicians that feel burned-out are women, according to federal data. 

“We have significant work to do in shoring up the safety and health of women in health care,” Dr. Howard said.

Mental health is also suffering among local and state public health workers. In a recent CDC survey of 26,000 of these workers, 53% reported symptoms of at least one mental health condition in the past 2 weeks.

“That is really an alarming proportion of public health workers who are as vital and essential as nurses and doctors are in our health care system,” Dr. Howard said.
 

Primary prevention approach

To tackle the burnout crisis, NIOSH plans to:

• Take a deep dive into understanding the personal, social, and economic burdens HCWs face on a daily basis.
• Assimilate the evidence and create a repository of best practices, resources, and interventions.
• Partner with key stakeholders, including the American Hospital Association, the American Nurses Association, National Nurses United, the Joint Commission.
• Identify and adapt tools for the health care workplace that emphasize stress reduction.

NIOSH also plans to “generate awareness through a national, multidimensional social marketing campaign to get the word out about stress so health care workers don’t feel so alone,” Dr. Howard said.

This five-part plan takes a primary prevention approach to identifying and eliminating risk factors for burnout and stress, he added.

Secondary prevention, “when damage has already been done and you’re trying to save a health care worker who is suffering from a mental health issue, that’s a lot harder than taking a good look at what you can do to organizational practices that lead to health care workers’ stress and burnout,” Dr. Howard said.

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

Joel Bervell recalls leaving his hometown of Seattle for the East Coast after being accepted into Yale University.

Still getting accustomed to the big move, Mr. Bervell, who had breezed through high school with straight As, went to see his chemistry professor for advice after getting a low grade on a test.

“He took one look at me and said, ‘Oh, if you’re on the football team, you don’t need to worry about it. So many people from the football team come into the class and end up dropping out, so if you need to drop this class, you can,’ ” Mr. Bervell says.

Mr. Bervell, who is Black, was not on the football team, nor did he receive a sports scholarship of any kind.

“For that professor to make an assumption of me, which to me felt like it was based on my race, made me less likely to want to go into a science field, where I felt like I was being judged before I even had a chance to prove myself,” Mr. Bervell says.

Discrimination can lead to particularly harmful outcomes for young adults entering college or starting off their careers, according to a new University of California, Los Angeles, study.

Researchers studied health data on 1,834 Americans ages 18-28 over a 10-year span. Findings show that the more instances of discrimination they experienced – including ageism, sexism, and racism – the more likely they were to face mental and behavioral struggles, like mental illness, drug use, severe psychological distress, and poor overall health.

Mr. Bervell, now 26, says he feels lucky that growing up, he was taught healthy ways to process his feelings and emotions.

“Instead of taking that and internalizing it, I said, ‘how can I use this to prove him wrong?’” he says. “Does that mean I need to work harder or does that mean I need to find a different mentor? Surround myself with different people?”

Mr. Bervell is currently a 3rd-year medical student at Washington State University.

When he’s not at the hospital seeing patients, you can find him educating his nearly 340,000 TikTok followers on topics like racial bias in medicine.
 

Acknowledge the impact

Most Black people don’t tie psychological distress to acts of racism, according to Rheeda Walker, PhD, psychology professor at the University of Houston and author of “The Unapologetic Guide to Black Mental Health” (Oakland, Calif.: New Harbinger Publications, 2020).

Many Black people even normalize it.

“Individuals deal with it [racism] as just another thing, like paying bills, going to work, and studying for class and not as the overwhelming psychological burden that it is,” says Dr. Walker.

And despite what some may say, racial discrimination is not merely “a thing of the past,” Dr. Walker says.

“Instead, discrimination has shifted form from more overt forms of discrimination to less obvious microaggression,” she says.

It’s also critical that young adults are taught how to deal with racism to avoid the risk of “internalizing that they deserve to be mistreated, and/or that they have to work twice as hard to overcome racism,” says Dr. Walker.

“Both scenarios can escalate hopelessness and worry, psychological features of depression and anxiety, respectively,” Dr. Walker says.
 

Embrace your emotions

Known around the office as “a big teddy bear,” Frederick Herman, a mortgage loan originator based in Charlotte, Va., was coaching a newer employee on how to make sales calls, a common practice in his line of work.

He says a day or 2 days later, his manager let him know that he had made an employee “very uncomfortable” by intimidating them while they were on the phone. Mr. Herman, 29, was told to watch his “aggressive” behavior.

“I’m a bigger Black man. I’m like 6’2, 300 lbs., somewhat muscular. So, if me talking or trying to coach her came off as intimidating, then there’s nothing that I could do or say differently than I was already doing to make her not feel intimidated,” Mr. Herman says.

“If a big teddy bear is now intimidating to you, that just tells me everything I need to know.”

This wasn’t the first time Mr. Herman had been reprimanded for being “too aggressive” or “showing off” when trying to help colleagues at work.

“I’ve had other experiences at work where I may not share my ideas, or I may get super anxious,” says Mr. Herman, a Black man of Haitian descent.

It’s important to allow yourself to feel your emotions after facing acts of discrimination, says Ebony Butler, PhD, a licensed psychologist and creator of My Therapy Cards, a card deck tailored for men, women, and teens of color, with self-care and reflection prompts.

This is a practice called “self-validation” and can reduce the tendency to blame oneself for the mistreatment, says Dr. Butler.

Mr. Herman, 29, says that he recently signed up for therapy to work through his struggles with anxiety.

Relaxation techniques, like grounding and mindfulness, can also be helpful, says Dr. Butler.

“Some example ways to practice grounding are immersing oneself in nature, walking bare feet on the ground, lying on the floor, practicing slow, deep breathing, or engaging the senses,” she says.

“When we are grounded and present, we can better manage our responses and plan our action steps.”
 

Utilize unique

If you find yourself in a racially charged school or workplace setting, don’t be intimidated, says Wendy Osefo, PhD, education professor at Johns Hopkins University, Baltimore, political commentator, and television personality.

Dr. Osefo made history in 2016 as the first Black woman to earn a PhD in public affairs/community development from Rutgers University.

“Your attitude should be that, no matter how different you might be, you belong, and you earned the right to occupy this space. You’re not less qualified than others who surround you,” she says.

Dr. Ofeso is also CEO of The 1954 Equity Project, an organization that gives minority students tools to succeed in higher education – like mentorships, peer support groups, and other resources and services – all while remaining their authentic selves.

No matter how uncomfortable it might be, staying true to who you are vs. conforming to the masses pays off, says Dr. Osefo.

“Being different is unique and allows you to bring a new and fresh perspective into an environment,” she says.

“Leaning into this uniqueness builds a level of confidence that will aid in your ability to be successful.”

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

Joel Bervell recalls leaving his hometown of Seattle for the East Coast after being accepted into Yale University.

Still getting accustomed to the big move, Mr. Bervell, who had breezed through high school with straight As, went to see his chemistry professor for advice after getting a low grade on a test.

“He took one look at me and said, ‘Oh, if you’re on the football team, you don’t need to worry about it. So many people from the football team come into the class and end up dropping out, so if you need to drop this class, you can,’ ” Mr. Bervell says.

Mr. Bervell, who is Black, was not on the football team, nor did he receive a sports scholarship of any kind.

“For that professor to make an assumption of me, which to me felt like it was based on my race, made me less likely to want to go into a science field, where I felt like I was being judged before I even had a chance to prove myself,” Mr. Bervell says.

Discrimination can lead to particularly harmful outcomes for young adults entering college or starting off their careers, according to a new University of California, Los Angeles, study.

Researchers studied health data on 1,834 Americans ages 18-28 over a 10-year span. Findings show that the more instances of discrimination they experienced – including ageism, sexism, and racism – the more likely they were to face mental and behavioral struggles, like mental illness, drug use, severe psychological distress, and poor overall health.

Mr. Bervell, now 26, says he feels lucky that growing up, he was taught healthy ways to process his feelings and emotions.

“Instead of taking that and internalizing it, I said, ‘how can I use this to prove him wrong?’” he says. “Does that mean I need to work harder or does that mean I need to find a different mentor? Surround myself with different people?”

Mr. Bervell is currently a 3rd-year medical student at Washington State University.

When he’s not at the hospital seeing patients, you can find him educating his nearly 340,000 TikTok followers on topics like racial bias in medicine.
 

Acknowledge the impact

Most Black people don’t tie psychological distress to acts of racism, according to Rheeda Walker, PhD, psychology professor at the University of Houston and author of “The Unapologetic Guide to Black Mental Health” (Oakland, Calif.: New Harbinger Publications, 2020).

Many Black people even normalize it.

“Individuals deal with it [racism] as just another thing, like paying bills, going to work, and studying for class and not as the overwhelming psychological burden that it is,” says Dr. Walker.

And despite what some may say, racial discrimination is not merely “a thing of the past,” Dr. Walker says.

“Instead, discrimination has shifted form from more overt forms of discrimination to less obvious microaggression,” she says.

It’s also critical that young adults are taught how to deal with racism to avoid the risk of “internalizing that they deserve to be mistreated, and/or that they have to work twice as hard to overcome racism,” says Dr. Walker.

“Both scenarios can escalate hopelessness and worry, psychological features of depression and anxiety, respectively,” Dr. Walker says.
 

Embrace your emotions

Known around the office as “a big teddy bear,” Frederick Herman, a mortgage loan originator based in Charlotte, Va., was coaching a newer employee on how to make sales calls, a common practice in his line of work.

He says a day or 2 days later, his manager let him know that he had made an employee “very uncomfortable” by intimidating them while they were on the phone. Mr. Herman, 29, was told to watch his “aggressive” behavior.

“I’m a bigger Black man. I’m like 6’2, 300 lbs., somewhat muscular. So, if me talking or trying to coach her came off as intimidating, then there’s nothing that I could do or say differently than I was already doing to make her not feel intimidated,” Mr. Herman says.

“If a big teddy bear is now intimidating to you, that just tells me everything I need to know.”

This wasn’t the first time Mr. Herman had been reprimanded for being “too aggressive” or “showing off” when trying to help colleagues at work.

“I’ve had other experiences at work where I may not share my ideas, or I may get super anxious,” says Mr. Herman, a Black man of Haitian descent.

It’s important to allow yourself to feel your emotions after facing acts of discrimination, says Ebony Butler, PhD, a licensed psychologist and creator of My Therapy Cards, a card deck tailored for men, women, and teens of color, with self-care and reflection prompts.

This is a practice called “self-validation” and can reduce the tendency to blame oneself for the mistreatment, says Dr. Butler.

Mr. Herman, 29, says that he recently signed up for therapy to work through his struggles with anxiety.

Relaxation techniques, like grounding and mindfulness, can also be helpful, says Dr. Butler.

“Some example ways to practice grounding are immersing oneself in nature, walking bare feet on the ground, lying on the floor, practicing slow, deep breathing, or engaging the senses,” she says.

“When we are grounded and present, we can better manage our responses and plan our action steps.”
 

Utilize unique

If you find yourself in a racially charged school or workplace setting, don’t be intimidated, says Wendy Osefo, PhD, education professor at Johns Hopkins University, Baltimore, political commentator, and television personality.

Dr. Osefo made history in 2016 as the first Black woman to earn a PhD in public affairs/community development from Rutgers University.

“Your attitude should be that, no matter how different you might be, you belong, and you earned the right to occupy this space. You’re not less qualified than others who surround you,” she says.

Dr. Ofeso is also CEO of The 1954 Equity Project, an organization that gives minority students tools to succeed in higher education – like mentorships, peer support groups, and other resources and services – all while remaining their authentic selves.

No matter how uncomfortable it might be, staying true to who you are vs. conforming to the masses pays off, says Dr. Osefo.

“Being different is unique and allows you to bring a new and fresh perspective into an environment,” she says.

“Leaning into this uniqueness builds a level of confidence that will aid in your ability to be successful.”

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

Joel Bervell recalls leaving his hometown of Seattle for the East Coast after being accepted into Yale University.

Still getting accustomed to the big move, Mr. Bervell, who had breezed through high school with straight As, went to see his chemistry professor for advice after getting a low grade on a test.

“He took one look at me and said, ‘Oh, if you’re on the football team, you don’t need to worry about it. So many people from the football team come into the class and end up dropping out, so if you need to drop this class, you can,’ ” Mr. Bervell says.

Mr. Bervell, who is Black, was not on the football team, nor did he receive a sports scholarship of any kind.

“For that professor to make an assumption of me, which to me felt like it was based on my race, made me less likely to want to go into a science field, where I felt like I was being judged before I even had a chance to prove myself,” Mr. Bervell says.

Discrimination can lead to particularly harmful outcomes for young adults entering college or starting off their careers, according to a new University of California, Los Angeles, study.

Researchers studied health data on 1,834 Americans ages 18-28 over a 10-year span. Findings show that the more instances of discrimination they experienced – including ageism, sexism, and racism – the more likely they were to face mental and behavioral struggles, like mental illness, drug use, severe psychological distress, and poor overall health.

Mr. Bervell, now 26, says he feels lucky that growing up, he was taught healthy ways to process his feelings and emotions.

“Instead of taking that and internalizing it, I said, ‘how can I use this to prove him wrong?’” he says. “Does that mean I need to work harder or does that mean I need to find a different mentor? Surround myself with different people?”

Mr. Bervell is currently a 3rd-year medical student at Washington State University.

When he’s not at the hospital seeing patients, you can find him educating his nearly 340,000 TikTok followers on topics like racial bias in medicine.
 

Acknowledge the impact

Most Black people don’t tie psychological distress to acts of racism, according to Rheeda Walker, PhD, psychology professor at the University of Houston and author of “The Unapologetic Guide to Black Mental Health” (Oakland, Calif.: New Harbinger Publications, 2020).

Many Black people even normalize it.

“Individuals deal with it [racism] as just another thing, like paying bills, going to work, and studying for class and not as the overwhelming psychological burden that it is,” says Dr. Walker.

And despite what some may say, racial discrimination is not merely “a thing of the past,” Dr. Walker says.

“Instead, discrimination has shifted form from more overt forms of discrimination to less obvious microaggression,” she says.

It’s also critical that young adults are taught how to deal with racism to avoid the risk of “internalizing that they deserve to be mistreated, and/or that they have to work twice as hard to overcome racism,” says Dr. Walker.

“Both scenarios can escalate hopelessness and worry, psychological features of depression and anxiety, respectively,” Dr. Walker says.
 

Embrace your emotions

Known around the office as “a big teddy bear,” Frederick Herman, a mortgage loan originator based in Charlotte, Va., was coaching a newer employee on how to make sales calls, a common practice in his line of work.

He says a day or 2 days later, his manager let him know that he had made an employee “very uncomfortable” by intimidating them while they were on the phone. Mr. Herman, 29, was told to watch his “aggressive” behavior.

“I’m a bigger Black man. I’m like 6’2, 300 lbs., somewhat muscular. So, if me talking or trying to coach her came off as intimidating, then there’s nothing that I could do or say differently than I was already doing to make her not feel intimidated,” Mr. Herman says.

“If a big teddy bear is now intimidating to you, that just tells me everything I need to know.”

This wasn’t the first time Mr. Herman had been reprimanded for being “too aggressive” or “showing off” when trying to help colleagues at work.

“I’ve had other experiences at work where I may not share my ideas, or I may get super anxious,” says Mr. Herman, a Black man of Haitian descent.

It’s important to allow yourself to feel your emotions after facing acts of discrimination, says Ebony Butler, PhD, a licensed psychologist and creator of My Therapy Cards, a card deck tailored for men, women, and teens of color, with self-care and reflection prompts.

This is a practice called “self-validation” and can reduce the tendency to blame oneself for the mistreatment, says Dr. Butler.

Mr. Herman, 29, says that he recently signed up for therapy to work through his struggles with anxiety.

Relaxation techniques, like grounding and mindfulness, can also be helpful, says Dr. Butler.

“Some example ways to practice grounding are immersing oneself in nature, walking bare feet on the ground, lying on the floor, practicing slow, deep breathing, or engaging the senses,” she says.

“When we are grounded and present, we can better manage our responses and plan our action steps.”
 

Utilize unique

If you find yourself in a racially charged school or workplace setting, don’t be intimidated, says Wendy Osefo, PhD, education professor at Johns Hopkins University, Baltimore, political commentator, and television personality.

Dr. Osefo made history in 2016 as the first Black woman to earn a PhD in public affairs/community development from Rutgers University.

“Your attitude should be that, no matter how different you might be, you belong, and you earned the right to occupy this space. You’re not less qualified than others who surround you,” she says.

Dr. Ofeso is also CEO of The 1954 Equity Project, an organization that gives minority students tools to succeed in higher education – like mentorships, peer support groups, and other resources and services – all while remaining their authentic selves.

No matter how uncomfortable it might be, staying true to who you are vs. conforming to the masses pays off, says Dr. Osefo.

“Being different is unique and allows you to bring a new and fresh perspective into an environment,” she says.

“Leaning into this uniqueness builds a level of confidence that will aid in your ability to be successful.”

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

Mounting evidence suggests selective serotonin reuptake inhibitors (SSRI) are associated with lower COVID-19 severity.

A large analysis of health records shows patients with COVID-19 taking an SSRI were significantly less likely to die of COVID-19 than a matched control group.

Data-driven approach

Investigators analyzed data from the Cerner Real World Data COVID-19 deidentified electronic health records database of 490,373 patients with COVID-19 across 87 health centers, including 3,401 patients who were prescribed SSRIs.

When compared with matched patients with COVID-19 taking SSRIs, patients taking fluoxetine were 28% less likely to die (relative risk, 0.72; 95% CI, 0.54-0.97; adjusted P = .03) and those taking either fluoxetine or fluvoxamine were 26% less likely to die (RR, 0.74; 95% CI, 0.55-0.99; adjusted P = .04) versus those not on these medications.

Patients with COVID-19 taking any kind of SSRI were 8% less likely to die than the matched controls (RR, 0.92; 95% CI, 0.85-0.99; adjusted P = .03).

“We observed a statistically significant reduction in mortality of COVID-19 patients who were already taking SSRIs. This is a demonstration of a data-driven approach for identifying new uses for existing drugs,” Dr. Sirota said in an interview.

“Our study simply shows an association between SSRIs and COVID-19 outcomes and doesn’t investigate the mechanism of action of why the drugs might work. Additional clinical trials need to be carried out before these drugs can be used in patients going forward,” she cautioned.

“There is currently an open-label trial investigating fluoxetine to reduce intubation and death after COVID-19. To our knowledge, there are no phase 3 randomized controlled trials taking place or planned,” study investigator Tomiko Oskotsky, MD, with UCSF, told this news organization.

Urgent need

The current results “confirm and expand on prior findings from observational, preclinical, and clinical studies suggesting that certain SSRI antidepressants, including fluoxetine or fluvoxamine, could be beneficial against COVID-19,” Nicolas Hoertel, MD, PhD, MPH, with Paris University and Corentin-Celton Hospital, France, writes in a linked editorial.

Dr. Hoertel notes that the anti-inflammatory properties of SSRIs may underlie their potential action against COVID-19, and other potential mechanisms may include reduction in platelet aggregation, decreased mast cell degranulation, increased melatonin levels, interference with endolysosomal viral trafficking, and antioxidant activities.

“Because most of the world’s population is currently unvaccinated and the COVID-19 pandemic is still active, effective treatments of COVID-19 – especially those that are easy to use, show good tolerability, can be administered orally, and have widespread availability at low cost to allow their use in resource-poor countries – are urgently needed to reduce COVID-19-related mortality and morbidity,” Dr. Hoertel points out.

“In this context, short-term use of fluoxetine or fluvoxamine, if proven effective, should be considered as a potential means of reaching this goal,” he adds.

The study was supported by the Christopher Hess Research Fund and, in part, by UCSF and the National Institutes of Health. Dr. Sirota has reported serving as a scientific advisor at Aria Pharmaceuticals. Dr. Hoertel has reported being listed as an inventor on a patent application related to methods of treating COVID-19, filed by Assistance Publique-Hopitaux de Paris, and receiving consulting fees and nonfinancial support from Lundbeck.

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

Mounting evidence suggests selective serotonin reuptake inhibitors (SSRI) are associated with lower COVID-19 severity.

A large analysis of health records shows patients with COVID-19 taking an SSRI were significantly less likely to die of COVID-19 than a matched control group.

Data-driven approach

Investigators analyzed data from the Cerner Real World Data COVID-19 deidentified electronic health records database of 490,373 patients with COVID-19 across 87 health centers, including 3,401 patients who were prescribed SSRIs.

When compared with matched patients with COVID-19 taking SSRIs, patients taking fluoxetine were 28% less likely to die (relative risk, 0.72; 95% CI, 0.54-0.97; adjusted P = .03) and those taking either fluoxetine or fluvoxamine were 26% less likely to die (RR, 0.74; 95% CI, 0.55-0.99; adjusted P = .04) versus those not on these medications.

Patients with COVID-19 taking any kind of SSRI were 8% less likely to die than the matched controls (RR, 0.92; 95% CI, 0.85-0.99; adjusted P = .03).

“We observed a statistically significant reduction in mortality of COVID-19 patients who were already taking SSRIs. This is a demonstration of a data-driven approach for identifying new uses for existing drugs,” Dr. Sirota said in an interview.

“Our study simply shows an association between SSRIs and COVID-19 outcomes and doesn’t investigate the mechanism of action of why the drugs might work. Additional clinical trials need to be carried out before these drugs can be used in patients going forward,” she cautioned.

“There is currently an open-label trial investigating fluoxetine to reduce intubation and death after COVID-19. To our knowledge, there are no phase 3 randomized controlled trials taking place or planned,” study investigator Tomiko Oskotsky, MD, with UCSF, told this news organization.

Urgent need

The current results “confirm and expand on prior findings from observational, preclinical, and clinical studies suggesting that certain SSRI antidepressants, including fluoxetine or fluvoxamine, could be beneficial against COVID-19,” Nicolas Hoertel, MD, PhD, MPH, with Paris University and Corentin-Celton Hospital, France, writes in a linked editorial.

Dr. Hoertel notes that the anti-inflammatory properties of SSRIs may underlie their potential action against COVID-19, and other potential mechanisms may include reduction in platelet aggregation, decreased mast cell degranulation, increased melatonin levels, interference with endolysosomal viral trafficking, and antioxidant activities.

“Because most of the world’s population is currently unvaccinated and the COVID-19 pandemic is still active, effective treatments of COVID-19 – especially those that are easy to use, show good tolerability, can be administered orally, and have widespread availability at low cost to allow their use in resource-poor countries – are urgently needed to reduce COVID-19-related mortality and morbidity,” Dr. Hoertel points out.

“In this context, short-term use of fluoxetine or fluvoxamine, if proven effective, should be considered as a potential means of reaching this goal,” he adds.

The study was supported by the Christopher Hess Research Fund and, in part, by UCSF and the National Institutes of Health. Dr. Sirota has reported serving as a scientific advisor at Aria Pharmaceuticals. Dr. Hoertel has reported being listed as an inventor on a patent application related to methods of treating COVID-19, filed by Assistance Publique-Hopitaux de Paris, and receiving consulting fees and nonfinancial support from Lundbeck.

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

Mounting evidence suggests selective serotonin reuptake inhibitors (SSRI) are associated with lower COVID-19 severity.

A large analysis of health records shows patients with COVID-19 taking an SSRI were significantly less likely to die of COVID-19 than a matched control group.

Data-driven approach

Investigators analyzed data from the Cerner Real World Data COVID-19 deidentified electronic health records database of 490,373 patients with COVID-19 across 87 health centers, including 3,401 patients who were prescribed SSRIs.

When compared with matched patients with COVID-19 taking SSRIs, patients taking fluoxetine were 28% less likely to die (relative risk, 0.72; 95% CI, 0.54-0.97; adjusted P = .03) and those taking either fluoxetine or fluvoxamine were 26% less likely to die (RR, 0.74; 95% CI, 0.55-0.99; adjusted P = .04) versus those not on these medications.

Patients with COVID-19 taking any kind of SSRI were 8% less likely to die than the matched controls (RR, 0.92; 95% CI, 0.85-0.99; adjusted P = .03).

“We observed a statistically significant reduction in mortality of COVID-19 patients who were already taking SSRIs. This is a demonstration of a data-driven approach for identifying new uses for existing drugs,” Dr. Sirota said in an interview.

“Our study simply shows an association between SSRIs and COVID-19 outcomes and doesn’t investigate the mechanism of action of why the drugs might work. Additional clinical trials need to be carried out before these drugs can be used in patients going forward,” she cautioned.

“There is currently an open-label trial investigating fluoxetine to reduce intubation and death after COVID-19. To our knowledge, there are no phase 3 randomized controlled trials taking place or planned,” study investigator Tomiko Oskotsky, MD, with UCSF, told this news organization.

Urgent need

The current results “confirm and expand on prior findings from observational, preclinical, and clinical studies suggesting that certain SSRI antidepressants, including fluoxetine or fluvoxamine, could be beneficial against COVID-19,” Nicolas Hoertel, MD, PhD, MPH, with Paris University and Corentin-Celton Hospital, France, writes in a linked editorial.

Dr. Hoertel notes that the anti-inflammatory properties of SSRIs may underlie their potential action against COVID-19, and other potential mechanisms may include reduction in platelet aggregation, decreased mast cell degranulation, increased melatonin levels, interference with endolysosomal viral trafficking, and antioxidant activities.

“Because most of the world’s population is currently unvaccinated and the COVID-19 pandemic is still active, effective treatments of COVID-19 – especially those that are easy to use, show good tolerability, can be administered orally, and have widespread availability at low cost to allow their use in resource-poor countries – are urgently needed to reduce COVID-19-related mortality and morbidity,” Dr. Hoertel points out.

“In this context, short-term use of fluoxetine or fluvoxamine, if proven effective, should be considered as a potential means of reaching this goal,” he adds.

The study was supported by the Christopher Hess Research Fund and, in part, by UCSF and the National Institutes of Health. Dr. Sirota has reported serving as a scientific advisor at Aria Pharmaceuticals. Dr. Hoertel has reported being listed as an inventor on a patent application related to methods of treating COVID-19, filed by Assistance Publique-Hopitaux de Paris, and receiving consulting fees and nonfinancial support from Lundbeck.

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

When parents of children with autism spectrum disorder (ASD) participating in the largest clinical trial of intranasal oxytocin to date came in for follow-up visits with investigators, they reported marked improvement in the children’s social functioning.

Kids who rarely communicated with their families began to interact more. Those who usually preferred to isolate themselves started joining their parents for meals. It all seemed so promising – until the data came in.

“Those sounded like real improvements to me, and it seemed like they increased over the period of the study,” lead investigator Linmarie Sikich, MD, an associate clinical professor of psychiatry with Duke University School of Medicine and the Duke Center for Autism and Brain Development, Durham, N.C., told this news organization. “Turns out it wasn’t oxytocin that was making that difference.”

Researchers found that after 24 weeks of daily treatment with intranasal oxytocin, there were no significant differences in social functioning between children who received active treatment and those in the placebo group.

The much-anticipated results were published online in The New England Journal of Medicine. To say that they are disappointing, Dr. Sikich said, is an understatement.
 

Increase in off-label use

Most studies in mouse models of ASD and small trials in children produced conflicting results, although there were modest improvements in social functioning associated with the use of intranasal oxytocin. Some clinicians were already prescribing it off label.

On the basis of this research and early feedback from parents of children, Dr. Sikich and colleagues were hopeful.

However, results from a rigorous, 5-year, $11.4 million randomized trial were negative. Yet, parents were convinced their child improved during the study, and there was a significant increase in off-label prescribing of a treatment her research says doesn’t work. What’s next for oxytocin?

Known as the “love hormone,” oxytocin is a neurotransmitter that is primarily synthesized in the hypothalamus. It plays a role in childbirth and lactation and is also involved in the regulation of social functioning and emotions. Research suggests low oxytocin levels are associated with diminished social functioning, regardless of ASD status.

Its potential as an autism therapy for children has been under study for a decade. Some findings link its use to improvements in core deficits associated with ASD, including repetitive behaviors, fixated or restricted interest, and social communication. A study published in 2020 showed that the treatment improved symptoms in high-functioning adults with ASD.

These were mostly small studies and were underpowered to reliably detect an effect of the therapy on social functioning. They often involved only a single dose of oxytocin. Some studies showed improvements, but others did not.

Still, interest in the treatment grew. Physicians began prescribing it for children with ASD, and parents began buying products containing oxytocin on the internet. Researchers feared this off-label use was becoming widespread, despite inconclusive evidence of efficacy.
 

High hopes

With support from a National Institutes of Health grant, Dr. Sikich and her team designed a phase 2, multicenter, randomized, double-blind, placebo-controlled study to determine whether the use of oxytocin in children with ASD works and is safe.

The challenges began before they even enrolled a single child. A number of behavioral assessment tools are used to measure social function in ASD, but there is no consensus on which one is best.

A simple blood test could determine how much oxytocin from the nasal spray was absorbed in the blood, but identifying how much made it to the brain would require fMRI, which is expensive and is challenging to use in this study population. Then there was the acquisition of the drug itself.

The Food and Drug Administration has approved intravenous oxytocin for inducing labor. Intranasal oxytocin is not approved for any indication and isn’t available commercially in the United States. Patients or researchers must secure the drug from a manufacturer in a country where it is approved or order it from a U.S. pharmacy that is capable of compounding IV oxytocin into an intranasal formulation.

The pharmacy in Switzerland Dr. Sikich planned to use couldn’t make enough for the study. Contracting with a compounding pharmacy in the United States was significantly more expensive and time consuming, but it was the researchers’ only option.

“If it hadn’t been something we expected to have a major benefit, I think we would have given up the project at multiple points along the line due to all of these challenges,” said Dr. Sikich.

In August 2014, with all the pieces finally in place, researchers began enrolling children aged 3-17 years. The final cohort included 290 participants with ASD, 146 in the oxytocin group and 144 in the placebo group. Of these, 48% had minimal verbal fluency, and 52% had fluent verbal speech.

Participants received daily synthetic oxytocin or placebo via a nasal spray for 24 weeks. The daily oxytocin dose was 48 IU for the first 7 weeks. After that, the dosage could be titrated to a maximum of 80 IU/d. The mean maximal total daily dose of oxytocin throughout the study was 67.6 ± 16.9 IU.
 

‘It just didn’t work’

Both study groups showed improvement in social withdrawal beginning at 4 weeks and continuing throughout the trial, as determined on the basis of caretakers’ responses on the Aberrant Behavior Checklist Modified Social Withdrawal Subscale, the study’s primary outcome measure.

Sociability and social motivation also improved in both groups, as measured by the Pervasive Developmental Disorders Behavior Inventory and the Social Responsiveness Scale.

But by the end of the trial, the difference between the groups in improvement of social function wasn’t significant (difference, -0.2 points; P = .61) after adjusting for age, verbal fluency, and baseline oxytocin level.

“We were so convinced that it would work,” Dr. Sikich said, “but it just didn’t.”

From observation, parents were also convinced the therapy was working. At the trial’s conclusion, fewer than half of caregivers correctly guessed whether their child was in the treatment group or the placebo group.

A lot of development changes can happen in a child over 6 months. It’s possible the improvements would have occurred regardless of the trial, Dr. Sikich said. Parents’ perceptions could also be a placebo effect. Their child was in a clinical trial of a drug they believed could improve social functioning, so in their mind, it did.

Caregivers received training in how to identify certain behavioral changes, which may have helped them spot an existing positive change they had previously overlooked. Or they may have worked with their child more intently as a result of their participation in the trial.

“People may start doing more things or doing them more intensively or purposefully, consciously or subconsciously, to try to help their child improve the skills or behaviors targeted by the active therapy in the study,” Dr. Sikich said. “These are things that might really help the child move forward which are completely separate from the medication being studied.”

The safety analysis offered more hopeful results. Only one serious adverse event from the treatment was reported: A 17-year-old participant taking a daily dose of 48 IU experienced a sedating effect while driving and had an accident.
 

Too soon to walk away?

Perhaps the most important take-away from the study is that even if it’s safe, intranasal oxytocin as it is currently used doesn’t work and clinicians shouldn’t prescribe it, said Daniel Geschwind, MD, PhD, director of the University of California, Los Angeles (UCLA) Center for Autism Research, who penned a commentary on the study and discussed the findings with this news organization.

“This study shows that using oxytocin the way it’s used in the community right now is not helping anybody, so why put a child through that?” added Dr. Geschwind, who also is a professor of genetics, neurology, and psychiatry at UCLA.

The trial highlights areas that need to be addressed in order to improve research in the field, he said. Establishing a consensus process to measure social functioning and figuring out a better way to access intranasal oxytocin would lead to studies that are more conclusive, comparable, and less expensive. Dr. Sikich agrees.

Despite the findings, Dr. Geschwind and other autism researchers say it’s too soon to walk away from oxytocin altogether, although it may be time to change the approach to autism research.

“We have to take a page from the playbook of modern medicine in other areas and begin to recognize that these syndromes are incredibly heterogeneous,” Dr. Geschwind says. “We can surmise, although we don’t know, that there might be different biological forms of autism that have different pathways involved that are going to respond differently to different medications.”

Calling the researchers’ efforts “heroic,” Karen Parker, PhD, an associate professor and associate chair of psychiatry and behavioral sciences at Stanford (Calif.) University, says efficacy trials such as this one are critical. However, Dr. Parker said in an interview, there are a number of questions that the study didn’t address.

The majority of medication dispensed in a standard intranasal device is sprayed into the back of the throat. Regular blood tests confirmed that oxytocin was getting into participants’ system, but, given how quickly oxytocin degrades in the blood, Dr. Parker said it’s hard to know just how much reached the brain.

It’s also unclear whether the results would have been different had the treatment been paired with behavioral therapy, an approach Dr. Parker suggests might benefit a subset of children with ASD.

A 2017 study from Dr. Parker’s lab found that children with ASD whose use of oxytocin at baseline was low derived greater benefit from synthetic oxytocin, something the new study failed to find. Still, Dr. Parker said, it’s possible oxytocin might increase social motivation and increase a child’s receptiveness to behavioral therapy.

“When you see a negative trial like this, it decreases enthusiasm for the therapy for autism in this context,” Dr. Parker said. “I hope people who are studying these syndromes will continue to explore oxytocin as a therapy.”

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Autism Centers of Excellence Program and the Department of Psychiatry and Behavioral Sciences at Duke University. Full disclosures of the authors’ possible conflicts of interest are available online.

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

When parents of children with autism spectrum disorder (ASD) participating in the largest clinical trial of intranasal oxytocin to date came in for follow-up visits with investigators, they reported marked improvement in the children’s social functioning.

Kids who rarely communicated with their families began to interact more. Those who usually preferred to isolate themselves started joining their parents for meals. It all seemed so promising – until the data came in.

“Those sounded like real improvements to me, and it seemed like they increased over the period of the study,” lead investigator Linmarie Sikich, MD, an associate clinical professor of psychiatry with Duke University School of Medicine and the Duke Center for Autism and Brain Development, Durham, N.C., told this news organization. “Turns out it wasn’t oxytocin that was making that difference.”

Researchers found that after 24 weeks of daily treatment with intranasal oxytocin, there were no significant differences in social functioning between children who received active treatment and those in the placebo group.

The much-anticipated results were published online in The New England Journal of Medicine. To say that they are disappointing, Dr. Sikich said, is an understatement.
 

Increase in off-label use

Most studies in mouse models of ASD and small trials in children produced conflicting results, although there were modest improvements in social functioning associated with the use of intranasal oxytocin. Some clinicians were already prescribing it off label.

On the basis of this research and early feedback from parents of children, Dr. Sikich and colleagues were hopeful.

However, results from a rigorous, 5-year, $11.4 million randomized trial were negative. Yet, parents were convinced their child improved during the study, and there was a significant increase in off-label prescribing of a treatment her research says doesn’t work. What’s next for oxytocin?

Known as the “love hormone,” oxytocin is a neurotransmitter that is primarily synthesized in the hypothalamus. It plays a role in childbirth and lactation and is also involved in the regulation of social functioning and emotions. Research suggests low oxytocin levels are associated with diminished social functioning, regardless of ASD status.

Its potential as an autism therapy for children has been under study for a decade. Some findings link its use to improvements in core deficits associated with ASD, including repetitive behaviors, fixated or restricted interest, and social communication. A study published in 2020 showed that the treatment improved symptoms in high-functioning adults with ASD.

These were mostly small studies and were underpowered to reliably detect an effect of the therapy on social functioning. They often involved only a single dose of oxytocin. Some studies showed improvements, but others did not.

Still, interest in the treatment grew. Physicians began prescribing it for children with ASD, and parents began buying products containing oxytocin on the internet. Researchers feared this off-label use was becoming widespread, despite inconclusive evidence of efficacy.
 

High hopes

With support from a National Institutes of Health grant, Dr. Sikich and her team designed a phase 2, multicenter, randomized, double-blind, placebo-controlled study to determine whether the use of oxytocin in children with ASD works and is safe.

The challenges began before they even enrolled a single child. A number of behavioral assessment tools are used to measure social function in ASD, but there is no consensus on which one is best.

A simple blood test could determine how much oxytocin from the nasal spray was absorbed in the blood, but identifying how much made it to the brain would require fMRI, which is expensive and is challenging to use in this study population. Then there was the acquisition of the drug itself.

The Food and Drug Administration has approved intravenous oxytocin for inducing labor. Intranasal oxytocin is not approved for any indication and isn’t available commercially in the United States. Patients or researchers must secure the drug from a manufacturer in a country where it is approved or order it from a U.S. pharmacy that is capable of compounding IV oxytocin into an intranasal formulation.

The pharmacy in Switzerland Dr. Sikich planned to use couldn’t make enough for the study. Contracting with a compounding pharmacy in the United States was significantly more expensive and time consuming, but it was the researchers’ only option.

“If it hadn’t been something we expected to have a major benefit, I think we would have given up the project at multiple points along the line due to all of these challenges,” said Dr. Sikich.

In August 2014, with all the pieces finally in place, researchers began enrolling children aged 3-17 years. The final cohort included 290 participants with ASD, 146 in the oxytocin group and 144 in the placebo group. Of these, 48% had minimal verbal fluency, and 52% had fluent verbal speech.

Participants received daily synthetic oxytocin or placebo via a nasal spray for 24 weeks. The daily oxytocin dose was 48 IU for the first 7 weeks. After that, the dosage could be titrated to a maximum of 80 IU/d. The mean maximal total daily dose of oxytocin throughout the study was 67.6 ± 16.9 IU.
 

‘It just didn’t work’

Both study groups showed improvement in social withdrawal beginning at 4 weeks and continuing throughout the trial, as determined on the basis of caretakers’ responses on the Aberrant Behavior Checklist Modified Social Withdrawal Subscale, the study’s primary outcome measure.

Sociability and social motivation also improved in both groups, as measured by the Pervasive Developmental Disorders Behavior Inventory and the Social Responsiveness Scale.

But by the end of the trial, the difference between the groups in improvement of social function wasn’t significant (difference, -0.2 points; P = .61) after adjusting for age, verbal fluency, and baseline oxytocin level.

“We were so convinced that it would work,” Dr. Sikich said, “but it just didn’t.”

From observation, parents were also convinced the therapy was working. At the trial’s conclusion, fewer than half of caregivers correctly guessed whether their child was in the treatment group or the placebo group.

A lot of development changes can happen in a child over 6 months. It’s possible the improvements would have occurred regardless of the trial, Dr. Sikich said. Parents’ perceptions could also be a placebo effect. Their child was in a clinical trial of a drug they believed could improve social functioning, so in their mind, it did.

Caregivers received training in how to identify certain behavioral changes, which may have helped them spot an existing positive change they had previously overlooked. Or they may have worked with their child more intently as a result of their participation in the trial.

“People may start doing more things or doing them more intensively or purposefully, consciously or subconsciously, to try to help their child improve the skills or behaviors targeted by the active therapy in the study,” Dr. Sikich said. “These are things that might really help the child move forward which are completely separate from the medication being studied.”

The safety analysis offered more hopeful results. Only one serious adverse event from the treatment was reported: A 17-year-old participant taking a daily dose of 48 IU experienced a sedating effect while driving and had an accident.
 

Too soon to walk away?

Perhaps the most important take-away from the study is that even if it’s safe, intranasal oxytocin as it is currently used doesn’t work and clinicians shouldn’t prescribe it, said Daniel Geschwind, MD, PhD, director of the University of California, Los Angeles (UCLA) Center for Autism Research, who penned a commentary on the study and discussed the findings with this news organization.

“This study shows that using oxytocin the way it’s used in the community right now is not helping anybody, so why put a child through that?” added Dr. Geschwind, who also is a professor of genetics, neurology, and psychiatry at UCLA.

The trial highlights areas that need to be addressed in order to improve research in the field, he said. Establishing a consensus process to measure social functioning and figuring out a better way to access intranasal oxytocin would lead to studies that are more conclusive, comparable, and less expensive. Dr. Sikich agrees.

Despite the findings, Dr. Geschwind and other autism researchers say it’s too soon to walk away from oxytocin altogether, although it may be time to change the approach to autism research.

“We have to take a page from the playbook of modern medicine in other areas and begin to recognize that these syndromes are incredibly heterogeneous,” Dr. Geschwind says. “We can surmise, although we don’t know, that there might be different biological forms of autism that have different pathways involved that are going to respond differently to different medications.”

Calling the researchers’ efforts “heroic,” Karen Parker, PhD, an associate professor and associate chair of psychiatry and behavioral sciences at Stanford (Calif.) University, says efficacy trials such as this one are critical. However, Dr. Parker said in an interview, there are a number of questions that the study didn’t address.

The majority of medication dispensed in a standard intranasal device is sprayed into the back of the throat. Regular blood tests confirmed that oxytocin was getting into participants’ system, but, given how quickly oxytocin degrades in the blood, Dr. Parker said it’s hard to know just how much reached the brain.

It’s also unclear whether the results would have been different had the treatment been paired with behavioral therapy, an approach Dr. Parker suggests might benefit a subset of children with ASD.

A 2017 study from Dr. Parker’s lab found that children with ASD whose use of oxytocin at baseline was low derived greater benefit from synthetic oxytocin, something the new study failed to find. Still, Dr. Parker said, it’s possible oxytocin might increase social motivation and increase a child’s receptiveness to behavioral therapy.

“When you see a negative trial like this, it decreases enthusiasm for the therapy for autism in this context,” Dr. Parker said. “I hope people who are studying these syndromes will continue to explore oxytocin as a therapy.”

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Autism Centers of Excellence Program and the Department of Psychiatry and Behavioral Sciences at Duke University. Full disclosures of the authors’ possible conflicts of interest are available online.

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

When parents of children with autism spectrum disorder (ASD) participating in the largest clinical trial of intranasal oxytocin to date came in for follow-up visits with investigators, they reported marked improvement in the children’s social functioning.

Kids who rarely communicated with their families began to interact more. Those who usually preferred to isolate themselves started joining their parents for meals. It all seemed so promising – until the data came in.

“Those sounded like real improvements to me, and it seemed like they increased over the period of the study,” lead investigator Linmarie Sikich, MD, an associate clinical professor of psychiatry with Duke University School of Medicine and the Duke Center for Autism and Brain Development, Durham, N.C., told this news organization. “Turns out it wasn’t oxytocin that was making that difference.”

Researchers found that after 24 weeks of daily treatment with intranasal oxytocin, there were no significant differences in social functioning between children who received active treatment and those in the placebo group.

The much-anticipated results were published online in The New England Journal of Medicine. To say that they are disappointing, Dr. Sikich said, is an understatement.
 

Increase in off-label use

Most studies in mouse models of ASD and small trials in children produced conflicting results, although there were modest improvements in social functioning associated with the use of intranasal oxytocin. Some clinicians were already prescribing it off label.

On the basis of this research and early feedback from parents of children, Dr. Sikich and colleagues were hopeful.

However, results from a rigorous, 5-year, $11.4 million randomized trial were negative. Yet, parents were convinced their child improved during the study, and there was a significant increase in off-label prescribing of a treatment her research says doesn’t work. What’s next for oxytocin?

Known as the “love hormone,” oxytocin is a neurotransmitter that is primarily synthesized in the hypothalamus. It plays a role in childbirth and lactation and is also involved in the regulation of social functioning and emotions. Research suggests low oxytocin levels are associated with diminished social functioning, regardless of ASD status.

Its potential as an autism therapy for children has been under study for a decade. Some findings link its use to improvements in core deficits associated with ASD, including repetitive behaviors, fixated or restricted interest, and social communication. A study published in 2020 showed that the treatment improved symptoms in high-functioning adults with ASD.

These were mostly small studies and were underpowered to reliably detect an effect of the therapy on social functioning. They often involved only a single dose of oxytocin. Some studies showed improvements, but others did not.

Still, interest in the treatment grew. Physicians began prescribing it for children with ASD, and parents began buying products containing oxytocin on the internet. Researchers feared this off-label use was becoming widespread, despite inconclusive evidence of efficacy.
 

High hopes

With support from a National Institutes of Health grant, Dr. Sikich and her team designed a phase 2, multicenter, randomized, double-blind, placebo-controlled study to determine whether the use of oxytocin in children with ASD works and is safe.

The challenges began before they even enrolled a single child. A number of behavioral assessment tools are used to measure social function in ASD, but there is no consensus on which one is best.

A simple blood test could determine how much oxytocin from the nasal spray was absorbed in the blood, but identifying how much made it to the brain would require fMRI, which is expensive and is challenging to use in this study population. Then there was the acquisition of the drug itself.

The Food and Drug Administration has approved intravenous oxytocin for inducing labor. Intranasal oxytocin is not approved for any indication and isn’t available commercially in the United States. Patients or researchers must secure the drug from a manufacturer in a country where it is approved or order it from a U.S. pharmacy that is capable of compounding IV oxytocin into an intranasal formulation.

The pharmacy in Switzerland Dr. Sikich planned to use couldn’t make enough for the study. Contracting with a compounding pharmacy in the United States was significantly more expensive and time consuming, but it was the researchers’ only option.

“If it hadn’t been something we expected to have a major benefit, I think we would have given up the project at multiple points along the line due to all of these challenges,” said Dr. Sikich.

In August 2014, with all the pieces finally in place, researchers began enrolling children aged 3-17 years. The final cohort included 290 participants with ASD, 146 in the oxytocin group and 144 in the placebo group. Of these, 48% had minimal verbal fluency, and 52% had fluent verbal speech.

Participants received daily synthetic oxytocin or placebo via a nasal spray for 24 weeks. The daily oxytocin dose was 48 IU for the first 7 weeks. After that, the dosage could be titrated to a maximum of 80 IU/d. The mean maximal total daily dose of oxytocin throughout the study was 67.6 ± 16.9 IU.
 

‘It just didn’t work’

Both study groups showed improvement in social withdrawal beginning at 4 weeks and continuing throughout the trial, as determined on the basis of caretakers’ responses on the Aberrant Behavior Checklist Modified Social Withdrawal Subscale, the study’s primary outcome measure.

Sociability and social motivation also improved in both groups, as measured by the Pervasive Developmental Disorders Behavior Inventory and the Social Responsiveness Scale.

But by the end of the trial, the difference between the groups in improvement of social function wasn’t significant (difference, -0.2 points; P = .61) after adjusting for age, verbal fluency, and baseline oxytocin level.

“We were so convinced that it would work,” Dr. Sikich said, “but it just didn’t.”

From observation, parents were also convinced the therapy was working. At the trial’s conclusion, fewer than half of caregivers correctly guessed whether their child was in the treatment group or the placebo group.

A lot of development changes can happen in a child over 6 months. It’s possible the improvements would have occurred regardless of the trial, Dr. Sikich said. Parents’ perceptions could also be a placebo effect. Their child was in a clinical trial of a drug they believed could improve social functioning, so in their mind, it did.

Caregivers received training in how to identify certain behavioral changes, which may have helped them spot an existing positive change they had previously overlooked. Or they may have worked with their child more intently as a result of their participation in the trial.

“People may start doing more things or doing them more intensively or purposefully, consciously or subconsciously, to try to help their child improve the skills or behaviors targeted by the active therapy in the study,” Dr. Sikich said. “These are things that might really help the child move forward which are completely separate from the medication being studied.”

The safety analysis offered more hopeful results. Only one serious adverse event from the treatment was reported: A 17-year-old participant taking a daily dose of 48 IU experienced a sedating effect while driving and had an accident.
 

Too soon to walk away?

Perhaps the most important take-away from the study is that even if it’s safe, intranasal oxytocin as it is currently used doesn’t work and clinicians shouldn’t prescribe it, said Daniel Geschwind, MD, PhD, director of the University of California, Los Angeles (UCLA) Center for Autism Research, who penned a commentary on the study and discussed the findings with this news organization.

“This study shows that using oxytocin the way it’s used in the community right now is not helping anybody, so why put a child through that?” added Dr. Geschwind, who also is a professor of genetics, neurology, and psychiatry at UCLA.

The trial highlights areas that need to be addressed in order to improve research in the field, he said. Establishing a consensus process to measure social functioning and figuring out a better way to access intranasal oxytocin would lead to studies that are more conclusive, comparable, and less expensive. Dr. Sikich agrees.

Despite the findings, Dr. Geschwind and other autism researchers say it’s too soon to walk away from oxytocin altogether, although it may be time to change the approach to autism research.

“We have to take a page from the playbook of modern medicine in other areas and begin to recognize that these syndromes are incredibly heterogeneous,” Dr. Geschwind says. “We can surmise, although we don’t know, that there might be different biological forms of autism that have different pathways involved that are going to respond differently to different medications.”

Calling the researchers’ efforts “heroic,” Karen Parker, PhD, an associate professor and associate chair of psychiatry and behavioral sciences at Stanford (Calif.) University, says efficacy trials such as this one are critical. However, Dr. Parker said in an interview, there are a number of questions that the study didn’t address.

The majority of medication dispensed in a standard intranasal device is sprayed into the back of the throat. Regular blood tests confirmed that oxytocin was getting into participants’ system, but, given how quickly oxytocin degrades in the blood, Dr. Parker said it’s hard to know just how much reached the brain.

It’s also unclear whether the results would have been different had the treatment been paired with behavioral therapy, an approach Dr. Parker suggests might benefit a subset of children with ASD.

A 2017 study from Dr. Parker’s lab found that children with ASD whose use of oxytocin at baseline was low derived greater benefit from synthetic oxytocin, something the new study failed to find. Still, Dr. Parker said, it’s possible oxytocin might increase social motivation and increase a child’s receptiveness to behavioral therapy.

“When you see a negative trial like this, it decreases enthusiasm for the therapy for autism in this context,” Dr. Parker said. “I hope people who are studying these syndromes will continue to explore oxytocin as a therapy.”

The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Autism Centers of Excellence Program and the Department of Psychiatry and Behavioral Sciences at Duke University. Full disclosures of the authors’ possible conflicts of interest are available online.

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

The Centers for Disease Control and Prevention reported that an estimated 100,306 Americans died from drug overdoses during the period from April 2020 to April 2021, a 28.5% increase from the previous year.

Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.

The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.

The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.

“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.

“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.

Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”

Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”

Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support. 

Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.

In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.

“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
 

Fake pills, fentanyl a huge issue

Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.

“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.

Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.

The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.

“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.

National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.

Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”

Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.

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

The Centers for Disease Control and Prevention reported that an estimated 100,306 Americans died from drug overdoses during the period from April 2020 to April 2021, a 28.5% increase from the previous year.

Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.

The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.

The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.

“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.

“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.

Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”

Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”

Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support. 

Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.

In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.

“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
 

Fake pills, fentanyl a huge issue

Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.

“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.

Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.

The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.

“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.

National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.

Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”

Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.

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

The Centers for Disease Control and Prevention reported that an estimated 100,306 Americans died from drug overdoses during the period from April 2020 to April 2021, a 28.5% increase from the previous year.

Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.

The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.

The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.

“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.

“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.

Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”

Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”

Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support. 

Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.

In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.

“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
 

Fake pills, fentanyl a huge issue

Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.

“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.

Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.

The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.

“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.

National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.

Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”

Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.

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

A majority of healthy preschoolers were able to recognize emotions shown in static pictures of adults with and without face masks, based on data from a cross-sectional study of 276 children.

Some are concerned about the effects of adults working in preschools wearing face masks on the ability of young children to learn to recognize emotions, study author Juliane Schneider, MD, of University Hospital Lausanne (Switzerland), and colleagues wrote. Previous studies using photographs of faces with digitally added masks have suggested that young children’s emotional recognition was worse with masked faces.

In the study published in JAMA Pediatrics, the researchers tested the impact of masks on the ability of preschool children to identify joy, anger, and sadness. The study included 135 girls and 141 boys aged 36-72 months with a mean age of 52.4 months. The tests were conducted at nine daycare centers.

Children were shown photographs of 15 actors (5 men and 10 women) with and without surgical face masks. The total data set included 90 pictures illustrating joy, anger, and sadness. The children were shown the pictures at random, and they could either name the emotion, point to a card with emoticons showing the three emotions, or respond “I don’t know” or “quit the experiment.” Test sessions lasted approximately 7 minutes per child. Effect sizes were calculated using X² and Cramer V tests.

Overall, 68.8% of the children correctly identified the emotion portrayed; the correct response rate was 70.6% for faces without face masks and 66.9% for those with face masks. Correct recognition of joy was significantly higher for faces without masks than for those with masks (94.8% vs. 87.3), as was correct recognition of sadness (54.1% vs. 48.9%; P < .001 for both). Recognition of anger was not significantly different for unmasked and masked faces (62.2% vs. 64.6%, P = .10).

No significant differences in correct responses appeared between boys and girls and the rate of correct responses increased significantly with age. The rates of “I don’t know,” and “quit the experiment” responses were 3.1% and 2.2%, respectively. In an analysis of incorrect responses, approximately 25% of the children confused anger and sadness, and 21% misidentified joy for images of anger or sadness.

“Overall, participants in this study, who had been exposed to face masks for nearly a year, recognized emotions on pictures better than has been reported in previous research, even with face masks,” the researchers wrote.

The study findings were limited by several factors including the use of static pictures versus real individuals, which limits generalizability, and the lack of data on children with developmental issues, the researchers noted.

Despite relatively small differences and weak effect size (Cramer V scores of 0.2 or less for all), the results show a stronger recognition of emotion, compared with other studies, and highlight the importance of investigating the impact of face masks on other aspects of child development as the COVID-19 pandemic persists, the researchers concluded.

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

A majority of healthy preschoolers were able to recognize emotions shown in static pictures of adults with and without face masks, based on data from a cross-sectional study of 276 children.

Some are concerned about the effects of adults working in preschools wearing face masks on the ability of young children to learn to recognize emotions, study author Juliane Schneider, MD, of University Hospital Lausanne (Switzerland), and colleagues wrote. Previous studies using photographs of faces with digitally added masks have suggested that young children’s emotional recognition was worse with masked faces.

In the study published in JAMA Pediatrics, the researchers tested the impact of masks on the ability of preschool children to identify joy, anger, and sadness. The study included 135 girls and 141 boys aged 36-72 months with a mean age of 52.4 months. The tests were conducted at nine daycare centers.

Children were shown photographs of 15 actors (5 men and 10 women) with and without surgical face masks. The total data set included 90 pictures illustrating joy, anger, and sadness. The children were shown the pictures at random, and they could either name the emotion, point to a card with emoticons showing the three emotions, or respond “I don’t know” or “quit the experiment.” Test sessions lasted approximately 7 minutes per child. Effect sizes were calculated using X² and Cramer V tests.

Overall, 68.8% of the children correctly identified the emotion portrayed; the correct response rate was 70.6% for faces without face masks and 66.9% for those with face masks. Correct recognition of joy was significantly higher for faces without masks than for those with masks (94.8% vs. 87.3), as was correct recognition of sadness (54.1% vs. 48.9%; P < .001 for both). Recognition of anger was not significantly different for unmasked and masked faces (62.2% vs. 64.6%, P = .10).

No significant differences in correct responses appeared between boys and girls and the rate of correct responses increased significantly with age. The rates of “I don’t know,” and “quit the experiment” responses were 3.1% and 2.2%, respectively. In an analysis of incorrect responses, approximately 25% of the children confused anger and sadness, and 21% misidentified joy for images of anger or sadness.

“Overall, participants in this study, who had been exposed to face masks for nearly a year, recognized emotions on pictures better than has been reported in previous research, even with face masks,” the researchers wrote.

The study findings were limited by several factors including the use of static pictures versus real individuals, which limits generalizability, and the lack of data on children with developmental issues, the researchers noted.

Despite relatively small differences and weak effect size (Cramer V scores of 0.2 or less for all), the results show a stronger recognition of emotion, compared with other studies, and highlight the importance of investigating the impact of face masks on other aspects of child development as the COVID-19 pandemic persists, the researchers concluded.

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

A majority of healthy preschoolers were able to recognize emotions shown in static pictures of adults with and without face masks, based on data from a cross-sectional study of 276 children.

Some are concerned about the effects of adults working in preschools wearing face masks on the ability of young children to learn to recognize emotions, study author Juliane Schneider, MD, of University Hospital Lausanne (Switzerland), and colleagues wrote. Previous studies using photographs of faces with digitally added masks have suggested that young children’s emotional recognition was worse with masked faces.

In the study published in JAMA Pediatrics, the researchers tested the impact of masks on the ability of preschool children to identify joy, anger, and sadness. The study included 135 girls and 141 boys aged 36-72 months with a mean age of 52.4 months. The tests were conducted at nine daycare centers.

Children were shown photographs of 15 actors (5 men and 10 women) with and without surgical face masks. The total data set included 90 pictures illustrating joy, anger, and sadness. The children were shown the pictures at random, and they could either name the emotion, point to a card with emoticons showing the three emotions, or respond “I don’t know” or “quit the experiment.” Test sessions lasted approximately 7 minutes per child. Effect sizes were calculated using X² and Cramer V tests.

Overall, 68.8% of the children correctly identified the emotion portrayed; the correct response rate was 70.6% for faces without face masks and 66.9% for those with face masks. Correct recognition of joy was significantly higher for faces without masks than for those with masks (94.8% vs. 87.3), as was correct recognition of sadness (54.1% vs. 48.9%; P < .001 for both). Recognition of anger was not significantly different for unmasked and masked faces (62.2% vs. 64.6%, P = .10).

No significant differences in correct responses appeared between boys and girls and the rate of correct responses increased significantly with age. The rates of “I don’t know,” and “quit the experiment” responses were 3.1% and 2.2%, respectively. In an analysis of incorrect responses, approximately 25% of the children confused anger and sadness, and 21% misidentified joy for images of anger or sadness.

“Overall, participants in this study, who had been exposed to face masks for nearly a year, recognized emotions on pictures better than has been reported in previous research, even with face masks,” the researchers wrote.

The study findings were limited by several factors including the use of static pictures versus real individuals, which limits generalizability, and the lack of data on children with developmental issues, the researchers noted.

Despite relatively small differences and weak effect size (Cramer V scores of 0.2 or less for all), the results show a stronger recognition of emotion, compared with other studies, and highlight the importance of investigating the impact of face masks on other aspects of child development as the COVID-19 pandemic persists, the researchers concluded.

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

When the COVID-19 pandemic engulfed the nation well over a year ago, Rebecca Hendrickson, MD, PhD, immersed herself in the shell-shocking revelations that clinicians began posting on social media. The accounts offered just a snapshot of the pandemic’s heavy psychological toll, and Dr. Hendrickson, a psychiatrist at the University of Washington in Seattle and an expert in posttraumatic stress disorder (PTSD), wanted to know more.

xavierarnau/Getty Images

She and her colleagues devised a survey to assess the impact of several pandemic-related factors, including increased work hours, social distancing restrictions, and lack of adequate personal protective equipment.

What began as a survey of health care workers soon expanded in scope. Of the more than 600 survey respondents to date, health care workers account for about 60%, while the rest are first responders – police officers, firefighters, paramedics, and emergency medical technicians – and nonclinical personnel, such as security guards and office staff, in health care settings. The respondents range in age from 19 to 72, and hail from all regions of the country.

“Our findings were really striking,” Dr. Hendrickson said, “including very high rates of thoughts of suicide and thoughts of leaving one’s current field, which were both strongly linked to COVID-19–related occupational stress exposure.”

The distress stemmed from a multitude of factors. Among the most demoralizing: witnessing patients die in isolation and being stretched thin to provide optimal care for all patients amid an unrelenting onslaught of COVID-19 cases, she said. For some health care workers, living in the garage or basement – to avoid infecting family members with the virus – also wore on their psyches.

Of all health care workers in the study, more than three-quarters reported symptoms that fell within the clinical range for depression (76%) and anxiety (78%). More than 25% noted that they had lost a family member or close colleague to the virus.

Dr. Hendrickson, who works with military veterans at the VA Puget Sound Hospital System’s Mental Illness Research, Education, and Clinical Center and its PTSD outpatient clinic, hadn’t expected the experience of loss to be so pervasive. She said the sheer number of people who “crossed the threshold” into despair concerned her deeply.
 

Signs and symptoms of PTSD

PTSD’s prevalence among health care workers has always been variable, said Jessica Gold, MD, assistant professor and director of wellness, engagement, and outreach in the department of psychiatry at Washington University in St. Louis.

As a psychiatrist who sees health care workers in her clinical practice, Dr. Gold has noted poor baseline mental health, including depression and trauma. Significant data have pointed to a relatively higher suicide rate among physicians than among the general population. These problems have been compounded by COVID-19.

“It has been an unrelenting series of new stressors,” she said, citing lack of resources; a feeling of being unable to help; and the high frequency of risk of death to patients, family and friends, and the caregivers themselves as just as few examples. “It is very likely going to increase our baseline trauma, and honestly, I don’t know that we can predict how. To me, trauma has no real timeline and can show up months or even years after the pandemic.”

PTSD can manifest itself in health care workers in several different ways. A few commonalities Dr. Gold has observed are sleep disruption (including insomnia and nightmares), work avoidance by taking disability or quitting, irritability or other changes in mood, trouble concentrating, and hypervigilance.

She said she has seen physical manifestations of trauma – such as body pain, stomachaches, and teeth grinding, which “you might not realize are at all related to trauma but ultimately are.” Sometimes, she added, “people have panic attacks on the way to work or right when they get to work, or are thinking about work.”

Dr. Gold noted that different types of treatment, such as cognitive-behavioral therapy and eye movement desensitization and reprocessing (EMDR), can be effective for PTSD. Medication is often necessary because of comorbid anxiety, depression, or eating disorders, said Dr. Gold, who is conducting a study on the pandemic’s effects on medical students.
 

The difficulties in isolating COVID-19 as a contributor

Not all researchers are convinced that a causal relationship has been established between the pandemic and worsening mental health among those in the health care sector.

With provider burnout being a long-standing concern in medicine, Ankur A. Butala, MD, assistant professor of neurology, psychiatry, and behavioral sciences at the Johns Hopkins University, Baltimore, said he remains a bit skeptical that acute stressors during the pandemic amounted to a uniquely potent driving force that can be extrapolated and quantified in a study.

“It’s hard to interpret a chronic, rolling, ongoing trauma like COVID-19 against tools or scales developed to investigate symptoms from a singular and acute trauma, like a school shooting or a [military] firefight,” Dr. Butala said.

In addition, he noted a reluctance to generalizing results from a study in which participants were recruited via social media as opposed to research methods involving more rigorous selection protocols.

Although Dr. Hendrickson acknowledged the study’s limitations, she said her team nonetheless found strong correlations between COVID-19-related stressors and self-reported struggles in completing work-related tasks, as well as increasing thoughts of leaving one’s current field. They adjusted for previous lifetime trauma exposure, age, gender, and a personal history of contracting COVID-19.

The underlying premise of the study could be confirmed with repeated surveys over time, Dr. Butala said, as the COVID-19 pandemic evolves and the vaccination effort unfolds.

Follow-up surveys are being sent to participants every 2 weeks and every 3 months to gauge their mood, for a total follow-up period of 9 months per individual. New participants are still welcome. “We will continue to enroll as long as it seems relevant,” Dr. Hendrickson said.

Carol S. North, MD, MPE, who has added to the growing research on the pandemic’s toll on mental health, noted that because symptom scales do not provide psychiatric diagnoses, it is difficult to attribute the prevalence of psychiatric disorders to the pandemic. Dr. North is chair and professor of crisis psychiatry at UT Southwestern Medical Center in Dallas, and director of the program in trauma and disaster at VA North Texas Health Care System.

The DSM-5 criteria exclude naturally occurring illness, such as a virus (even during a pandemic) as a qualifying trauma for the diagnosis of PTSD. According to current criteria by the American Psychiatric Association, COVID-19 and the pandemic are not defined as trauma, Dr. North said, while noting that “just because it’s not trauma or PTSD does not mean that the pandemic should be discounted as not stressful; people are finding it very stressful.”

Identifying the exact source of distress would still be difficult, Dr. North said, as the pandemic has produced severe economic consequences and prolonged social isolation, as well as occurring alongside nationwide protests over racial and ethnic divisions. Studies to date haven’t effectively separated out for these stressors, making it impossible to weigh their relative impact.

Furthermore, “most of us face many other stressors in our daily lives, such as grief, losses, broken relationships, and personal failures,” she said. “All of these may contribute to psychological distress, and research is needed to determine how much was a product of the virus, other aspects of the pandemic, or unrelated life stressors.”
 

A rallying cry for new interventions

Despite such doubts, a growing number of studies are reporting that health care workers and first responders are experiencing intensified PTSD, depression, anxiety, and insomnia as a result of the pandemic, said Hrayr Pierre Attarian, MD, professor of neurology at Northwestern University, Chicago. These results should act as a rallying cry for implementing more policies tailored to prevent burnout, he said.

“What we are seeing during this terrible pandemic is burnout on steroids,” said Dr. Attarian, medical director of Northwestern’s Center for Sleep Disorders. There are already high burnout rates, “so this should be doubly important.”

Rooting out this problem starts at the institutional level, but merely advising providers to “be well” wouldn’t make inroads. “There needs to be fluid dialogue between health care workers and the leadership,” he said.

Among his proposed remedies: Access to confidential and free mental health resources, increased administrative support, flexible hours, respect for work-life balance, and forgiveness for occasional errors that don’t result in harm.

“Sometimes even the perception that a mistake has been made is taken as proof of guilt,” Dr. Attarian said. “It is not conducive to wellness. Extra income does not replace a nurturing work environment.”

Furthermore, “as a profession, we must stop glorifying ‘overwork.’ We must stop wearing ‘lack of sleep’ as badge of honor,” he said. “Sleep is a biological imperative like self-preservation, hunger, and thirst. When we don’t sleep anxiety, pain, and depression get amplified. Our perception of distress is off, as is our judgment.”

The Federation of State Physician Health Programs provides a directory that physicians can use for referrals to confidential consultation or treatment.

Christopher Bundy, MD, MPH, executive medical director of Washington Physicians Health Program in Seattle, has been following Dr. Hendrickson’s longitudinal study with keen interest. As president of the Federation of State Physician Health Programs, he hopes to translate the findings into practice.

“Obviously, the COVID-19 pandemic has been a ‘black swan’ in terms of workforce sustainability issues,” Dr. Bundy said, citing “high rates of burnout, disillusionment, and dissatisfaction.” He sees some similarities with his former role in treating war veterans.

“The invisible wounds of combat, the psychological scars don’t really become apparent until after you’re out of the war zone,” said Dr. Bundy, clinical associate professor of psychiatry at the University of Washington.

Likewise, he expects the “emotional chickens will come home to roost as the pandemic subsides.” Until then, “people are just focused on survival, and in doing their jobs and protecting their patients.” Eventually, “their own wounds inside the pandemic will take hold.”
 

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

When the COVID-19 pandemic engulfed the nation well over a year ago, Rebecca Hendrickson, MD, PhD, immersed herself in the shell-shocking revelations that clinicians began posting on social media. The accounts offered just a snapshot of the pandemic’s heavy psychological toll, and Dr. Hendrickson, a psychiatrist at the University of Washington in Seattle and an expert in posttraumatic stress disorder (PTSD), wanted to know more.

xavierarnau/Getty Images

She and her colleagues devised a survey to assess the impact of several pandemic-related factors, including increased work hours, social distancing restrictions, and lack of adequate personal protective equipment.

What began as a survey of health care workers soon expanded in scope. Of the more than 600 survey respondents to date, health care workers account for about 60%, while the rest are first responders – police officers, firefighters, paramedics, and emergency medical technicians – and nonclinical personnel, such as security guards and office staff, in health care settings. The respondents range in age from 19 to 72, and hail from all regions of the country.

“Our findings were really striking,” Dr. Hendrickson said, “including very high rates of thoughts of suicide and thoughts of leaving one’s current field, which were both strongly linked to COVID-19–related occupational stress exposure.”

The distress stemmed from a multitude of factors. Among the most demoralizing: witnessing patients die in isolation and being stretched thin to provide optimal care for all patients amid an unrelenting onslaught of COVID-19 cases, she said. For some health care workers, living in the garage or basement – to avoid infecting family members with the virus – also wore on their psyches.

Of all health care workers in the study, more than three-quarters reported symptoms that fell within the clinical range for depression (76%) and anxiety (78%). More than 25% noted that they had lost a family member or close colleague to the virus.

Dr. Hendrickson, who works with military veterans at the VA Puget Sound Hospital System’s Mental Illness Research, Education, and Clinical Center and its PTSD outpatient clinic, hadn’t expected the experience of loss to be so pervasive. She said the sheer number of people who “crossed the threshold” into despair concerned her deeply.
 

Signs and symptoms of PTSD

PTSD’s prevalence among health care workers has always been variable, said Jessica Gold, MD, assistant professor and director of wellness, engagement, and outreach in the department of psychiatry at Washington University in St. Louis.

As a psychiatrist who sees health care workers in her clinical practice, Dr. Gold has noted poor baseline mental health, including depression and trauma. Significant data have pointed to a relatively higher suicide rate among physicians than among the general population. These problems have been compounded by COVID-19.

“It has been an unrelenting series of new stressors,” she said, citing lack of resources; a feeling of being unable to help; and the high frequency of risk of death to patients, family and friends, and the caregivers themselves as just as few examples. “It is very likely going to increase our baseline trauma, and honestly, I don’t know that we can predict how. To me, trauma has no real timeline and can show up months or even years after the pandemic.”

PTSD can manifest itself in health care workers in several different ways. A few commonalities Dr. Gold has observed are sleep disruption (including insomnia and nightmares), work avoidance by taking disability or quitting, irritability or other changes in mood, trouble concentrating, and hypervigilance.

She said she has seen physical manifestations of trauma – such as body pain, stomachaches, and teeth grinding, which “you might not realize are at all related to trauma but ultimately are.” Sometimes, she added, “people have panic attacks on the way to work or right when they get to work, or are thinking about work.”

Dr. Gold noted that different types of treatment, such as cognitive-behavioral therapy and eye movement desensitization and reprocessing (EMDR), can be effective for PTSD. Medication is often necessary because of comorbid anxiety, depression, or eating disorders, said Dr. Gold, who is conducting a study on the pandemic’s effects on medical students.
 

The difficulties in isolating COVID-19 as a contributor

Not all researchers are convinced that a causal relationship has been established between the pandemic and worsening mental health among those in the health care sector.

With provider burnout being a long-standing concern in medicine, Ankur A. Butala, MD, assistant professor of neurology, psychiatry, and behavioral sciences at the Johns Hopkins University, Baltimore, said he remains a bit skeptical that acute stressors during the pandemic amounted to a uniquely potent driving force that can be extrapolated and quantified in a study.

“It’s hard to interpret a chronic, rolling, ongoing trauma like COVID-19 against tools or scales developed to investigate symptoms from a singular and acute trauma, like a school shooting or a [military] firefight,” Dr. Butala said.

In addition, he noted a reluctance to generalizing results from a study in which participants were recruited via social media as opposed to research methods involving more rigorous selection protocols.

Although Dr. Hendrickson acknowledged the study’s limitations, she said her team nonetheless found strong correlations between COVID-19-related stressors and self-reported struggles in completing work-related tasks, as well as increasing thoughts of leaving one’s current field. They adjusted for previous lifetime trauma exposure, age, gender, and a personal history of contracting COVID-19.

The underlying premise of the study could be confirmed with repeated surveys over time, Dr. Butala said, as the COVID-19 pandemic evolves and the vaccination effort unfolds.

Follow-up surveys are being sent to participants every 2 weeks and every 3 months to gauge their mood, for a total follow-up period of 9 months per individual. New participants are still welcome. “We will continue to enroll as long as it seems relevant,” Dr. Hendrickson said.

Carol S. North, MD, MPE, who has added to the growing research on the pandemic’s toll on mental health, noted that because symptom scales do not provide psychiatric diagnoses, it is difficult to attribute the prevalence of psychiatric disorders to the pandemic. Dr. North is chair and professor of crisis psychiatry at UT Southwestern Medical Center in Dallas, and director of the program in trauma and disaster at VA North Texas Health Care System.

The DSM-5 criteria exclude naturally occurring illness, such as a virus (even during a pandemic) as a qualifying trauma for the diagnosis of PTSD. According to current criteria by the American Psychiatric Association, COVID-19 and the pandemic are not defined as trauma, Dr. North said, while noting that “just because it’s not trauma or PTSD does not mean that the pandemic should be discounted as not stressful; people are finding it very stressful.”

Identifying the exact source of distress would still be difficult, Dr. North said, as the pandemic has produced severe economic consequences and prolonged social isolation, as well as occurring alongside nationwide protests over racial and ethnic divisions. Studies to date haven’t effectively separated out for these stressors, making it impossible to weigh their relative impact.

Furthermore, “most of us face many other stressors in our daily lives, such as grief, losses, broken relationships, and personal failures,” she said. “All of these may contribute to psychological distress, and research is needed to determine how much was a product of the virus, other aspects of the pandemic, or unrelated life stressors.”
 

A rallying cry for new interventions

Despite such doubts, a growing number of studies are reporting that health care workers and first responders are experiencing intensified PTSD, depression, anxiety, and insomnia as a result of the pandemic, said Hrayr Pierre Attarian, MD, professor of neurology at Northwestern University, Chicago. These results should act as a rallying cry for implementing more policies tailored to prevent burnout, he said.

“What we are seeing during this terrible pandemic is burnout on steroids,” said Dr. Attarian, medical director of Northwestern’s Center for Sleep Disorders. There are already high burnout rates, “so this should be doubly important.”

Rooting out this problem starts at the institutional level, but merely advising providers to “be well” wouldn’t make inroads. “There needs to be fluid dialogue between health care workers and the leadership,” he said.

Among his proposed remedies: Access to confidential and free mental health resources, increased administrative support, flexible hours, respect for work-life balance, and forgiveness for occasional errors that don’t result in harm.

“Sometimes even the perception that a mistake has been made is taken as proof of guilt,” Dr. Attarian said. “It is not conducive to wellness. Extra income does not replace a nurturing work environment.”

Furthermore, “as a profession, we must stop glorifying ‘overwork.’ We must stop wearing ‘lack of sleep’ as badge of honor,” he said. “Sleep is a biological imperative like self-preservation, hunger, and thirst. When we don’t sleep anxiety, pain, and depression get amplified. Our perception of distress is off, as is our judgment.”

The Federation of State Physician Health Programs provides a directory that physicians can use for referrals to confidential consultation or treatment.

Christopher Bundy, MD, MPH, executive medical director of Washington Physicians Health Program in Seattle, has been following Dr. Hendrickson’s longitudinal study with keen interest. As president of the Federation of State Physician Health Programs, he hopes to translate the findings into practice.

“Obviously, the COVID-19 pandemic has been a ‘black swan’ in terms of workforce sustainability issues,” Dr. Bundy said, citing “high rates of burnout, disillusionment, and dissatisfaction.” He sees some similarities with his former role in treating war veterans.

“The invisible wounds of combat, the psychological scars don’t really become apparent until after you’re out of the war zone,” said Dr. Bundy, clinical associate professor of psychiatry at the University of Washington.

Likewise, he expects the “emotional chickens will come home to roost as the pandemic subsides.” Until then, “people are just focused on survival, and in doing their jobs and protecting their patients.” Eventually, “their own wounds inside the pandemic will take hold.”
 

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

When the COVID-19 pandemic engulfed the nation well over a year ago, Rebecca Hendrickson, MD, PhD, immersed herself in the shell-shocking revelations that clinicians began posting on social media. The accounts offered just a snapshot of the pandemic’s heavy psychological toll, and Dr. Hendrickson, a psychiatrist at the University of Washington in Seattle and an expert in posttraumatic stress disorder (PTSD), wanted to know more.

xavierarnau/Getty Images

She and her colleagues devised a survey to assess the impact of several pandemic-related factors, including increased work hours, social distancing restrictions, and lack of adequate personal protective equipment.

What began as a survey of health care workers soon expanded in scope. Of the more than 600 survey respondents to date, health care workers account for about 60%, while the rest are first responders – police officers, firefighters, paramedics, and emergency medical technicians – and nonclinical personnel, such as security guards and office staff, in health care settings. The respondents range in age from 19 to 72, and hail from all regions of the country.

“Our findings were really striking,” Dr. Hendrickson said, “including very high rates of thoughts of suicide and thoughts of leaving one’s current field, which were both strongly linked to COVID-19–related occupational stress exposure.”

The distress stemmed from a multitude of factors. Among the most demoralizing: witnessing patients die in isolation and being stretched thin to provide optimal care for all patients amid an unrelenting onslaught of COVID-19 cases, she said. For some health care workers, living in the garage or basement – to avoid infecting family members with the virus – also wore on their psyches.

Of all health care workers in the study, more than three-quarters reported symptoms that fell within the clinical range for depression (76%) and anxiety (78%). More than 25% noted that they had lost a family member or close colleague to the virus.

Dr. Hendrickson, who works with military veterans at the VA Puget Sound Hospital System’s Mental Illness Research, Education, and Clinical Center and its PTSD outpatient clinic, hadn’t expected the experience of loss to be so pervasive. She said the sheer number of people who “crossed the threshold” into despair concerned her deeply.
 

Signs and symptoms of PTSD

PTSD’s prevalence among health care workers has always been variable, said Jessica Gold, MD, assistant professor and director of wellness, engagement, and outreach in the department of psychiatry at Washington University in St. Louis.

As a psychiatrist who sees health care workers in her clinical practice, Dr. Gold has noted poor baseline mental health, including depression and trauma. Significant data have pointed to a relatively higher suicide rate among physicians than among the general population. These problems have been compounded by COVID-19.

“It has been an unrelenting series of new stressors,” she said, citing lack of resources; a feeling of being unable to help; and the high frequency of risk of death to patients, family and friends, and the caregivers themselves as just as few examples. “It is very likely going to increase our baseline trauma, and honestly, I don’t know that we can predict how. To me, trauma has no real timeline and can show up months or even years after the pandemic.”

PTSD can manifest itself in health care workers in several different ways. A few commonalities Dr. Gold has observed are sleep disruption (including insomnia and nightmares), work avoidance by taking disability or quitting, irritability or other changes in mood, trouble concentrating, and hypervigilance.

She said she has seen physical manifestations of trauma – such as body pain, stomachaches, and teeth grinding, which “you might not realize are at all related to trauma but ultimately are.” Sometimes, she added, “people have panic attacks on the way to work or right when they get to work, or are thinking about work.”

Dr. Gold noted that different types of treatment, such as cognitive-behavioral therapy and eye movement desensitization and reprocessing (EMDR), can be effective for PTSD. Medication is often necessary because of comorbid anxiety, depression, or eating disorders, said Dr. Gold, who is conducting a study on the pandemic’s effects on medical students.
 

The difficulties in isolating COVID-19 as a contributor

Not all researchers are convinced that a causal relationship has been established between the pandemic and worsening mental health among those in the health care sector.

With provider burnout being a long-standing concern in medicine, Ankur A. Butala, MD, assistant professor of neurology, psychiatry, and behavioral sciences at the Johns Hopkins University, Baltimore, said he remains a bit skeptical that acute stressors during the pandemic amounted to a uniquely potent driving force that can be extrapolated and quantified in a study.

“It’s hard to interpret a chronic, rolling, ongoing trauma like COVID-19 against tools or scales developed to investigate symptoms from a singular and acute trauma, like a school shooting or a [military] firefight,” Dr. Butala said.

In addition, he noted a reluctance to generalizing results from a study in which participants were recruited via social media as opposed to research methods involving more rigorous selection protocols.

Although Dr. Hendrickson acknowledged the study’s limitations, she said her team nonetheless found strong correlations between COVID-19-related stressors and self-reported struggles in completing work-related tasks, as well as increasing thoughts of leaving one’s current field. They adjusted for previous lifetime trauma exposure, age, gender, and a personal history of contracting COVID-19.

The underlying premise of the study could be confirmed with repeated surveys over time, Dr. Butala said, as the COVID-19 pandemic evolves and the vaccination effort unfolds.

Follow-up surveys are being sent to participants every 2 weeks and every 3 months to gauge their mood, for a total follow-up period of 9 months per individual. New participants are still welcome. “We will continue to enroll as long as it seems relevant,” Dr. Hendrickson said.

Carol S. North, MD, MPE, who has added to the growing research on the pandemic’s toll on mental health, noted that because symptom scales do not provide psychiatric diagnoses, it is difficult to attribute the prevalence of psychiatric disorders to the pandemic. Dr. North is chair and professor of crisis psychiatry at UT Southwestern Medical Center in Dallas, and director of the program in trauma and disaster at VA North Texas Health Care System.

The DSM-5 criteria exclude naturally occurring illness, such as a virus (even during a pandemic) as a qualifying trauma for the diagnosis of PTSD. According to current criteria by the American Psychiatric Association, COVID-19 and the pandemic are not defined as trauma, Dr. North said, while noting that “just because it’s not trauma or PTSD does not mean that the pandemic should be discounted as not stressful; people are finding it very stressful.”

Identifying the exact source of distress would still be difficult, Dr. North said, as the pandemic has produced severe economic consequences and prolonged social isolation, as well as occurring alongside nationwide protests over racial and ethnic divisions. Studies to date haven’t effectively separated out for these stressors, making it impossible to weigh their relative impact.

Furthermore, “most of us face many other stressors in our daily lives, such as grief, losses, broken relationships, and personal failures,” she said. “All of these may contribute to psychological distress, and research is needed to determine how much was a product of the virus, other aspects of the pandemic, or unrelated life stressors.”
 

A rallying cry for new interventions

Despite such doubts, a growing number of studies are reporting that health care workers and first responders are experiencing intensified PTSD, depression, anxiety, and insomnia as a result of the pandemic, said Hrayr Pierre Attarian, MD, professor of neurology at Northwestern University, Chicago. These results should act as a rallying cry for implementing more policies tailored to prevent burnout, he said.

“What we are seeing during this terrible pandemic is burnout on steroids,” said Dr. Attarian, medical director of Northwestern’s Center for Sleep Disorders. There are already high burnout rates, “so this should be doubly important.”

Rooting out this problem starts at the institutional level, but merely advising providers to “be well” wouldn’t make inroads. “There needs to be fluid dialogue between health care workers and the leadership,” he said.

Among his proposed remedies: Access to confidential and free mental health resources, increased administrative support, flexible hours, respect for work-life balance, and forgiveness for occasional errors that don’t result in harm.

“Sometimes even the perception that a mistake has been made is taken as proof of guilt,” Dr. Attarian said. “It is not conducive to wellness. Extra income does not replace a nurturing work environment.”

Furthermore, “as a profession, we must stop glorifying ‘overwork.’ We must stop wearing ‘lack of sleep’ as badge of honor,” he said. “Sleep is a biological imperative like self-preservation, hunger, and thirst. When we don’t sleep anxiety, pain, and depression get amplified. Our perception of distress is off, as is our judgment.”

The Federation of State Physician Health Programs provides a directory that physicians can use for referrals to confidential consultation or treatment.

Christopher Bundy, MD, MPH, executive medical director of Washington Physicians Health Program in Seattle, has been following Dr. Hendrickson’s longitudinal study with keen interest. As president of the Federation of State Physician Health Programs, he hopes to translate the findings into practice.

“Obviously, the COVID-19 pandemic has been a ‘black swan’ in terms of workforce sustainability issues,” Dr. Bundy said, citing “high rates of burnout, disillusionment, and dissatisfaction.” He sees some similarities with his former role in treating war veterans.

“The invisible wounds of combat, the psychological scars don’t really become apparent until after you’re out of the war zone,” said Dr. Bundy, clinical associate professor of psychiatry at the University of Washington.

Likewise, he expects the “emotional chickens will come home to roost as the pandemic subsides.” Until then, “people are just focused on survival, and in doing their jobs and protecting their patients.” Eventually, “their own wounds inside the pandemic will take hold.”
 

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

A single infusion of ketamine rapidly improves distorted thinking and reasoning to reduce suicidal thoughts, independent of the drug’s effect on severe depression, new research shows.

“Previously it was shown that ketamine rapidly improved depression and that explained part of the rapid improvement in suicidal ideation,” senior author J. John Mann, MD, with Columbia University, New York, said in an interview.

“What was unclear was what else changed that could decrease suicidal ideation and the risk for suicidal behavior. This study identifies a second new domain of improvement – namely rapid improvement in several cognitive functions that can potentially reduce suicide risk,” said Dr. Mann.

The study was published online Nov. 2, 2021, in the Journal of Clinical Psychiatry.
 

Boosts cognitive function

A total of 78 adults with major depressive disorder and clinically significant suicidal ideation underwent neuropsychological testing before, and 1 day after, double-blind treatment with a single intravenous infusion of ketamine or midazolam.

“Ketamine produced rapid improvement in suicidal ideation and mood” compared with midazolam, the authors reported.

Ketamine was linked to specific improvement in reaction time and cognitive control/interference processing – a measure that has been associated with previous suicide attempt in depression.

A subgroup of patients whose suicidal ideation did not remit on midazolam were later treated with unblinded ketamine and retested. In these individuals, reaction time and cognitive control/interference processing also improved relative to preketamine assessments.

Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood, the researchers noted.

Nonetheless, they say ketamine had a “positive therapeutic effect” on neurocognition 1 day after treatment on at least one measure associated with suicidal behavior in the context of depression.

The results suggest “additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior,” they wrote.

“Ketamine modulates many neurotransmitter systems including glutamate transmission which is crucial for learning and memory. It increases the number of synapses or connections between neurons. These effects are fundamental to cognition and are logical explanations of the beneficial effects observed in this study,” Dr. Mann said in an interview.

“Our study helped us gain a better understanding of how ketamine works in the brain and how quickly it can improve distorted thinking. Being able to think more clearly can make someone feel less suicidal,” study investigator Ravi. N. Shah, MD, chief innovation officer, Columbia Psychiatry, said in a news release.
 

Important research with caveats

In a comment, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York, said the study is important and “adds to a growing understanding of how ketamine affects brain systems and thinking in the context of depression and suicide risk.”

“One reason this study is significant is that prior studies have shown that ketamine can have harmful effects on cognitive functioning in the context of ketamine misuse and exposures to high doses for long periods of time,” Dr. Murrough, who wasn’t involved in the study, said in an interview.

“In contrast in this study, a single low-dose treatment of ketamine can have the opposite effects, actually boosting some markers of cognitive functioning, at least in the short-term,” he noted.

Dr. Murrough said one caveat to the study is that it only examined the effect of ketamine on cognition once, 1 day after a single treatment.

“While this is an important initial observation, we don’t yet have any understanding of how persistent this effect on cognition is, or how this observed change may be related to any benefit ketamine may have on depression or suicide risk,” Dr. Murrough said.

“In fact, the researchers found that there was no association between change in cognitive functioning following ketamine and change in depression or suicidal thinking. The patients who showed improved cognitive function following ketamine did not differ in terms of mood or suicide risk compared to patients who did not show an improvement in cognition,” Dr. Murrough noted.

“This raises the important question of what is the relevance of change in cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research in order to improve outcomes for patients with depression and who are at risk for suicide,” he added.

Also weighing in, Roger S. McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit, University of Toronto, said the study is “very interesting and in keeping” with some previous work that he and his colleagues have done showing that ketamine “seems to benefit aspects of cognition which is a core element in depression.”

“It’s a testable hypothesis that the improvement in cognition now being reported and replicated could play some role in the improved quality of life and functioning with this treatment and as well reduce reducing suicide,” said Dr. McIntyre.

This study was supported by the National Institute of Mental Health. Dr. Mann receives royalties for commercial use of the Columbia-Suicide Severity Rating Scale, which was not used in this study. Dr. Murrough’s institution was involved in research involving esketamine (Spravato) for treatment-resistant depression and receives financial remuneration from the manufacturer of esketamine. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.

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

A single infusion of ketamine rapidly improves distorted thinking and reasoning to reduce suicidal thoughts, independent of the drug’s effect on severe depression, new research shows.

“Previously it was shown that ketamine rapidly improved depression and that explained part of the rapid improvement in suicidal ideation,” senior author J. John Mann, MD, with Columbia University, New York, said in an interview.

“What was unclear was what else changed that could decrease suicidal ideation and the risk for suicidal behavior. This study identifies a second new domain of improvement – namely rapid improvement in several cognitive functions that can potentially reduce suicide risk,” said Dr. Mann.

The study was published online Nov. 2, 2021, in the Journal of Clinical Psychiatry.
 

Boosts cognitive function

A total of 78 adults with major depressive disorder and clinically significant suicidal ideation underwent neuropsychological testing before, and 1 day after, double-blind treatment with a single intravenous infusion of ketamine or midazolam.

“Ketamine produced rapid improvement in suicidal ideation and mood” compared with midazolam, the authors reported.

Ketamine was linked to specific improvement in reaction time and cognitive control/interference processing – a measure that has been associated with previous suicide attempt in depression.

A subgroup of patients whose suicidal ideation did not remit on midazolam were later treated with unblinded ketamine and retested. In these individuals, reaction time and cognitive control/interference processing also improved relative to preketamine assessments.

Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood, the researchers noted.

Nonetheless, they say ketamine had a “positive therapeutic effect” on neurocognition 1 day after treatment on at least one measure associated with suicidal behavior in the context of depression.

The results suggest “additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior,” they wrote.

“Ketamine modulates many neurotransmitter systems including glutamate transmission which is crucial for learning and memory. It increases the number of synapses or connections between neurons. These effects are fundamental to cognition and are logical explanations of the beneficial effects observed in this study,” Dr. Mann said in an interview.

“Our study helped us gain a better understanding of how ketamine works in the brain and how quickly it can improve distorted thinking. Being able to think more clearly can make someone feel less suicidal,” study investigator Ravi. N. Shah, MD, chief innovation officer, Columbia Psychiatry, said in a news release.
 

Important research with caveats

In a comment, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York, said the study is important and “adds to a growing understanding of how ketamine affects brain systems and thinking in the context of depression and suicide risk.”

“One reason this study is significant is that prior studies have shown that ketamine can have harmful effects on cognitive functioning in the context of ketamine misuse and exposures to high doses for long periods of time,” Dr. Murrough, who wasn’t involved in the study, said in an interview.

“In contrast in this study, a single low-dose treatment of ketamine can have the opposite effects, actually boosting some markers of cognitive functioning, at least in the short-term,” he noted.

Dr. Murrough said one caveat to the study is that it only examined the effect of ketamine on cognition once, 1 day after a single treatment.

“While this is an important initial observation, we don’t yet have any understanding of how persistent this effect on cognition is, or how this observed change may be related to any benefit ketamine may have on depression or suicide risk,” Dr. Murrough said.

“In fact, the researchers found that there was no association between change in cognitive functioning following ketamine and change in depression or suicidal thinking. The patients who showed improved cognitive function following ketamine did not differ in terms of mood or suicide risk compared to patients who did not show an improvement in cognition,” Dr. Murrough noted.

“This raises the important question of what is the relevance of change in cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research in order to improve outcomes for patients with depression and who are at risk for suicide,” he added.

Also weighing in, Roger S. McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit, University of Toronto, said the study is “very interesting and in keeping” with some previous work that he and his colleagues have done showing that ketamine “seems to benefit aspects of cognition which is a core element in depression.”

“It’s a testable hypothesis that the improvement in cognition now being reported and replicated could play some role in the improved quality of life and functioning with this treatment and as well reduce reducing suicide,” said Dr. McIntyre.

This study was supported by the National Institute of Mental Health. Dr. Mann receives royalties for commercial use of the Columbia-Suicide Severity Rating Scale, which was not used in this study. Dr. Murrough’s institution was involved in research involving esketamine (Spravato) for treatment-resistant depression and receives financial remuneration from the manufacturer of esketamine. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.

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

A single infusion of ketamine rapidly improves distorted thinking and reasoning to reduce suicidal thoughts, independent of the drug’s effect on severe depression, new research shows.

“Previously it was shown that ketamine rapidly improved depression and that explained part of the rapid improvement in suicidal ideation,” senior author J. John Mann, MD, with Columbia University, New York, said in an interview.

“What was unclear was what else changed that could decrease suicidal ideation and the risk for suicidal behavior. This study identifies a second new domain of improvement – namely rapid improvement in several cognitive functions that can potentially reduce suicide risk,” said Dr. Mann.

The study was published online Nov. 2, 2021, in the Journal of Clinical Psychiatry.
 

Boosts cognitive function

A total of 78 adults with major depressive disorder and clinically significant suicidal ideation underwent neuropsychological testing before, and 1 day after, double-blind treatment with a single intravenous infusion of ketamine or midazolam.

“Ketamine produced rapid improvement in suicidal ideation and mood” compared with midazolam, the authors reported.

Ketamine was linked to specific improvement in reaction time and cognitive control/interference processing – a measure that has been associated with previous suicide attempt in depression.

A subgroup of patients whose suicidal ideation did not remit on midazolam were later treated with unblinded ketamine and retested. In these individuals, reaction time and cognitive control/interference processing also improved relative to preketamine assessments.

Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood, the researchers noted.

Nonetheless, they say ketamine had a “positive therapeutic effect” on neurocognition 1 day after treatment on at least one measure associated with suicidal behavior in the context of depression.

The results suggest “additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior,” they wrote.

“Ketamine modulates many neurotransmitter systems including glutamate transmission which is crucial for learning and memory. It increases the number of synapses or connections between neurons. These effects are fundamental to cognition and are logical explanations of the beneficial effects observed in this study,” Dr. Mann said in an interview.

“Our study helped us gain a better understanding of how ketamine works in the brain and how quickly it can improve distorted thinking. Being able to think more clearly can make someone feel less suicidal,” study investigator Ravi. N. Shah, MD, chief innovation officer, Columbia Psychiatry, said in a news release.
 

Important research with caveats

In a comment, James Murrough, MD, PhD, director of the Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York, said the study is important and “adds to a growing understanding of how ketamine affects brain systems and thinking in the context of depression and suicide risk.”

“One reason this study is significant is that prior studies have shown that ketamine can have harmful effects on cognitive functioning in the context of ketamine misuse and exposures to high doses for long periods of time,” Dr. Murrough, who wasn’t involved in the study, said in an interview.

“In contrast in this study, a single low-dose treatment of ketamine can have the opposite effects, actually boosting some markers of cognitive functioning, at least in the short-term,” he noted.

Dr. Murrough said one caveat to the study is that it only examined the effect of ketamine on cognition once, 1 day after a single treatment.

“While this is an important initial observation, we don’t yet have any understanding of how persistent this effect on cognition is, or how this observed change may be related to any benefit ketamine may have on depression or suicide risk,” Dr. Murrough said.

“In fact, the researchers found that there was no association between change in cognitive functioning following ketamine and change in depression or suicidal thinking. The patients who showed improved cognitive function following ketamine did not differ in terms of mood or suicide risk compared to patients who did not show an improvement in cognition,” Dr. Murrough noted.

“This raises the important question of what is the relevance of change in cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research in order to improve outcomes for patients with depression and who are at risk for suicide,” he added.

Also weighing in, Roger S. McIntyre, MD, professor of psychiatry and pharmacology and head of the mood disorders psychopharmacology unit, University of Toronto, said the study is “very interesting and in keeping” with some previous work that he and his colleagues have done showing that ketamine “seems to benefit aspects of cognition which is a core element in depression.”

“It’s a testable hypothesis that the improvement in cognition now being reported and replicated could play some role in the improved quality of life and functioning with this treatment and as well reduce reducing suicide,” said Dr. McIntyre.

This study was supported by the National Institute of Mental Health. Dr. Mann receives royalties for commercial use of the Columbia-Suicide Severity Rating Scale, which was not used in this study. Dr. Murrough’s institution was involved in research involving esketamine (Spravato) for treatment-resistant depression and receives financial remuneration from the manufacturer of esketamine. Dr. McIntyre has received research grant support from the Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is also CEO of AltMed.

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