The COVID-19 pandemic has had a negative impact on the mental health of people worldwide, and a disproportionate effect on peripartum women. In this article, we discuss the reasons for this disparity, review the limited literature on this topic, and suggest strategies to safeguard the mental health of peripartum women during the COVID-19 pandemic.

Catastrophic events and women’s mental health

During the peripartum period, women have increased psychosocial and physical health needs.¹ In addition, women are disproportionately affected by natural disasters and catastrophic events,² which are predictors of psychiatric symptoms during the peripartum period.³ Mass tragedies previously associated with maternal stress include wildfires, hurricanes, migrations, earthquakes, and tsunamis.^4,5 For example, pregnant women who survived severe exposure during Hurricane Katrina (ie, feeling that one’s life was in danger, experiencing illness or injury to self or a family member, walking through floodwaters) in 2005 had a significantly increased risk of developing posttraumatic stress disorder (PTSD) and depression compared with pregnant women who did not have such exposure.⁶ After the 2011 Tōhoku earthquake and tsunami in Japan, the prevalence of psychological distress in pregnant women increased, especially among those living in the area directly affected by the tsunami.⁵

Epidemics and pandemics also can adversely affect peripartum women’s mental health. Studies conducted before the COVID-19 pandemic found that previous infectious disease outbreaks such as severe acute respiratory syndrome (SARS), the 2009 influenza A (H1N1) pandemic, and Zika had negative emotional impacts on pregnant women.⁷ Our review of the limited literature published to date suggests that COVID-19 is having similar adverse effects.

COVID-19 poses both medical and psychiatric threats

COVID-19 infection is a physical threat to pregnant women who are already vulnerable due to the hormonal and immunological changes inherent to pregnancy. A meta-analysis of 39 studies with a total of 1,316 pregnant women indicated that the most frequently reported symptoms of COVID-19 infection were cough, fever, and myalgias.⁸ However, COVID-19 infection during pregnancy is also associated with an increase in pregnancy complications and adverse birth outcomes.⁹ According to the CDC, compared with their nonpregnant counterparts, pregnant women are at greater risk for severe COVID-19 infection and adverse birth outcomes such as preterm birth.¹⁰ Pregnant women who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; the virus responsible for COVID-19) risk ICU admission, caesarean section, and perinatal death.⁸ A Swedish study of 2,682 pregnant women found an increase in preeclampsia among women who tested positive for SARS-CoV-2, a finding attributed to COVID-19’s pattern of systemic effects.¹¹ Vertical transmission of the novel coronavirus from mother to fetus appears to be rare but possible.¹²

In addition to the physical dangers of becoming infected with COVID-19, the perceived threat of infection is an added source of anxiety for some peripartum women. In addition to the concerns involved in any pregnancy, COVID-19–related sources of distress for pregnant women include worrying about harm to the fetus during pregnancy, the possibility of vertical transmission, and exposures during antenatal appointments, during employment, or from a partner.^8,13

The death toll from factors associated with COVID-19 adds to the mental health burden. For every person who dies of COVID-19, an estimated 9 others may develop prolonged grief or PTSD due to the loss of someone they loved.^14,15 A systematic review found that PTSD in the perinatal period is associated with negative birth and child outcomes, including low birth weight and decreased rates of breastfeeding.¹⁶ The COVID-19 pandemic has disrupted human interactions, from social distancing rules and lockdowns of businesses and social activities to panic buying of grocery staples and increased economic insecurity.¹ These changes have been accompanied by a rise in mental health challenges. For example, according to an August 2020 CDC survey, 40.9% of US adults reported at least 1 adverse mental or behavioral health condition, including symptoms of anxiety or depression (30.9%), symptoms of a trauma- and stressor-related disorder related to the pandemic (26.3%), and having started or increased substance use to cope with stress or emotions related to COVID-19 (13.3%).¹⁷

COVID-19–related traumas and stressors appear to affect women more than men. A study from China found that compared with men, women had significantly higher levels of self-reported pandemic-related anxiety, depression, and posttraumatic stress symptoms (PTSS).¹⁸ This trend has been observed in other parts of the world. A study conducted by the UK Office of National Statistics reported anxiety levels were 24% higher in women vs men as reflected by scores on a self-rated anxiety scale.¹⁹

Continue to: Many factors influence...

Many factors influence the disproportionate impact of COVID-19 on women in general, and peripartum women in particular (Box^20-26).

Box

Psychiatric diagnoses in peripartum women

Multiple studies and meta-analyses have begun to assess the impact of the COVID-19 pandemic on maternal mental health. One meta-analysis of 8 studies conducted in 5 countries determined that COVID-19 significantly increases the risk of anxiety in women during the peripartum period.²⁷ Results of another meta-analysis of 23 studies with >24,000 participants indicated that the prevalence of anxiety, depression, and insomnia in peripartum women was significantly higher during the pandemic than in pre-pandemic times.²⁸

In an online survey of 4,451 pregnant women in the United States, nearly one-third of respondents reported elevated levels of pandemic-related stress as measured by the newly-developed Pandemic-Related Pregnancy Stress Scale.³ The rates were even higher among women who were already at risk for elevated stress levels, such as those who had survived abuse, those giving birth for the first time, or those experiencing high-risk pregnancies.³ Living in a pandemic “hot spot” also appeared to impact peripartum stress levels.

COVID-19 has adverse effects on women’s mental health specifically during the postpartum period. One study from a center in Italy found a high prevalence of depressive symptoms and PTSS in the postpartum period, with COVID-19–related factors playing an “indirect role” compared with prenatal experiences and other individual factors.² A British study of mothers of infants age ≤12 months found that traveling for work, the impact of lockdown on food affordability, and having an income of less than £30,000 per year (approximately $41,000) predicted poorer mental health during the pandemic.²⁹ Results of a study from China indicated that more than one-quarter of pregnant and postpartum women experienced depression during the pandemic, and women who worried about infection risk or missing pediatric visits were at increased risk.³⁰

How to mitigate these risks

The increase in pandemic-related mental health concerns in the general population and specifically in peripartum women is a global health care challenge. Investing in mitigation strategies is necessary not only to address the current pandemic, but also to help prepare for the possibility of future traumatic events, such as another global pandemic.

Continue to: For pregnant women...

For pregnant women, ensuring access to outdoor space, increasing participation in healthy activities, and minimizing disruptions to prenatal care can protect against pandemic-related stress.³ Physical activity is an effective treatment for mild to moderate depressive symptoms. Because of the significant decrease in exercise among pregnant women during the pandemic, encouraging safe forms of physical activity such as online fitness classes could improve mental health outcomes for these patients.²⁷ When counseling peripartum women, psychiatrists need to be creative in recommending fitness interventions to target mood symptoms, such as by suggesting virtual or at-home programs.

In an online survey, 118 obstetricians called for increased mental health resources for peripartum women, such as easier access to a helpline, educational videos, and mental health professionals.¹³ Increased screening for psychiatric disorders throughout the peripartum period can help identify women at greater risk, and advancements in telepsychiatry could help meet the increased need for psychiatric care during COVID-19. Psychiatrists and other mental health clinicians should consider reaching out to their colleagues who specialize in women’s health to establish new partnerships and create teams of multidisciplinary professionals.

Similarly, psychiatrists should familiarize themselves with telehealth services available to peripartum patients who could benefit from such services. Telehealth options can increase women’s access to peripartum care for both medical and psychiatric illnesses. Online options such as women’s support groups, parenting classes, and labor coaching seminars also represent valuable virtual tools to strengthen women’s social supports.

Women who need inpatient treatment for severe peripartum depression or anxiety might be particularly reluctant to receive this care during COVID-19 due to fears of becoming infected and of being separated from their infant and family while hospitalized. Clinicians should remain vigilant in screening peripartum women for mood disorders that might represent a danger to mothers and infants, and not allow concerns about COVID-19 to interfere with recommendations for psychiatric hospitalizations, when necessary. The creation of small, women-only inpatient behavioral units can help address this situation, especially given the possibility of frequent visits with infants and other peripartum support. Investment into such units is critical for supporting peripartum mental health, even in nonpandemic times.

What about vaccination? As of mid-May 2021, no large clinical trials of any COVID-19 vaccine that included pregnant women had been completed. However, 2 small preliminary studies suggested that the mRNA vaccines are safe and effective during pregnancy.^31,32 When counseling peripartum patients on the risks and benefits, clinicians need to rely on this evidence, animal trials, and limited data from inadvertent exposures during pregnancy. While every woman will weigh the risks and benefits for her own circumstances, the CDC, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine have all stated that the mRNA vaccines should be offered to pregnant and breastfeeding individuals who are eligible for vaccination.³³ Rasmussen et al³³ have published a useful resource for clinicians regarding COVID-19 vaccination and pregnant women.

Continue to: Bottom Line

During the COVID-19 pandemic, peripartum women have experienced increased rates of anxiety, depression, and stress. Psychiatric clinicians can help these patients by remaining vigilant in screening for psychiatric disorders, encouraging them to engage in activities to mitigate COVID-19’s adverse psychological effects, and referring them to care via telehealth and other resources as appropriate.

Related Resources

• Hu YJ, Wake M, Saffery R. Clarifying the sweeping consequences of COVID-19 in pregnant women, newborns, and children with existing cohorts. JAMA Pediatr. 2021; 75(2):117-118. doi: 10.1001/jamapediatrics.2020.2395
• Tomfohr-Madsen LM, Racine N, Giesbrecht GF, et al. Depression and anxiety in pregnancy during COVID-19: a rapid review and meta-analysis. Psychiatry Res. 2021; 300:113912. doi: 10.1016/j.psychres.2021.113912

The COVID-19 pandemic has had a negative impact on the mental health of people worldwide, and a disproportionate effect on peripartum women. In this article, we discuss the reasons for this disparity, review the limited literature on this topic, and suggest strategies to safeguard the mental health of peripartum women during the COVID-19 pandemic.

Catastrophic events and women’s mental health

During the peripartum period, women have increased psychosocial and physical health needs.¹ In addition, women are disproportionately affected by natural disasters and catastrophic events,² which are predictors of psychiatric symptoms during the peripartum period.³ Mass tragedies previously associated with maternal stress include wildfires, hurricanes, migrations, earthquakes, and tsunamis.^4,5 For example, pregnant women who survived severe exposure during Hurricane Katrina (ie, feeling that one’s life was in danger, experiencing illness or injury to self or a family member, walking through floodwaters) in 2005 had a significantly increased risk of developing posttraumatic stress disorder (PTSD) and depression compared with pregnant women who did not have such exposure.⁶ After the 2011 Tōhoku earthquake and tsunami in Japan, the prevalence of psychological distress in pregnant women increased, especially among those living in the area directly affected by the tsunami.⁵

Epidemics and pandemics also can adversely affect peripartum women’s mental health. Studies conducted before the COVID-19 pandemic found that previous infectious disease outbreaks such as severe acute respiratory syndrome (SARS), the 2009 influenza A (H1N1) pandemic, and Zika had negative emotional impacts on pregnant women.⁷ Our review of the limited literature published to date suggests that COVID-19 is having similar adverse effects.

COVID-19 poses both medical and psychiatric threats

COVID-19 infection is a physical threat to pregnant women who are already vulnerable due to the hormonal and immunological changes inherent to pregnancy. A meta-analysis of 39 studies with a total of 1,316 pregnant women indicated that the most frequently reported symptoms of COVID-19 infection were cough, fever, and myalgias.⁸ However, COVID-19 infection during pregnancy is also associated with an increase in pregnancy complications and adverse birth outcomes.⁹ According to the CDC, compared with their nonpregnant counterparts, pregnant women are at greater risk for severe COVID-19 infection and adverse birth outcomes such as preterm birth.¹⁰ Pregnant women who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; the virus responsible for COVID-19) risk ICU admission, caesarean section, and perinatal death.⁸ A Swedish study of 2,682 pregnant women found an increase in preeclampsia among women who tested positive for SARS-CoV-2, a finding attributed to COVID-19’s pattern of systemic effects.¹¹ Vertical transmission of the novel coronavirus from mother to fetus appears to be rare but possible.¹²

In addition to the physical dangers of becoming infected with COVID-19, the perceived threat of infection is an added source of anxiety for some peripartum women. In addition to the concerns involved in any pregnancy, COVID-19–related sources of distress for pregnant women include worrying about harm to the fetus during pregnancy, the possibility of vertical transmission, and exposures during antenatal appointments, during employment, or from a partner.^8,13

The death toll from factors associated with COVID-19 adds to the mental health burden. For every person who dies of COVID-19, an estimated 9 others may develop prolonged grief or PTSD due to the loss of someone they loved.^14,15 A systematic review found that PTSD in the perinatal period is associated with negative birth and child outcomes, including low birth weight and decreased rates of breastfeeding.¹⁶ The COVID-19 pandemic has disrupted human interactions, from social distancing rules and lockdowns of businesses and social activities to panic buying of grocery staples and increased economic insecurity.¹ These changes have been accompanied by a rise in mental health challenges. For example, according to an August 2020 CDC survey, 40.9% of US adults reported at least 1 adverse mental or behavioral health condition, including symptoms of anxiety or depression (30.9%), symptoms of a trauma- and stressor-related disorder related to the pandemic (26.3%), and having started or increased substance use to cope with stress or emotions related to COVID-19 (13.3%).¹⁷

COVID-19–related traumas and stressors appear to affect women more than men. A study from China found that compared with men, women had significantly higher levels of self-reported pandemic-related anxiety, depression, and posttraumatic stress symptoms (PTSS).¹⁸ This trend has been observed in other parts of the world. A study conducted by the UK Office of National Statistics reported anxiety levels were 24% higher in women vs men as reflected by scores on a self-rated anxiety scale.¹⁹

Continue to: Many factors influence...

Many factors influence the disproportionate impact of COVID-19 on women in general, and peripartum women in particular (Box^20-26).

Box

Psychiatric diagnoses in peripartum women

Multiple studies and meta-analyses have begun to assess the impact of the COVID-19 pandemic on maternal mental health. One meta-analysis of 8 studies conducted in 5 countries determined that COVID-19 significantly increases the risk of anxiety in women during the peripartum period.²⁷ Results of another meta-analysis of 23 studies with >24,000 participants indicated that the prevalence of anxiety, depression, and insomnia in peripartum women was significantly higher during the pandemic than in pre-pandemic times.²⁸

In an online survey of 4,451 pregnant women in the United States, nearly one-third of respondents reported elevated levels of pandemic-related stress as measured by the newly-developed Pandemic-Related Pregnancy Stress Scale.³ The rates were even higher among women who were already at risk for elevated stress levels, such as those who had survived abuse, those giving birth for the first time, or those experiencing high-risk pregnancies.³ Living in a pandemic “hot spot” also appeared to impact peripartum stress levels.

COVID-19 has adverse effects on women’s mental health specifically during the postpartum period. One study from a center in Italy found a high prevalence of depressive symptoms and PTSS in the postpartum period, with COVID-19–related factors playing an “indirect role” compared with prenatal experiences and other individual factors.² A British study of mothers of infants age ≤12 months found that traveling for work, the impact of lockdown on food affordability, and having an income of less than £30,000 per year (approximately $41,000) predicted poorer mental health during the pandemic.²⁹ Results of a study from China indicated that more than one-quarter of pregnant and postpartum women experienced depression during the pandemic, and women who worried about infection risk or missing pediatric visits were at increased risk.³⁰

How to mitigate these risks

The increase in pandemic-related mental health concerns in the general population and specifically in peripartum women is a global health care challenge. Investing in mitigation strategies is necessary not only to address the current pandemic, but also to help prepare for the possibility of future traumatic events, such as another global pandemic.

Continue to: For pregnant women...

For pregnant women, ensuring access to outdoor space, increasing participation in healthy activities, and minimizing disruptions to prenatal care can protect against pandemic-related stress.³ Physical activity is an effective treatment for mild to moderate depressive symptoms. Because of the significant decrease in exercise among pregnant women during the pandemic, encouraging safe forms of physical activity such as online fitness classes could improve mental health outcomes for these patients.²⁷ When counseling peripartum women, psychiatrists need to be creative in recommending fitness interventions to target mood symptoms, such as by suggesting virtual or at-home programs.

In an online survey, 118 obstetricians called for increased mental health resources for peripartum women, such as easier access to a helpline, educational videos, and mental health professionals.¹³ Increased screening for psychiatric disorders throughout the peripartum period can help identify women at greater risk, and advancements in telepsychiatry could help meet the increased need for psychiatric care during COVID-19. Psychiatrists and other mental health clinicians should consider reaching out to their colleagues who specialize in women’s health to establish new partnerships and create teams of multidisciplinary professionals.

Similarly, psychiatrists should familiarize themselves with telehealth services available to peripartum patients who could benefit from such services. Telehealth options can increase women’s access to peripartum care for both medical and psychiatric illnesses. Online options such as women’s support groups, parenting classes, and labor coaching seminars also represent valuable virtual tools to strengthen women’s social supports.

Women who need inpatient treatment for severe peripartum depression or anxiety might be particularly reluctant to receive this care during COVID-19 due to fears of becoming infected and of being separated from their infant and family while hospitalized. Clinicians should remain vigilant in screening peripartum women for mood disorders that might represent a danger to mothers and infants, and not allow concerns about COVID-19 to interfere with recommendations for psychiatric hospitalizations, when necessary. The creation of small, women-only inpatient behavioral units can help address this situation, especially given the possibility of frequent visits with infants and other peripartum support. Investment into such units is critical for supporting peripartum mental health, even in nonpandemic times.

What about vaccination? As of mid-May 2021, no large clinical trials of any COVID-19 vaccine that included pregnant women had been completed. However, 2 small preliminary studies suggested that the mRNA vaccines are safe and effective during pregnancy.^31,32 When counseling peripartum patients on the risks and benefits, clinicians need to rely on this evidence, animal trials, and limited data from inadvertent exposures during pregnancy. While every woman will weigh the risks and benefits for her own circumstances, the CDC, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine have all stated that the mRNA vaccines should be offered to pregnant and breastfeeding individuals who are eligible for vaccination.³³ Rasmussen et al³³ have published a useful resource for clinicians regarding COVID-19 vaccination and pregnant women.

Continue to: Bottom Line

During the COVID-19 pandemic, peripartum women have experienced increased rates of anxiety, depression, and stress. Psychiatric clinicians can help these patients by remaining vigilant in screening for psychiatric disorders, encouraging them to engage in activities to mitigate COVID-19’s adverse psychological effects, and referring them to care via telehealth and other resources as appropriate.

Related Resources

• Hu YJ, Wake M, Saffery R. Clarifying the sweeping consequences of COVID-19 in pregnant women, newborns, and children with existing cohorts. JAMA Pediatr. 2021; 75(2):117-118. doi: 10.1001/jamapediatrics.2020.2395
• Tomfohr-Madsen LM, Racine N, Giesbrecht GF, et al. Depression and anxiety in pregnancy during COVID-19: a rapid review and meta-analysis. Psychiatry Res. 2021; 300:113912. doi: 10.1016/j.psychres.2021.113912

The COVID-19 pandemic has had a negative impact on the mental health of people worldwide, and a disproportionate effect on peripartum women. In this article, we discuss the reasons for this disparity, review the limited literature on this topic, and suggest strategies to safeguard the mental health of peripartum women during the COVID-19 pandemic.

Catastrophic events and women’s mental health

During the peripartum period, women have increased psychosocial and physical health needs.¹ In addition, women are disproportionately affected by natural disasters and catastrophic events,² which are predictors of psychiatric symptoms during the peripartum period.³ Mass tragedies previously associated with maternal stress include wildfires, hurricanes, migrations, earthquakes, and tsunamis.^4,5 For example, pregnant women who survived severe exposure during Hurricane Katrina (ie, feeling that one’s life was in danger, experiencing illness or injury to self or a family member, walking through floodwaters) in 2005 had a significantly increased risk of developing posttraumatic stress disorder (PTSD) and depression compared with pregnant women who did not have such exposure.⁶ After the 2011 Tōhoku earthquake and tsunami in Japan, the prevalence of psychological distress in pregnant women increased, especially among those living in the area directly affected by the tsunami.⁵

Epidemics and pandemics also can adversely affect peripartum women’s mental health. Studies conducted before the COVID-19 pandemic found that previous infectious disease outbreaks such as severe acute respiratory syndrome (SARS), the 2009 influenza A (H1N1) pandemic, and Zika had negative emotional impacts on pregnant women.⁷ Our review of the limited literature published to date suggests that COVID-19 is having similar adverse effects.

COVID-19 poses both medical and psychiatric threats

COVID-19 infection is a physical threat to pregnant women who are already vulnerable due to the hormonal and immunological changes inherent to pregnancy. A meta-analysis of 39 studies with a total of 1,316 pregnant women indicated that the most frequently reported symptoms of COVID-19 infection were cough, fever, and myalgias.⁸ However, COVID-19 infection during pregnancy is also associated with an increase in pregnancy complications and adverse birth outcomes.⁹ According to the CDC, compared with their nonpregnant counterparts, pregnant women are at greater risk for severe COVID-19 infection and adverse birth outcomes such as preterm birth.¹⁰ Pregnant women who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; the virus responsible for COVID-19) risk ICU admission, caesarean section, and perinatal death.⁸ A Swedish study of 2,682 pregnant women found an increase in preeclampsia among women who tested positive for SARS-CoV-2, a finding attributed to COVID-19’s pattern of systemic effects.¹¹ Vertical transmission of the novel coronavirus from mother to fetus appears to be rare but possible.¹²

In addition to the physical dangers of becoming infected with COVID-19, the perceived threat of infection is an added source of anxiety for some peripartum women. In addition to the concerns involved in any pregnancy, COVID-19–related sources of distress for pregnant women include worrying about harm to the fetus during pregnancy, the possibility of vertical transmission, and exposures during antenatal appointments, during employment, or from a partner.^8,13

The death toll from factors associated with COVID-19 adds to the mental health burden. For every person who dies of COVID-19, an estimated 9 others may develop prolonged grief or PTSD due to the loss of someone they loved.^14,15 A systematic review found that PTSD in the perinatal period is associated with negative birth and child outcomes, including low birth weight and decreased rates of breastfeeding.¹⁶ The COVID-19 pandemic has disrupted human interactions, from social distancing rules and lockdowns of businesses and social activities to panic buying of grocery staples and increased economic insecurity.¹ These changes have been accompanied by a rise in mental health challenges. For example, according to an August 2020 CDC survey, 40.9% of US adults reported at least 1 adverse mental or behavioral health condition, including symptoms of anxiety or depression (30.9%), symptoms of a trauma- and stressor-related disorder related to the pandemic (26.3%), and having started or increased substance use to cope with stress or emotions related to COVID-19 (13.3%).¹⁷

COVID-19–related traumas and stressors appear to affect women more than men. A study from China found that compared with men, women had significantly higher levels of self-reported pandemic-related anxiety, depression, and posttraumatic stress symptoms (PTSS).¹⁸ This trend has been observed in other parts of the world. A study conducted by the UK Office of National Statistics reported anxiety levels were 24% higher in women vs men as reflected by scores on a self-rated anxiety scale.¹⁹

Continue to: Many factors influence...

Many factors influence the disproportionate impact of COVID-19 on women in general, and peripartum women in particular (Box^20-26).

Box

Psychiatric diagnoses in peripartum women

Multiple studies and meta-analyses have begun to assess the impact of the COVID-19 pandemic on maternal mental health. One meta-analysis of 8 studies conducted in 5 countries determined that COVID-19 significantly increases the risk of anxiety in women during the peripartum period.²⁷ Results of another meta-analysis of 23 studies with >24,000 participants indicated that the prevalence of anxiety, depression, and insomnia in peripartum women was significantly higher during the pandemic than in pre-pandemic times.²⁸

In an online survey of 4,451 pregnant women in the United States, nearly one-third of respondents reported elevated levels of pandemic-related stress as measured by the newly-developed Pandemic-Related Pregnancy Stress Scale.³ The rates were even higher among women who were already at risk for elevated stress levels, such as those who had survived abuse, those giving birth for the first time, or those experiencing high-risk pregnancies.³ Living in a pandemic “hot spot” also appeared to impact peripartum stress levels.

COVID-19 has adverse effects on women’s mental health specifically during the postpartum period. One study from a center in Italy found a high prevalence of depressive symptoms and PTSS in the postpartum period, with COVID-19–related factors playing an “indirect role” compared with prenatal experiences and other individual factors.² A British study of mothers of infants age ≤12 months found that traveling for work, the impact of lockdown on food affordability, and having an income of less than £30,000 per year (approximately $41,000) predicted poorer mental health during the pandemic.²⁹ Results of a study from China indicated that more than one-quarter of pregnant and postpartum women experienced depression during the pandemic, and women who worried about infection risk or missing pediatric visits were at increased risk.³⁰

How to mitigate these risks

The increase in pandemic-related mental health concerns in the general population and specifically in peripartum women is a global health care challenge. Investing in mitigation strategies is necessary not only to address the current pandemic, but also to help prepare for the possibility of future traumatic events, such as another global pandemic.

Continue to: For pregnant women...

For pregnant women, ensuring access to outdoor space, increasing participation in healthy activities, and minimizing disruptions to prenatal care can protect against pandemic-related stress.³ Physical activity is an effective treatment for mild to moderate depressive symptoms. Because of the significant decrease in exercise among pregnant women during the pandemic, encouraging safe forms of physical activity such as online fitness classes could improve mental health outcomes for these patients.²⁷ When counseling peripartum women, psychiatrists need to be creative in recommending fitness interventions to target mood symptoms, such as by suggesting virtual or at-home programs.

In an online survey, 118 obstetricians called for increased mental health resources for peripartum women, such as easier access to a helpline, educational videos, and mental health professionals.¹³ Increased screening for psychiatric disorders throughout the peripartum period can help identify women at greater risk, and advancements in telepsychiatry could help meet the increased need for psychiatric care during COVID-19. Psychiatrists and other mental health clinicians should consider reaching out to their colleagues who specialize in women’s health to establish new partnerships and create teams of multidisciplinary professionals.

Similarly, psychiatrists should familiarize themselves with telehealth services available to peripartum patients who could benefit from such services. Telehealth options can increase women’s access to peripartum care for both medical and psychiatric illnesses. Online options such as women’s support groups, parenting classes, and labor coaching seminars also represent valuable virtual tools to strengthen women’s social supports.

Women who need inpatient treatment for severe peripartum depression or anxiety might be particularly reluctant to receive this care during COVID-19 due to fears of becoming infected and of being separated from their infant and family while hospitalized. Clinicians should remain vigilant in screening peripartum women for mood disorders that might represent a danger to mothers and infants, and not allow concerns about COVID-19 to interfere with recommendations for psychiatric hospitalizations, when necessary. The creation of small, women-only inpatient behavioral units can help address this situation, especially given the possibility of frequent visits with infants and other peripartum support. Investment into such units is critical for supporting peripartum mental health, even in nonpandemic times.

What about vaccination? As of mid-May 2021, no large clinical trials of any COVID-19 vaccine that included pregnant women had been completed. However, 2 small preliminary studies suggested that the mRNA vaccines are safe and effective during pregnancy.^31,32 When counseling peripartum patients on the risks and benefits, clinicians need to rely on this evidence, animal trials, and limited data from inadvertent exposures during pregnancy. While every woman will weigh the risks and benefits for her own circumstances, the CDC, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine have all stated that the mRNA vaccines should be offered to pregnant and breastfeeding individuals who are eligible for vaccination.³³ Rasmussen et al³³ have published a useful resource for clinicians regarding COVID-19 vaccination and pregnant women.

Continue to: Bottom Line

During the COVID-19 pandemic, peripartum women have experienced increased rates of anxiety, depression, and stress. Psychiatric clinicians can help these patients by remaining vigilant in screening for psychiatric disorders, encouraging them to engage in activities to mitigate COVID-19’s adverse psychological effects, and referring them to care via telehealth and other resources as appropriate.

Related Resources

• Hu YJ, Wake M, Saffery R. Clarifying the sweeping consequences of COVID-19 in pregnant women, newborns, and children with existing cohorts. JAMA Pediatr. 2021; 75(2):117-118. doi: 10.1001/jamapediatrics.2020.2395
• Tomfohr-Madsen LM, Racine N, Giesbrecht GF, et al. Depression and anxiety in pregnancy during COVID-19: a rapid review and meta-analysis. Psychiatry Res. 2021; 300:113912. doi: 10.1016/j.psychres.2021.113912

Ms. C, age 44, who has major depressive disorder (MDD), anxiety, obsessive-compulsive disorder (OCD) (religious subtype), and has experienced multiple episodes of treatment-resistant catatonia, is brought to the emergency department (ED) by her parents. She has immobility, mutism, rigidity, and decreased oral intake that she has experienced for 1 day.

The night before, Ms. C had been stressed about an upcoming job interview. She cancelled the interview and went to her bedroom. Later that night her parents found her lying on the floor, immobile.

Before the onset of her psychiatric symptoms, Ms. C had been high functioning. She had been an athlete in college and had a career as a school psychologist. The Sidebar summarizes Ms. C’s psychiatric history, which includes similar complex episodes and multiple hospitalizations. She also has a history of hypothyroidism.

SIDEBAR

In the ED, the psychiatry team evaluates Ms. C. She displays a similar pattern of mutism, immobility, and rigidity as she did upon her initial presentation. Her father reports that she had been compliant with her medications but had not taken them the previous night. Ms. C screens positive for catatonia on the Bush-Francis Catatonia Rating Scale (BFCRS). Her severity score of 10/69 indicates a mild presentation. She is diagnosed with catatonia and is administered IV lorazepam, 2 mg, with no response.

Because Ms. C has been hospitalized many times for similar presentations, the treatment team decides to initiate a trial of IV ketamine.

Catatonia can manifest in many different ways in patients with psychiatric illness. If left untreated, it is associated with a high rate of mortality.¹ Catatonia often is described along a continuum from retarded/stuporous to excited, and presentations can vary substantially. The physiologic and psychological mechanisms of catatonia are poorly understood.

Traditionally, most patients respond well to low-dose benzodiazepines, with electroconvulsive therapy as a second-line intervention for refractory and malignant cases. However, these interventions are not always successful or readily available.

Continue to: Research into the anesthetic ketamine...

Research into the anesthetic ketamine is gradually expanding, and the use of this agent for treating various psychiatric illnesses, including both unipolar and bipolar depression, has been increasing.² Empiric evidence suggests ketamine is effective for certain psychiatric disorders, but the mechanism of action remains unclear. Although the evidence base is small, additional cases demonstrating the effectiveness of ketamine in the treatment of acute catatonia might make it a therapeutic option for use by psychiatrists and emergency medicine clinicians.

In this article, we discuss ketamine’s possible role in the treatment of catatonia, possible adverse effects, dosing strategies, and theories about ketamine’s mechanism of action.

Ketamine’s utility in psychiatry

Ketamine is a rapid-acting anesthetic that acts primarily by antagonizing N-methyl-d-aspartate (NMDA) receptors in the CNS. It is characterized by dissociative anesthesia as it disrupts association pathways in the brain.³ Ketamine has been shown to be efficacious in treating MDD and posttraumatic stress disorder, and for the long-term management of chronic pain disorders, including fibromyalgia and many neuro­pathic conditions.^4-7 Esketamine is an intranasal formulation of ketamine that is FDA-approved for treatment-resistant depression.⁸ There is scant literature describing using ketamine for treating catatonia.

Previously, ketamine had been thought to induce a catatonic state, which was supported by a neurophysiologic model of catatonia that suggested the condition was caused in part by glutamate hypo­activity at the NMDA receptor.⁹ However, recent studies have shown that the NMDA receptor antagonists amantadine and memantine may be useful for treatment-refractory cases of catatonia, which suggests that a broader model of glutamatergic dysfunction, and not simply glutamate hypoactivity, may be more accurate.^10,11 Denysenko et al¹² proposed that the efficacy of memantine for patients with lorazepam-resistant catatonia could be explained by increases in dopamine levels in the frontal cortex and striatum. While this effect could explain why amantadine has anticatatonic effects, it does not explain why other NMDA antagonists such as ketamine are potentially pro-catatonic. Other proposed physiologic mechanisms explaining this difference include the fact that memantine and ketamine have differing effects on brain-derived neurotrophic factor (BDNF) expression and certain glutamatergic postsynaptic density proteins.^13,14

Ketamine originally was used for sedation, and much of its safety and risk profile has been developed from decades of administration as an anesthetic. Studies have found that ketamine has a large therapeutic window in children and adults.^15,16 Moreover, it does not depress the respiratory system. As an anesthetic, ketamine has a rapid onset and a quick resolution, with its sedative and disorienting effects resolving within 30 to 120 minutes.¹⁷ Ketamine’s rapid onset of action extends beyond its sedating effects. Trials with the intranasal spray esketamine for treatment-resistant depression have demonstrated an onset antidepressant effects within 2 days.¹⁸ This is much faster than that of traditional antidepressants, such as selective serotonin reuptake inhibitors.¹⁸ Based on these features, ketamine has the potential to be a useful medication in the emergency psychiatric setting, particularly for acute presentations such as catatonia.

Continue to: Beware of the potential risks

Although ketamine may be clinically useful, it also carries some risks. Adverse effects associated with ketamine include sedation, dissociation, hallucinations, elevated blood pressure, nausea, increased heart rate, vomiting, dizziness, fatigue, blurred vision, itching, and emesis. Clinicians also should be aware that some patients may use illicit ketamine, either as self-treatment to control depressive symptoms or for recreational purposes. When misused/abused, long-term use of ketamine can cause neurologic damage.¹⁹ Studies also have reported rare occurrences of recurrent hallucinations even after discontinuation of ketamine.²⁰ Animal studies have demonstrated addiction and cognitive deficits with repeated use of ketamine in rodents.²¹ This research has led to concerns that chronic use of ketamine to treat illnesses such as depression might lead to similar long-term adverse outcomes.

Dosing

As a sedative, IV ketamine dosing is generally 1 to 2 mg/kg, and IM ketamine dosing is 3 to 5 mg/kg.¹⁶ As an antidepressant, small clinical trials have suggested that the preferred dose of IV ketamine may be 0.5 to 1 mg/kg, with dose-dependent increases in dissociation and blood pressure.²¹ Studies have also demonstrated that once-daily IV ketamine, 0.5 mg/kg administered over 40 minutes, led to greater improvements in patients with MDD than placebo, whereas once-daily IV ketamine, 0.2 mg/kg, did not.²⁰

CASE CONTINUED

The team begins to treat Ms. C with IV ketamine. Ketamine, 0.2 mg/kg, is used to calculate the initial dose, and a total of 10 mg is administered over 10 minutes. Fifteen minutes after administration, Ms. C is able to move around in her bed, make eye contact, and nod to questions. She has purposeful movements, such as examining her IV line, scratching her head, and repositioning herself in the bed. After a few more minutes, she makes eye contact with her father, and nods to him during conversation. She is able to make a few noises but does not speak.

Later that day, Ms. C is discharged home (in a wheelchair) with her parents, on a medication regimen of fluvoxamine, 100 mg/d; lorazepam, 1 mg 4 times a day; and olanzapine, 5 mg/d. She is scheduled for an outpatient follow-up appointment 5 days later. Her parents are given instructions and several precautions to ensure that Ms. C receives proper nutrition until her appointment. That evening, Ms. C is able to eat voluntarily.

Five days later, Ms. C visits the outpatient psychiatric clinic and is verbal and ambulatory. Her father reports that she has become more verbal. During her follow-up interview, she is observed to be more subdued and less verbal than her baseline, but is vocal and able to voice her understanding of the treatment plan.

Continue to: After 3 months of being stable...

After 3 months of being stable on her outpatient regimen, Ms. C’s catatonic symptoms return, including refusing to eat and mutism. She is administered IV lorazepam, 4 mg, with no response and is admitted to the hospital for placement of a nasogastric feeding tube to address malnutrition. After several days, Ms. C responds to lorazepam, 4 mg every 6 hours. Six days later, after she begins eating and taking her medications voluntarily and the nasogastric tube is removed, Ms. C is discharged to home.

Findings need to be replicated in larger studies

Although some research has indicated that ketamine may be pro-catatonic, Ms. C’s improvement after receiving ketamine suggests that perhaps the situation is more complex.^12,22 The exact mechanisms underlying catatonia remain uncertain. Carroll et al⁹ described 4 theories, and only 1 of them involved glutamate. Additionally, ketamine’s mechanism of action may extend beyond NMDA antagonism. In our case, Ms. C’s low BFCRS score during her most recent visit to the ED suggests she may have had a milder or less typical form of catatonia compared with her previous presentations (Sidebar). However, Ms. C’s clinical improvement after receiving ketamine is noteworthy.

A review of the literature yielded only 1 other case report that described using ketamine to treat catatonia.²³ Iserson et al²³ reported that their patient’s catatonic symptoms resolved after a total of 12.5 mg of ketamine was administered in 0.03 mg/kg boluses every 3 minutes. Compared with our own protocol, ketamine was administered at a much slower rate in this case, although both total doses of ketamine were comparable and well below the dose used for sedation. Additionally, in Iserson et al,²³ lorazepam was not administered before ketamine because lorazepam was not readily available in the treatment setting. In our case, Ms. C may have had a delayed response to the IV lorazepam she received an hour before the ketamine dose; however, she exhibited a distinct clinical improvement 10 to 15 minutes after IV ketamine was administered. Nevertheless, both cases demonstrated rapid resolution of catatonic symptoms following administration of ketamine.

The marked improvement after the ketamine infusion allowed Ms. C to be discharged from the ED the same day, which was never possible after her previous catatonic episodes. Five days after discharge, she was walking, eating, talking, and able to attend to her activities of daily living without any change to her other medications. Moreover, these effects outlasted the duration of ketamine. Ms. C remained stable for 5 months until she destabilized in June 2020. At that time, she did not respond to lorazepam in the ED, needed to be hospitalized, and required a nasogastric feeding tube. Ketamine was not trialed during this presentation, so it remains to be seen if the patient’s response to ketamine was an isolated incident, or whether it could potentially spare her from future hospitalizations.

Bottom Line

In our case report, a woman with a long history of catatonia responded to a single infusion of IV ketamine, and the beneficial effects lasted for months. More research evaluating the efficacy of ketamine is needed to determine if this agent has a place in the treatment of catatonia.

Continue to: Related Resources

• Dubovsky SL, Dubovsky AN. Catatonia: How to identify and treat it. Current Psychiatry. 2018;17(8):16-26.
• Iserson KV, Durga D. Catatonia-like syndrome treated with low-dose ketamine. J Emerg Med. 2020;58(5):771-774.

Drug Brand Names

Amantadine • Gocovri
Dextroamphetamine sulfate/levoamphetamine sulfate • Evekeo
Divalproex sodium • Depakote
Duloxetine • Cymbalta
Esketamine • Spravato
Fluoxetine • Prozac
Fludrocortisone • Florinef
Fluvoxamine • Luvox
Ketamine • Ketalar
Levothyroxine • Synthroid
Lorazepam • Ativan
Memantine • Namenda
Mirtazapine • Remeron
Olanzapine • Zyprexa
Risperidone • Risperdal
Ziprasidone • Geodon
Zolpidem • Ambien

Ms. C, age 44, who has major depressive disorder (MDD), anxiety, obsessive-compulsive disorder (OCD) (religious subtype), and has experienced multiple episodes of treatment-resistant catatonia, is brought to the emergency department (ED) by her parents. She has immobility, mutism, rigidity, and decreased oral intake that she has experienced for 1 day.

The night before, Ms. C had been stressed about an upcoming job interview. She cancelled the interview and went to her bedroom. Later that night her parents found her lying on the floor, immobile.

Before the onset of her psychiatric symptoms, Ms. C had been high functioning. She had been an athlete in college and had a career as a school psychologist. The Sidebar summarizes Ms. C’s psychiatric history, which includes similar complex episodes and multiple hospitalizations. She also has a history of hypothyroidism.

SIDEBAR

In the ED, the psychiatry team evaluates Ms. C. She displays a similar pattern of mutism, immobility, and rigidity as she did upon her initial presentation. Her father reports that she had been compliant with her medications but had not taken them the previous night. Ms. C screens positive for catatonia on the Bush-Francis Catatonia Rating Scale (BFCRS). Her severity score of 10/69 indicates a mild presentation. She is diagnosed with catatonia and is administered IV lorazepam, 2 mg, with no response.

Because Ms. C has been hospitalized many times for similar presentations, the treatment team decides to initiate a trial of IV ketamine.

Catatonia can manifest in many different ways in patients with psychiatric illness. If left untreated, it is associated with a high rate of mortality.¹ Catatonia often is described along a continuum from retarded/stuporous to excited, and presentations can vary substantially. The physiologic and psychological mechanisms of catatonia are poorly understood.

Traditionally, most patients respond well to low-dose benzodiazepines, with electroconvulsive therapy as a second-line intervention for refractory and malignant cases. However, these interventions are not always successful or readily available.

Continue to: Research into the anesthetic ketamine...

Research into the anesthetic ketamine is gradually expanding, and the use of this agent for treating various psychiatric illnesses, including both unipolar and bipolar depression, has been increasing.² Empiric evidence suggests ketamine is effective for certain psychiatric disorders, but the mechanism of action remains unclear. Although the evidence base is small, additional cases demonstrating the effectiveness of ketamine in the treatment of acute catatonia might make it a therapeutic option for use by psychiatrists and emergency medicine clinicians.

In this article, we discuss ketamine’s possible role in the treatment of catatonia, possible adverse effects, dosing strategies, and theories about ketamine’s mechanism of action.

Ketamine’s utility in psychiatry

Ketamine is a rapid-acting anesthetic that acts primarily by antagonizing N-methyl-d-aspartate (NMDA) receptors in the CNS. It is characterized by dissociative anesthesia as it disrupts association pathways in the brain.³ Ketamine has been shown to be efficacious in treating MDD and posttraumatic stress disorder, and for the long-term management of chronic pain disorders, including fibromyalgia and many neuro­pathic conditions.^4-7 Esketamine is an intranasal formulation of ketamine that is FDA-approved for treatment-resistant depression.⁸ There is scant literature describing using ketamine for treating catatonia.

Previously, ketamine had been thought to induce a catatonic state, which was supported by a neurophysiologic model of catatonia that suggested the condition was caused in part by glutamate hypo­activity at the NMDA receptor.⁹ However, recent studies have shown that the NMDA receptor antagonists amantadine and memantine may be useful for treatment-refractory cases of catatonia, which suggests that a broader model of glutamatergic dysfunction, and not simply glutamate hypoactivity, may be more accurate.^10,11 Denysenko et al¹² proposed that the efficacy of memantine for patients with lorazepam-resistant catatonia could be explained by increases in dopamine levels in the frontal cortex and striatum. While this effect could explain why amantadine has anticatatonic effects, it does not explain why other NMDA antagonists such as ketamine are potentially pro-catatonic. Other proposed physiologic mechanisms explaining this difference include the fact that memantine and ketamine have differing effects on brain-derived neurotrophic factor (BDNF) expression and certain glutamatergic postsynaptic density proteins.^13,14

Ketamine originally was used for sedation, and much of its safety and risk profile has been developed from decades of administration as an anesthetic. Studies have found that ketamine has a large therapeutic window in children and adults.^15,16 Moreover, it does not depress the respiratory system. As an anesthetic, ketamine has a rapid onset and a quick resolution, with its sedative and disorienting effects resolving within 30 to 120 minutes.¹⁷ Ketamine’s rapid onset of action extends beyond its sedating effects. Trials with the intranasal spray esketamine for treatment-resistant depression have demonstrated an onset antidepressant effects within 2 days.¹⁸ This is much faster than that of traditional antidepressants, such as selective serotonin reuptake inhibitors.¹⁸ Based on these features, ketamine has the potential to be a useful medication in the emergency psychiatric setting, particularly for acute presentations such as catatonia.

Continue to: Beware of the potential risks

Although ketamine may be clinically useful, it also carries some risks. Adverse effects associated with ketamine include sedation, dissociation, hallucinations, elevated blood pressure, nausea, increased heart rate, vomiting, dizziness, fatigue, blurred vision, itching, and emesis. Clinicians also should be aware that some patients may use illicit ketamine, either as self-treatment to control depressive symptoms or for recreational purposes. When misused/abused, long-term use of ketamine can cause neurologic damage.¹⁹ Studies also have reported rare occurrences of recurrent hallucinations even after discontinuation of ketamine.²⁰ Animal studies have demonstrated addiction and cognitive deficits with repeated use of ketamine in rodents.²¹ This research has led to concerns that chronic use of ketamine to treat illnesses such as depression might lead to similar long-term adverse outcomes.

Dosing

As a sedative, IV ketamine dosing is generally 1 to 2 mg/kg, and IM ketamine dosing is 3 to 5 mg/kg.¹⁶ As an antidepressant, small clinical trials have suggested that the preferred dose of IV ketamine may be 0.5 to 1 mg/kg, with dose-dependent increases in dissociation and blood pressure.²¹ Studies have also demonstrated that once-daily IV ketamine, 0.5 mg/kg administered over 40 minutes, led to greater improvements in patients with MDD than placebo, whereas once-daily IV ketamine, 0.2 mg/kg, did not.²⁰

CASE CONTINUED

The team begins to treat Ms. C with IV ketamine. Ketamine, 0.2 mg/kg, is used to calculate the initial dose, and a total of 10 mg is administered over 10 minutes. Fifteen minutes after administration, Ms. C is able to move around in her bed, make eye contact, and nod to questions. She has purposeful movements, such as examining her IV line, scratching her head, and repositioning herself in the bed. After a few more minutes, she makes eye contact with her father, and nods to him during conversation. She is able to make a few noises but does not speak.

Later that day, Ms. C is discharged home (in a wheelchair) with her parents, on a medication regimen of fluvoxamine, 100 mg/d; lorazepam, 1 mg 4 times a day; and olanzapine, 5 mg/d. She is scheduled for an outpatient follow-up appointment 5 days later. Her parents are given instructions and several precautions to ensure that Ms. C receives proper nutrition until her appointment. That evening, Ms. C is able to eat voluntarily.

Five days later, Ms. C visits the outpatient psychiatric clinic and is verbal and ambulatory. Her father reports that she has become more verbal. During her follow-up interview, she is observed to be more subdued and less verbal than her baseline, but is vocal and able to voice her understanding of the treatment plan.

Continue to: After 3 months of being stable...

After 3 months of being stable on her outpatient regimen, Ms. C’s catatonic symptoms return, including refusing to eat and mutism. She is administered IV lorazepam, 4 mg, with no response and is admitted to the hospital for placement of a nasogastric feeding tube to address malnutrition. After several days, Ms. C responds to lorazepam, 4 mg every 6 hours. Six days later, after she begins eating and taking her medications voluntarily and the nasogastric tube is removed, Ms. C is discharged to home.

Findings need to be replicated in larger studies

Although some research has indicated that ketamine may be pro-catatonic, Ms. C’s improvement after receiving ketamine suggests that perhaps the situation is more complex.^12,22 The exact mechanisms underlying catatonia remain uncertain. Carroll et al⁹ described 4 theories, and only 1 of them involved glutamate. Additionally, ketamine’s mechanism of action may extend beyond NMDA antagonism. In our case, Ms. C’s low BFCRS score during her most recent visit to the ED suggests she may have had a milder or less typical form of catatonia compared with her previous presentations (Sidebar). However, Ms. C’s clinical improvement after receiving ketamine is noteworthy.

A review of the literature yielded only 1 other case report that described using ketamine to treat catatonia.²³ Iserson et al²³ reported that their patient’s catatonic symptoms resolved after a total of 12.5 mg of ketamine was administered in 0.03 mg/kg boluses every 3 minutes. Compared with our own protocol, ketamine was administered at a much slower rate in this case, although both total doses of ketamine were comparable and well below the dose used for sedation. Additionally, in Iserson et al,²³ lorazepam was not administered before ketamine because lorazepam was not readily available in the treatment setting. In our case, Ms. C may have had a delayed response to the IV lorazepam she received an hour before the ketamine dose; however, she exhibited a distinct clinical improvement 10 to 15 minutes after IV ketamine was administered. Nevertheless, both cases demonstrated rapid resolution of catatonic symptoms following administration of ketamine.

The marked improvement after the ketamine infusion allowed Ms. C to be discharged from the ED the same day, which was never possible after her previous catatonic episodes. Five days after discharge, she was walking, eating, talking, and able to attend to her activities of daily living without any change to her other medications. Moreover, these effects outlasted the duration of ketamine. Ms. C remained stable for 5 months until she destabilized in June 2020. At that time, she did not respond to lorazepam in the ED, needed to be hospitalized, and required a nasogastric feeding tube. Ketamine was not trialed during this presentation, so it remains to be seen if the patient’s response to ketamine was an isolated incident, or whether it could potentially spare her from future hospitalizations.

Bottom Line

In our case report, a woman with a long history of catatonia responded to a single infusion of IV ketamine, and the beneficial effects lasted for months. More research evaluating the efficacy of ketamine is needed to determine if this agent has a place in the treatment of catatonia.

Continue to: Related Resources

• Dubovsky SL, Dubovsky AN. Catatonia: How to identify and treat it. Current Psychiatry. 2018;17(8):16-26.
• Iserson KV, Durga D. Catatonia-like syndrome treated with low-dose ketamine. J Emerg Med. 2020;58(5):771-774.

Drug Brand Names

Amantadine • Gocovri
Dextroamphetamine sulfate/levoamphetamine sulfate • Evekeo
Divalproex sodium • Depakote
Duloxetine • Cymbalta
Esketamine • Spravato
Fluoxetine • Prozac
Fludrocortisone • Florinef
Fluvoxamine • Luvox
Ketamine • Ketalar
Levothyroxine • Synthroid
Lorazepam • Ativan
Memantine • Namenda
Mirtazapine • Remeron
Olanzapine • Zyprexa
Risperidone • Risperdal
Ziprasidone • Geodon
Zolpidem • Ambien

Ms. C, age 44, who has major depressive disorder (MDD), anxiety, obsessive-compulsive disorder (OCD) (religious subtype), and has experienced multiple episodes of treatment-resistant catatonia, is brought to the emergency department (ED) by her parents. She has immobility, mutism, rigidity, and decreased oral intake that she has experienced for 1 day.

The night before, Ms. C had been stressed about an upcoming job interview. She cancelled the interview and went to her bedroom. Later that night her parents found her lying on the floor, immobile.

Before the onset of her psychiatric symptoms, Ms. C had been high functioning. She had been an athlete in college and had a career as a school psychologist. The Sidebar summarizes Ms. C’s psychiatric history, which includes similar complex episodes and multiple hospitalizations. She also has a history of hypothyroidism.

SIDEBAR

In the ED, the psychiatry team evaluates Ms. C. She displays a similar pattern of mutism, immobility, and rigidity as she did upon her initial presentation. Her father reports that she had been compliant with her medications but had not taken them the previous night. Ms. C screens positive for catatonia on the Bush-Francis Catatonia Rating Scale (BFCRS). Her severity score of 10/69 indicates a mild presentation. She is diagnosed with catatonia and is administered IV lorazepam, 2 mg, with no response.

Because Ms. C has been hospitalized many times for similar presentations, the treatment team decides to initiate a trial of IV ketamine.

Catatonia can manifest in many different ways in patients with psychiatric illness. If left untreated, it is associated with a high rate of mortality.¹ Catatonia often is described along a continuum from retarded/stuporous to excited, and presentations can vary substantially. The physiologic and psychological mechanisms of catatonia are poorly understood.

Traditionally, most patients respond well to low-dose benzodiazepines, with electroconvulsive therapy as a second-line intervention for refractory and malignant cases. However, these interventions are not always successful or readily available.

Continue to: Research into the anesthetic ketamine...

Research into the anesthetic ketamine is gradually expanding, and the use of this agent for treating various psychiatric illnesses, including both unipolar and bipolar depression, has been increasing.² Empiric evidence suggests ketamine is effective for certain psychiatric disorders, but the mechanism of action remains unclear. Although the evidence base is small, additional cases demonstrating the effectiveness of ketamine in the treatment of acute catatonia might make it a therapeutic option for use by psychiatrists and emergency medicine clinicians.

In this article, we discuss ketamine’s possible role in the treatment of catatonia, possible adverse effects, dosing strategies, and theories about ketamine’s mechanism of action.

Ketamine’s utility in psychiatry

Ketamine is a rapid-acting anesthetic that acts primarily by antagonizing N-methyl-d-aspartate (NMDA) receptors in the CNS. It is characterized by dissociative anesthesia as it disrupts association pathways in the brain.³ Ketamine has been shown to be efficacious in treating MDD and posttraumatic stress disorder, and for the long-term management of chronic pain disorders, including fibromyalgia and many neuro­pathic conditions.^4-7 Esketamine is an intranasal formulation of ketamine that is FDA-approved for treatment-resistant depression.⁸ There is scant literature describing using ketamine for treating catatonia.

Previously, ketamine had been thought to induce a catatonic state, which was supported by a neurophysiologic model of catatonia that suggested the condition was caused in part by glutamate hypo­activity at the NMDA receptor.⁹ However, recent studies have shown that the NMDA receptor antagonists amantadine and memantine may be useful for treatment-refractory cases of catatonia, which suggests that a broader model of glutamatergic dysfunction, and not simply glutamate hypoactivity, may be more accurate.^10,11 Denysenko et al¹² proposed that the efficacy of memantine for patients with lorazepam-resistant catatonia could be explained by increases in dopamine levels in the frontal cortex and striatum. While this effect could explain why amantadine has anticatatonic effects, it does not explain why other NMDA antagonists such as ketamine are potentially pro-catatonic. Other proposed physiologic mechanisms explaining this difference include the fact that memantine and ketamine have differing effects on brain-derived neurotrophic factor (BDNF) expression and certain glutamatergic postsynaptic density proteins.^13,14

Ketamine originally was used for sedation, and much of its safety and risk profile has been developed from decades of administration as an anesthetic. Studies have found that ketamine has a large therapeutic window in children and adults.^15,16 Moreover, it does not depress the respiratory system. As an anesthetic, ketamine has a rapid onset and a quick resolution, with its sedative and disorienting effects resolving within 30 to 120 minutes.¹⁷ Ketamine’s rapid onset of action extends beyond its sedating effects. Trials with the intranasal spray esketamine for treatment-resistant depression have demonstrated an onset antidepressant effects within 2 days.¹⁸ This is much faster than that of traditional antidepressants, such as selective serotonin reuptake inhibitors.¹⁸ Based on these features, ketamine has the potential to be a useful medication in the emergency psychiatric setting, particularly for acute presentations such as catatonia.

Continue to: Beware of the potential risks

Although ketamine may be clinically useful, it also carries some risks. Adverse effects associated with ketamine include sedation, dissociation, hallucinations, elevated blood pressure, nausea, increased heart rate, vomiting, dizziness, fatigue, blurred vision, itching, and emesis. Clinicians also should be aware that some patients may use illicit ketamine, either as self-treatment to control depressive symptoms or for recreational purposes. When misused/abused, long-term use of ketamine can cause neurologic damage.¹⁹ Studies also have reported rare occurrences of recurrent hallucinations even after discontinuation of ketamine.²⁰ Animal studies have demonstrated addiction and cognitive deficits with repeated use of ketamine in rodents.²¹ This research has led to concerns that chronic use of ketamine to treat illnesses such as depression might lead to similar long-term adverse outcomes.

Dosing

As a sedative, IV ketamine dosing is generally 1 to 2 mg/kg, and IM ketamine dosing is 3 to 5 mg/kg.¹⁶ As an antidepressant, small clinical trials have suggested that the preferred dose of IV ketamine may be 0.5 to 1 mg/kg, with dose-dependent increases in dissociation and blood pressure.²¹ Studies have also demonstrated that once-daily IV ketamine, 0.5 mg/kg administered over 40 minutes, led to greater improvements in patients with MDD than placebo, whereas once-daily IV ketamine, 0.2 mg/kg, did not.²⁰

CASE CONTINUED

The team begins to treat Ms. C with IV ketamine. Ketamine, 0.2 mg/kg, is used to calculate the initial dose, and a total of 10 mg is administered over 10 minutes. Fifteen minutes after administration, Ms. C is able to move around in her bed, make eye contact, and nod to questions. She has purposeful movements, such as examining her IV line, scratching her head, and repositioning herself in the bed. After a few more minutes, she makes eye contact with her father, and nods to him during conversation. She is able to make a few noises but does not speak.

Later that day, Ms. C is discharged home (in a wheelchair) with her parents, on a medication regimen of fluvoxamine, 100 mg/d; lorazepam, 1 mg 4 times a day; and olanzapine, 5 mg/d. She is scheduled for an outpatient follow-up appointment 5 days later. Her parents are given instructions and several precautions to ensure that Ms. C receives proper nutrition until her appointment. That evening, Ms. C is able to eat voluntarily.

Five days later, Ms. C visits the outpatient psychiatric clinic and is verbal and ambulatory. Her father reports that she has become more verbal. During her follow-up interview, she is observed to be more subdued and less verbal than her baseline, but is vocal and able to voice her understanding of the treatment plan.

Continue to: After 3 months of being stable...

After 3 months of being stable on her outpatient regimen, Ms. C’s catatonic symptoms return, including refusing to eat and mutism. She is administered IV lorazepam, 4 mg, with no response and is admitted to the hospital for placement of a nasogastric feeding tube to address malnutrition. After several days, Ms. C responds to lorazepam, 4 mg every 6 hours. Six days later, after she begins eating and taking her medications voluntarily and the nasogastric tube is removed, Ms. C is discharged to home.

Findings need to be replicated in larger studies

Although some research has indicated that ketamine may be pro-catatonic, Ms. C’s improvement after receiving ketamine suggests that perhaps the situation is more complex.^12,22 The exact mechanisms underlying catatonia remain uncertain. Carroll et al⁹ described 4 theories, and only 1 of them involved glutamate. Additionally, ketamine’s mechanism of action may extend beyond NMDA antagonism. In our case, Ms. C’s low BFCRS score during her most recent visit to the ED suggests she may have had a milder or less typical form of catatonia compared with her previous presentations (Sidebar). However, Ms. C’s clinical improvement after receiving ketamine is noteworthy.

A review of the literature yielded only 1 other case report that described using ketamine to treat catatonia.²³ Iserson et al²³ reported that their patient’s catatonic symptoms resolved after a total of 12.5 mg of ketamine was administered in 0.03 mg/kg boluses every 3 minutes. Compared with our own protocol, ketamine was administered at a much slower rate in this case, although both total doses of ketamine were comparable and well below the dose used for sedation. Additionally, in Iserson et al,²³ lorazepam was not administered before ketamine because lorazepam was not readily available in the treatment setting. In our case, Ms. C may have had a delayed response to the IV lorazepam she received an hour before the ketamine dose; however, she exhibited a distinct clinical improvement 10 to 15 minutes after IV ketamine was administered. Nevertheless, both cases demonstrated rapid resolution of catatonic symptoms following administration of ketamine.

The marked improvement after the ketamine infusion allowed Ms. C to be discharged from the ED the same day, which was never possible after her previous catatonic episodes. Five days after discharge, she was walking, eating, talking, and able to attend to her activities of daily living without any change to her other medications. Moreover, these effects outlasted the duration of ketamine. Ms. C remained stable for 5 months until she destabilized in June 2020. At that time, she did not respond to lorazepam in the ED, needed to be hospitalized, and required a nasogastric feeding tube. Ketamine was not trialed during this presentation, so it remains to be seen if the patient’s response to ketamine was an isolated incident, or whether it could potentially spare her from future hospitalizations.

Bottom Line

In our case report, a woman with a long history of catatonia responded to a single infusion of IV ketamine, and the beneficial effects lasted for months. More research evaluating the efficacy of ketamine is needed to determine if this agent has a place in the treatment of catatonia.

Continue to: Related Resources

• Dubovsky SL, Dubovsky AN. Catatonia: How to identify and treat it. Current Psychiatry. 2018;17(8):16-26.
• Iserson KV, Durga D. Catatonia-like syndrome treated with low-dose ketamine. J Emerg Med. 2020;58(5):771-774.

Drug Brand Names

Amantadine • Gocovri
Dextroamphetamine sulfate/levoamphetamine sulfate • Evekeo
Divalproex sodium • Depakote
Duloxetine • Cymbalta
Esketamine • Spravato
Fluoxetine • Prozac
Fludrocortisone • Florinef
Fluvoxamine • Luvox
Ketamine • Ketalar
Levothyroxine • Synthroid
Lorazepam • Ativan
Memantine • Namenda
Mirtazapine • Remeron
Olanzapine • Zyprexa
Risperidone • Risperdal
Ziprasidone • Geodon
Zolpidem • Ambien

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

The COVID-19 pandemic has brought to the fore inequalities in health care.¹ In a letter recently published in the American Journal of Psychiatry, Nadkarni et al² addressed the reality that there is not equal access to quality care (in this case, telepsychiatry). They reported challenges in converting their psychiatry ambulatory care center to a virtual platform at Brigham and Women’s Hospital, which is affiliated with Harvard Medical School.

Previously, I had reported in Current Psychiatry that patients at our small community mental health clinic outside Baltimore have much less audiovisual capability (they were able to receive telepsychiatry services via phone only, and not via video conferencing on a computer, smartphone, or tablet).³ Of 100 consecutive patients, we used telepsychiatry for 82 (18 were seen in person, including 14 who were seen for administration of long-acting injectable medications). Of the 82 patients receiving telepsychiatry from our facility, only 9 had video conferencing sessions (10.9%).

I repeated the survey approximately 3 months later. Preliminary data of these 125 total patients showed a slightly higher percentage (12.6%) had video conferencing sessions.

Factors associated with limited access to technology

Similar to what was reported by Nadkarni et al,² in our extremely vulnerable population, socioeconomic factors affect access. Our patients are low income, and often do not own computers or smart phones. Nearly all our patients receive medical assistance and/or Medicare. Our patients are more likely to be members of a racial minority group—4 times the national average. Our patients are older.⁴ Patient age varies from 16 to 83 years; the mean age is 54, and the median age is 56. Educational level is low. Nearly all of our patients who participate in video conferencing sessions are female. Approximately 15 of our patients have comorbid intellectual and developmental disabilities diagnoses, and at least that many have subsyndromal symptoms. Constantino et al⁵ commented on the multiple negative consequences of the COVID-19 pandemic on individuals with intellectual and developmental disabilities, including “frank disparities in access” to technology as well as gaps left by relying exclusively on telehealth.

Among our patients, being low income, a member of a racial minority group, older, less educated, male, and developmentally and/or intellectually disabled are risk factors for less access to video conferencing.³ Nadkarni et al² also noted less broadband access for rural residents and less access and lack of digital health literacy in patients with limited English proficiency.

As Nadkarni et al² suggested, we did contact our legislators, and emergency rules are continuing. For now, we are managing fiscally. Although that certainly is important, it does not address the issue of inequality.

Continue to: With this information...

With this information, we are strongly encouraging our patients to participate in video conferencing sessions. We suspect that for some patients, the possibility of them participating in video conferencing sessions is greater than they have acknowledged. We are stepping up education and support, both informally through the patient’s family and friends, and more formally through case managers who “lend” patients a device during home visits.

In summary, this inequality in access to the technology needed for telepsychiatry will loom even more prominently as we all move forward, both clinically and in policymaking.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

The COVID-19 pandemic has brought to the fore inequalities in health care.¹ In a letter recently published in the American Journal of Psychiatry, Nadkarni et al² addressed the reality that there is not equal access to quality care (in this case, telepsychiatry). They reported challenges in converting their psychiatry ambulatory care center to a virtual platform at Brigham and Women’s Hospital, which is affiliated with Harvard Medical School.

Previously, I had reported in Current Psychiatry that patients at our small community mental health clinic outside Baltimore have much less audiovisual capability (they were able to receive telepsychiatry services via phone only, and not via video conferencing on a computer, smartphone, or tablet).³ Of 100 consecutive patients, we used telepsychiatry for 82 (18 were seen in person, including 14 who were seen for administration of long-acting injectable medications). Of the 82 patients receiving telepsychiatry from our facility, only 9 had video conferencing sessions (10.9%).

I repeated the survey approximately 3 months later. Preliminary data of these 125 total patients showed a slightly higher percentage (12.6%) had video conferencing sessions.

Factors associated with limited access to technology

Similar to what was reported by Nadkarni et al,² in our extremely vulnerable population, socioeconomic factors affect access. Our patients are low income, and often do not own computers or smart phones. Nearly all our patients receive medical assistance and/or Medicare. Our patients are more likely to be members of a racial minority group—4 times the national average. Our patients are older.⁴ Patient age varies from 16 to 83 years; the mean age is 54, and the median age is 56. Educational level is low. Nearly all of our patients who participate in video conferencing sessions are female. Approximately 15 of our patients have comorbid intellectual and developmental disabilities diagnoses, and at least that many have subsyndromal symptoms. Constantino et al⁵ commented on the multiple negative consequences of the COVID-19 pandemic on individuals with intellectual and developmental disabilities, including “frank disparities in access” to technology as well as gaps left by relying exclusively on telehealth.

Among our patients, being low income, a member of a racial minority group, older, less educated, male, and developmentally and/or intellectually disabled are risk factors for less access to video conferencing.³ Nadkarni et al² also noted less broadband access for rural residents and less access and lack of digital health literacy in patients with limited English proficiency.

As Nadkarni et al² suggested, we did contact our legislators, and emergency rules are continuing. For now, we are managing fiscally. Although that certainly is important, it does not address the issue of inequality.

Continue to: With this information...

With this information, we are strongly encouraging our patients to participate in video conferencing sessions. We suspect that for some patients, the possibility of them participating in video conferencing sessions is greater than they have acknowledged. We are stepping up education and support, both informally through the patient’s family and friends, and more formally through case managers who “lend” patients a device during home visits.

In summary, this inequality in access to the technology needed for telepsychiatry will loom even more prominently as we all move forward, both clinically and in policymaking.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

The COVID-19 pandemic has brought to the fore inequalities in health care.¹ In a letter recently published in the American Journal of Psychiatry, Nadkarni et al² addressed the reality that there is not equal access to quality care (in this case, telepsychiatry). They reported challenges in converting their psychiatry ambulatory care center to a virtual platform at Brigham and Women’s Hospital, which is affiliated with Harvard Medical School.

Previously, I had reported in Current Psychiatry that patients at our small community mental health clinic outside Baltimore have much less audiovisual capability (they were able to receive telepsychiatry services via phone only, and not via video conferencing on a computer, smartphone, or tablet).³ Of 100 consecutive patients, we used telepsychiatry for 82 (18 were seen in person, including 14 who were seen for administration of long-acting injectable medications). Of the 82 patients receiving telepsychiatry from our facility, only 9 had video conferencing sessions (10.9%).

I repeated the survey approximately 3 months later. Preliminary data of these 125 total patients showed a slightly higher percentage (12.6%) had video conferencing sessions.

Factors associated with limited access to technology

Similar to what was reported by Nadkarni et al,² in our extremely vulnerable population, socioeconomic factors affect access. Our patients are low income, and often do not own computers or smart phones. Nearly all our patients receive medical assistance and/or Medicare. Our patients are more likely to be members of a racial minority group—4 times the national average. Our patients are older.⁴ Patient age varies from 16 to 83 years; the mean age is 54, and the median age is 56. Educational level is low. Nearly all of our patients who participate in video conferencing sessions are female. Approximately 15 of our patients have comorbid intellectual and developmental disabilities diagnoses, and at least that many have subsyndromal symptoms. Constantino et al⁵ commented on the multiple negative consequences of the COVID-19 pandemic on individuals with intellectual and developmental disabilities, including “frank disparities in access” to technology as well as gaps left by relying exclusively on telehealth.

Among our patients, being low income, a member of a racial minority group, older, less educated, male, and developmentally and/or intellectually disabled are risk factors for less access to video conferencing.³ Nadkarni et al² also noted less broadband access for rural residents and less access and lack of digital health literacy in patients with limited English proficiency.

As Nadkarni et al² suggested, we did contact our legislators, and emergency rules are continuing. For now, we are managing fiscally. Although that certainly is important, it does not address the issue of inequality.

Continue to: With this information...

With this information, we are strongly encouraging our patients to participate in video conferencing sessions. We suspect that for some patients, the possibility of them participating in video conferencing sessions is greater than they have acknowledged. We are stepping up education and support, both informally through the patient’s family and friends, and more formally through case managers who “lend” patients a device during home visits.

In summary, this inequality in access to the technology needed for telepsychiatry will loom even more prominently as we all move forward, both clinically and in policymaking.

I wanted to thank Dr. Nasrallah for his bold article, “Treatment resistance is a myth!” (From the Editor, Current Psychiatry, March 2021, p. 14-16,28). “Treatment resistance” has become an overused catchphrase, largely for commercial purposes, that sends a distorted view to the public that current psychiatric treatments are ineffective. We have proven, safe, and effective treatments as covered in the article. So, instead of “treatment resistance,” we should be publicizing that “treatment works!” to encourage people to seek help for mental disorders and addictions.

Stanley N. Caroff, MD
Professor of Psychiatry
Perelman School of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania

I thought Dr. Nasrallah’s editorial on treatment resistance was excellent. In my experience, bipolar depression often is not diagnosed in patients with long-standing depression. These patients do worse on antidepressants, which is interpreted by the clinician as treatment-resistant major depressive disorder. The other issue for me is that individuals with bipolar disorder with psychotic features are often diagnosed with schizophrenia or schizo­affective disorder and never receive a trial of lithium, which could alter the course of their illness in a dramatic fashion. For me, the under­utilization of lithium is a real quality problem in our field. Keep up the good work!

Bruce J. Schwartz, MD
Deputy Chairman & Professor of PsychiatryMontefiore Medical Center and Albert Einstein College of Medicine
New York, New York

I read with great enthusiasm Dr. Nasrallah’s editorial “Today’s psychiatric neuroscience advances were science fiction during my residency” (From the Editor, Current Psychiatry, April 2021, p. 5-7,12,24) and I, too, can see how our field has come a long way since my days of residency. However, as I read the article, I could not stop thinking about how many of the advances Dr. Nasrallah mentioned are still science fiction for the communities I work with.

I have spent all my professional life serving in the public sector, mainly in New York, and can tell you that many of the brain exploration methods, methodologies, and clinical advances mentioned in this article unfortunately are still a dream for us. Still, we remain hopeful that someday those transformative advances will come to us, too, especially as the technology innovates and improves!

Vania Castillo, MD
New York, New York

Dr. Nasrallah responds

Thank you for your comments. Please remember that every single treatment you are currently using in the public mental health system was a research discovery at one point in the past, and it took many years to bring it to clinical practice. Translating basic neuroscience discoveries, such as the ones I mentioned in my editorial, into clinical practice not only takes time to develop and get approved for use, but also requires substantial funding and a cadre of psychiatric physician-scientists, both of which are in short supply.

“Warp speed” COVID-19 vaccine development was possible only because the deadly pandemic became such an urgent national crisis that the government opened its coffers and diverted billions of dollars to pharmaceutical companies, with a massive infrastructure of human talent and biotechnology, making this veritable “moonshot” a reality in 1 year instead of many. Regrettably, even though neuropsychiatric disorders are a serious societal plague that causes disability and early mortality from suicide, homicide, substance use, cardiovascular risk, and accelerated aging, they do not command the urgency of an infectious viral pandemic that rapidly killed millions and shut down societies all over the world.

You probably heard the saying “a journey of a thousand miles begins with a single step.” I believe we are more than one step—maybe more than 100 steps—toward the type of breakthroughs that we all crave for our long-suffering psychiatric patients. I am grateful for the medical advances we have made over the past 10 to 15 years, such as neuromodulation, rapid-acting parenteral antidepressants, nondopaminergic antipsychotics, therapeutic hallucinogens, early recognition and intervention, and many promising neurobiologic leads and novel therapeutic targets for the brain disorders we deal with every day.

The brain is the most complex, challenging, and physically inaccessible organ to explore and treat. In medicine, we can do heart, lung, liver, and kidney biopsies, but it is far too dangerous to do brain biopsies that would help uncover the molecular and cellular underpinnings of neuropsychiatric disorders. Yet thankfully, our knowledge of the brain structure and function in health and disease has grown by >100,000% over the past few decades compared to the preceding millennia of dark ignorance. Someday, we shall overcome.

Disclosures
The authors report no financial relationships with any companies whose products are mentioned in their letters, or with manufacturers of competing products.

I wanted to thank Dr. Nasrallah for his bold article, “Treatment resistance is a myth!” (From the Editor, Current Psychiatry, March 2021, p. 14-16,28). “Treatment resistance” has become an overused catchphrase, largely for commercial purposes, that sends a distorted view to the public that current psychiatric treatments are ineffective. We have proven, safe, and effective treatments as covered in the article. So, instead of “treatment resistance,” we should be publicizing that “treatment works!” to encourage people to seek help for mental disorders and addictions.

Stanley N. Caroff, MD
Professor of Psychiatry
Perelman School of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania

I thought Dr. Nasrallah’s editorial on treatment resistance was excellent. In my experience, bipolar depression often is not diagnosed in patients with long-standing depression. These patients do worse on antidepressants, which is interpreted by the clinician as treatment-resistant major depressive disorder. The other issue for me is that individuals with bipolar disorder with psychotic features are often diagnosed with schizophrenia or schizo­affective disorder and never receive a trial of lithium, which could alter the course of their illness in a dramatic fashion. For me, the under­utilization of lithium is a real quality problem in our field. Keep up the good work!

Bruce J. Schwartz, MD
Deputy Chairman & Professor of PsychiatryMontefiore Medical Center and Albert Einstein College of Medicine
New York, New York

I read with great enthusiasm Dr. Nasrallah’s editorial “Today’s psychiatric neuroscience advances were science fiction during my residency” (From the Editor, Current Psychiatry, April 2021, p. 5-7,12,24) and I, too, can see how our field has come a long way since my days of residency. However, as I read the article, I could not stop thinking about how many of the advances Dr. Nasrallah mentioned are still science fiction for the communities I work with.

I have spent all my professional life serving in the public sector, mainly in New York, and can tell you that many of the brain exploration methods, methodologies, and clinical advances mentioned in this article unfortunately are still a dream for us. Still, we remain hopeful that someday those transformative advances will come to us, too, especially as the technology innovates and improves!

Vania Castillo, MD
New York, New York

Dr. Nasrallah responds

Thank you for your comments. Please remember that every single treatment you are currently using in the public mental health system was a research discovery at one point in the past, and it took many years to bring it to clinical practice. Translating basic neuroscience discoveries, such as the ones I mentioned in my editorial, into clinical practice not only takes time to develop and get approved for use, but also requires substantial funding and a cadre of psychiatric physician-scientists, both of which are in short supply.

“Warp speed” COVID-19 vaccine development was possible only because the deadly pandemic became such an urgent national crisis that the government opened its coffers and diverted billions of dollars to pharmaceutical companies, with a massive infrastructure of human talent and biotechnology, making this veritable “moonshot” a reality in 1 year instead of many. Regrettably, even though neuropsychiatric disorders are a serious societal plague that causes disability and early mortality from suicide, homicide, substance use, cardiovascular risk, and accelerated aging, they do not command the urgency of an infectious viral pandemic that rapidly killed millions and shut down societies all over the world.

You probably heard the saying “a journey of a thousand miles begins with a single step.” I believe we are more than one step—maybe more than 100 steps—toward the type of breakthroughs that we all crave for our long-suffering psychiatric patients. I am grateful for the medical advances we have made over the past 10 to 15 years, such as neuromodulation, rapid-acting parenteral antidepressants, nondopaminergic antipsychotics, therapeutic hallucinogens, early recognition and intervention, and many promising neurobiologic leads and novel therapeutic targets for the brain disorders we deal with every day.

The brain is the most complex, challenging, and physically inaccessible organ to explore and treat. In medicine, we can do heart, lung, liver, and kidney biopsies, but it is far too dangerous to do brain biopsies that would help uncover the molecular and cellular underpinnings of neuropsychiatric disorders. Yet thankfully, our knowledge of the brain structure and function in health and disease has grown by >100,000% over the past few decades compared to the preceding millennia of dark ignorance. Someday, we shall overcome.

Disclosures
The authors report no financial relationships with any companies whose products are mentioned in their letters, or with manufacturers of competing products.

I wanted to thank Dr. Nasrallah for his bold article, “Treatment resistance is a myth!” (From the Editor, Current Psychiatry, March 2021, p. 14-16,28). “Treatment resistance” has become an overused catchphrase, largely for commercial purposes, that sends a distorted view to the public that current psychiatric treatments are ineffective. We have proven, safe, and effective treatments as covered in the article. So, instead of “treatment resistance,” we should be publicizing that “treatment works!” to encourage people to seek help for mental disorders and addictions.

Stanley N. Caroff, MD
Professor of Psychiatry
Perelman School of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania

I thought Dr. Nasrallah’s editorial on treatment resistance was excellent. In my experience, bipolar depression often is not diagnosed in patients with long-standing depression. These patients do worse on antidepressants, which is interpreted by the clinician as treatment-resistant major depressive disorder. The other issue for me is that individuals with bipolar disorder with psychotic features are often diagnosed with schizophrenia or schizo­affective disorder and never receive a trial of lithium, which could alter the course of their illness in a dramatic fashion. For me, the under­utilization of lithium is a real quality problem in our field. Keep up the good work!

Bruce J. Schwartz, MD
Deputy Chairman & Professor of PsychiatryMontefiore Medical Center and Albert Einstein College of Medicine
New York, New York

I read with great enthusiasm Dr. Nasrallah’s editorial “Today’s psychiatric neuroscience advances were science fiction during my residency” (From the Editor, Current Psychiatry, April 2021, p. 5-7,12,24) and I, too, can see how our field has come a long way since my days of residency. However, as I read the article, I could not stop thinking about how many of the advances Dr. Nasrallah mentioned are still science fiction for the communities I work with.

I have spent all my professional life serving in the public sector, mainly in New York, and can tell you that many of the brain exploration methods, methodologies, and clinical advances mentioned in this article unfortunately are still a dream for us. Still, we remain hopeful that someday those transformative advances will come to us, too, especially as the technology innovates and improves!

Vania Castillo, MD
New York, New York

Dr. Nasrallah responds

Thank you for your comments. Please remember that every single treatment you are currently using in the public mental health system was a research discovery at one point in the past, and it took many years to bring it to clinical practice. Translating basic neuroscience discoveries, such as the ones I mentioned in my editorial, into clinical practice not only takes time to develop and get approved for use, but also requires substantial funding and a cadre of psychiatric physician-scientists, both of which are in short supply.

“Warp speed” COVID-19 vaccine development was possible only because the deadly pandemic became such an urgent national crisis that the government opened its coffers and diverted billions of dollars to pharmaceutical companies, with a massive infrastructure of human talent and biotechnology, making this veritable “moonshot” a reality in 1 year instead of many. Regrettably, even though neuropsychiatric disorders are a serious societal plague that causes disability and early mortality from suicide, homicide, substance use, cardiovascular risk, and accelerated aging, they do not command the urgency of an infectious viral pandemic that rapidly killed millions and shut down societies all over the world.

You probably heard the saying “a journey of a thousand miles begins with a single step.” I believe we are more than one step—maybe more than 100 steps—toward the type of breakthroughs that we all crave for our long-suffering psychiatric patients. I am grateful for the medical advances we have made over the past 10 to 15 years, such as neuromodulation, rapid-acting parenteral antidepressants, nondopaminergic antipsychotics, therapeutic hallucinogens, early recognition and intervention, and many promising neurobiologic leads and novel therapeutic targets for the brain disorders we deal with every day.

The brain is the most complex, challenging, and physically inaccessible organ to explore and treat. In medicine, we can do heart, lung, liver, and kidney biopsies, but it is far too dangerous to do brain biopsies that would help uncover the molecular and cellular underpinnings of neuropsychiatric disorders. Yet thankfully, our knowledge of the brain structure and function in health and disease has grown by >100,000% over the past few decades compared to the preceding millennia of dark ignorance. Someday, we shall overcome.

Disclosures
The authors report no financial relationships with any companies whose products are mentioned in their letters, or with manufacturers of competing products.

For this Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Altha J. Stewart, MD. Dr. Stewart is Senior Associate Dean for Community Health Engagement at the University of Tennessee Health Science Center (UTHSC)–Memphis. She also serves as Chief of the Division of Social and Community Psychiatry and Director, Center for Health in Justice Involved Youth at UTHSC, where she manages community-based programs serving children impacted by trauma and mental illness and their families. In 2018, she was elected President of the American Psychiatric Association, the first African American individual elected in the 175-year history of the organization.

Dr. Aftab: Structural racism in academic and organized psychiatry is an issue that is close to your heart. What is your perspective on the current state of structural racism in American psychiatry, and what do you think we can do about it?

Dr. Stewart: That’s a good question to start with because I think the conversations that we need to have in academia in general and in academic psychiatry specifically really do frame the current issues that we are facing, whether we’re talking about eliminating health disparities or achieving mental health equity. Historically, from the very beginning these discussions have been structured in a racist manner. The early days of American psychiatry were very clearly directed towards maintaining a system that excluded large segments of the population of the time, since a particularly violent form of chattel slavery was being practiced in this country.

The mental health care system was primarily designed for the landowning white men of some standing in society, and so there was never any intent to do much in the way of providing quality humane service to people who were not part of that group. What we have today is a system that was designed for a racist societal structure, that was intended to perpetuate certain behaviors, policies, and practices that had at their core a racist framework. We have to acknowledge and start from this beginning point. This is not to blame anyone currently alive. These are larger structural problems. Before we can begin setting up strategic plans and other actions, we have to go back and acknowledge how we got here. We have to accept the responsibility for being here, and then we have to allow the conversations that need to happen to happen in a safe way, without further alienating people, or maligning and demeaning people who are for the most part well-intentioned but perhaps operating on automatic pilot in a system that is structurally racist.

Dr. Aftab: Do you think that the conversations that need to happen are taking place?

Dr. Stewart: Yes, I think they are beginning to happen. I do a fair number of talks and grand rounds, and what I discover when I meet with different academic departments and different groups is that most places now have a diversity committee, or the residents and students have assigned themselves as diversity leaders. They are really pushing to have these conversations, to insert these conversations into the training and education curricula. The structures in power are so deeply entrenched that many people, particularly younger people, are easily frustrated by the lack of forward motion. One of the things that seasoned leaders in psychiatry have to do is to help everyone understand that the movement forward might be glacial in the beginning, but any movement forward is good when it comes to this. The psychiatrists of my generation talked about cultural competence in psychiatry, but generations of today talk about structural competence. These are similar concepts, except that cultural competency worked within the traditional model, while structural competency recognizes that the system itself needs to change. I find this development very encouraging.

Dr. Aftab: What do you see as some of the strengths of our profession?

Continue to: Dr. Stewart

Dr. Stewart: I am a hopeful optimist when it comes to psychiatry. I have dedicated my professional life to psychiatry and specifically to community psychiatry. Throughout the time that I have practiced psychiatry, I have been encouraged that what we do as a medical specialty really does improve the quality of life for the people we serve. Situationally right now, we’re in a unique position because the COVID pandemic has laid open and then laid bare the whole issue of how we deal with psychological distress, whether it’s diagnosed mental illness or a natural, normal response to a catastrophic event. We are the experts in this. This is our sweet spot, our wheelhouse, whatever analogy you prefer. This is the moment where we assert our expertise as the leaders—not as service add-ons, not as followers, not as adjuncts, but as the leaders.

I am so impressed with the next generation of psychiatrists. They have a wonderful blend of pride and privilege at what they have been able to accomplish to get to the point where they are doctors and psychiatrists, but they have aligned that with a strong core sense of social justice, and they are moved by their responsibility to the people in the society around them.

Another strength of our profession is what we consider to be the “art” of psychiatry. That is, the way we marry the relational aspects of psychiatry with the biological, technical, and digital aspects to arrive at a happy collaboration that benefits people. It is our great skill to engage people, to interact with them therapeutically, to recognize and acknowledge the nonverbal cues. This skill will be even more important in the age of online mental health services. I’m an “old-school” therapist. I like that face-to-face interaction. I think it’s important to preserve that aspect of our practice, even as we move towards online services.

Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?

Dr. Stewart: I don’t think we can afford to remain in status quo, because we need to constantly think and rethink, evaluate and re-evaluate, assess things in the light of new information. Particularly if we’re talking about people who rely on public funding to get even the bare minimum services, status quo doesn’t cut it. It’s not good enough. I had a teacher during my residency, a child psychiatrist, who used to say, “Good, better, best. Never let it rest, until your good is better and your better is best.” Something about that has stuck with me. As my career progressed, I heard variations of it, including one from former Surgeon General of the United States David Satcher, who was not a psychiatrist, but pulled together the group that published the first Surgeon General’s report on mental health, followed by the Surgeon General’s report on mental health, culture, race, and ethnicity. He had the penetrating insight that risk factors are not to be accepted as predictive factors due to protective factors. If I am at risk for mental illness or a chronic medical condition based on my race or ethnicity or socioeconomic status or employment status, this does not mean that I am destined to experience that illness. In fact, we are not doing our job if we accept these outcomes as inevitable and make no attempt to change them. So, for me, if we accept the status quo, we give up on the message of “Good, better, best. Never let it rest, until your good is better and your better is best.”

Continue to: Dr. Aftab

Dr. Aftab: What is your perception of the threats that psychiatry faces or is likely to face in the future?

Dr. Stewart: Well, this is going to sound harsh, and I do hope that the readers do not feel that I intend it to be harsh. We get in our own way. I work in the public sector, for example, and the reality is that there aren’t enough psychiatrists to provide all the necessary psychiatric services for the people who need them. So many mental health clinics and practices employ other mental health professionals, whether they are psychologists or nurse practitioners or physician assistants with special training in mental health to provide those services. To have a blanket concern about anyone who is not an MD practicing in what is considered “our area” just begs the question that if we can’t do it and we don’t have enough psychiatrists to do it, should people just not get mental health treatment? Is that the solution? I don’t think so. I don’t think that’s what people want, either, but because of the energy that gets aroused around these issues, we lose sight of that end goal. I think the answer is that we must take leadership for ensuring that our colleagues are well-trained, maybe not as well-trained as physicians, but well-trained enough to provide good care working under our supervision.

Dr. Aftab: What do you envision for the future of psychiatry? What sort of opportunities lie ahead for us?

Dr. Stewart: I think we are moving naturally into the space of integrated or collaborative care. I think we’re going to have to acknowledge that going forward, the path to being a good psychiatrist means that we will also be consultants. Not just the consultation-liaison kind of consultant that we typically think of, but a consultant to the rest of medicine around shaping programs, addressing how we treat comorbid illness, looking at ways to minimize the morbidity and mortality associated with some of the chronic medical and mental diseases. We’re moving naturally in that direction. For some people, that must be frightening. All throughout medicine people are witnessing change, and we need to adapt. I would hope that the specialty that is designed to help others deal with change will figure out how to use those skills to help themselves deal with the changes that are coming!

For this Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Altha J. Stewart, MD. Dr. Stewart is Senior Associate Dean for Community Health Engagement at the University of Tennessee Health Science Center (UTHSC)–Memphis. She also serves as Chief of the Division of Social and Community Psychiatry and Director, Center for Health in Justice Involved Youth at UTHSC, where she manages community-based programs serving children impacted by trauma and mental illness and their families. In 2018, she was elected President of the American Psychiatric Association, the first African American individual elected in the 175-year history of the organization.

Dr. Aftab: Structural racism in academic and organized psychiatry is an issue that is close to your heart. What is your perspective on the current state of structural racism in American psychiatry, and what do you think we can do about it?

Dr. Stewart: That’s a good question to start with because I think the conversations that we need to have in academia in general and in academic psychiatry specifically really do frame the current issues that we are facing, whether we’re talking about eliminating health disparities or achieving mental health equity. Historically, from the very beginning these discussions have been structured in a racist manner. The early days of American psychiatry were very clearly directed towards maintaining a system that excluded large segments of the population of the time, since a particularly violent form of chattel slavery was being practiced in this country.

The mental health care system was primarily designed for the landowning white men of some standing in society, and so there was never any intent to do much in the way of providing quality humane service to people who were not part of that group. What we have today is a system that was designed for a racist societal structure, that was intended to perpetuate certain behaviors, policies, and practices that had at their core a racist framework. We have to acknowledge and start from this beginning point. This is not to blame anyone currently alive. These are larger structural problems. Before we can begin setting up strategic plans and other actions, we have to go back and acknowledge how we got here. We have to accept the responsibility for being here, and then we have to allow the conversations that need to happen to happen in a safe way, without further alienating people, or maligning and demeaning people who are for the most part well-intentioned but perhaps operating on automatic pilot in a system that is structurally racist.

Dr. Aftab: Do you think that the conversations that need to happen are taking place?

Dr. Stewart: Yes, I think they are beginning to happen. I do a fair number of talks and grand rounds, and what I discover when I meet with different academic departments and different groups is that most places now have a diversity committee, or the residents and students have assigned themselves as diversity leaders. They are really pushing to have these conversations, to insert these conversations into the training and education curricula. The structures in power are so deeply entrenched that many people, particularly younger people, are easily frustrated by the lack of forward motion. One of the things that seasoned leaders in psychiatry have to do is to help everyone understand that the movement forward might be glacial in the beginning, but any movement forward is good when it comes to this. The psychiatrists of my generation talked about cultural competence in psychiatry, but generations of today talk about structural competence. These are similar concepts, except that cultural competency worked within the traditional model, while structural competency recognizes that the system itself needs to change. I find this development very encouraging.

Dr. Aftab: What do you see as some of the strengths of our profession?

Continue to: Dr. Stewart

Dr. Stewart: I am a hopeful optimist when it comes to psychiatry. I have dedicated my professional life to psychiatry and specifically to community psychiatry. Throughout the time that I have practiced psychiatry, I have been encouraged that what we do as a medical specialty really does improve the quality of life for the people we serve. Situationally right now, we’re in a unique position because the COVID pandemic has laid open and then laid bare the whole issue of how we deal with psychological distress, whether it’s diagnosed mental illness or a natural, normal response to a catastrophic event. We are the experts in this. This is our sweet spot, our wheelhouse, whatever analogy you prefer. This is the moment where we assert our expertise as the leaders—not as service add-ons, not as followers, not as adjuncts, but as the leaders.

I am so impressed with the next generation of psychiatrists. They have a wonderful blend of pride and privilege at what they have been able to accomplish to get to the point where they are doctors and psychiatrists, but they have aligned that with a strong core sense of social justice, and they are moved by their responsibility to the people in the society around them.

Another strength of our profession is what we consider to be the “art” of psychiatry. That is, the way we marry the relational aspects of psychiatry with the biological, technical, and digital aspects to arrive at a happy collaboration that benefits people. It is our great skill to engage people, to interact with them therapeutically, to recognize and acknowledge the nonverbal cues. This skill will be even more important in the age of online mental health services. I’m an “old-school” therapist. I like that face-to-face interaction. I think it’s important to preserve that aspect of our practice, even as we move towards online services.

Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?

Dr. Stewart: I don’t think we can afford to remain in status quo, because we need to constantly think and rethink, evaluate and re-evaluate, assess things in the light of new information. Particularly if we’re talking about people who rely on public funding to get even the bare minimum services, status quo doesn’t cut it. It’s not good enough. I had a teacher during my residency, a child psychiatrist, who used to say, “Good, better, best. Never let it rest, until your good is better and your better is best.” Something about that has stuck with me. As my career progressed, I heard variations of it, including one from former Surgeon General of the United States David Satcher, who was not a psychiatrist, but pulled together the group that published the first Surgeon General’s report on mental health, followed by the Surgeon General’s report on mental health, culture, race, and ethnicity. He had the penetrating insight that risk factors are not to be accepted as predictive factors due to protective factors. If I am at risk for mental illness or a chronic medical condition based on my race or ethnicity or socioeconomic status or employment status, this does not mean that I am destined to experience that illness. In fact, we are not doing our job if we accept these outcomes as inevitable and make no attempt to change them. So, for me, if we accept the status quo, we give up on the message of “Good, better, best. Never let it rest, until your good is better and your better is best.”

Continue to: Dr. Aftab

Dr. Aftab: What is your perception of the threats that psychiatry faces or is likely to face in the future?

Dr. Stewart: Well, this is going to sound harsh, and I do hope that the readers do not feel that I intend it to be harsh. We get in our own way. I work in the public sector, for example, and the reality is that there aren’t enough psychiatrists to provide all the necessary psychiatric services for the people who need them. So many mental health clinics and practices employ other mental health professionals, whether they are psychologists or nurse practitioners or physician assistants with special training in mental health to provide those services. To have a blanket concern about anyone who is not an MD practicing in what is considered “our area” just begs the question that if we can’t do it and we don’t have enough psychiatrists to do it, should people just not get mental health treatment? Is that the solution? I don’t think so. I don’t think that’s what people want, either, but because of the energy that gets aroused around these issues, we lose sight of that end goal. I think the answer is that we must take leadership for ensuring that our colleagues are well-trained, maybe not as well-trained as physicians, but well-trained enough to provide good care working under our supervision.

Dr. Aftab: What do you envision for the future of psychiatry? What sort of opportunities lie ahead for us?

Dr. Stewart: I think we are moving naturally into the space of integrated or collaborative care. I think we’re going to have to acknowledge that going forward, the path to being a good psychiatrist means that we will also be consultants. Not just the consultation-liaison kind of consultant that we typically think of, but a consultant to the rest of medicine around shaping programs, addressing how we treat comorbid illness, looking at ways to minimize the morbidity and mortality associated with some of the chronic medical and mental diseases. We’re moving naturally in that direction. For some people, that must be frightening. All throughout medicine people are witnessing change, and we need to adapt. I would hope that the specialty that is designed to help others deal with change will figure out how to use those skills to help themselves deal with the changes that are coming!

For this Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Altha J. Stewart, MD. Dr. Stewart is Senior Associate Dean for Community Health Engagement at the University of Tennessee Health Science Center (UTHSC)–Memphis. She also serves as Chief of the Division of Social and Community Psychiatry and Director, Center for Health in Justice Involved Youth at UTHSC, where she manages community-based programs serving children impacted by trauma and mental illness and their families. In 2018, she was elected President of the American Psychiatric Association, the first African American individual elected in the 175-year history of the organization.

Dr. Aftab: Structural racism in academic and organized psychiatry is an issue that is close to your heart. What is your perspective on the current state of structural racism in American psychiatry, and what do you think we can do about it?

Dr. Stewart: That’s a good question to start with because I think the conversations that we need to have in academia in general and in academic psychiatry specifically really do frame the current issues that we are facing, whether we’re talking about eliminating health disparities or achieving mental health equity. Historically, from the very beginning these discussions have been structured in a racist manner. The early days of American psychiatry were very clearly directed towards maintaining a system that excluded large segments of the population of the time, since a particularly violent form of chattel slavery was being practiced in this country.

The mental health care system was primarily designed for the landowning white men of some standing in society, and so there was never any intent to do much in the way of providing quality humane service to people who were not part of that group. What we have today is a system that was designed for a racist societal structure, that was intended to perpetuate certain behaviors, policies, and practices that had at their core a racist framework. We have to acknowledge and start from this beginning point. This is not to blame anyone currently alive. These are larger structural problems. Before we can begin setting up strategic plans and other actions, we have to go back and acknowledge how we got here. We have to accept the responsibility for being here, and then we have to allow the conversations that need to happen to happen in a safe way, without further alienating people, or maligning and demeaning people who are for the most part well-intentioned but perhaps operating on automatic pilot in a system that is structurally racist.

Dr. Aftab: Do you think that the conversations that need to happen are taking place?

Dr. Stewart: Yes, I think they are beginning to happen. I do a fair number of talks and grand rounds, and what I discover when I meet with different academic departments and different groups is that most places now have a diversity committee, or the residents and students have assigned themselves as diversity leaders. They are really pushing to have these conversations, to insert these conversations into the training and education curricula. The structures in power are so deeply entrenched that many people, particularly younger people, are easily frustrated by the lack of forward motion. One of the things that seasoned leaders in psychiatry have to do is to help everyone understand that the movement forward might be glacial in the beginning, but any movement forward is good when it comes to this. The psychiatrists of my generation talked about cultural competence in psychiatry, but generations of today talk about structural competence. These are similar concepts, except that cultural competency worked within the traditional model, while structural competency recognizes that the system itself needs to change. I find this development very encouraging.

Dr. Aftab: What do you see as some of the strengths of our profession?

Continue to: Dr. Stewart

Dr. Stewart: I am a hopeful optimist when it comes to psychiatry. I have dedicated my professional life to psychiatry and specifically to community psychiatry. Throughout the time that I have practiced psychiatry, I have been encouraged that what we do as a medical specialty really does improve the quality of life for the people we serve. Situationally right now, we’re in a unique position because the COVID pandemic has laid open and then laid bare the whole issue of how we deal with psychological distress, whether it’s diagnosed mental illness or a natural, normal response to a catastrophic event. We are the experts in this. This is our sweet spot, our wheelhouse, whatever analogy you prefer. This is the moment where we assert our expertise as the leaders—not as service add-ons, not as followers, not as adjuncts, but as the leaders.

I am so impressed with the next generation of psychiatrists. They have a wonderful blend of pride and privilege at what they have been able to accomplish to get to the point where they are doctors and psychiatrists, but they have aligned that with a strong core sense of social justice, and they are moved by their responsibility to the people in the society around them.

Another strength of our profession is what we consider to be the “art” of psychiatry. That is, the way we marry the relational aspects of psychiatry with the biological, technical, and digital aspects to arrive at a happy collaboration that benefits people. It is our great skill to engage people, to interact with them therapeutically, to recognize and acknowledge the nonverbal cues. This skill will be even more important in the age of online mental health services. I’m an “old-school” therapist. I like that face-to-face interaction. I think it’s important to preserve that aspect of our practice, even as we move towards online services.

Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?

Dr. Stewart: I don’t think we can afford to remain in status quo, because we need to constantly think and rethink, evaluate and re-evaluate, assess things in the light of new information. Particularly if we’re talking about people who rely on public funding to get even the bare minimum services, status quo doesn’t cut it. It’s not good enough. I had a teacher during my residency, a child psychiatrist, who used to say, “Good, better, best. Never let it rest, until your good is better and your better is best.” Something about that has stuck with me. As my career progressed, I heard variations of it, including one from former Surgeon General of the United States David Satcher, who was not a psychiatrist, but pulled together the group that published the first Surgeon General’s report on mental health, followed by the Surgeon General’s report on mental health, culture, race, and ethnicity. He had the penetrating insight that risk factors are not to be accepted as predictive factors due to protective factors. If I am at risk for mental illness or a chronic medical condition based on my race or ethnicity or socioeconomic status or employment status, this does not mean that I am destined to experience that illness. In fact, we are not doing our job if we accept these outcomes as inevitable and make no attempt to change them. So, for me, if we accept the status quo, we give up on the message of “Good, better, best. Never let it rest, until your good is better and your better is best.”

Continue to: Dr. Aftab

Dr. Aftab: What is your perception of the threats that psychiatry faces or is likely to face in the future?

Dr. Stewart: Well, this is going to sound harsh, and I do hope that the readers do not feel that I intend it to be harsh. We get in our own way. I work in the public sector, for example, and the reality is that there aren’t enough psychiatrists to provide all the necessary psychiatric services for the people who need them. So many mental health clinics and practices employ other mental health professionals, whether they are psychologists or nurse practitioners or physician assistants with special training in mental health to provide those services. To have a blanket concern about anyone who is not an MD practicing in what is considered “our area” just begs the question that if we can’t do it and we don’t have enough psychiatrists to do it, should people just not get mental health treatment? Is that the solution? I don’t think so. I don’t think that’s what people want, either, but because of the energy that gets aroused around these issues, we lose sight of that end goal. I think the answer is that we must take leadership for ensuring that our colleagues are well-trained, maybe not as well-trained as physicians, but well-trained enough to provide good care working under our supervision.

Dr. Aftab: What do you envision for the future of psychiatry? What sort of opportunities lie ahead for us?

Dr. Stewart: I think we are moving naturally into the space of integrated or collaborative care. I think we’re going to have to acknowledge that going forward, the path to being a good psychiatrist means that we will also be consultants. Not just the consultation-liaison kind of consultant that we typically think of, but a consultant to the rest of medicine around shaping programs, addressing how we treat comorbid illness, looking at ways to minimize the morbidity and mortality associated with some of the chronic medical and mental diseases. We’re moving naturally in that direction. For some people, that must be frightening. All throughout medicine people are witnessing change, and we need to adapt. I would hope that the specialty that is designed to help others deal with change will figure out how to use those skills to help themselves deal with the changes that are coming!

Lithium is one of the most widely used mood stabilizers and is considered a first-line treatment for bipolar disorder because of its proven antimanic and prophylactic effects.¹ This medication also can reduce the risk of suicide in patients with bipolar disorder.² However, it has a narrow therapeutic index. While lithium has many reversible adverse effects—such as tremors, gastrointestinal disturbance, and thyroid dysfunction—its perceived irreversible nephrotoxic effects makes some clinicians hesitant to prescribe it.^3,4 In this article, we describe the relationship between lithium and nephrotoxicity, explain the apparent contradiction in published research regarding this topic, and offer suggestions for how to determine whether you should continue treatment with lithium for a patient who develops renal changes.

A lithium dilemma

Many psychiatrists have faced the dilemma of whether to discontinue lithium upon the appearance of glomerular renal changes and risk exposing patients to relapse or suicide, or to continue prescribing lithium and risk development of end stage renal disease (ESRD). Discontinuing lithium is not associated with the reversal of renal changes and kidney recovery,⁵ and exposes patients to psychiatric risks, such as mood recurrence and increased risk of suicide.⁶ Switching from lithium to another mood stabilizer is associated with a host of adverse effects, including diabetes mellitus and weight gain, and mood stabilizer use is not associated with reduced renal risk in patients with bipolar disorder.⁵ For example, Markowitz et al⁶ evaluated 24 patients with renal insufficiency after an average of 13.6 years of chronic lithium treatment. Despite stopping lithium, 8 patients out of the 19 available for follow-up (42%) developed ESRD.⁶ This study also found that serum creatinine levels >2.5 mg/dL are a predictor of progression to ESRD.⁶

Discontinuing lithium is associated with high rates of mood recurrence (60% to 70%), especially for patients who had been stable on lithium for years.^7,8 If lithium is tapered slowly, the risk of mood recurrence may drop to approximately 42% over the subsequent 18 months, but this is nearly 3-fold greater than the risk of mood recurrence in patients with good response to valproate who are switched to another mood stabilizer (16.7%, c² = 4.3, P = .048),⁹ which suggests that stopping lithium is particularly problematic. Considering the lifetime consequences of bipolar illness, for most patients who have been receiving lithium for a long time, the recommendation is to continue lithium.^10,11

The reasons for conflicting evidence

Many studies indicate that there is either no statistically significant association or a very low association between lithium and developing ESRD,^12-16 while others suggest that long-term lithium treatment increases the risk of chronic nephropathy to a clinically relevant degree (note that these arguments are not mutually exclusive).^6,17-22 Much of this confusion has to do with not making a distinction between renal tubular dysfunction, which occurs early and in approximately one-half of patients treated with lithium,²³ and glomerular dysfunction, which occurs late and is associated with reductions in glomerular filtration and ESRD.²⁴ Adding to the confusion is that even without lithium, the rate of renal disease in patients with mood disorders is 2- to 3-fold higher than that of the general population.²⁵ Lithium treatment is associated with a rate that is higher still,^25-27 but this effect is erroneously exaggerated in studies that examined patients treated with lithium without comparison to a mood-disorder control group.

Renal tubular dysfunction presents as diabetes insipidus with polyuria and polydipsia, which is related to a reduced ability to concentrate the urine.²⁸ Reduced glomerular filtration rate (GFR) as a consequence of lithium treatment occurs in 15% of patients²³ and represents approximately 0.22% of patients on dialysis.¹⁸ Lithium-related reduction in GFR is a slowly progressive process that typically requires >20 years of lithium use to result in ESRD.¹⁸ While some decline in GFR may be seen within 1 year after starting lithium, the average age of patients who develop ESRD is 65 years.⁶ Interestingly, short-term animal studies have suggested that lithium may have antiproteinuric, protective, and pro-reparative effects in acute kidney injury.²⁹

Anatomical anomalies in lithium-related glomerular dysfunction

In a study conducted before improved imaging technology was developed, Markowitz et al⁶ used renal biopsy to evaluate lithium-related nephropathy in 24 patients.⁶ Findings revealed chronic tubulointerstitial nephritis in all patients, along with a wide range of abnormalities, including tubular atrophy and interstitial fibrosis interspersed with microcyst formation arising from distal tubules or collecting ducts.⁶ Focal segmental glomerulosclerosis (FSGS) was found in 50% of patients. This might have been a result of nephron loss and compensatory hypertrophy of surviving nephrons, which suggests that FSGS is possibly a post-adaptive effect (rather than a direct damaging effect) of lithium on the glomerulus. The most noticeable finding was the appearance of microcysts in 62.5% of patients.⁶ It is important to note that these biopsy techniques sampled a relatively small fraction of the kidney volume, and that microcysts might have been more prevalent.

Recently, noninvasive imaging techniques have been used to detect microcysts in patients developing lithium-related nephropathy. While ultrasound and computed tomography (CT) can detect renal microcysts, magnetic resonance imaging (MRI), specifically the half-Fourier acquisition single-shot turbo spin-echo T2-weighted and gadolinium-enhanced (FISP three-dimensional MR angiographic) sequence, is the best noninvasive technology to demonstrate the presence of renal microcysts of a diameter of 1 to 2 mm.³⁰ Ultrasound is sometimes difficult to utilize because while classic cysts appear as anechoic, lithium-induced microcysts may have the appearance of small echogenic foci.^31,32 When evaluated by CT, renal microcysts may appear as hypodense lesions.

Continue to: Recent small studies...

Recent small studies have shown that MRI can detect renal microcysts in approximately 100% of patients who are receiving chronic lithium treatment and have renal insufficiency. One MRI study found renal microcysts in all 16 patients.³³ In another MRI study of 4 patients, all were positive for renal microcysts.³⁴ The relationship between MRI findings and renal function impairment in patients receiving long-term lithium therapy is still not clear; however, 1 study that examined 35 patients who received lithium reported that the number of cysts is generally related to the duration of lithium therapy.³⁵ Thus, microcysts seem to present long before the elevation in creatinine, and nearly always present in patients with some glomerular dysfunction.

Cystic renal lesions have a wide variety of differential diagnoses, including simple renal cysts; glomerulocystic kidney disease; medullary cystic kidney disease and acquired cystic kidney disease; and multicystic dysplastic kidney and autosomal dominant polycystic kidney disease.³⁶ In patients who have a long history of lithium use, lithium-related nephrotoxicity should be added to the differential diagnosis. The ubiquitous presence of renal microcysts and their relationship to duration of lithium exposure and renal function suggest that they may be intimately related to lithium-related ESRD.³⁷

This association appears to be sufficiently reliable and clinicians can use T2-weighted MRI to determine if renal dysfunction is related to lithium. Lithium-related renal microcysts are visualized as multiple bilateral hyperintense foci with a diameter of 1 to 3 mm that involve both the cortex and medulla, tend to be symmetrically distributed throughout the kidney, and are associated with normal-sized kidneys.^33,36 Large cysts are unlikely to be related to lithium; only microcysts are associated with lithium treatment. For examples of how these cysts appear on MRI, see Figure 1, Figure 2, and Figure 3. The exact mechanism of lithium-related nephrotoxicity is unclear, but may be related to the mTOR (mammalian target of rapamycin) pathway or GSK-3beta (glycogen synthase kinase-3beta) (Box^6,37-44).

Box 1

Take-home points

In patients receiving chronic lithium treatment, it can take 20 years to produce a significant reduction in GFR. Switching patients who respond to lithium to other mood-stabilizing agents is associated with a significantly increased risk for mood recurrence and adverse consequences from the alternate medication. Because ESRD may occur more frequently in patients with mood disorders than in the general population, renal disease may be misattributed to lithium use. In approximately one-half of patients, renal disease will continue to progress after discontinuing lithium, which essentially eliminates the benefit of switching medications. This means that the decision to switch a patient who has responded well to lithium treatment for a decade or more to an alternate agent to avoid progression to ESRD may be associated with a very high potential cost but limited benefit.

One solution might be to more accurately identify patients with lithium-related glomerular disease, so that the potential benefit of switching may outweigh potential harm. The presence of renal microcysts on MRI of the kidney may be used to provide some of that reassurance. On renal biopsy, >60% of patients will have documented microcysts, and on MRI, it may approach 100%. The presence of microcysts provides potential evidence that reduced glomerular function is related to lithium. However, the absence of renal microcysts may not be as instructive—a negative MRI of the kidneys may not be sufficient evidence to rule out lithium as the culprit.

Continue to: Bottom Line

Lithium is an effective treatment for bipolar disorder, but its perceived irreversible nephrotoxic effects make some clinicians hesitant to prescribe it. Discontinuing lithium or switching to another medication also carries risks. For most patients who have been receiving lithium for a long time, the recommendation is to obtain a renal MRI and to cautiously continue lithium if the patient does not have microcysts.

Related Resources

• Hayes JF, Osborn DPJ, Francis E, et al. Prediction of individuals at high risk of chronic kidney disease during treatment with lithium for bipolar disorder. BMC Med. 2021;19(1):99. doi: 10.1186/s12916-021-01964-z
• Pelekanos M, Foo K. A resident’s guide to lithium. Current Psychiatry. 2021;20(4):e3-e7. doi:10.12788/cp.0113

Drug Brand Names

Lithium • Eskalith, Lithobid
Sirolimus • Rapamune
Valproate • Depacon

Lithium is one of the most widely used mood stabilizers and is considered a first-line treatment for bipolar disorder because of its proven antimanic and prophylactic effects.¹ This medication also can reduce the risk of suicide in patients with bipolar disorder.² However, it has a narrow therapeutic index. While lithium has many reversible adverse effects—such as tremors, gastrointestinal disturbance, and thyroid dysfunction—its perceived irreversible nephrotoxic effects makes some clinicians hesitant to prescribe it.^3,4 In this article, we describe the relationship between lithium and nephrotoxicity, explain the apparent contradiction in published research regarding this topic, and offer suggestions for how to determine whether you should continue treatment with lithium for a patient who develops renal changes.

A lithium dilemma

Many psychiatrists have faced the dilemma of whether to discontinue lithium upon the appearance of glomerular renal changes and risk exposing patients to relapse or suicide, or to continue prescribing lithium and risk development of end stage renal disease (ESRD). Discontinuing lithium is not associated with the reversal of renal changes and kidney recovery,⁵ and exposes patients to psychiatric risks, such as mood recurrence and increased risk of suicide.⁶ Switching from lithium to another mood stabilizer is associated with a host of adverse effects, including diabetes mellitus and weight gain, and mood stabilizer use is not associated with reduced renal risk in patients with bipolar disorder.⁵ For example, Markowitz et al⁶ evaluated 24 patients with renal insufficiency after an average of 13.6 years of chronic lithium treatment. Despite stopping lithium, 8 patients out of the 19 available for follow-up (42%) developed ESRD.⁶ This study also found that serum creatinine levels >2.5 mg/dL are a predictor of progression to ESRD.⁶

Discontinuing lithium is associated with high rates of mood recurrence (60% to 70%), especially for patients who had been stable on lithium for years.^7,8 If lithium is tapered slowly, the risk of mood recurrence may drop to approximately 42% over the subsequent 18 months, but this is nearly 3-fold greater than the risk of mood recurrence in patients with good response to valproate who are switched to another mood stabilizer (16.7%, c² = 4.3, P = .048),⁹ which suggests that stopping lithium is particularly problematic. Considering the lifetime consequences of bipolar illness, for most patients who have been receiving lithium for a long time, the recommendation is to continue lithium.^10,11

The reasons for conflicting evidence

Many studies indicate that there is either no statistically significant association or a very low association between lithium and developing ESRD,^12-16 while others suggest that long-term lithium treatment increases the risk of chronic nephropathy to a clinically relevant degree (note that these arguments are not mutually exclusive).^6,17-22 Much of this confusion has to do with not making a distinction between renal tubular dysfunction, which occurs early and in approximately one-half of patients treated with lithium,²³ and glomerular dysfunction, which occurs late and is associated with reductions in glomerular filtration and ESRD.²⁴ Adding to the confusion is that even without lithium, the rate of renal disease in patients with mood disorders is 2- to 3-fold higher than that of the general population.²⁵ Lithium treatment is associated with a rate that is higher still,^25-27 but this effect is erroneously exaggerated in studies that examined patients treated with lithium without comparison to a mood-disorder control group.

Renal tubular dysfunction presents as diabetes insipidus with polyuria and polydipsia, which is related to a reduced ability to concentrate the urine.²⁸ Reduced glomerular filtration rate (GFR) as a consequence of lithium treatment occurs in 15% of patients²³ and represents approximately 0.22% of patients on dialysis.¹⁸ Lithium-related reduction in GFR is a slowly progressive process that typically requires >20 years of lithium use to result in ESRD.¹⁸ While some decline in GFR may be seen within 1 year after starting lithium, the average age of patients who develop ESRD is 65 years.⁶ Interestingly, short-term animal studies have suggested that lithium may have antiproteinuric, protective, and pro-reparative effects in acute kidney injury.²⁹

Anatomical anomalies in lithium-related glomerular dysfunction

In a study conducted before improved imaging technology was developed, Markowitz et al⁶ used renal biopsy to evaluate lithium-related nephropathy in 24 patients.⁶ Findings revealed chronic tubulointerstitial nephritis in all patients, along with a wide range of abnormalities, including tubular atrophy and interstitial fibrosis interspersed with microcyst formation arising from distal tubules or collecting ducts.⁶ Focal segmental glomerulosclerosis (FSGS) was found in 50% of patients. This might have been a result of nephron loss and compensatory hypertrophy of surviving nephrons, which suggests that FSGS is possibly a post-adaptive effect (rather than a direct damaging effect) of lithium on the glomerulus. The most noticeable finding was the appearance of microcysts in 62.5% of patients.⁶ It is important to note that these biopsy techniques sampled a relatively small fraction of the kidney volume, and that microcysts might have been more prevalent.

Recently, noninvasive imaging techniques have been used to detect microcysts in patients developing lithium-related nephropathy. While ultrasound and computed tomography (CT) can detect renal microcysts, magnetic resonance imaging (MRI), specifically the half-Fourier acquisition single-shot turbo spin-echo T2-weighted and gadolinium-enhanced (FISP three-dimensional MR angiographic) sequence, is the best noninvasive technology to demonstrate the presence of renal microcysts of a diameter of 1 to 2 mm.³⁰ Ultrasound is sometimes difficult to utilize because while classic cysts appear as anechoic, lithium-induced microcysts may have the appearance of small echogenic foci.^31,32 When evaluated by CT, renal microcysts may appear as hypodense lesions.

Continue to: Recent small studies...

Recent small studies have shown that MRI can detect renal microcysts in approximately 100% of patients who are receiving chronic lithium treatment and have renal insufficiency. One MRI study found renal microcysts in all 16 patients.³³ In another MRI study of 4 patients, all were positive for renal microcysts.³⁴ The relationship between MRI findings and renal function impairment in patients receiving long-term lithium therapy is still not clear; however, 1 study that examined 35 patients who received lithium reported that the number of cysts is generally related to the duration of lithium therapy.³⁵ Thus, microcysts seem to present long before the elevation in creatinine, and nearly always present in patients with some glomerular dysfunction.

Cystic renal lesions have a wide variety of differential diagnoses, including simple renal cysts; glomerulocystic kidney disease; medullary cystic kidney disease and acquired cystic kidney disease; and multicystic dysplastic kidney and autosomal dominant polycystic kidney disease.³⁶ In patients who have a long history of lithium use, lithium-related nephrotoxicity should be added to the differential diagnosis. The ubiquitous presence of renal microcysts and their relationship to duration of lithium exposure and renal function suggest that they may be intimately related to lithium-related ESRD.³⁷

This association appears to be sufficiently reliable and clinicians can use T2-weighted MRI to determine if renal dysfunction is related to lithium. Lithium-related renal microcysts are visualized as multiple bilateral hyperintense foci with a diameter of 1 to 3 mm that involve both the cortex and medulla, tend to be symmetrically distributed throughout the kidney, and are associated with normal-sized kidneys.^33,36 Large cysts are unlikely to be related to lithium; only microcysts are associated with lithium treatment. For examples of how these cysts appear on MRI, see Figure 1, Figure 2, and Figure 3. The exact mechanism of lithium-related nephrotoxicity is unclear, but may be related to the mTOR (mammalian target of rapamycin) pathway or GSK-3beta (glycogen synthase kinase-3beta) (Box^6,37-44).

Box 1

Take-home points

In patients receiving chronic lithium treatment, it can take 20 years to produce a significant reduction in GFR. Switching patients who respond to lithium to other mood-stabilizing agents is associated with a significantly increased risk for mood recurrence and adverse consequences from the alternate medication. Because ESRD may occur more frequently in patients with mood disorders than in the general population, renal disease may be misattributed to lithium use. In approximately one-half of patients, renal disease will continue to progress after discontinuing lithium, which essentially eliminates the benefit of switching medications. This means that the decision to switch a patient who has responded well to lithium treatment for a decade or more to an alternate agent to avoid progression to ESRD may be associated with a very high potential cost but limited benefit.

One solution might be to more accurately identify patients with lithium-related glomerular disease, so that the potential benefit of switching may outweigh potential harm. The presence of renal microcysts on MRI of the kidney may be used to provide some of that reassurance. On renal biopsy, >60% of patients will have documented microcysts, and on MRI, it may approach 100%. The presence of microcysts provides potential evidence that reduced glomerular function is related to lithium. However, the absence of renal microcysts may not be as instructive—a negative MRI of the kidneys may not be sufficient evidence to rule out lithium as the culprit.

Continue to: Bottom Line

Lithium is an effective treatment for bipolar disorder, but its perceived irreversible nephrotoxic effects make some clinicians hesitant to prescribe it. Discontinuing lithium or switching to another medication also carries risks. For most patients who have been receiving lithium for a long time, the recommendation is to obtain a renal MRI and to cautiously continue lithium if the patient does not have microcysts.

Related Resources

• Hayes JF, Osborn DPJ, Francis E, et al. Prediction of individuals at high risk of chronic kidney disease during treatment with lithium for bipolar disorder. BMC Med. 2021;19(1):99. doi: 10.1186/s12916-021-01964-z
• Pelekanos M, Foo K. A resident’s guide to lithium. Current Psychiatry. 2021;20(4):e3-e7. doi:10.12788/cp.0113

Drug Brand Names

Lithium • Eskalith, Lithobid
Sirolimus • Rapamune
Valproate • Depacon

Lithium is one of the most widely used mood stabilizers and is considered a first-line treatment for bipolar disorder because of its proven antimanic and prophylactic effects.¹ This medication also can reduce the risk of suicide in patients with bipolar disorder.² However, it has a narrow therapeutic index. While lithium has many reversible adverse effects—such as tremors, gastrointestinal disturbance, and thyroid dysfunction—its perceived irreversible nephrotoxic effects makes some clinicians hesitant to prescribe it.^3,4 In this article, we describe the relationship between lithium and nephrotoxicity, explain the apparent contradiction in published research regarding this topic, and offer suggestions for how to determine whether you should continue treatment with lithium for a patient who develops renal changes.

A lithium dilemma

Many psychiatrists have faced the dilemma of whether to discontinue lithium upon the appearance of glomerular renal changes and risk exposing patients to relapse or suicide, or to continue prescribing lithium and risk development of end stage renal disease (ESRD). Discontinuing lithium is not associated with the reversal of renal changes and kidney recovery,⁵ and exposes patients to psychiatric risks, such as mood recurrence and increased risk of suicide.⁶ Switching from lithium to another mood stabilizer is associated with a host of adverse effects, including diabetes mellitus and weight gain, and mood stabilizer use is not associated with reduced renal risk in patients with bipolar disorder.⁵ For example, Markowitz et al⁶ evaluated 24 patients with renal insufficiency after an average of 13.6 years of chronic lithium treatment. Despite stopping lithium, 8 patients out of the 19 available for follow-up (42%) developed ESRD.⁶ This study also found that serum creatinine levels >2.5 mg/dL are a predictor of progression to ESRD.⁶

Discontinuing lithium is associated with high rates of mood recurrence (60% to 70%), especially for patients who had been stable on lithium for years.^7,8 If lithium is tapered slowly, the risk of mood recurrence may drop to approximately 42% over the subsequent 18 months, but this is nearly 3-fold greater than the risk of mood recurrence in patients with good response to valproate who are switched to another mood stabilizer (16.7%, c² = 4.3, P = .048),⁹ which suggests that stopping lithium is particularly problematic. Considering the lifetime consequences of bipolar illness, for most patients who have been receiving lithium for a long time, the recommendation is to continue lithium.^10,11

The reasons for conflicting evidence

Many studies indicate that there is either no statistically significant association or a very low association between lithium and developing ESRD,^12-16 while others suggest that long-term lithium treatment increases the risk of chronic nephropathy to a clinically relevant degree (note that these arguments are not mutually exclusive).^6,17-22 Much of this confusion has to do with not making a distinction between renal tubular dysfunction, which occurs early and in approximately one-half of patients treated with lithium,²³ and glomerular dysfunction, which occurs late and is associated with reductions in glomerular filtration and ESRD.²⁴ Adding to the confusion is that even without lithium, the rate of renal disease in patients with mood disorders is 2- to 3-fold higher than that of the general population.²⁵ Lithium treatment is associated with a rate that is higher still,^25-27 but this effect is erroneously exaggerated in studies that examined patients treated with lithium without comparison to a mood-disorder control group.

Renal tubular dysfunction presents as diabetes insipidus with polyuria and polydipsia, which is related to a reduced ability to concentrate the urine.²⁸ Reduced glomerular filtration rate (GFR) as a consequence of lithium treatment occurs in 15% of patients²³ and represents approximately 0.22% of patients on dialysis.¹⁸ Lithium-related reduction in GFR is a slowly progressive process that typically requires >20 years of lithium use to result in ESRD.¹⁸ While some decline in GFR may be seen within 1 year after starting lithium, the average age of patients who develop ESRD is 65 years.⁶ Interestingly, short-term animal studies have suggested that lithium may have antiproteinuric, protective, and pro-reparative effects in acute kidney injury.²⁹

Anatomical anomalies in lithium-related glomerular dysfunction

In a study conducted before improved imaging technology was developed, Markowitz et al⁶ used renal biopsy to evaluate lithium-related nephropathy in 24 patients.⁶ Findings revealed chronic tubulointerstitial nephritis in all patients, along with a wide range of abnormalities, including tubular atrophy and interstitial fibrosis interspersed with microcyst formation arising from distal tubules or collecting ducts.⁶ Focal segmental glomerulosclerosis (FSGS) was found in 50% of patients. This might have been a result of nephron loss and compensatory hypertrophy of surviving nephrons, which suggests that FSGS is possibly a post-adaptive effect (rather than a direct damaging effect) of lithium on the glomerulus. The most noticeable finding was the appearance of microcysts in 62.5% of patients.⁶ It is important to note that these biopsy techniques sampled a relatively small fraction of the kidney volume, and that microcysts might have been more prevalent.

Recently, noninvasive imaging techniques have been used to detect microcysts in patients developing lithium-related nephropathy. While ultrasound and computed tomography (CT) can detect renal microcysts, magnetic resonance imaging (MRI), specifically the half-Fourier acquisition single-shot turbo spin-echo T2-weighted and gadolinium-enhanced (FISP three-dimensional MR angiographic) sequence, is the best noninvasive technology to demonstrate the presence of renal microcysts of a diameter of 1 to 2 mm.³⁰ Ultrasound is sometimes difficult to utilize because while classic cysts appear as anechoic, lithium-induced microcysts may have the appearance of small echogenic foci.^31,32 When evaluated by CT, renal microcysts may appear as hypodense lesions.

Continue to: Recent small studies...

Recent small studies have shown that MRI can detect renal microcysts in approximately 100% of patients who are receiving chronic lithium treatment and have renal insufficiency. One MRI study found renal microcysts in all 16 patients.³³ In another MRI study of 4 patients, all were positive for renal microcysts.³⁴ The relationship between MRI findings and renal function impairment in patients receiving long-term lithium therapy is still not clear; however, 1 study that examined 35 patients who received lithium reported that the number of cysts is generally related to the duration of lithium therapy.³⁵ Thus, microcysts seem to present long before the elevation in creatinine, and nearly always present in patients with some glomerular dysfunction.

Cystic renal lesions have a wide variety of differential diagnoses, including simple renal cysts; glomerulocystic kidney disease; medullary cystic kidney disease and acquired cystic kidney disease; and multicystic dysplastic kidney and autosomal dominant polycystic kidney disease.³⁶ In patients who have a long history of lithium use, lithium-related nephrotoxicity should be added to the differential diagnosis. The ubiquitous presence of renal microcysts and their relationship to duration of lithium exposure and renal function suggest that they may be intimately related to lithium-related ESRD.³⁷

This association appears to be sufficiently reliable and clinicians can use T2-weighted MRI to determine if renal dysfunction is related to lithium. Lithium-related renal microcysts are visualized as multiple bilateral hyperintense foci with a diameter of 1 to 3 mm that involve both the cortex and medulla, tend to be symmetrically distributed throughout the kidney, and are associated with normal-sized kidneys.^33,36 Large cysts are unlikely to be related to lithium; only microcysts are associated with lithium treatment. For examples of how these cysts appear on MRI, see Figure 1, Figure 2, and Figure 3. The exact mechanism of lithium-related nephrotoxicity is unclear, but may be related to the mTOR (mammalian target of rapamycin) pathway or GSK-3beta (glycogen synthase kinase-3beta) (Box^6,37-44).

Box 1

Take-home points

In patients receiving chronic lithium treatment, it can take 20 years to produce a significant reduction in GFR. Switching patients who respond to lithium to other mood-stabilizing agents is associated with a significantly increased risk for mood recurrence and adverse consequences from the alternate medication. Because ESRD may occur more frequently in patients with mood disorders than in the general population, renal disease may be misattributed to lithium use. In approximately one-half of patients, renal disease will continue to progress after discontinuing lithium, which essentially eliminates the benefit of switching medications. This means that the decision to switch a patient who has responded well to lithium treatment for a decade or more to an alternate agent to avoid progression to ESRD may be associated with a very high potential cost but limited benefit.

One solution might be to more accurately identify patients with lithium-related glomerular disease, so that the potential benefit of switching may outweigh potential harm. The presence of renal microcysts on MRI of the kidney may be used to provide some of that reassurance. On renal biopsy, >60% of patients will have documented microcysts, and on MRI, it may approach 100%. The presence of microcysts provides potential evidence that reduced glomerular function is related to lithium. However, the absence of renal microcysts may not be as instructive—a negative MRI of the kidneys may not be sufficient evidence to rule out lithium as the culprit.

Continue to: Bottom Line

Lithium is an effective treatment for bipolar disorder, but its perceived irreversible nephrotoxic effects make some clinicians hesitant to prescribe it. Discontinuing lithium or switching to another medication also carries risks. For most patients who have been receiving lithium for a long time, the recommendation is to obtain a renal MRI and to cautiously continue lithium if the patient does not have microcysts.

Related Resources

• Hayes JF, Osborn DPJ, Francis E, et al. Prediction of individuals at high risk of chronic kidney disease during treatment with lithium for bipolar disorder. BMC Med. 2021;19(1):99. doi: 10.1186/s12916-021-01964-z
• Pelekanos M, Foo K. A resident’s guide to lithium. Current Psychiatry. 2021;20(4):e3-e7. doi:10.12788/cp.0113

Drug Brand Names

Lithium • Eskalith, Lithobid
Sirolimus • Rapamune
Valproate • Depacon

Deep endometriosis, including bowel endometriosis, happens in more than 10% of all women with endometriosis. Because it can be debilitating and difficult to diagnose, how is it identified?

Dr. Kho: Diagnosing deep infiltrating endometriosis (DIE) is one of the biggest challenges in the field. Currently, the gold standard is still histologic confirmation of endometriosis lesions, but I think the paradigm is shifting significantly. Advanced centers are now moving towards the use of imaging to visualize suspected endometriosis better. In skilled hands, ultrasonography and MRI can accurately detect DIE. The advantage of visualizing suspected deep endometriosis before surgery is that we can offer better counseling to patients and offer medical or surgical treatments or a combination of both. When the patient chooses surgery, we can be better prepared with a multidisciplinary team to remove the lesions completely.

The treatment of deep endometriosis can be challenging because it does not always respond to medical therapy, such as oral contraceptive pills or GnRH agonists. What treatment options have shown effectiveness?

Dr. Kho: It should be understood that we need to manage the symptoms and not the lesions. Just because there are endometriosis lesions identified does NOT mean that they need to be removed. The decision should be based on what the treatment goals are. A good discussion with the patient is important to determine what the treatment objectives are. Are we managing pain? Are we surgically treating infertility? Are we treating something else, such as bowel obstruction or blood in the urine? These questions and their answers should be first and foremost in the clinician’s mind.

Different medical treatment therapies are available and have been shown to be effective in managing endometriosis symptoms without having to immediately resort to surgery as with certain cases of suspected DIE. These medical management options include combined estrogen and progesterone contraceptive formulations, progesterone-only formulations, and GnRH agonists and antagonists. Patients should be counseled about the different options and their associated risks. Often, patients need to switch from one form to another when side effects encumber them. 

If imaging or an exam reveals incidental findings of suspected deep endometriosis, it does not mean that treatment is required because some patients can be without symptoms or have no issues. But when the indication for pain or desire to achieve a pregnancy is clear, and the decision is to proceed with treatment, there are some guidelines: 

• If the pain is severe and affects the patient’s daily quality of life, for example, with large, deep lesions, surgical excision appears to be effective in improving the patient’s quality of life. 
• If infertility is the main indication, then other factors need to be considered. Has she had previous surgeries? What is her age? What is her ovarian reserve? What is the condition of the tubes? Is the use of artificial reproductive technology, or ART, an option for the couple? What is her cancer risk? 
• Lastly, what is the extent of the lesion(s)? Both medical and surgical approaches for treatment carry risks. For surgery, complications can be severe with long-term consequences. Therefore, it is important to discuss all of this in detail with the patient. 

When we understand what the main goal of the treatment is for endometriosis—such as either to treat pain or to achieve pregnancy, or both—we can tailor our surgical approach to achieve the goal(s). For example, in a patient who wants to achieve a pregnancy in the future, we may opt to do only what is necessary to remove endometriosis and relieve pain without impairing the patient’s fertility potential and overall quality of life.   

Post-operatively, if the patient does not desire to become pregnant, medications to suppress the ovaries are an option to reduce the chance of disease recurrence.  

What pearls can you provide when it comes to surgical techniques available and benefits for short- and long-term risks and limitations?

Dr. Kho: The surgeon should tailor his or her level of radicality to excise endometriosis to achieve the treatment goals that are mutually agreed on with the patient. For the surgeon bringing the patient into surgery, go in prepared. I strongly believe in preoperative imaging to provide the best mapping of the disease and in having other specialists or surgeons available—whether it be a urologist, a colorectal surgeon, a thoracic surgeon, a vascular surgeon, or an orthopedic surgeon (if needed)—depending on where the lesions are located.  

Because we know that the best surgical outcomes come from surgeons with the highest volume, providers should be willing to refer patients with advanced disease to centers that specialize in the treatment of endometriosis. Many providers with this expertise undergo additional training to advance their skills. Advanced centers in endometriosis also provide patients with a multidisciplinary team to provide the best care.  

What is the most optimal setup for a multidisciplinary team treating deep infiltrating endometriosis?

Dr. Kho: You will find that advanced centers for endometriosis will have in place a multidisciplinary team that includes a pain specialist, a surgical specialist, a pain psychologist, physical therapy, urologist, colorectal surgeon, and other sub-specialty surgeons to be able to look at the patients from all the different aspects. Often a reproductive endocrinologist or REI specialist would also be part of the group. 

At our center, we have what we call a “benign tumor board,” where we discuss complex cases with representatives from different areas. This allows us to discuss the case, review what is known in the literature, and collectively develop a treatment plan.

Is there anything that was not covered in this discussion that you would like to mention?

Dr. Kho: Something that should be mentioned is that ovarian endometriosis is often associated with advanced endometriosis, often Stage 3 or 4. Clinicians should be aware that when imaging suggests the presence of ovarian endometriosis, studies show that the disease is isolated in the ovary in only 15% of cases—meaning that there is an 85% chance that endometriosis is present elsewhere in the pelvis. Therefore, the surgeon should be prepared for more extensive dissection when they bring the patient into surgery.

Deep endometriosis, including bowel endometriosis, happens in more than 10% of all women with endometriosis. Because it can be debilitating and difficult to diagnose, how is it identified?

Dr. Kho: Diagnosing deep infiltrating endometriosis (DIE) is one of the biggest challenges in the field. Currently, the gold standard is still histologic confirmation of endometriosis lesions, but I think the paradigm is shifting significantly. Advanced centers are now moving towards the use of imaging to visualize suspected endometriosis better. In skilled hands, ultrasonography and MRI can accurately detect DIE. The advantage of visualizing suspected deep endometriosis before surgery is that we can offer better counseling to patients and offer medical or surgical treatments or a combination of both. When the patient chooses surgery, we can be better prepared with a multidisciplinary team to remove the lesions completely.

The treatment of deep endometriosis can be challenging because it does not always respond to medical therapy, such as oral contraceptive pills or GnRH agonists. What treatment options have shown effectiveness?

Dr. Kho: It should be understood that we need to manage the symptoms and not the lesions. Just because there are endometriosis lesions identified does NOT mean that they need to be removed. The decision should be based on what the treatment goals are. A good discussion with the patient is important to determine what the treatment objectives are. Are we managing pain? Are we surgically treating infertility? Are we treating something else, such as bowel obstruction or blood in the urine? These questions and their answers should be first and foremost in the clinician’s mind.

Different medical treatment therapies are available and have been shown to be effective in managing endometriosis symptoms without having to immediately resort to surgery as with certain cases of suspected DIE. These medical management options include combined estrogen and progesterone contraceptive formulations, progesterone-only formulations, and GnRH agonists and antagonists. Patients should be counseled about the different options and their associated risks. Often, patients need to switch from one form to another when side effects encumber them. 

If imaging or an exam reveals incidental findings of suspected deep endometriosis, it does not mean that treatment is required because some patients can be without symptoms or have no issues. But when the indication for pain or desire to achieve a pregnancy is clear, and the decision is to proceed with treatment, there are some guidelines: 

• If the pain is severe and affects the patient’s daily quality of life, for example, with large, deep lesions, surgical excision appears to be effective in improving the patient’s quality of life. 
• If infertility is the main indication, then other factors need to be considered. Has she had previous surgeries? What is her age? What is her ovarian reserve? What is the condition of the tubes? Is the use of artificial reproductive technology, or ART, an option for the couple? What is her cancer risk? 
• Lastly, what is the extent of the lesion(s)? Both medical and surgical approaches for treatment carry risks. For surgery, complications can be severe with long-term consequences. Therefore, it is important to discuss all of this in detail with the patient. 

When we understand what the main goal of the treatment is for endometriosis—such as either to treat pain or to achieve pregnancy, or both—we can tailor our surgical approach to achieve the goal(s). For example, in a patient who wants to achieve a pregnancy in the future, we may opt to do only what is necessary to remove endometriosis and relieve pain without impairing the patient’s fertility potential and overall quality of life.   

Post-operatively, if the patient does not desire to become pregnant, medications to suppress the ovaries are an option to reduce the chance of disease recurrence.  

What pearls can you provide when it comes to surgical techniques available and benefits for short- and long-term risks and limitations?

Dr. Kho: The surgeon should tailor his or her level of radicality to excise endometriosis to achieve the treatment goals that are mutually agreed on with the patient. For the surgeon bringing the patient into surgery, go in prepared. I strongly believe in preoperative imaging to provide the best mapping of the disease and in having other specialists or surgeons available—whether it be a urologist, a colorectal surgeon, a thoracic surgeon, a vascular surgeon, or an orthopedic surgeon (if needed)—depending on where the lesions are located.  

Because we know that the best surgical outcomes come from surgeons with the highest volume, providers should be willing to refer patients with advanced disease to centers that specialize in the treatment of endometriosis. Many providers with this expertise undergo additional training to advance their skills. Advanced centers in endometriosis also provide patients with a multidisciplinary team to provide the best care.  

What is the most optimal setup for a multidisciplinary team treating deep infiltrating endometriosis?

Dr. Kho: You will find that advanced centers for endometriosis will have in place a multidisciplinary team that includes a pain specialist, a surgical specialist, a pain psychologist, physical therapy, urologist, colorectal surgeon, and other sub-specialty surgeons to be able to look at the patients from all the different aspects. Often a reproductive endocrinologist or REI specialist would also be part of the group. 

At our center, we have what we call a “benign tumor board,” where we discuss complex cases with representatives from different areas. This allows us to discuss the case, review what is known in the literature, and collectively develop a treatment plan.

Is there anything that was not covered in this discussion that you would like to mention?

Dr. Kho: Something that should be mentioned is that ovarian endometriosis is often associated with advanced endometriosis, often Stage 3 or 4. Clinicians should be aware that when imaging suggests the presence of ovarian endometriosis, studies show that the disease is isolated in the ovary in only 15% of cases—meaning that there is an 85% chance that endometriosis is present elsewhere in the pelvis. Therefore, the surgeon should be prepared for more extensive dissection when they bring the patient into surgery.

Deep endometriosis, including bowel endometriosis, happens in more than 10% of all women with endometriosis. Because it can be debilitating and difficult to diagnose, how is it identified?

Dr. Kho: Diagnosing deep infiltrating endometriosis (DIE) is one of the biggest challenges in the field. Currently, the gold standard is still histologic confirmation of endometriosis lesions, but I think the paradigm is shifting significantly. Advanced centers are now moving towards the use of imaging to visualize suspected endometriosis better. In skilled hands, ultrasonography and MRI can accurately detect DIE. The advantage of visualizing suspected deep endometriosis before surgery is that we can offer better counseling to patients and offer medical or surgical treatments or a combination of both. When the patient chooses surgery, we can be better prepared with a multidisciplinary team to remove the lesions completely.

The treatment of deep endometriosis can be challenging because it does not always respond to medical therapy, such as oral contraceptive pills or GnRH agonists. What treatment options have shown effectiveness?

Dr. Kho: It should be understood that we need to manage the symptoms and not the lesions. Just because there are endometriosis lesions identified does NOT mean that they need to be removed. The decision should be based on what the treatment goals are. A good discussion with the patient is important to determine what the treatment objectives are. Are we managing pain? Are we surgically treating infertility? Are we treating something else, such as bowel obstruction or blood in the urine? These questions and their answers should be first and foremost in the clinician’s mind.

Different medical treatment therapies are available and have been shown to be effective in managing endometriosis symptoms without having to immediately resort to surgery as with certain cases of suspected DIE. These medical management options include combined estrogen and progesterone contraceptive formulations, progesterone-only formulations, and GnRH agonists and antagonists. Patients should be counseled about the different options and their associated risks. Often, patients need to switch from one form to another when side effects encumber them. 

If imaging or an exam reveals incidental findings of suspected deep endometriosis, it does not mean that treatment is required because some patients can be without symptoms or have no issues. But when the indication for pain or desire to achieve a pregnancy is clear, and the decision is to proceed with treatment, there are some guidelines: 

• If the pain is severe and affects the patient’s daily quality of life, for example, with large, deep lesions, surgical excision appears to be effective in improving the patient’s quality of life. 
• If infertility is the main indication, then other factors need to be considered. Has she had previous surgeries? What is her age? What is her ovarian reserve? What is the condition of the tubes? Is the use of artificial reproductive technology, or ART, an option for the couple? What is her cancer risk? 
• Lastly, what is the extent of the lesion(s)? Both medical and surgical approaches for treatment carry risks. For surgery, complications can be severe with long-term consequences. Therefore, it is important to discuss all of this in detail with the patient. 

When we understand what the main goal of the treatment is for endometriosis—such as either to treat pain or to achieve pregnancy, or both—we can tailor our surgical approach to achieve the goal(s). For example, in a patient who wants to achieve a pregnancy in the future, we may opt to do only what is necessary to remove endometriosis and relieve pain without impairing the patient’s fertility potential and overall quality of life.   

Post-operatively, if the patient does not desire to become pregnant, medications to suppress the ovaries are an option to reduce the chance of disease recurrence.  

What pearls can you provide when it comes to surgical techniques available and benefits for short- and long-term risks and limitations?

Dr. Kho: The surgeon should tailor his or her level of radicality to excise endometriosis to achieve the treatment goals that are mutually agreed on with the patient. For the surgeon bringing the patient into surgery, go in prepared. I strongly believe in preoperative imaging to provide the best mapping of the disease and in having other specialists or surgeons available—whether it be a urologist, a colorectal surgeon, a thoracic surgeon, a vascular surgeon, or an orthopedic surgeon (if needed)—depending on where the lesions are located.  

Because we know that the best surgical outcomes come from surgeons with the highest volume, providers should be willing to refer patients with advanced disease to centers that specialize in the treatment of endometriosis. Many providers with this expertise undergo additional training to advance their skills. Advanced centers in endometriosis also provide patients with a multidisciplinary team to provide the best care.  

What is the most optimal setup for a multidisciplinary team treating deep infiltrating endometriosis?

Dr. Kho: You will find that advanced centers for endometriosis will have in place a multidisciplinary team that includes a pain specialist, a surgical specialist, a pain psychologist, physical therapy, urologist, colorectal surgeon, and other sub-specialty surgeons to be able to look at the patients from all the different aspects. Often a reproductive endocrinologist or REI specialist would also be part of the group. 

At our center, we have what we call a “benign tumor board,” where we discuss complex cases with representatives from different areas. This allows us to discuss the case, review what is known in the literature, and collectively develop a treatment plan.

Is there anything that was not covered in this discussion that you would like to mention?

Dr. Kho: Something that should be mentioned is that ovarian endometriosis is often associated with advanced endometriosis, often Stage 3 or 4. Clinicians should be aware that when imaging suggests the presence of ovarian endometriosis, studies show that the disease is isolated in the ovary in only 15% of cases—meaning that there is an 85% chance that endometriosis is present elsewhere in the pelvis. Therefore, the surgeon should be prepared for more extensive dissection when they bring the patient into surgery.

DDW is now history. While rejoicing that DDW happened (as opposed to when it couldn’t in 2020), the virtual format precluded all those hallway conversations, meetings with mentors and small group (after hour) discussions. This year, AGA saved substantial monies in travel costs. Of note, at Michigan Medicine, we track the miles patients did not have to travel because of our conversion to virtual care (currently about 30% of all ambulatory visits). To date, our “virtual first” protocol has saved over 24 million patient travel-miles since February 2020 (average of 62 miles per patient visit).

The pandemic forced rapid adoption of virtual care and alternative care delivery models. As patients adapted to telehealth, businesses saw opportunities. Health systems have begun to downsize their brick-and-mortar footprints for both clinical and office space. Hospital at Home models are developing as viable alternatives to inpatient care using a hybrid system of on-site nurses and remote physician supervision.

Digital health start-ups are developing rapidly, and equity funding for digital health companies has reached an all-time high of $26.5 billion in 2020. Multiple companies went public through traditional initial public offerings or special purpose acquisition companies. Sameer Berry, MD, recently collected an inventory of major GI digital health companies counted at least 16 with more appearing each month. These companies focus on management of a single condition (for example IBS or Celiac) or full-service virtual GI care that includes “at-risk” financial contracts

I am delighted to announce that Megan Adams, MD, JD, MSc, has been chosen to be the fourth editor in chief of GI & Hepatology News. She and her team will transition into editorial control during Fall 2021. I have known Megan since meeting her at an AGA young faculty function almost 10 years ago. She is extremely talented and knowledgeable about gastroenterology from a variety of viewpoints. She has recruited a strong and dedicated editorial board.

I have enjoyed the last 5 years leading the current board as we have brought breaking news to the GI community. I wish to publicly thank our editorial board and the Frontline staff who monthly publish AGA’s official newspaper.

John I. Allen, MD, MBA, AGAF
Editor in Chief

DDW is now history. While rejoicing that DDW happened (as opposed to when it couldn’t in 2020), the virtual format precluded all those hallway conversations, meetings with mentors and small group (after hour) discussions. This year, AGA saved substantial monies in travel costs. Of note, at Michigan Medicine, we track the miles patients did not have to travel because of our conversion to virtual care (currently about 30% of all ambulatory visits). To date, our “virtual first” protocol has saved over 24 million patient travel-miles since February 2020 (average of 62 miles per patient visit).

The pandemic forced rapid adoption of virtual care and alternative care delivery models. As patients adapted to telehealth, businesses saw opportunities. Health systems have begun to downsize their brick-and-mortar footprints for both clinical and office space. Hospital at Home models are developing as viable alternatives to inpatient care using a hybrid system of on-site nurses and remote physician supervision.

Digital health start-ups are developing rapidly, and equity funding for digital health companies has reached an all-time high of $26.5 billion in 2020. Multiple companies went public through traditional initial public offerings or special purpose acquisition companies. Sameer Berry, MD, recently collected an inventory of major GI digital health companies counted at least 16 with more appearing each month. These companies focus on management of a single condition (for example IBS or Celiac) or full-service virtual GI care that includes “at-risk” financial contracts

I am delighted to announce that Megan Adams, MD, JD, MSc, has been chosen to be the fourth editor in chief of GI & Hepatology News. She and her team will transition into editorial control during Fall 2021. I have known Megan since meeting her at an AGA young faculty function almost 10 years ago. She is extremely talented and knowledgeable about gastroenterology from a variety of viewpoints. She has recruited a strong and dedicated editorial board.

I have enjoyed the last 5 years leading the current board as we have brought breaking news to the GI community. I wish to publicly thank our editorial board and the Frontline staff who monthly publish AGA’s official newspaper.

John I. Allen, MD, MBA, AGAF
Editor in Chief

DDW is now history. While rejoicing that DDW happened (as opposed to when it couldn’t in 2020), the virtual format precluded all those hallway conversations, meetings with mentors and small group (after hour) discussions. This year, AGA saved substantial monies in travel costs. Of note, at Michigan Medicine, we track the miles patients did not have to travel because of our conversion to virtual care (currently about 30% of all ambulatory visits). To date, our “virtual first” protocol has saved over 24 million patient travel-miles since February 2020 (average of 62 miles per patient visit).

The pandemic forced rapid adoption of virtual care and alternative care delivery models. As patients adapted to telehealth, businesses saw opportunities. Health systems have begun to downsize their brick-and-mortar footprints for both clinical and office space. Hospital at Home models are developing as viable alternatives to inpatient care using a hybrid system of on-site nurses and remote physician supervision.

Digital health start-ups are developing rapidly, and equity funding for digital health companies has reached an all-time high of $26.5 billion in 2020. Multiple companies went public through traditional initial public offerings or special purpose acquisition companies. Sameer Berry, MD, recently collected an inventory of major GI digital health companies counted at least 16 with more appearing each month. These companies focus on management of a single condition (for example IBS or Celiac) or full-service virtual GI care that includes “at-risk” financial contracts

I am delighted to announce that Megan Adams, MD, JD, MSc, has been chosen to be the fourth editor in chief of GI & Hepatology News. She and her team will transition into editorial control during Fall 2021. I have known Megan since meeting her at an AGA young faculty function almost 10 years ago. She is extremely talented and knowledgeable about gastroenterology from a variety of viewpoints. She has recruited a strong and dedicated editorial board.

I have enjoyed the last 5 years leading the current board as we have brought breaking news to the GI community. I wish to publicly thank our editorial board and the Frontline staff who monthly publish AGA’s official newspaper.

John I. Allen, MD, MBA, AGAF
Editor in Chief

In the past, chemotherapy was the go-to treatment for patients with HR+/HER2- breast cancer with visceral metastases, which most commonly involve lung and liver. Dr Adam M. Brufsky, of the University of Pittsburgh School of Medicine, reports that the advent of CDK4/6 inhibitors offers an opportunity for several different courses of action appropriate to subgroups within this population of patients.

Three CDK4/6 inhibitors are FDA approved for clinical practice. Dr Brufsky summarizes results from three studies of CDK4/6 inhibitors — abemaciclib, ribociclib, and palbociclib — where these agents were used as second-line therapy after progression on a nonsteroidal aromatase inhibitor. In combination with fulvestrant, all three offered significant benefits in progression-free survival (PFS) and two in overall survival (OS). Among those who derived survival benefit were patients who had visceral metatases, who constituted 56%, 27% and 60% of the respective studies.

For patients who show progression on CDK4/6 inhibitors, additional treatment can be determined by genomic sequencing. Combination therapy with alpelisib and fulvestrant has been shown to lengthen PFS in patients whose tumors have PIK3 mutations. Patients without PIK3 mutations can be treated with fulvestrant or a combination of fulvestrant and everolimus.

--

Adam M. Brufsky, MD, PhD, Professor, Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine; Associate Chief, Department of Medicine, Division of Hematology-Oncology, UPMC-Hillman Cancer Center, Pittsburgh, Pennsylvania. 

Adam M. Brufsky, MD, PhD, has disclosed the following relevant financial relationships: 
Received income in an amount equal to or greater than $250 from: Seattle Genetics; Roche; AstraZeneca; Puma; Daiichi Sankyo.

In the past, chemotherapy was the go-to treatment for patients with HR+/HER2- breast cancer with visceral metastases, which most commonly involve lung and liver. Dr Adam M. Brufsky, of the University of Pittsburgh School of Medicine, reports that the advent of CDK4/6 inhibitors offers an opportunity for several different courses of action appropriate to subgroups within this population of patients.

Three CDK4/6 inhibitors are FDA approved for clinical practice. Dr Brufsky summarizes results from three studies of CDK4/6 inhibitors — abemaciclib, ribociclib, and palbociclib — where these agents were used as second-line therapy after progression on a nonsteroidal aromatase inhibitor. In combination with fulvestrant, all three offered significant benefits in progression-free survival (PFS) and two in overall survival (OS). Among those who derived survival benefit were patients who had visceral metatases, who constituted 56%, 27% and 60% of the respective studies.

For patients who show progression on CDK4/6 inhibitors, additional treatment can be determined by genomic sequencing. Combination therapy with alpelisib and fulvestrant has been shown to lengthen PFS in patients whose tumors have PIK3 mutations. Patients without PIK3 mutations can be treated with fulvestrant or a combination of fulvestrant and everolimus.

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Adam M. Brufsky, MD, PhD, Professor, Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine; Associate Chief, Department of Medicine, Division of Hematology-Oncology, UPMC-Hillman Cancer Center, Pittsburgh, Pennsylvania. 

Adam M. Brufsky, MD, PhD, has disclosed the following relevant financial relationships: 
Received income in an amount equal to or greater than $250 from: Seattle Genetics; Roche; AstraZeneca; Puma; Daiichi Sankyo.

In the past, chemotherapy was the go-to treatment for patients with HR+/HER2- breast cancer with visceral metastases, which most commonly involve lung and liver. Dr Adam M. Brufsky, of the University of Pittsburgh School of Medicine, reports that the advent of CDK4/6 inhibitors offers an opportunity for several different courses of action appropriate to subgroups within this population of patients.

Three CDK4/6 inhibitors are FDA approved for clinical practice. Dr Brufsky summarizes results from three studies of CDK4/6 inhibitors — abemaciclib, ribociclib, and palbociclib — where these agents were used as second-line therapy after progression on a nonsteroidal aromatase inhibitor. In combination with fulvestrant, all three offered significant benefits in progression-free survival (PFS) and two in overall survival (OS). Among those who derived survival benefit were patients who had visceral metatases, who constituted 56%, 27% and 60% of the respective studies.

For patients who show progression on CDK4/6 inhibitors, additional treatment can be determined by genomic sequencing. Combination therapy with alpelisib and fulvestrant has been shown to lengthen PFS in patients whose tumors have PIK3 mutations. Patients without PIK3 mutations can be treated with fulvestrant or a combination of fulvestrant and everolimus.

--

Adam M. Brufsky, MD, PhD, Professor, Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh School of Medicine; Associate Chief, Department of Medicine, Division of Hematology-Oncology, UPMC-Hillman Cancer Center, Pittsburgh, Pennsylvania. 

Adam M. Brufsky, MD, PhD, has disclosed the following relevant financial relationships: 
Received income in an amount equal to or greater than $250 from: Seattle Genetics; Roche; AstraZeneca; Puma; Daiichi Sankyo.

Credit cards have made it easier for psychiatrists who work in outpatient settings to collect payment for their services. Accepting credit cards saves time in sessions for clinical matters, leads to higher rates of collecting payments for patients who do not show up for appointments, and avoids having to manage bounced checks and collection agencies.¹ No federal or state laws prohibit businesses from storing consumers’ credit card information. However, psychiatric practices are legally obligated to have safeguards in place to protect sensitive information and limit liability exposures.² There are several steps to take when storing your patients’ credit card information.

Establish a payment policy. Create a policy that outlines your practice’s credit card procedures, including when credit cards will be charged and under what circumstances, how patients will be notified, and how credit card information will be stored.² Give your patients a copy of this policy and review it with them at their first appointment and any time you change this policy.² Get consent from your patients before using and storing their credit card information.²

Use secure methods to store this information. Most medical practices photocopy/write down their patients’ credit card information and store it in the patient’s electronic/paper medical record, or they use an online service to store it electronically.² Online services usually provide a higher level of protection than the patient’s medical record.² Ensure that electronic data that includes credit card numbers is robustly encrypted, or that paper records are locked in a secure place, such as in a safe or file drawer that requires a key/combination lock.³ Payment Card Industry (PCI) regulations prohibit storing a credit card’s security code (a three- or four-digit number on the front or back of the card).³ This code is used to allow merchants to verify whether a customer authorizing a transaction over the phone or via the internet physically possesses the card.³ PCI regulations also prohibit storing data contained in the card’s magnetic strip.³ This data contains information about the account that is not displayed on the card, assists with authorizing transactions, and ensures that credit cards cannot be easily counterfeited.³

Understand all federal and state laws and regulations. If your practice collects patient billing information, you are considered a “merchant” and are subject to federal and state laws and regulations that protect consumer credit card information.² These laws and regulations include (but are not limited to)²:

• Health Insurance Portability and Accountability Act (HIPAA) and similar state privacy laws
• Federal Trade Commission Act (FTCA) and similar state business laws
• Payment Card Industry Data Security Standard (PCI DSS), which was not devised by federal or state government.

HIPAA and state privacy laws require psychiatrists to implement “reasonable” security measures to protect payment information, regardless of how that information is stored.^2,4 Because HIPAA does not define “reasonable,” psychiatrists have latitude in determining which security measures to implement.^2,4 Locking the information in a file cabinet and locking the room where the file cabinet is kept (for paper storage) or using HIPAA-compliant encrypted storage programs (for electronic storage) are examples of “reasonable” security measures.²

FTCA requires businesses to use “appropriate” and “reasonable” security measures to protect credit card information.^2,5 Because FTCA does not specify these terms,^2,5 psychiatrists have leeway in determining which security measures to implement. Federal law requires all businesses to delete a card’s expiration date and shorten the account information to include no more than the last 5 digits of the card number that is printed on all sales receipts.⁶ FTCA also requires businesses to get prior authorization from individuals before charging their credit card.² For example, if a patient previously used a credit card to pay for a session, the psychiatrist cannot later use the credit card to charge for a missed appointment without notifying the patient and getting their authorization.²

PCI DSS applies to entities that store, process, and/or transmit cardholder data.⁷ Any business that accepts credit card payments must comply with PCI DSS, which includes 12 requirements.⁷ Examples of these requirements include using firewalls to protect cardholder data and restricting access to cardholder data to a “need-to-know” basis. Businesses that do not comply with PCI DSS can be subjected to fines and/or have their contracts terminated by the credit card companies.² Fines can range from $5,000 to $100,000 per month for data breaches where you are found negligible.¹

Credit cards have made it easier for psychiatrists who work in outpatient settings to collect payment for their services. Accepting credit cards saves time in sessions for clinical matters, leads to higher rates of collecting payments for patients who do not show up for appointments, and avoids having to manage bounced checks and collection agencies.¹ No federal or state laws prohibit businesses from storing consumers’ credit card information. However, psychiatric practices are legally obligated to have safeguards in place to protect sensitive information and limit liability exposures.² There are several steps to take when storing your patients’ credit card information.

Establish a payment policy. Create a policy that outlines your practice’s credit card procedures, including when credit cards will be charged and under what circumstances, how patients will be notified, and how credit card information will be stored.² Give your patients a copy of this policy and review it with them at their first appointment and any time you change this policy.² Get consent from your patients before using and storing their credit card information.²

Use secure methods to store this information. Most medical practices photocopy/write down their patients’ credit card information and store it in the patient’s electronic/paper medical record, or they use an online service to store it electronically.² Online services usually provide a higher level of protection than the patient’s medical record.² Ensure that electronic data that includes credit card numbers is robustly encrypted, or that paper records are locked in a secure place, such as in a safe or file drawer that requires a key/combination lock.³ Payment Card Industry (PCI) regulations prohibit storing a credit card’s security code (a three- or four-digit number on the front or back of the card).³ This code is used to allow merchants to verify whether a customer authorizing a transaction over the phone or via the internet physically possesses the card.³ PCI regulations also prohibit storing data contained in the card’s magnetic strip.³ This data contains information about the account that is not displayed on the card, assists with authorizing transactions, and ensures that credit cards cannot be easily counterfeited.³

Understand all federal and state laws and regulations. If your practice collects patient billing information, you are considered a “merchant” and are subject to federal and state laws and regulations that protect consumer credit card information.² These laws and regulations include (but are not limited to)²:

• Health Insurance Portability and Accountability Act (HIPAA) and similar state privacy laws
• Federal Trade Commission Act (FTCA) and similar state business laws
• Payment Card Industry Data Security Standard (PCI DSS), which was not devised by federal or state government.

HIPAA and state privacy laws require psychiatrists to implement “reasonable” security measures to protect payment information, regardless of how that information is stored.^2,4 Because HIPAA does not define “reasonable,” psychiatrists have latitude in determining which security measures to implement.^2,4 Locking the information in a file cabinet and locking the room where the file cabinet is kept (for paper storage) or using HIPAA-compliant encrypted storage programs (for electronic storage) are examples of “reasonable” security measures.²

FTCA requires businesses to use “appropriate” and “reasonable” security measures to protect credit card information.^2,5 Because FTCA does not specify these terms,^2,5 psychiatrists have leeway in determining which security measures to implement. Federal law requires all businesses to delete a card’s expiration date and shorten the account information to include no more than the last 5 digits of the card number that is printed on all sales receipts.⁶ FTCA also requires businesses to get prior authorization from individuals before charging their credit card.² For example, if a patient previously used a credit card to pay for a session, the psychiatrist cannot later use the credit card to charge for a missed appointment without notifying the patient and getting their authorization.²

PCI DSS applies to entities that store, process, and/or transmit cardholder data.⁷ Any business that accepts credit card payments must comply with PCI DSS, which includes 12 requirements.⁷ Examples of these requirements include using firewalls to protect cardholder data and restricting access to cardholder data to a “need-to-know” basis. Businesses that do not comply with PCI DSS can be subjected to fines and/or have their contracts terminated by the credit card companies.² Fines can range from $5,000 to $100,000 per month for data breaches where you are found negligible.¹

Credit cards have made it easier for psychiatrists who work in outpatient settings to collect payment for their services. Accepting credit cards saves time in sessions for clinical matters, leads to higher rates of collecting payments for patients who do not show up for appointments, and avoids having to manage bounced checks and collection agencies.¹ No federal or state laws prohibit businesses from storing consumers’ credit card information. However, psychiatric practices are legally obligated to have safeguards in place to protect sensitive information and limit liability exposures.² There are several steps to take when storing your patients’ credit card information.

Establish a payment policy. Create a policy that outlines your practice’s credit card procedures, including when credit cards will be charged and under what circumstances, how patients will be notified, and how credit card information will be stored.² Give your patients a copy of this policy and review it with them at their first appointment and any time you change this policy.² Get consent from your patients before using and storing their credit card information.²

Use secure methods to store this information. Most medical practices photocopy/write down their patients’ credit card information and store it in the patient’s electronic/paper medical record, or they use an online service to store it electronically.² Online services usually provide a higher level of protection than the patient’s medical record.² Ensure that electronic data that includes credit card numbers is robustly encrypted, or that paper records are locked in a secure place, such as in a safe or file drawer that requires a key/combination lock.³ Payment Card Industry (PCI) regulations prohibit storing a credit card’s security code (a three- or four-digit number on the front or back of the card).³ This code is used to allow merchants to verify whether a customer authorizing a transaction over the phone or via the internet physically possesses the card.³ PCI regulations also prohibit storing data contained in the card’s magnetic strip.³ This data contains information about the account that is not displayed on the card, assists with authorizing transactions, and ensures that credit cards cannot be easily counterfeited.³

Understand all federal and state laws and regulations. If your practice collects patient billing information, you are considered a “merchant” and are subject to federal and state laws and regulations that protect consumer credit card information.² These laws and regulations include (but are not limited to)²:

• Health Insurance Portability and Accountability Act (HIPAA) and similar state privacy laws
• Federal Trade Commission Act (FTCA) and similar state business laws
• Payment Card Industry Data Security Standard (PCI DSS), which was not devised by federal or state government.

HIPAA and state privacy laws require psychiatrists to implement “reasonable” security measures to protect payment information, regardless of how that information is stored.^2,4 Because HIPAA does not define “reasonable,” psychiatrists have latitude in determining which security measures to implement.^2,4 Locking the information in a file cabinet and locking the room where the file cabinet is kept (for paper storage) or using HIPAA-compliant encrypted storage programs (for electronic storage) are examples of “reasonable” security measures.²

FTCA requires businesses to use “appropriate” and “reasonable” security measures to protect credit card information.^2,5 Because FTCA does not specify these terms,^2,5 psychiatrists have leeway in determining which security measures to implement. Federal law requires all businesses to delete a card’s expiration date and shorten the account information to include no more than the last 5 digits of the card number that is printed on all sales receipts.⁶ FTCA also requires businesses to get prior authorization from individuals before charging their credit card.² For example, if a patient previously used a credit card to pay for a session, the psychiatrist cannot later use the credit card to charge for a missed appointment without notifying the patient and getting their authorization.²

PCI DSS applies to entities that store, process, and/or transmit cardholder data.⁷ Any business that accepts credit card payments must comply with PCI DSS, which includes 12 requirements.⁷ Examples of these requirements include using firewalls to protect cardholder data and restricting access to cardholder data to a “need-to-know” basis. Businesses that do not comply with PCI DSS can be subjected to fines and/or have their contracts terminated by the credit card companies.² Fines can range from $5,000 to $100,000 per month for data breaches where you are found negligible.¹