Lee S. Cohen, MD

The first of May is marked as the World Maternal Mental Health Day, a time for patient groups, medical societies, clinicians, and other colleagues who care for women to highlight maternal mental health and to advocate for increased awareness, enhanced access to care, decrease in stigma, and development of the most effective treatments.

In this spirit, and within the context of greater mental health awareness, I wanted to highlight the ironic dichotomy we see in reproductive psychiatry today. Namely, although we have many useful treatments available in the field to treat maternal psychiatric illness, there are barriers to accessing mental healthcare that prevent women from receiving treatment and getting well.

Thinking back on the last few years from the other side of the pandemic, when COVID concerns turned the experience of motherhood on its side in so many ways, we can only acknowledge that it is an important time in the field of reproductive psychiatry. We have seen not only the development of new pharmacologic (neurosteroids) and nonpharmacologic therapies (transcranial magnetic stimulation, cognitive-behaviorial therapy for perinatal depression), but also the focus on new digital apps for perinatal depression that may be scalable and that may help bridge the voids in access to effective treatment from the most rural to the most urban settings.

Cohen_Lee_S_BOSTON_web.jpg

In a previous column, I wrote about the potential difficulties of identifying at-risk women with postpartum psychiatric illness, particularly within the context of disparate data collection methods and management of data. Hospital systems that favor paper screening methods rather than digital platforms pose special problems. I also noted an even larger concern: namely, once screened, it can be very challenging to engage women with postpartum depression in treatment, and women may ultimately not navigate to care for a variety of reasons. These components are but one part of the so-called “perinatal treatment cascade.” When we look at access to care, patients would ideally move from depression screening as an example and, following endorsement of significant symptoms, would receive a referral, which would result in the patient being seen, followed up, and getting well. But that is not what is happening.

A recent preliminary study published as a short communication in the Archives of Women’s Mental Health highlighted this issue. The authors used the Edinburgh Postnatal Depression Scale (EPDS) to follow symptoms of depression in 145 pregnant women in ob.gyn. services, and found that there were low levels of adherence to psychiatric screenings and referrals in the perinatal period. Another study published in the Journal of Clinical Psychiatry found 30.8% of women with postpartum depression were identified clinically, 15.8% received treatment, and 3.2% achieved remission. That is the gulf, in 2024, that we have not managed to bridge.

The findings show the difficulty women experience accessing perinatal mental health resources. While we’ve known for a long time that the “perinatal treatment cascade” is real, what we don’t understand are the variables in the mix, particularly for patients in marginalized groups. We also do not know where women fall off the curve with regard to accessing care. In my mind, if we’re going to make a difference, we need to know the answer to that question.

Part of the issue is that the research into understanding why women fall off the curve is incomplete. You cannot simply hand a sheet to a woman with an EPDS score of 12 who’s depressed and has a newborn and expect her to navigate to care. What we should really be doing is investing in care navigation for women.

The situation is analogous to diagnosing and treating cardiac abnormalities in a catheterization laboratory. If a patient has a blocked coronary artery and needs a stent, then they need to go to the cath lab. We haven’t yet figured out the process in reproductive psychiatry to optimize the likelihood that patients will be screened and then referred to receive the best available treatment.

Some of our ob.gyn. colleagues have been working to improve access to perinatal mental health services, such as offering on-site services, and offering training and services to patients and providers on screening, assessment, and treatment. At the Center for Women’s Mental Health, we are conducting the Screening and Treatment Enhancement for Postpartum Depression study, which is a universal screening and referral program for women at our center. While some progress is being made, there are still far too many women who are falling through the cracks and not receiving the care they need.

It is both ironic and sad that the growing number of available treatments in reproductive psychiatry are scalable, yet we haven’t figured out how to facilitate access to care. While we should be excited about new treatments, we also need to take the time to understand what the barriers are for at-risk women accessing mental healthcare in the postpartum period.
 

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

The first of May is marked as the World Maternal Mental Health Day, a time for patient groups, medical societies, clinicians, and other colleagues who care for women to highlight maternal mental health and to advocate for increased awareness, enhanced access to care, decrease in stigma, and development of the most effective treatments.

In this spirit, and within the context of greater mental health awareness, I wanted to highlight the ironic dichotomy we see in reproductive psychiatry today. Namely, although we have many useful treatments available in the field to treat maternal psychiatric illness, there are barriers to accessing mental healthcare that prevent women from receiving treatment and getting well.

Thinking back on the last few years from the other side of the pandemic, when COVID concerns turned the experience of motherhood on its side in so many ways, we can only acknowledge that it is an important time in the field of reproductive psychiatry. We have seen not only the development of new pharmacologic (neurosteroids) and nonpharmacologic therapies (transcranial magnetic stimulation, cognitive-behaviorial therapy for perinatal depression), but also the focus on new digital apps for perinatal depression that may be scalable and that may help bridge the voids in access to effective treatment from the most rural to the most urban settings.

Cohen_Lee_S_BOSTON_web.jpg

In a previous column, I wrote about the potential difficulties of identifying at-risk women with postpartum psychiatric illness, particularly within the context of disparate data collection methods and management of data. Hospital systems that favor paper screening methods rather than digital platforms pose special problems. I also noted an even larger concern: namely, once screened, it can be very challenging to engage women with postpartum depression in treatment, and women may ultimately not navigate to care for a variety of reasons. These components are but one part of the so-called “perinatal treatment cascade.” When we look at access to care, patients would ideally move from depression screening as an example and, following endorsement of significant symptoms, would receive a referral, which would result in the patient being seen, followed up, and getting well. But that is not what is happening.

A recent preliminary study published as a short communication in the Archives of Women’s Mental Health highlighted this issue. The authors used the Edinburgh Postnatal Depression Scale (EPDS) to follow symptoms of depression in 145 pregnant women in ob.gyn. services, and found that there were low levels of adherence to psychiatric screenings and referrals in the perinatal period. Another study published in the Journal of Clinical Psychiatry found 30.8% of women with postpartum depression were identified clinically, 15.8% received treatment, and 3.2% achieved remission. That is the gulf, in 2024, that we have not managed to bridge.

The findings show the difficulty women experience accessing perinatal mental health resources. While we’ve known for a long time that the “perinatal treatment cascade” is real, what we don’t understand are the variables in the mix, particularly for patients in marginalized groups. We also do not know where women fall off the curve with regard to accessing care. In my mind, if we’re going to make a difference, we need to know the answer to that question.

Part of the issue is that the research into understanding why women fall off the curve is incomplete. You cannot simply hand a sheet to a woman with an EPDS score of 12 who’s depressed and has a newborn and expect her to navigate to care. What we should really be doing is investing in care navigation for women.

The situation is analogous to diagnosing and treating cardiac abnormalities in a catheterization laboratory. If a patient has a blocked coronary artery and needs a stent, then they need to go to the cath lab. We haven’t yet figured out the process in reproductive psychiatry to optimize the likelihood that patients will be screened and then referred to receive the best available treatment.

Some of our ob.gyn. colleagues have been working to improve access to perinatal mental health services, such as offering on-site services, and offering training and services to patients and providers on screening, assessment, and treatment. At the Center for Women’s Mental Health, we are conducting the Screening and Treatment Enhancement for Postpartum Depression study, which is a universal screening and referral program for women at our center. While some progress is being made, there are still far too many women who are falling through the cracks and not receiving the care they need.

It is both ironic and sad that the growing number of available treatments in reproductive psychiatry are scalable, yet we haven’t figured out how to facilitate access to care. While we should be excited about new treatments, we also need to take the time to understand what the barriers are for at-risk women accessing mental healthcare in the postpartum period.
 

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

The first of May is marked as the World Maternal Mental Health Day, a time for patient groups, medical societies, clinicians, and other colleagues who care for women to highlight maternal mental health and to advocate for increased awareness, enhanced access to care, decrease in stigma, and development of the most effective treatments.

In this spirit, and within the context of greater mental health awareness, I wanted to highlight the ironic dichotomy we see in reproductive psychiatry today. Namely, although we have many useful treatments available in the field to treat maternal psychiatric illness, there are barriers to accessing mental healthcare that prevent women from receiving treatment and getting well.

Thinking back on the last few years from the other side of the pandemic, when COVID concerns turned the experience of motherhood on its side in so many ways, we can only acknowledge that it is an important time in the field of reproductive psychiatry. We have seen not only the development of new pharmacologic (neurosteroids) and nonpharmacologic therapies (transcranial magnetic stimulation, cognitive-behaviorial therapy for perinatal depression), but also the focus on new digital apps for perinatal depression that may be scalable and that may help bridge the voids in access to effective treatment from the most rural to the most urban settings.

Cohen_Lee_S_BOSTON_web.jpg

In a previous column, I wrote about the potential difficulties of identifying at-risk women with postpartum psychiatric illness, particularly within the context of disparate data collection methods and management of data. Hospital systems that favor paper screening methods rather than digital platforms pose special problems. I also noted an even larger concern: namely, once screened, it can be very challenging to engage women with postpartum depression in treatment, and women may ultimately not navigate to care for a variety of reasons. These components are but one part of the so-called “perinatal treatment cascade.” When we look at access to care, patients would ideally move from depression screening as an example and, following endorsement of significant symptoms, would receive a referral, which would result in the patient being seen, followed up, and getting well. But that is not what is happening.

A recent preliminary study published as a short communication in the Archives of Women’s Mental Health highlighted this issue. The authors used the Edinburgh Postnatal Depression Scale (EPDS) to follow symptoms of depression in 145 pregnant women in ob.gyn. services, and found that there were low levels of adherence to psychiatric screenings and referrals in the perinatal period. Another study published in the Journal of Clinical Psychiatry found 30.8% of women with postpartum depression were identified clinically, 15.8% received treatment, and 3.2% achieved remission. That is the gulf, in 2024, that we have not managed to bridge.

The findings show the difficulty women experience accessing perinatal mental health resources. While we’ve known for a long time that the “perinatal treatment cascade” is real, what we don’t understand are the variables in the mix, particularly for patients in marginalized groups. We also do not know where women fall off the curve with regard to accessing care. In my mind, if we’re going to make a difference, we need to know the answer to that question.

Part of the issue is that the research into understanding why women fall off the curve is incomplete. You cannot simply hand a sheet to a woman with an EPDS score of 12 who’s depressed and has a newborn and expect her to navigate to care. What we should really be doing is investing in care navigation for women.

The situation is analogous to diagnosing and treating cardiac abnormalities in a catheterization laboratory. If a patient has a blocked coronary artery and needs a stent, then they need to go to the cath lab. We haven’t yet figured out the process in reproductive psychiatry to optimize the likelihood that patients will be screened and then referred to receive the best available treatment.

Some of our ob.gyn. colleagues have been working to improve access to perinatal mental health services, such as offering on-site services, and offering training and services to patients and providers on screening, assessment, and treatment. At the Center for Women’s Mental Health, we are conducting the Screening and Treatment Enhancement for Postpartum Depression study, which is a universal screening and referral program for women at our center. While some progress is being made, there are still far too many women who are falling through the cracks and not receiving the care they need.

It is both ironic and sad that the growing number of available treatments in reproductive psychiatry are scalable, yet we haven’t figured out how to facilitate access to care. While we should be excited about new treatments, we also need to take the time to understand what the barriers are for at-risk women accessing mental healthcare in the postpartum period.
 

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

The past year has been a challenging time for many, both at the local level and globally, with divisive undercurrents across many communities. Many times, the end of the year is an opportunity for reflection. As I reflect on the state of perinatal psychiatry in the new year, I see several evolving issues that I’d like to share in this first column of 2024.

In 2023, the American College of Obstetricians and Gynecologists published new recommendations meant to enhance the well-being of pregnant and postpartum women and families. A main message from discussion papers borne out of these recommendations was that as a field, we should be doing more than identifying perinatal illness. We should be screening women at risk for postpartum psychiatric illness and see that those suffering from posttraumatic stress disorder (PTSD) have access to care and “wrap-around services” from clinicians with varying expertise.

Cohen_Lee_S_BOSTON_web.jpg

Screening is a primary way we identify patients at risk for psychiatric illness and also those who are suffering at the time of a screen. One problem I see in the near future is our disparate collection and management of data. When we look closely across health care systems, it’s not clear how screening data are captured, let alone managed. What is being done in one hospital system may be very different from what is being done elsewhere. Some clinicians are adopting digital platforms to identify those with postpartum depression, while others are practicing as they always have, either through a paper screening process or with queries as part of a clinical encounter.

Given this amalgam of methods for collecting and storing information, there does not appear to be a systematic way clinicians and researchers are recording whether women are meeting criteria for significant depressive symptoms or frank postpartum psychiatric illness. It is clear a more cohesive method for collection and management is needed to optimize the likelihood that next steps can be taken to get patients the care they need.

However, screening is only one part of the story. Certainly, in our own center, one of our greatest interests, both clinically and on the research side, is what happens after screening. Through our center’s initiation of the Screening and Treatment Enhancement for Postpartum Depression (STEPS for PPD) project funded by the Marriott Foundation, we are evaluating the outcomes of women who are screened at 6 weeks postpartum with significant depressive symptoms, and who are then given an opportunity to engage with a perinatal social worker who can assist with direct psychotherapy, arranging for referrals, and navigating care for a new mother.

What we are learning as we enroll women through the initial stages of STEPS for PPD is that screening and identifying women who likely suffer from PPD simply is not enough. In fact, once identified with a depression screening tool, women who are suffering from postpartum depression can be very challenging to engage clinically. What I am learning decades after starting to work with perinatal patients is that even with a screening system and effective tools for treatment of PPD, optimizing engagement with these depressed women seems a critical and understudied step on the road to optimizing positive clinical outcomes.

A recent study published in the Journal of Women’s Health explored gaps in care for perinatal depression and found that patients without a history of psychiatric illness prior to pregnancy were less likely to be screened for depression and 80% less likely to receive care if they developed depression compared with women with a previous history of psychiatric illness (J Womens Health (Larchmt). 2023 Oct;32[10]:1111-9).

That history may help women navigate to care, while women for whom psychiatric illness is a new experience may be less likely to engage, be referred for care, and receive appropriate treatment. The study indicates that, as a field, we must strive to ensure universal screening for depression in perinatal populations.

While we have always been particularly interested in populations of patients at highest risk for PPD, helping women at risk for PPD in the general population without a history of psychiatric illness is a large public health issue and will be an even larger undertaking. As women’s mental health is gaining more appropriate focus, both at the local level and even in the recent White House Initiative on Women’s Health Research, the focus has been on screening and developing new treatments.

We are not lacking in pharmacologic agents nor nonpharmacologic options as treatments for women experiencing PPD. Newer alternative treatments are being explored, such as transcranial magnetic stimulation (TMS) and even psychedelics as a potential therapy for PPD. But perhaps what we’ve learned in 2023 and as we move into a new year, is that the problem of tackling PPD is not only about having the right tools, but is about helping women navigate to the care that they need.

The COVID-19 pandemic brought with it an explosion of telehealth options that have enhanced the odds women can find support during such a challenging time; as society has returned to some semblance of normal, nearly all support groups for postpartum women have remained online.

When we set up Virtual Rounds at the Center for Women’s Mental Health at the beginning of the pandemic, I was struck by the community of colleagues at various stages of their careers dedicated to mitigating the suffering associated with perinatal psychiatric illness. As I’ve often said, it takes a village to care for these patients. We need help from colleagues with varying expertise — from lactation consultants, psychiatrists, psychologists, obstetricians, nurse practitioners, support group leaders, and a host of others — who can help reach these women.

At the end of the day, helping depressed women find resources is a challenge that we have not met in this country. We should be excited that we have so many treatment options to offer patients — whether it be a new first-in-class medication, TMS, or digital apps to ensure patients are receiving effective treatment. But there should also be a focus on reaching women who still need treatment, particularly in underserved communities where resources are sparse or nonexistent. Identifying the path to reaching these women where they are and getting them well should be a top priority in 2024.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. STEPS for PPD is funded by the Marriott Foundation. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

The past year has been a challenging time for many, both at the local level and globally, with divisive undercurrents across many communities. Many times, the end of the year is an opportunity for reflection. As I reflect on the state of perinatal psychiatry in the new year, I see several evolving issues that I’d like to share in this first column of 2024.

In 2023, the American College of Obstetricians and Gynecologists published new recommendations meant to enhance the well-being of pregnant and postpartum women and families. A main message from discussion papers borne out of these recommendations was that as a field, we should be doing more than identifying perinatal illness. We should be screening women at risk for postpartum psychiatric illness and see that those suffering from posttraumatic stress disorder (PTSD) have access to care and “wrap-around services” from clinicians with varying expertise.

Cohen_Lee_S_BOSTON_web.jpg

Screening is a primary way we identify patients at risk for psychiatric illness and also those who are suffering at the time of a screen. One problem I see in the near future is our disparate collection and management of data. When we look closely across health care systems, it’s not clear how screening data are captured, let alone managed. What is being done in one hospital system may be very different from what is being done elsewhere. Some clinicians are adopting digital platforms to identify those with postpartum depression, while others are practicing as they always have, either through a paper screening process or with queries as part of a clinical encounter.

Given this amalgam of methods for collecting and storing information, there does not appear to be a systematic way clinicians and researchers are recording whether women are meeting criteria for significant depressive symptoms or frank postpartum psychiatric illness. It is clear a more cohesive method for collection and management is needed to optimize the likelihood that next steps can be taken to get patients the care they need.

However, screening is only one part of the story. Certainly, in our own center, one of our greatest interests, both clinically and on the research side, is what happens after screening. Through our center’s initiation of the Screening and Treatment Enhancement for Postpartum Depression (STEPS for PPD) project funded by the Marriott Foundation, we are evaluating the outcomes of women who are screened at 6 weeks postpartum with significant depressive symptoms, and who are then given an opportunity to engage with a perinatal social worker who can assist with direct psychotherapy, arranging for referrals, and navigating care for a new mother.

What we are learning as we enroll women through the initial stages of STEPS for PPD is that screening and identifying women who likely suffer from PPD simply is not enough. In fact, once identified with a depression screening tool, women who are suffering from postpartum depression can be very challenging to engage clinically. What I am learning decades after starting to work with perinatal patients is that even with a screening system and effective tools for treatment of PPD, optimizing engagement with these depressed women seems a critical and understudied step on the road to optimizing positive clinical outcomes.

A recent study published in the Journal of Women’s Health explored gaps in care for perinatal depression and found that patients without a history of psychiatric illness prior to pregnancy were less likely to be screened for depression and 80% less likely to receive care if they developed depression compared with women with a previous history of psychiatric illness (J Womens Health (Larchmt). 2023 Oct;32[10]:1111-9).

That history may help women navigate to care, while women for whom psychiatric illness is a new experience may be less likely to engage, be referred for care, and receive appropriate treatment. The study indicates that, as a field, we must strive to ensure universal screening for depression in perinatal populations.

While we have always been particularly interested in populations of patients at highest risk for PPD, helping women at risk for PPD in the general population without a history of psychiatric illness is a large public health issue and will be an even larger undertaking. As women’s mental health is gaining more appropriate focus, both at the local level and even in the recent White House Initiative on Women’s Health Research, the focus has been on screening and developing new treatments.

We are not lacking in pharmacologic agents nor nonpharmacologic options as treatments for women experiencing PPD. Newer alternative treatments are being explored, such as transcranial magnetic stimulation (TMS) and even psychedelics as a potential therapy for PPD. But perhaps what we’ve learned in 2023 and as we move into a new year, is that the problem of tackling PPD is not only about having the right tools, but is about helping women navigate to the care that they need.

The COVID-19 pandemic brought with it an explosion of telehealth options that have enhanced the odds women can find support during such a challenging time; as society has returned to some semblance of normal, nearly all support groups for postpartum women have remained online.

When we set up Virtual Rounds at the Center for Women’s Mental Health at the beginning of the pandemic, I was struck by the community of colleagues at various stages of their careers dedicated to mitigating the suffering associated with perinatal psychiatric illness. As I’ve often said, it takes a village to care for these patients. We need help from colleagues with varying expertise — from lactation consultants, psychiatrists, psychologists, obstetricians, nurse practitioners, support group leaders, and a host of others — who can help reach these women.

At the end of the day, helping depressed women find resources is a challenge that we have not met in this country. We should be excited that we have so many treatment options to offer patients — whether it be a new first-in-class medication, TMS, or digital apps to ensure patients are receiving effective treatment. But there should also be a focus on reaching women who still need treatment, particularly in underserved communities where resources are sparse or nonexistent. Identifying the path to reaching these women where they are and getting them well should be a top priority in 2024.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. STEPS for PPD is funded by the Marriott Foundation. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

The past year has been a challenging time for many, both at the local level and globally, with divisive undercurrents across many communities. Many times, the end of the year is an opportunity for reflection. As I reflect on the state of perinatal psychiatry in the new year, I see several evolving issues that I’d like to share in this first column of 2024.

In 2023, the American College of Obstetricians and Gynecologists published new recommendations meant to enhance the well-being of pregnant and postpartum women and families. A main message from discussion papers borne out of these recommendations was that as a field, we should be doing more than identifying perinatal illness. We should be screening women at risk for postpartum psychiatric illness and see that those suffering from posttraumatic stress disorder (PTSD) have access to care and “wrap-around services” from clinicians with varying expertise.

Cohen_Lee_S_BOSTON_web.jpg

Screening is a primary way we identify patients at risk for psychiatric illness and also those who are suffering at the time of a screen. One problem I see in the near future is our disparate collection and management of data. When we look closely across health care systems, it’s not clear how screening data are captured, let alone managed. What is being done in one hospital system may be very different from what is being done elsewhere. Some clinicians are adopting digital platforms to identify those with postpartum depression, while others are practicing as they always have, either through a paper screening process or with queries as part of a clinical encounter.

Given this amalgam of methods for collecting and storing information, there does not appear to be a systematic way clinicians and researchers are recording whether women are meeting criteria for significant depressive symptoms or frank postpartum psychiatric illness. It is clear a more cohesive method for collection and management is needed to optimize the likelihood that next steps can be taken to get patients the care they need.

However, screening is only one part of the story. Certainly, in our own center, one of our greatest interests, both clinically and on the research side, is what happens after screening. Through our center’s initiation of the Screening and Treatment Enhancement for Postpartum Depression (STEPS for PPD) project funded by the Marriott Foundation, we are evaluating the outcomes of women who are screened at 6 weeks postpartum with significant depressive symptoms, and who are then given an opportunity to engage with a perinatal social worker who can assist with direct psychotherapy, arranging for referrals, and navigating care for a new mother.

What we are learning as we enroll women through the initial stages of STEPS for PPD is that screening and identifying women who likely suffer from PPD simply is not enough. In fact, once identified with a depression screening tool, women who are suffering from postpartum depression can be very challenging to engage clinically. What I am learning decades after starting to work with perinatal patients is that even with a screening system and effective tools for treatment of PPD, optimizing engagement with these depressed women seems a critical and understudied step on the road to optimizing positive clinical outcomes.

A recent study published in the Journal of Women’s Health explored gaps in care for perinatal depression and found that patients without a history of psychiatric illness prior to pregnancy were less likely to be screened for depression and 80% less likely to receive care if they developed depression compared with women with a previous history of psychiatric illness (J Womens Health (Larchmt). 2023 Oct;32[10]:1111-9).

That history may help women navigate to care, while women for whom psychiatric illness is a new experience may be less likely to engage, be referred for care, and receive appropriate treatment. The study indicates that, as a field, we must strive to ensure universal screening for depression in perinatal populations.

While we have always been particularly interested in populations of patients at highest risk for PPD, helping women at risk for PPD in the general population without a history of psychiatric illness is a large public health issue and will be an even larger undertaking. As women’s mental health is gaining more appropriate focus, both at the local level and even in the recent White House Initiative on Women’s Health Research, the focus has been on screening and developing new treatments.

We are not lacking in pharmacologic agents nor nonpharmacologic options as treatments for women experiencing PPD. Newer alternative treatments are being explored, such as transcranial magnetic stimulation (TMS) and even psychedelics as a potential therapy for PPD. But perhaps what we’ve learned in 2023 and as we move into a new year, is that the problem of tackling PPD is not only about having the right tools, but is about helping women navigate to the care that they need.

The COVID-19 pandemic brought with it an explosion of telehealth options that have enhanced the odds women can find support during such a challenging time; as society has returned to some semblance of normal, nearly all support groups for postpartum women have remained online.

When we set up Virtual Rounds at the Center for Women’s Mental Health at the beginning of the pandemic, I was struck by the community of colleagues at various stages of their careers dedicated to mitigating the suffering associated with perinatal psychiatric illness. As I’ve often said, it takes a village to care for these patients. We need help from colleagues with varying expertise — from lactation consultants, psychiatrists, psychologists, obstetricians, nurse practitioners, support group leaders, and a host of others — who can help reach these women.

At the end of the day, helping depressed women find resources is a challenge that we have not met in this country. We should be excited that we have so many treatment options to offer patients — whether it be a new first-in-class medication, TMS, or digital apps to ensure patients are receiving effective treatment. But there should also be a focus on reaching women who still need treatment, particularly in underserved communities where resources are sparse or nonexistent. Identifying the path to reaching these women where they are and getting them well should be a top priority in 2024.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. STEPS for PPD is funded by the Marriott Foundation. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.

With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.

Cohen_Lee_S_BOSTON_web.jpg

When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.

It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.

Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.

FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.

Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.

The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.

Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
 

Looking ahead

While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.

In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.

To come out on the “other side” of the PLLR, we will need to find a way to accelerate our ability to identify signals of risk or information that is reassuring (or not reassuring) so that clinicians and patients are not left waiting for the next paper to come out, which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.

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

For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.

With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.

Cohen_Lee_S_BOSTON_web.jpg

When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.

It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.

Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.

FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.

Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.

The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.

Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
 

Looking ahead

While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.

In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.

To come out on the “other side” of the PLLR, we will need to find a way to accelerate our ability to identify signals of risk or information that is reassuring (or not reassuring) so that clinicians and patients are not left waiting for the next paper to come out, which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.

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

For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.

With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.

Cohen_Lee_S_BOSTON_web.jpg

When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.

It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.

Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.

FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.

Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.

The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.

Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
 

Looking ahead

While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.

In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.

To come out on the “other side” of the PLLR, we will need to find a way to accelerate our ability to identify signals of risk or information that is reassuring (or not reassuring) so that clinicians and patients are not left waiting for the next paper to come out, which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.

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

Postpartum depression (PPD) remains the most common complication in modern obstetrics, and a leading cause of postpartum mortality in the first year of life. The last 15 years have brought considerable progress with respect to adoption of systematic screening for PPD across America. Screening for PPD, most often using the Edinburgh Postnatal Depression Scale (EPDS), has become part of routine obstetrical care, and is also widely used in pediatric settings.

That is the good news. But the flip side of the identification of those women whose scores on the EPDS suggest significant depressive symptoms is that the number of these patients who, following identification, receive referrals for adequate treatment that gets them well is unfortunately low. This “perinatal treatment cascade” refers to the majority of women who, on the other side of identification of PPD, fail to receive adequate treatment and continue to have persistent depression (Cox E. et al. J Clin Psychiatry. 2016 Sep;77[9]:1189-1200). This is perhaps the greatest challenge to the field and to clinicians – how do we, on the other side of screening, see that these women get access to care and get well with the available treatments at hand?

Cohen_Lee_S_BOSTON_web.jpg

Recently, a widely read and circulated article was published in The Wall Street Journal about the challenges associated with navigating care resources for women suffering from PPD. In that article, it was made clear, based on clinical vignette after clinical vignette from postpartum women across America, that neither obstetricians, mental health professionals, nor pediatricians are the “clinical home” for women suffering from postpartum mood and anxiety disorders. The article painfully highlights the system-wide failure to coordinate mental health care for women suffering from postpartum psychiatric illness.

Within a day of the publication of The Wall Street Journal article, the Food and Drug Administration approved zuranolone (Zurzuvae; Sage Therapeutics; Cambridge, Mass.) for the treatment of PPD following the review of two studies demonstrating the superiority of the new medicine over placebo. Women who were enrolled met criteria for major depressive disorder based on Diagnostic and Statistical Manual of Mental Disorders criteria beginning in no earlier than the third trimester of pregnancy or later than 4 weeks of delivery. The two studies included a combined sample size of approximately 350 patients suffering from severe PPD. In the studies, women received either 50 mg or 40 mg of zuranolone, or placebo for 14 days. Treatment was associated with a significant change in the Hamilton Depression Rating Scale at day 15, and treatment response was maintained at day 42, which was 4 weeks after the last dose of study medication.

Zuranolone is a neuroactive steroid, which is taken orally, unlike brexanolone (Zulresso; Sage Therapeutics; Cambridge, Mass.), which requires intravenous administration. Zuranolone will be commercially available based on estimates around the fourth quarter of 2023. The most common side effects are drowsiness, dizziness, and sedation, and the FDA label will have a boxed warning about zuranolone’s potential to impact a person’s driving ability, and performance of potentially hazardous activities.

It is noteworthy that while this new medication received FDA approval for the PPD indication, it did not receive FDA approval for the treatment of major depressive disorder (MDD), and the agency issued a Complete Response Letter to the manufacturers noting their application did not provide substantial evidence of effectiveness in MDD. The FDA said in the Complete Response Letter that an additional study or studies will be needed; the manufacturers are currently evaluating next steps.
 

Where zuranolone fits into the treatment algorithm for severe PPD

Many clinicians who support women with PPD will wonder, upon hearing this news, where zuranolone fits into the treatment algorithm for severe postpartum major depression. Some relevant issues that may determine the answer are the following:

Cost. The cost of brexanolone was substantial, at $34,000 per year, and was viewed by some as a limiting factor in terms of its very limited uptake. As of this column’s publication, zuranolone’s manufacturer has not stated how much the medication will cost.

Breastfeeding. Unlike selective serotonin reuptake inhibitors, which have been demonstrated to be effective for the treatment of PPD and safe during pregnancy and lactation, we have sparse data on the safety of zuranolone for women who wish to breastfeed. It is also unclear whether women eligible for zuranolone would, based on the limited data on safety in lactation, choose deferral of breastfeeding for 14 days in exchange for treatment.

Duration of treatment. While zuranolone was studied in the context of 14 days of acute treatment, then out to day 42, we have no published data on what happens on the other side of this brief interval. As a simple example, in a patient with a history of recurrent major depression previously treated with antidepressants, but where antidepressants were perhaps deferred during pregnancy, is PPD to be treated with zuranolone for 14 days? Or, hypothetically, should it be followed by empiric antidepressant treatment at day 14? Alternatively, are patient and clinician supposed to wait until recurrence occurs before pursuing adjunctive antidepressant therapy whether it is pharmacologic, nonpharmacologic, or both?

Treatment in patients with bipolar disorder. It is also unclear whether treatment with zuranolone applies to other populations of postpartum women. Certainly, for women with bipolar depression, which is common in postpartum women given the vulnerability of bipolar women to new onset of depression or postpartum depressive relapse of underlying disorder, we simply have no data regarding where zuranolone might fit in with respect to this group of patients.

The answers to these questions may help to determine whether zuranolone, a new antidepressant with efficacy, quick time to onset, and a novel mechanism of action is a “game changer.” The article in The Wall Street Journal provided me with some optimism, as it gave PPD and the issues surrounding PPD the attention it deserves in a major periodical. As a new treatment, it may help alleviate suffering at a critical time for patients and their families. We are inching closer to mitigation of stigma associated with this common illness.

Thinking back across the last 3 decades of my treating women suffering from PPD, I have reflected on what has gotten these patients well. I concluded that successful treatment of PPD is not a “one-stop shop,” but rather typically includes a combination of pharmacologic and nonpharmacologic interventions, along with family and community-based support groups, as well as a culture that reduces stigma and by so doing lessens the toll of this important and too frequently incompletely-treated illness.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. The Center for Women’s Mental Health at MGH was a non-enrolling site for the pivotal phase 3 SKYLARK trial evaluating zuranolone. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

Postpartum depression (PPD) remains the most common complication in modern obstetrics, and a leading cause of postpartum mortality in the first year of life. The last 15 years have brought considerable progress with respect to adoption of systematic screening for PPD across America. Screening for PPD, most often using the Edinburgh Postnatal Depression Scale (EPDS), has become part of routine obstetrical care, and is also widely used in pediatric settings.

That is the good news. But the flip side of the identification of those women whose scores on the EPDS suggest significant depressive symptoms is that the number of these patients who, following identification, receive referrals for adequate treatment that gets them well is unfortunately low. This “perinatal treatment cascade” refers to the majority of women who, on the other side of identification of PPD, fail to receive adequate treatment and continue to have persistent depression (Cox E. et al. J Clin Psychiatry. 2016 Sep;77[9]:1189-1200). This is perhaps the greatest challenge to the field and to clinicians – how do we, on the other side of screening, see that these women get access to care and get well with the available treatments at hand?

Cohen_Lee_S_BOSTON_web.jpg

Recently, a widely read and circulated article was published in The Wall Street Journal about the challenges associated with navigating care resources for women suffering from PPD. In that article, it was made clear, based on clinical vignette after clinical vignette from postpartum women across America, that neither obstetricians, mental health professionals, nor pediatricians are the “clinical home” for women suffering from postpartum mood and anxiety disorders. The article painfully highlights the system-wide failure to coordinate mental health care for women suffering from postpartum psychiatric illness.

Within a day of the publication of The Wall Street Journal article, the Food and Drug Administration approved zuranolone (Zurzuvae; Sage Therapeutics; Cambridge, Mass.) for the treatment of PPD following the review of two studies demonstrating the superiority of the new medicine over placebo. Women who were enrolled met criteria for major depressive disorder based on Diagnostic and Statistical Manual of Mental Disorders criteria beginning in no earlier than the third trimester of pregnancy or later than 4 weeks of delivery. The two studies included a combined sample size of approximately 350 patients suffering from severe PPD. In the studies, women received either 50 mg or 40 mg of zuranolone, or placebo for 14 days. Treatment was associated with a significant change in the Hamilton Depression Rating Scale at day 15, and treatment response was maintained at day 42, which was 4 weeks after the last dose of study medication.

Zuranolone is a neuroactive steroid, which is taken orally, unlike brexanolone (Zulresso; Sage Therapeutics; Cambridge, Mass.), which requires intravenous administration. Zuranolone will be commercially available based on estimates around the fourth quarter of 2023. The most common side effects are drowsiness, dizziness, and sedation, and the FDA label will have a boxed warning about zuranolone’s potential to impact a person’s driving ability, and performance of potentially hazardous activities.

It is noteworthy that while this new medication received FDA approval for the PPD indication, it did not receive FDA approval for the treatment of major depressive disorder (MDD), and the agency issued a Complete Response Letter to the manufacturers noting their application did not provide substantial evidence of effectiveness in MDD. The FDA said in the Complete Response Letter that an additional study or studies will be needed; the manufacturers are currently evaluating next steps.
 

Where zuranolone fits into the treatment algorithm for severe PPD

Many clinicians who support women with PPD will wonder, upon hearing this news, where zuranolone fits into the treatment algorithm for severe postpartum major depression. Some relevant issues that may determine the answer are the following:

Cost. The cost of brexanolone was substantial, at $34,000 per year, and was viewed by some as a limiting factor in terms of its very limited uptake. As of this column’s publication, zuranolone’s manufacturer has not stated how much the medication will cost.

Breastfeeding. Unlike selective serotonin reuptake inhibitors, which have been demonstrated to be effective for the treatment of PPD and safe during pregnancy and lactation, we have sparse data on the safety of zuranolone for women who wish to breastfeed. It is also unclear whether women eligible for zuranolone would, based on the limited data on safety in lactation, choose deferral of breastfeeding for 14 days in exchange for treatment.

Duration of treatment. While zuranolone was studied in the context of 14 days of acute treatment, then out to day 42, we have no published data on what happens on the other side of this brief interval. As a simple example, in a patient with a history of recurrent major depression previously treated with antidepressants, but where antidepressants were perhaps deferred during pregnancy, is PPD to be treated with zuranolone for 14 days? Or, hypothetically, should it be followed by empiric antidepressant treatment at day 14? Alternatively, are patient and clinician supposed to wait until recurrence occurs before pursuing adjunctive antidepressant therapy whether it is pharmacologic, nonpharmacologic, or both?

Treatment in patients with bipolar disorder. It is also unclear whether treatment with zuranolone applies to other populations of postpartum women. Certainly, for women with bipolar depression, which is common in postpartum women given the vulnerability of bipolar women to new onset of depression or postpartum depressive relapse of underlying disorder, we simply have no data regarding where zuranolone might fit in with respect to this group of patients.

The answers to these questions may help to determine whether zuranolone, a new antidepressant with efficacy, quick time to onset, and a novel mechanism of action is a “game changer.” The article in The Wall Street Journal provided me with some optimism, as it gave PPD and the issues surrounding PPD the attention it deserves in a major periodical. As a new treatment, it may help alleviate suffering at a critical time for patients and their families. We are inching closer to mitigation of stigma associated with this common illness.

Thinking back across the last 3 decades of my treating women suffering from PPD, I have reflected on what has gotten these patients well. I concluded that successful treatment of PPD is not a “one-stop shop,” but rather typically includes a combination of pharmacologic and nonpharmacologic interventions, along with family and community-based support groups, as well as a culture that reduces stigma and by so doing lessens the toll of this important and too frequently incompletely-treated illness.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. The Center for Women’s Mental Health at MGH was a non-enrolling site for the pivotal phase 3 SKYLARK trial evaluating zuranolone. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

Postpartum depression (PPD) remains the most common complication in modern obstetrics, and a leading cause of postpartum mortality in the first year of life. The last 15 years have brought considerable progress with respect to adoption of systematic screening for PPD across America. Screening for PPD, most often using the Edinburgh Postnatal Depression Scale (EPDS), has become part of routine obstetrical care, and is also widely used in pediatric settings.

That is the good news. But the flip side of the identification of those women whose scores on the EPDS suggest significant depressive symptoms is that the number of these patients who, following identification, receive referrals for adequate treatment that gets them well is unfortunately low. This “perinatal treatment cascade” refers to the majority of women who, on the other side of identification of PPD, fail to receive adequate treatment and continue to have persistent depression (Cox E. et al. J Clin Psychiatry. 2016 Sep;77[9]:1189-1200). This is perhaps the greatest challenge to the field and to clinicians – how do we, on the other side of screening, see that these women get access to care and get well with the available treatments at hand?

Cohen_Lee_S_BOSTON_web.jpg

Recently, a widely read and circulated article was published in The Wall Street Journal about the challenges associated with navigating care resources for women suffering from PPD. In that article, it was made clear, based on clinical vignette after clinical vignette from postpartum women across America, that neither obstetricians, mental health professionals, nor pediatricians are the “clinical home” for women suffering from postpartum mood and anxiety disorders. The article painfully highlights the system-wide failure to coordinate mental health care for women suffering from postpartum psychiatric illness.

Within a day of the publication of The Wall Street Journal article, the Food and Drug Administration approved zuranolone (Zurzuvae; Sage Therapeutics; Cambridge, Mass.) for the treatment of PPD following the review of two studies demonstrating the superiority of the new medicine over placebo. Women who were enrolled met criteria for major depressive disorder based on Diagnostic and Statistical Manual of Mental Disorders criteria beginning in no earlier than the third trimester of pregnancy or later than 4 weeks of delivery. The two studies included a combined sample size of approximately 350 patients suffering from severe PPD. In the studies, women received either 50 mg or 40 mg of zuranolone, or placebo for 14 days. Treatment was associated with a significant change in the Hamilton Depression Rating Scale at day 15, and treatment response was maintained at day 42, which was 4 weeks after the last dose of study medication.

Zuranolone is a neuroactive steroid, which is taken orally, unlike brexanolone (Zulresso; Sage Therapeutics; Cambridge, Mass.), which requires intravenous administration. Zuranolone will be commercially available based on estimates around the fourth quarter of 2023. The most common side effects are drowsiness, dizziness, and sedation, and the FDA label will have a boxed warning about zuranolone’s potential to impact a person’s driving ability, and performance of potentially hazardous activities.

It is noteworthy that while this new medication received FDA approval for the PPD indication, it did not receive FDA approval for the treatment of major depressive disorder (MDD), and the agency issued a Complete Response Letter to the manufacturers noting their application did not provide substantial evidence of effectiveness in MDD. The FDA said in the Complete Response Letter that an additional study or studies will be needed; the manufacturers are currently evaluating next steps.
 

Where zuranolone fits into the treatment algorithm for severe PPD

Many clinicians who support women with PPD will wonder, upon hearing this news, where zuranolone fits into the treatment algorithm for severe postpartum major depression. Some relevant issues that may determine the answer are the following:

Cost. The cost of brexanolone was substantial, at $34,000 per year, and was viewed by some as a limiting factor in terms of its very limited uptake. As of this column’s publication, zuranolone’s manufacturer has not stated how much the medication will cost.

Breastfeeding. Unlike selective serotonin reuptake inhibitors, which have been demonstrated to be effective for the treatment of PPD and safe during pregnancy and lactation, we have sparse data on the safety of zuranolone for women who wish to breastfeed. It is also unclear whether women eligible for zuranolone would, based on the limited data on safety in lactation, choose deferral of breastfeeding for 14 days in exchange for treatment.

Duration of treatment. While zuranolone was studied in the context of 14 days of acute treatment, then out to day 42, we have no published data on what happens on the other side of this brief interval. As a simple example, in a patient with a history of recurrent major depression previously treated with antidepressants, but where antidepressants were perhaps deferred during pregnancy, is PPD to be treated with zuranolone for 14 days? Or, hypothetically, should it be followed by empiric antidepressant treatment at day 14? Alternatively, are patient and clinician supposed to wait until recurrence occurs before pursuing adjunctive antidepressant therapy whether it is pharmacologic, nonpharmacologic, or both?

Treatment in patients with bipolar disorder. It is also unclear whether treatment with zuranolone applies to other populations of postpartum women. Certainly, for women with bipolar depression, which is common in postpartum women given the vulnerability of bipolar women to new onset of depression or postpartum depressive relapse of underlying disorder, we simply have no data regarding where zuranolone might fit in with respect to this group of patients.

The answers to these questions may help to determine whether zuranolone, a new antidepressant with efficacy, quick time to onset, and a novel mechanism of action is a “game changer.” The article in The Wall Street Journal provided me with some optimism, as it gave PPD and the issues surrounding PPD the attention it deserves in a major periodical. As a new treatment, it may help alleviate suffering at a critical time for patients and their families. We are inching closer to mitigation of stigma associated with this common illness.

Thinking back across the last 3 decades of my treating women suffering from PPD, I have reflected on what has gotten these patients well. I concluded that successful treatment of PPD is not a “one-stop shop,” but rather typically includes a combination of pharmacologic and nonpharmacologic interventions, along with family and community-based support groups, as well as a culture that reduces stigma and by so doing lessens the toll of this important and too frequently incompletely-treated illness.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. The Center for Women’s Mental Health at MGH was a non-enrolling site for the pivotal phase 3 SKYLARK trial evaluating zuranolone. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

A growing number of women ask about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy.

The last several decades have brought an increasing level of comfort with respect to antidepressant use during pregnancy, which derives from several factors.

Cohen_Lee_S_BOSTON_web.jpg

First, it’s been well described that there’s an increased risk of relapse and morbidity associated with discontinuation of antidepressants proximate to pregnancy, particularly in women with histories of recurrent disease (JAMA Psychiatry. 2023;80[5]:441-50 and JAMA. 2006;295[5]:499-507).

Second, there’s an obvious increased confidence about using antidepressants during pregnancy given the robust reproductive safety data about antidepressants with respect to both teratogenesis and risk for organ malformation. Other studies also fail to demonstrate a relationship between fetal exposure to antidepressants and risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD) and autism. These latter studies have been reviewed extensively in systematic reviews of meta-analyses addressing this question.

However, there are women who, as they approach the question of antidepressant use during pregnancy, would prefer a nonpharmacologic approach to managing depression in the setting of either a planned pregnancy, or sometimes in the setting of acute onset of depressive symptoms during pregnancy. Other women are more comfortable with the data in hand regarding the reproductive safety of antidepressants and continue antidepressants that have afforded emotional well-being, particularly if the road to well-being or euthymia has been a long one.

Still, we at Massachusetts General Hospital (MGH) Center for Women’s Mental Health along with multidisciplinary colleagues with whom we engage during our weekly Virtual Rounds community have observed a growing number of women asking about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy. They ask about these options for personal reasons, regardless of what we may know (and what we may not know) about existing pharmacologic interventions. In these scenarios, it is important to keep in mind that it is not about what we as clinicians necessarily know about these medicines per se that drives treatment, but rather about the private calculus that women and their partners apply about risk and benefit of pharmacologic treatment during pregnancy.
 

Nonpharmacologic treatment options

Mindfulness-based cognitive therapy (MBCT), cognitive behavioral therapy (CBT), and behavioral activation are therapies all of which have an evidence base with respect to their effectiveness for either the acute treatment of both depression (and perinatal depression specifically) or for mitigating risk for depressive relapse (MBCT). Several investigations are underway evaluating digital apps that utilize MBCT and CBT in these patient populations as well.

New treatments for which we have none or exceedingly sparse data to support use during pregnancy are neurosteroids. We are asked all the time about the use of neurosteroids such as brexanolone or zuranolone during pregnancy. Given the data on effectiveness of these agents for treatment of postpartum depression, the question about use during pregnancy is intuitive. But at this point in time, absent data, their use during pregnancy cannot be recommended.

With respect to newer nonpharmacologic approaches that have been looked at for treatment of major depressive disorder, the Food and Drug Administration has approved transcranial magnetic stimulation (TMS), a noninvasive form of neuromodulating therapy that use magnetic pulses to stimulate specific regions of the brain that have been implicated in psychiatric illness.

While there are no safety concerns that have been noted about use of TMS, the data regarding its use during pregnancy are still relatively limited, but it has been used to treat certain neurologic conditions during pregnancy. We now have a small randomized controlled study using TMS during pregnancy and multiple small case series suggesting a signal of efficacy in women with perinatal major depressive disorder. Side effects of TMS use during pregnancy have included hypotension, which has sometimes required repositioning of subjects, particularly later in pregnancy. Unlike electroconvulsive therapy, (ECT), often used when clinicians have exhausted other treatment options, TMS has no risk of seizure associated with its use.

TMS is now entering into the clinical arena in a more robust way. In certain settings, insurance companies are reimbursing for TMS treatment more often than was the case previously, making it a more viable option for a larger number of patients. There are also several exciting newer protocols, including theta burst stimulation, a new form of TMS treatment with less of a time commitment, and which may be more cost effective. However, data on this modality of treatment remain limited.
 

Where TMS fits in treating depression during pregnancy

The real question we are getting asked in clinic, both in person and during virtual rounds with multidisciplinary colleagues from across the world, is where TMS might fit into the algorithm for treating of depression during pregnancy. Where is it appropriate to be thinking about TMS in pregnancy, and where should it perhaps be deferred at this moment (and where is it not appropriate)?

It is probably of limited value (and possibly of potential harm) to switch to TMS in patients who have severe recurrent major depression and who are on maintenance antidepressant, and who believe that a switch to TMS will be effective for relapse prevention; there are simply no data currently suggesting that TMS can be used as a relapse prevention tool, unlike certain other nonpharmacologic interventions.

What about managing relapse of major depressive disorder during pregnancy in a patient who had responded to an antidepressant? We have seen patients with histories of severe recurrent disease who are managed well on antidepressants during pregnancy who then have breakthrough symptoms and inquire about using TMS as an augmentation strategy. Although we don’t have clear data supporting the use of TMS as an adjunct in that setting, in those patients, one could argue that a trial of TMS may be appropriate – as opposed to introducing multiple medicines to recapture euthymia during pregnancy where the benefit is unclear and where more exposure is implied by having to do potentially multiple trials.

Other patients with new onset of depression during pregnancy who, for personal reasons, will not take an antidepressant or pursue other nonpharmacologic interventions will frequently ask about TMS. It’s important to at least have a potential referral source in mind given the increased popularity of TMS and the increased availability of TMS in the community in various centers – as opposed to previously where it was more restricted to large academic medical centers.

I think it is a time of excitement in reproductive psychiatry where we have a growing number of tools to treat perinatal depression – from medications to digital tools. These tools – either alone or in combination with medicines that we’ve been using for years – are able to afford women a greater number of choices with respect to the treatment of perinatal depression than was available even 5 years ago. That takes us closer to an ability to use interventions that truly combine patient wishes and “precision perinatal psychiatry,” where we can match effective therapies with the individual clinical presentations and wishes with which patients come to us.

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

A growing number of women ask about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy.

The last several decades have brought an increasing level of comfort with respect to antidepressant use during pregnancy, which derives from several factors.

Cohen_Lee_S_BOSTON_web.jpg

First, it’s been well described that there’s an increased risk of relapse and morbidity associated with discontinuation of antidepressants proximate to pregnancy, particularly in women with histories of recurrent disease (JAMA Psychiatry. 2023;80[5]:441-50 and JAMA. 2006;295[5]:499-507).

Second, there’s an obvious increased confidence about using antidepressants during pregnancy given the robust reproductive safety data about antidepressants with respect to both teratogenesis and risk for organ malformation. Other studies also fail to demonstrate a relationship between fetal exposure to antidepressants and risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD) and autism. These latter studies have been reviewed extensively in systematic reviews of meta-analyses addressing this question.

However, there are women who, as they approach the question of antidepressant use during pregnancy, would prefer a nonpharmacologic approach to managing depression in the setting of either a planned pregnancy, or sometimes in the setting of acute onset of depressive symptoms during pregnancy. Other women are more comfortable with the data in hand regarding the reproductive safety of antidepressants and continue antidepressants that have afforded emotional well-being, particularly if the road to well-being or euthymia has been a long one.

Still, we at Massachusetts General Hospital (MGH) Center for Women’s Mental Health along with multidisciplinary colleagues with whom we engage during our weekly Virtual Rounds community have observed a growing number of women asking about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy. They ask about these options for personal reasons, regardless of what we may know (and what we may not know) about existing pharmacologic interventions. In these scenarios, it is important to keep in mind that it is not about what we as clinicians necessarily know about these medicines per se that drives treatment, but rather about the private calculus that women and their partners apply about risk and benefit of pharmacologic treatment during pregnancy.
 

Nonpharmacologic treatment options

Mindfulness-based cognitive therapy (MBCT), cognitive behavioral therapy (CBT), and behavioral activation are therapies all of which have an evidence base with respect to their effectiveness for either the acute treatment of both depression (and perinatal depression specifically) or for mitigating risk for depressive relapse (MBCT). Several investigations are underway evaluating digital apps that utilize MBCT and CBT in these patient populations as well.

New treatments for which we have none or exceedingly sparse data to support use during pregnancy are neurosteroids. We are asked all the time about the use of neurosteroids such as brexanolone or zuranolone during pregnancy. Given the data on effectiveness of these agents for treatment of postpartum depression, the question about use during pregnancy is intuitive. But at this point in time, absent data, their use during pregnancy cannot be recommended.

With respect to newer nonpharmacologic approaches that have been looked at for treatment of major depressive disorder, the Food and Drug Administration has approved transcranial magnetic stimulation (TMS), a noninvasive form of neuromodulating therapy that use magnetic pulses to stimulate specific regions of the brain that have been implicated in psychiatric illness.

While there are no safety concerns that have been noted about use of TMS, the data regarding its use during pregnancy are still relatively limited, but it has been used to treat certain neurologic conditions during pregnancy. We now have a small randomized controlled study using TMS during pregnancy and multiple small case series suggesting a signal of efficacy in women with perinatal major depressive disorder. Side effects of TMS use during pregnancy have included hypotension, which has sometimes required repositioning of subjects, particularly later in pregnancy. Unlike electroconvulsive therapy, (ECT), often used when clinicians have exhausted other treatment options, TMS has no risk of seizure associated with its use.

TMS is now entering into the clinical arena in a more robust way. In certain settings, insurance companies are reimbursing for TMS treatment more often than was the case previously, making it a more viable option for a larger number of patients. There are also several exciting newer protocols, including theta burst stimulation, a new form of TMS treatment with less of a time commitment, and which may be more cost effective. However, data on this modality of treatment remain limited.
 

Where TMS fits in treating depression during pregnancy

The real question we are getting asked in clinic, both in person and during virtual rounds with multidisciplinary colleagues from across the world, is where TMS might fit into the algorithm for treating of depression during pregnancy. Where is it appropriate to be thinking about TMS in pregnancy, and where should it perhaps be deferred at this moment (and where is it not appropriate)?

It is probably of limited value (and possibly of potential harm) to switch to TMS in patients who have severe recurrent major depression and who are on maintenance antidepressant, and who believe that a switch to TMS will be effective for relapse prevention; there are simply no data currently suggesting that TMS can be used as a relapse prevention tool, unlike certain other nonpharmacologic interventions.

What about managing relapse of major depressive disorder during pregnancy in a patient who had responded to an antidepressant? We have seen patients with histories of severe recurrent disease who are managed well on antidepressants during pregnancy who then have breakthrough symptoms and inquire about using TMS as an augmentation strategy. Although we don’t have clear data supporting the use of TMS as an adjunct in that setting, in those patients, one could argue that a trial of TMS may be appropriate – as opposed to introducing multiple medicines to recapture euthymia during pregnancy where the benefit is unclear and where more exposure is implied by having to do potentially multiple trials.

Other patients with new onset of depression during pregnancy who, for personal reasons, will not take an antidepressant or pursue other nonpharmacologic interventions will frequently ask about TMS. It’s important to at least have a potential referral source in mind given the increased popularity of TMS and the increased availability of TMS in the community in various centers – as opposed to previously where it was more restricted to large academic medical centers.

I think it is a time of excitement in reproductive psychiatry where we have a growing number of tools to treat perinatal depression – from medications to digital tools. These tools – either alone or in combination with medicines that we’ve been using for years – are able to afford women a greater number of choices with respect to the treatment of perinatal depression than was available even 5 years ago. That takes us closer to an ability to use interventions that truly combine patient wishes and “precision perinatal psychiatry,” where we can match effective therapies with the individual clinical presentations and wishes with which patients come to us.

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

A growing number of women ask about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy.

The last several decades have brought an increasing level of comfort with respect to antidepressant use during pregnancy, which derives from several factors.

Cohen_Lee_S_BOSTON_web.jpg

First, it’s been well described that there’s an increased risk of relapse and morbidity associated with discontinuation of antidepressants proximate to pregnancy, particularly in women with histories of recurrent disease (JAMA Psychiatry. 2023;80[5]:441-50 and JAMA. 2006;295[5]:499-507).

Second, there’s an obvious increased confidence about using antidepressants during pregnancy given the robust reproductive safety data about antidepressants with respect to both teratogenesis and risk for organ malformation. Other studies also fail to demonstrate a relationship between fetal exposure to antidepressants and risk for subsequent development of attention-deficit/hyperactivity disorder (ADHD) and autism. These latter studies have been reviewed extensively in systematic reviews of meta-analyses addressing this question.

However, there are women who, as they approach the question of antidepressant use during pregnancy, would prefer a nonpharmacologic approach to managing depression in the setting of either a planned pregnancy, or sometimes in the setting of acute onset of depressive symptoms during pregnancy. Other women are more comfortable with the data in hand regarding the reproductive safety of antidepressants and continue antidepressants that have afforded emotional well-being, particularly if the road to well-being or euthymia has been a long one.

Still, we at Massachusetts General Hospital (MGH) Center for Women’s Mental Health along with multidisciplinary colleagues with whom we engage during our weekly Virtual Rounds community have observed a growing number of women asking about nonpharmacologic approaches for either the treatment of acute perinatal depression or for relapse prevention during pregnancy. They ask about these options for personal reasons, regardless of what we may know (and what we may not know) about existing pharmacologic interventions. In these scenarios, it is important to keep in mind that it is not about what we as clinicians necessarily know about these medicines per se that drives treatment, but rather about the private calculus that women and their partners apply about risk and benefit of pharmacologic treatment during pregnancy.
 

Nonpharmacologic treatment options

Mindfulness-based cognitive therapy (MBCT), cognitive behavioral therapy (CBT), and behavioral activation are therapies all of which have an evidence base with respect to their effectiveness for either the acute treatment of both depression (and perinatal depression specifically) or for mitigating risk for depressive relapse (MBCT). Several investigations are underway evaluating digital apps that utilize MBCT and CBT in these patient populations as well.

New treatments for which we have none or exceedingly sparse data to support use during pregnancy are neurosteroids. We are asked all the time about the use of neurosteroids such as brexanolone or zuranolone during pregnancy. Given the data on effectiveness of these agents for treatment of postpartum depression, the question about use during pregnancy is intuitive. But at this point in time, absent data, their use during pregnancy cannot be recommended.

With respect to newer nonpharmacologic approaches that have been looked at for treatment of major depressive disorder, the Food and Drug Administration has approved transcranial magnetic stimulation (TMS), a noninvasive form of neuromodulating therapy that use magnetic pulses to stimulate specific regions of the brain that have been implicated in psychiatric illness.

While there are no safety concerns that have been noted about use of TMS, the data regarding its use during pregnancy are still relatively limited, but it has been used to treat certain neurologic conditions during pregnancy. We now have a small randomized controlled study using TMS during pregnancy and multiple small case series suggesting a signal of efficacy in women with perinatal major depressive disorder. Side effects of TMS use during pregnancy have included hypotension, which has sometimes required repositioning of subjects, particularly later in pregnancy. Unlike electroconvulsive therapy, (ECT), often used when clinicians have exhausted other treatment options, TMS has no risk of seizure associated with its use.

TMS is now entering into the clinical arena in a more robust way. In certain settings, insurance companies are reimbursing for TMS treatment more often than was the case previously, making it a more viable option for a larger number of patients. There are also several exciting newer protocols, including theta burst stimulation, a new form of TMS treatment with less of a time commitment, and which may be more cost effective. However, data on this modality of treatment remain limited.
 

Where TMS fits in treating depression during pregnancy

The real question we are getting asked in clinic, both in person and during virtual rounds with multidisciplinary colleagues from across the world, is where TMS might fit into the algorithm for treating of depression during pregnancy. Where is it appropriate to be thinking about TMS in pregnancy, and where should it perhaps be deferred at this moment (and where is it not appropriate)?

It is probably of limited value (and possibly of potential harm) to switch to TMS in patients who have severe recurrent major depression and who are on maintenance antidepressant, and who believe that a switch to TMS will be effective for relapse prevention; there are simply no data currently suggesting that TMS can be used as a relapse prevention tool, unlike certain other nonpharmacologic interventions.

What about managing relapse of major depressive disorder during pregnancy in a patient who had responded to an antidepressant? We have seen patients with histories of severe recurrent disease who are managed well on antidepressants during pregnancy who then have breakthrough symptoms and inquire about using TMS as an augmentation strategy. Although we don’t have clear data supporting the use of TMS as an adjunct in that setting, in those patients, one could argue that a trial of TMS may be appropriate – as opposed to introducing multiple medicines to recapture euthymia during pregnancy where the benefit is unclear and where more exposure is implied by having to do potentially multiple trials.

Other patients with new onset of depression during pregnancy who, for personal reasons, will not take an antidepressant or pursue other nonpharmacologic interventions will frequently ask about TMS. It’s important to at least have a potential referral source in mind given the increased popularity of TMS and the increased availability of TMS in the community in various centers – as opposed to previously where it was more restricted to large academic medical centers.

I think it is a time of excitement in reproductive psychiatry where we have a growing number of tools to treat perinatal depression – from medications to digital tools. These tools – either alone or in combination with medicines that we’ve been using for years – are able to afford women a greater number of choices with respect to the treatment of perinatal depression than was available even 5 years ago. That takes us closer to an ability to use interventions that truly combine patient wishes and “precision perinatal psychiatry,” where we can match effective therapies with the individual clinical presentations and wishes with which patients come to us.

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

Postpartum/perinatal depression (PPD) remains the most common complication in modern obstetrics, with a prevalence of 10%-15% based on multiple studies over the last 2 decades. Over those same 2 decades, there has been growing interest and motivation across the country – from small community hospitals to major academic centers – to promote screening. Such screening is integrated into obstetrical practices, typically using the Edinburgh Postnatal Depression Scale (EPDS), the most widely used validated screen for PPD globally.

As mentioned in previous columns, the U.S. Preventive Services Task Force recommended screening for PPD in 2016, which includes screening women at highest risk, and both acutely treating and preventing PPD.

Since then, screening women for a common clinical problem like PPD has been widely adopted by clinicians representing a broad spectrum of interdisciplinary care. Providers who are engaged in the treatment of postpartum women – obstetricians, psychiatrists, doulas, lactation consultants, facilitators of postpartum support groups, and advocacy groups among others – are included.

Cohen_Lee_S_BOSTON_web.jpg

An open question and one of great concern recently to our group and others has been what happens after screening. It is clear that identification of PPD per se is not necessarily a challenge, and we have multiple effective treatments from antidepressants to mindfulness-based cognitive therapy to cognitive-behavioral interventions. There is also a growing number of digital applications aimed at mitigation of depressive symptoms in women with postpartum major depressive disorder. One unanswered question is how to engage women after identification of PPD and how to facilitate access to care in a way that maximizes the likelihood that women who actually are suffering from PPD get adequate treatment.

The “perinatal treatment cascade” refers to the majority of women who, on the other side of identification of PPD, fail to receive adequate treatment and continue to have persistent depression. This is perhaps the greatest challenge to the field and to clinicians – how do we, on the other side of screening, see that these women get access to care and get well?

With that backdrop, it is surprising that the Canadian Task Force on Preventive Health Care has recently recommended against screening with systematic questionnaires, noting that benefits were unclear and not a particular advantage relative to standard practice. The recommendation carries an assumption that standard practice involves queries about mental health. While the task force continues to recommend screening for PPD, their recommendation against screening with a standardized questionnaire represents a bold, sweeping, if not myopic view.

While the Canadian Task Force on Preventive Health Care made their recommendation based on a single randomized controlled trial with the assumption that women were getting mental health counseling, and that women liked getting mental health engagement around their depression, that is not a uniform part of practice. Thus, it is puzzling why the task force would make the recommendation based on such sparse data.

The way to optimize access to care and referral systems for women who are suffering from PPD is not to remove a part of the system that’s already working. Well-validated questionnaires such as the EPDS are easy to administer and are routinely integrated into the electronic health systems records of both small and large centers. These questionnaires are an inexpensive way to increase the likelihood that women get identified and referred for a spectrum of potentially helpful interventions.

PPD is also easy to treat with medications and a wide spectrum of nonpharmacologic interventions. Novel interventions are also being explored to maximize access for women with postpartum mood and anxiety disorders such as peer-delivered behavioral activation and cognitive-behavioral therapy, which could be community based and implemented from urban to rural settings across the United States.

What may need the greatest study is the path to accessing effective treatments and resources for these women and this problem has prompted our group to explore these issues in our more recent investigations. Better understanding of those factors that limit access to mental health providers with expertise in perinatal mental health to the logistical issues of navigating the health care system for sleep-deprived new moms and their families demands greater attention and clearer answers.

The whole field has an obligation to postpartum women to figure out the amalgam of practitioners, resources, and platforms that need to be used to engage women so that they get effective treatment – because we have effective treatments. But the solution to improving perinatal mental health outcomes, unlike the approach of our colleagues in Canada, is not to be found in abandoning questionnaire-based screening, but in identifying the best ways to prevent PPD and to maximize access to care.

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

Postpartum/perinatal depression (PPD) remains the most common complication in modern obstetrics, with a prevalence of 10%-15% based on multiple studies over the last 2 decades. Over those same 2 decades, there has been growing interest and motivation across the country – from small community hospitals to major academic centers – to promote screening. Such screening is integrated into obstetrical practices, typically using the Edinburgh Postnatal Depression Scale (EPDS), the most widely used validated screen for PPD globally.

As mentioned in previous columns, the U.S. Preventive Services Task Force recommended screening for PPD in 2016, which includes screening women at highest risk, and both acutely treating and preventing PPD.

Since then, screening women for a common clinical problem like PPD has been widely adopted by clinicians representing a broad spectrum of interdisciplinary care. Providers who are engaged in the treatment of postpartum women – obstetricians, psychiatrists, doulas, lactation consultants, facilitators of postpartum support groups, and advocacy groups among others – are included.

Cohen_Lee_S_BOSTON_web.jpg

An open question and one of great concern recently to our group and others has been what happens after screening. It is clear that identification of PPD per se is not necessarily a challenge, and we have multiple effective treatments from antidepressants to mindfulness-based cognitive therapy to cognitive-behavioral interventions. There is also a growing number of digital applications aimed at mitigation of depressive symptoms in women with postpartum major depressive disorder. One unanswered question is how to engage women after identification of PPD and how to facilitate access to care in a way that maximizes the likelihood that women who actually are suffering from PPD get adequate treatment.

The “perinatal treatment cascade” refers to the majority of women who, on the other side of identification of PPD, fail to receive adequate treatment and continue to have persistent depression. This is perhaps the greatest challenge to the field and to clinicians – how do we, on the other side of screening, see that these women get access to care and get well?

With that backdrop, it is surprising that the Canadian Task Force on Preventive Health Care has recently recommended against screening with systematic questionnaires, noting that benefits were unclear and not a particular advantage relative to standard practice. The recommendation carries an assumption that standard practice involves queries about mental health. While the task force continues to recommend screening for PPD, their recommendation against screening with a standardized questionnaire represents a bold, sweeping, if not myopic view.

While the Canadian Task Force on Preventive Health Care made their recommendation based on a single randomized controlled trial with the assumption that women were getting mental health counseling, and that women liked getting mental health engagement around their depression, that is not a uniform part of practice. Thus, it is puzzling why the task force would make the recommendation based on such sparse data.

The way to optimize access to care and referral systems for women who are suffering from PPD is not to remove a part of the system that’s already working. Well-validated questionnaires such as the EPDS are easy to administer and are routinely integrated into the electronic health systems records of both small and large centers. These questionnaires are an inexpensive way to increase the likelihood that women get identified and referred for a spectrum of potentially helpful interventions.

PPD is also easy to treat with medications and a wide spectrum of nonpharmacologic interventions. Novel interventions are also being explored to maximize access for women with postpartum mood and anxiety disorders such as peer-delivered behavioral activation and cognitive-behavioral therapy, which could be community based and implemented from urban to rural settings across the United States.

What may need the greatest study is the path to accessing effective treatments and resources for these women and this problem has prompted our group to explore these issues in our more recent investigations. Better understanding of those factors that limit access to mental health providers with expertise in perinatal mental health to the logistical issues of navigating the health care system for sleep-deprived new moms and their families demands greater attention and clearer answers.

The whole field has an obligation to postpartum women to figure out the amalgam of practitioners, resources, and platforms that need to be used to engage women so that they get effective treatment – because we have effective treatments. But the solution to improving perinatal mental health outcomes, unlike the approach of our colleagues in Canada, is not to be found in abandoning questionnaire-based screening, but in identifying the best ways to prevent PPD and to maximize access to care.

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

Postpartum/perinatal depression (PPD) remains the most common complication in modern obstetrics, with a prevalence of 10%-15% based on multiple studies over the last 2 decades. Over those same 2 decades, there has been growing interest and motivation across the country – from small community hospitals to major academic centers – to promote screening. Such screening is integrated into obstetrical practices, typically using the Edinburgh Postnatal Depression Scale (EPDS), the most widely used validated screen for PPD globally.

As mentioned in previous columns, the U.S. Preventive Services Task Force recommended screening for PPD in 2016, which includes screening women at highest risk, and both acutely treating and preventing PPD.

Since then, screening women for a common clinical problem like PPD has been widely adopted by clinicians representing a broad spectrum of interdisciplinary care. Providers who are engaged in the treatment of postpartum women – obstetricians, psychiatrists, doulas, lactation consultants, facilitators of postpartum support groups, and advocacy groups among others – are included.

Cohen_Lee_S_BOSTON_web.jpg

An open question and one of great concern recently to our group and others has been what happens after screening. It is clear that identification of PPD per se is not necessarily a challenge, and we have multiple effective treatments from antidepressants to mindfulness-based cognitive therapy to cognitive-behavioral interventions. There is also a growing number of digital applications aimed at mitigation of depressive symptoms in women with postpartum major depressive disorder. One unanswered question is how to engage women after identification of PPD and how to facilitate access to care in a way that maximizes the likelihood that women who actually are suffering from PPD get adequate treatment.

The “perinatal treatment cascade” refers to the majority of women who, on the other side of identification of PPD, fail to receive adequate treatment and continue to have persistent depression. This is perhaps the greatest challenge to the field and to clinicians – how do we, on the other side of screening, see that these women get access to care and get well?

With that backdrop, it is surprising that the Canadian Task Force on Preventive Health Care has recently recommended against screening with systematic questionnaires, noting that benefits were unclear and not a particular advantage relative to standard practice. The recommendation carries an assumption that standard practice involves queries about mental health. While the task force continues to recommend screening for PPD, their recommendation against screening with a standardized questionnaire represents a bold, sweeping, if not myopic view.

While the Canadian Task Force on Preventive Health Care made their recommendation based on a single randomized controlled trial with the assumption that women were getting mental health counseling, and that women liked getting mental health engagement around their depression, that is not a uniform part of practice. Thus, it is puzzling why the task force would make the recommendation based on such sparse data.

The way to optimize access to care and referral systems for women who are suffering from PPD is not to remove a part of the system that’s already working. Well-validated questionnaires such as the EPDS are easy to administer and are routinely integrated into the electronic health systems records of both small and large centers. These questionnaires are an inexpensive way to increase the likelihood that women get identified and referred for a spectrum of potentially helpful interventions.

PPD is also easy to treat with medications and a wide spectrum of nonpharmacologic interventions. Novel interventions are also being explored to maximize access for women with postpartum mood and anxiety disorders such as peer-delivered behavioral activation and cognitive-behavioral therapy, which could be community based and implemented from urban to rural settings across the United States.

What may need the greatest study is the path to accessing effective treatments and resources for these women and this problem has prompted our group to explore these issues in our more recent investigations. Better understanding of those factors that limit access to mental health providers with expertise in perinatal mental health to the logistical issues of navigating the health care system for sleep-deprived new moms and their families demands greater attention and clearer answers.

The whole field has an obligation to postpartum women to figure out the amalgam of practitioners, resources, and platforms that need to be used to engage women so that they get effective treatment – because we have effective treatments. But the solution to improving perinatal mental health outcomes, unlike the approach of our colleagues in Canada, is not to be found in abandoning questionnaire-based screening, but in identifying the best ways to prevent PPD and to maximize access to care.

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

Much of the focus of reproductive psychiatry over the last 1 to 2 decades has been on issues regarding risk of fetal exposure to psychiatric medications in the context of the specific risk for teratogenesis or organ malformation. Concerns and questions are mostly focused on exposure to any number of medications that women take during the first trimester, as it is during that period that the major organs are formed.

More recently, there has been appropriate interest in the effect of fetal exposure to psychiatric medications with respect to risk for obstetrical and neonatal complications. This particularly has been the case with respect to antidepressants where fetal exposure to these medications, which while associated with symptoms of transient jitteriness and irritability about 20% of the time, have not been associated with symptoms requiring frank clinical intervention.

Concerning mood stabilizers, the risk for organ dysgenesis following fetal exposure to sodium valproate has been very well established, and we’ve known for over a decade about the adverse effects of fetal exposure to sodium valproate on behavioral outcomes (Lancet Neurol. 2013 Mar;12[3]:244-52). We also now have ample data on lamotrigine, one of the most widely used medicines by reproductive-age women for treatment of bipolar disorder that supports the absence of a risk of organ malformation in first-trimester exposure.

Most recently, in a study of 292 children of women with epilepsy, an evaluation of women being treated with more modern anticonvulsants such as lamotrigine and levetiracetam alone or as polytherapy was performed. The results showed no difference in language, motor, cognitive, social, emotional, and general adaptive functioning in children exposed to either lamotrigine or levetiracetam relative to unexposed children of women with epilepsy. However, the researchers found an increase in anti-epileptic drug plasma level appeared to be associated with decreased motor and sensory function. These are reassuring data that really confirm earlier work, which failed to reveal a signal of concern for lamotrigine and now provide some of the first data on levetiracetam, which is widely used by reproductive-age women with epilepsy (JAMA Neurol. 2021 Aug 1;78[8]:927-936). While one caveat of the study is a short follow-up of 2 years, the absence of a signal of concern is reassuring. With more and more data demonstrating bipolar disorder is an illness that requires chronic treatment for many people, and that discontinuation is associated with high risk for relapse, it is an advance in the field to have data on risk for teratogenesis and data on longer-term neurobehavioral outcomes.

There is vast information regarding reproductive safety, organ malformation, and acute neonatal outcomes for antidepressants. The last decade has brought interest in and analysis of specific reports of increased risk of both autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) following fetal exposure to antidepressants. What can be said based on reviews of pooled meta-analyses is that the risk for ASD and ADHD has been put to rest for most clinicians and patients (J Clin Psychiatry. 2020 May 26;81[3]:20f13463). With other neurodevelopmental disorders, results have been somewhat inconclusive. Over the last 5-10 years, there have been sporadic reports of concerns about problems in a specific domain of neurodevelopment in offspring of women who have used antidepressants during pregnancy, whether it be speech, language, or motor functioning, but no signal of concern has been consistent.

In a previous column, I addressed a Danish study that showed no increased risk of longer-term sequelae after fetal exposure to antidepressants. Now, a new study has examined 1.93 million pregnancies in the Medicaid Analytic eXtract and 1.25 million pregnancies in the IBM MarketScan Research Database with follow-up up to 14 years of age where the specific interval for fetal exposure was from gestational age of 19 weeks to delivery, as that is the period that corresponds most to synaptogenesis in the brain. The researchers examined a spectrum of neurodevelopmental disorders such as developmental speech issues, ADHD, ASD, dyslexia, and learning disorders, among others. They found a twofold increased risk for neurodevelopmental disorders in the unadjusted models that flattened to no finding when factoring in environmental and genetic risk variables, highlighting the importance of dealing appropriately with confounders when performing these analyses. Those confounders examined include the mother’s use of alcohol and tobacco, and her body mass index and overall general health (JAMA Intern Med. 2022;182[11]:1149-60).

Given the consistency of these results with earlier data, patients can be increasingly comfortable as they weigh the benefits and risks of antidepressant use during pregnancy, factoring in the risk of fetal exposure with added data on long-term neurobehavioral sequelae. With that said, we need to remember the importance of initiatives to address alcohol consumption, poor nutrition, tobacco use, elevated BMI, and general health during pregnancy. These are modifiable risks that we as clinicians should focus on in order to optimize outcomes during pregnancy.

We have come so far in knowledge about fetal exposure to antidepressants relative to other classes of medications women take during pregnancy, about which, frankly, we are still starved for data. As use of psychiatric medications during pregnancy continues to grow, we can rest a bit more comfortably. But we should also address some of the other behaviors that have adverse effects on maternal and child well-being.

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

Much of the focus of reproductive psychiatry over the last 1 to 2 decades has been on issues regarding risk of fetal exposure to psychiatric medications in the context of the specific risk for teratogenesis or organ malformation. Concerns and questions are mostly focused on exposure to any number of medications that women take during the first trimester, as it is during that period that the major organs are formed.

More recently, there has been appropriate interest in the effect of fetal exposure to psychiatric medications with respect to risk for obstetrical and neonatal complications. This particularly has been the case with respect to antidepressants where fetal exposure to these medications, which while associated with symptoms of transient jitteriness and irritability about 20% of the time, have not been associated with symptoms requiring frank clinical intervention.

Concerning mood stabilizers, the risk for organ dysgenesis following fetal exposure to sodium valproate has been very well established, and we’ve known for over a decade about the adverse effects of fetal exposure to sodium valproate on behavioral outcomes (Lancet Neurol. 2013 Mar;12[3]:244-52). We also now have ample data on lamotrigine, one of the most widely used medicines by reproductive-age women for treatment of bipolar disorder that supports the absence of a risk of organ malformation in first-trimester exposure.

Most recently, in a study of 292 children of women with epilepsy, an evaluation of women being treated with more modern anticonvulsants such as lamotrigine and levetiracetam alone or as polytherapy was performed. The results showed no difference in language, motor, cognitive, social, emotional, and general adaptive functioning in children exposed to either lamotrigine or levetiracetam relative to unexposed children of women with epilepsy. However, the researchers found an increase in anti-epileptic drug plasma level appeared to be associated with decreased motor and sensory function. These are reassuring data that really confirm earlier work, which failed to reveal a signal of concern for lamotrigine and now provide some of the first data on levetiracetam, which is widely used by reproductive-age women with epilepsy (JAMA Neurol. 2021 Aug 1;78[8]:927-936). While one caveat of the study is a short follow-up of 2 years, the absence of a signal of concern is reassuring. With more and more data demonstrating bipolar disorder is an illness that requires chronic treatment for many people, and that discontinuation is associated with high risk for relapse, it is an advance in the field to have data on risk for teratogenesis and data on longer-term neurobehavioral outcomes.

There is vast information regarding reproductive safety, organ malformation, and acute neonatal outcomes for antidepressants. The last decade has brought interest in and analysis of specific reports of increased risk of both autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) following fetal exposure to antidepressants. What can be said based on reviews of pooled meta-analyses is that the risk for ASD and ADHD has been put to rest for most clinicians and patients (J Clin Psychiatry. 2020 May 26;81[3]:20f13463). With other neurodevelopmental disorders, results have been somewhat inconclusive. Over the last 5-10 years, there have been sporadic reports of concerns about problems in a specific domain of neurodevelopment in offspring of women who have used antidepressants during pregnancy, whether it be speech, language, or motor functioning, but no signal of concern has been consistent.

In a previous column, I addressed a Danish study that showed no increased risk of longer-term sequelae after fetal exposure to antidepressants. Now, a new study has examined 1.93 million pregnancies in the Medicaid Analytic eXtract and 1.25 million pregnancies in the IBM MarketScan Research Database with follow-up up to 14 years of age where the specific interval for fetal exposure was from gestational age of 19 weeks to delivery, as that is the period that corresponds most to synaptogenesis in the brain. The researchers examined a spectrum of neurodevelopmental disorders such as developmental speech issues, ADHD, ASD, dyslexia, and learning disorders, among others. They found a twofold increased risk for neurodevelopmental disorders in the unadjusted models that flattened to no finding when factoring in environmental and genetic risk variables, highlighting the importance of dealing appropriately with confounders when performing these analyses. Those confounders examined include the mother’s use of alcohol and tobacco, and her body mass index and overall general health (JAMA Intern Med. 2022;182[11]:1149-60).

Given the consistency of these results with earlier data, patients can be increasingly comfortable as they weigh the benefits and risks of antidepressant use during pregnancy, factoring in the risk of fetal exposure with added data on long-term neurobehavioral sequelae. With that said, we need to remember the importance of initiatives to address alcohol consumption, poor nutrition, tobacco use, elevated BMI, and general health during pregnancy. These are modifiable risks that we as clinicians should focus on in order to optimize outcomes during pregnancy.

We have come so far in knowledge about fetal exposure to antidepressants relative to other classes of medications women take during pregnancy, about which, frankly, we are still starved for data. As use of psychiatric medications during pregnancy continues to grow, we can rest a bit more comfortably. But we should also address some of the other behaviors that have adverse effects on maternal and child well-being.

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

Much of the focus of reproductive psychiatry over the last 1 to 2 decades has been on issues regarding risk of fetal exposure to psychiatric medications in the context of the specific risk for teratogenesis or organ malformation. Concerns and questions are mostly focused on exposure to any number of medications that women take during the first trimester, as it is during that period that the major organs are formed.

More recently, there has been appropriate interest in the effect of fetal exposure to psychiatric medications with respect to risk for obstetrical and neonatal complications. This particularly has been the case with respect to antidepressants where fetal exposure to these medications, which while associated with symptoms of transient jitteriness and irritability about 20% of the time, have not been associated with symptoms requiring frank clinical intervention.

Concerning mood stabilizers, the risk for organ dysgenesis following fetal exposure to sodium valproate has been very well established, and we’ve known for over a decade about the adverse effects of fetal exposure to sodium valproate on behavioral outcomes (Lancet Neurol. 2013 Mar;12[3]:244-52). We also now have ample data on lamotrigine, one of the most widely used medicines by reproductive-age women for treatment of bipolar disorder that supports the absence of a risk of organ malformation in first-trimester exposure.

Most recently, in a study of 292 children of women with epilepsy, an evaluation of women being treated with more modern anticonvulsants such as lamotrigine and levetiracetam alone or as polytherapy was performed. The results showed no difference in language, motor, cognitive, social, emotional, and general adaptive functioning in children exposed to either lamotrigine or levetiracetam relative to unexposed children of women with epilepsy. However, the researchers found an increase in anti-epileptic drug plasma level appeared to be associated with decreased motor and sensory function. These are reassuring data that really confirm earlier work, which failed to reveal a signal of concern for lamotrigine and now provide some of the first data on levetiracetam, which is widely used by reproductive-age women with epilepsy (JAMA Neurol. 2021 Aug 1;78[8]:927-936). While one caveat of the study is a short follow-up of 2 years, the absence of a signal of concern is reassuring. With more and more data demonstrating bipolar disorder is an illness that requires chronic treatment for many people, and that discontinuation is associated with high risk for relapse, it is an advance in the field to have data on risk for teratogenesis and data on longer-term neurobehavioral outcomes.

There is vast information regarding reproductive safety, organ malformation, and acute neonatal outcomes for antidepressants. The last decade has brought interest in and analysis of specific reports of increased risk of both autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) following fetal exposure to antidepressants. What can be said based on reviews of pooled meta-analyses is that the risk for ASD and ADHD has been put to rest for most clinicians and patients (J Clin Psychiatry. 2020 May 26;81[3]:20f13463). With other neurodevelopmental disorders, results have been somewhat inconclusive. Over the last 5-10 years, there have been sporadic reports of concerns about problems in a specific domain of neurodevelopment in offspring of women who have used antidepressants during pregnancy, whether it be speech, language, or motor functioning, but no signal of concern has been consistent.

In a previous column, I addressed a Danish study that showed no increased risk of longer-term sequelae after fetal exposure to antidepressants. Now, a new study has examined 1.93 million pregnancies in the Medicaid Analytic eXtract and 1.25 million pregnancies in the IBM MarketScan Research Database with follow-up up to 14 years of age where the specific interval for fetal exposure was from gestational age of 19 weeks to delivery, as that is the period that corresponds most to synaptogenesis in the brain. The researchers examined a spectrum of neurodevelopmental disorders such as developmental speech issues, ADHD, ASD, dyslexia, and learning disorders, among others. They found a twofold increased risk for neurodevelopmental disorders in the unadjusted models that flattened to no finding when factoring in environmental and genetic risk variables, highlighting the importance of dealing appropriately with confounders when performing these analyses. Those confounders examined include the mother’s use of alcohol and tobacco, and her body mass index and overall general health (JAMA Intern Med. 2022;182[11]:1149-60).

Given the consistency of these results with earlier data, patients can be increasingly comfortable as they weigh the benefits and risks of antidepressant use during pregnancy, factoring in the risk of fetal exposure with added data on long-term neurobehavioral sequelae. With that said, we need to remember the importance of initiatives to address alcohol consumption, poor nutrition, tobacco use, elevated BMI, and general health during pregnancy. These are modifiable risks that we as clinicians should focus on in order to optimize outcomes during pregnancy.

We have come so far in knowledge about fetal exposure to antidepressants relative to other classes of medications women take during pregnancy, about which, frankly, we are still starved for data. As use of psychiatric medications during pregnancy continues to grow, we can rest a bit more comfortably. But we should also address some of the other behaviors that have adverse effects on maternal and child well-being.

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

The last 15 years have brought increased effort to screen for postpartum psychiatric illness. That’s exceedingly welcome given the morbidity and potential mortality associated with postpartum psychiatric disorders across the country.

From small community hospitals to major academic centers, screening for postpartum depression is part of the clinical fabric of routine obstetrical care. There is a growing appreciation for the complexity of perinatal psychiatric illness, particularly with respect to the commingling of both mood and anxiety disorders during the postpartum period. However, willingness to treat and appreciation of the urgency to treat with both pharmacologic and nonpharmacologic interventions can vary. For women who suffer from postpartum depression and their families, there are real-world implications of both treating and failing to treat this illness, and there is an urgent need to really help these women “climb out of the darkness” that is and defines postpartum depression.

Cohen_Lee_S_BOSTON_web.jpg

Less common but of great clinical importance is postpartum psychosis, which occurs in approximately 1 in 1,000-2,000 women based on estimates from several studies. As noted in previous columns, the presentation is a dramatic one, with the typical onset of psychotic symptoms in the first days to weeks post partum. The disorder typically has a mood component and is not an exacerbation of underlying chronic psychotic illness. While there have been few systematic treatment studies, the clinical consensus is treatment usually includes hospitalization to ensure the safety of both the patient and infant. Use of medications, including mood stabilizers, antipsychotics, and benzodiazepines may be appropriate when expeditious treatment is needed.

Appropriate treatment by informed clinical staff is essential, as untreated or incompletely treated postpartum psychosis with its attendant morbidity and potential mortality is a very real concern. As I speak with women across the country with histories of postpartum psychosis, I’m often told of the difficult exchanges that women and their partners have at EDs in various clinical settings where diagnosis was delayed, or treatment was incomplete because of staff without expertise in postpartum psychosis management.

Another dilemma that patients and clinicians face after acute treatment is treatment duration, which is derived from how we conceptualize the illness. Even for experts in the area, there is not a consensus on whether postpartum psychosis should be considered as bipolar disorder or whether it is a circumscribed diagnostic entity. This issue has been hotly debated for many years and is one of the reasons why the illness is not included in the DSM classification system.

At Massachusetts General Hospital, we are systematically studying a large cohort of women with histories of postpartum psychosis as part of the MGH Postpartum Psychosis Project to better understand the phenomenology of postpartum psychosis, and also to understand the possible genomic underpinning of the illness. Most recently, we are conducting a neuroimaging study of women with histories of postpartum psychosis, compared with women in a healthy control group. We hope the results of this novel investigation will help to answer whether there is a neural signature identifiable with neuroimaging techniques such as functional MRI, if those findings are similar to other findings of neural circuitry we see in other forms of psychotic illness, or if the illness has a more distinct neural signature.

A question patients and colleagues often ask is what is the long-term nature of postpartum psychosis. If one considers it clearly to be bipolar disorder, the most intuitive approach would be long-term treatment with mood stabilizers. We now have a growing amount of data on the longitudinal course of postpartum psychosis. In one meta-analysis, 64% of women who had an episode of postpartum psychosis developed episodes of recurrent psychiatric disorder mostly consistent with bipolar illness. However, 36% of women appear to have more circumscribed illness without recurrence. In those women with recurrent disease, the presumption was those patients who had bipolar disorder and their presentation postpartum was simply their index episode of bipolar illness. However, there were other women who looked as if they had developed subsequent illness over the 11-26 years of follow-up, and those women did not receive long-term treatment.

A more recent prospective study of 106 women with postpartum psychosis who had their medication tapered and discontinued showed that 32% of women went on to have recurrent disease with a median time to illness of 20.3 months, and those patients presented primarily with illness that looked like bipolar disorder.

These accumulating data support the impression we’ve had for years that there’s a very strong relationship between bipolar disorder and postpartum psychiatric illness. Regardless of what side of the debate you fall on, the acute treatment is really the same. The real question for the clinician is what to do over the long term. Frequently, patients feel very strongly about a taper and discontinuation of medicine, and even the data show between 30% and 45% of women seem to have relatively circumscribed disease. There may be an issue in terms of prophylaxis if a patient gets pregnant and delivers another child, but that’s a separate issue. The issue is really whether there is a way to “thread the clinical needle” and meet patients where they are who do not want to continue long-term treatment.

I think we are at a point where we could argue the clinical treatment algorithm for patients who present with a new-onset manic-like psychosis postpartum is clear: initial treatment to stabilize, and then treatment with mood stabilizers for at least 12 months to follow is indicated. However, it may also be reasonable to taper treatment at 12-18 months, particularly for patients who have discussed this option with their clinician and who have been totally well for a year. (Women with previously documented bipolar disorder who have episodes of postpartum psychosis should obviously be treated with longer-term treatment aimed at maintenance of euthymia, as discontinuation of mood stabilizer is well known to be associated with risk for relapse.)

It should be noted that the longitudinal course and the treatment implications for women with postpartum psychosis are not etched in stone absent a clear evidence base driving care guidelines. Treatment must still be individualized. Women with underlying mood diatheses will typically declare themselves over time, and others may do well if they discontinue treatment, particularly if they are followed closely and instructed to present to a clinician at the earliest symptoms of mood dysregulation. The good news is we’ve seen an evolution of both interest and expertise in acute management of postpartum psychosis and a richer appreciation of the potential heterogeneity of this sample of women. There may be some variability in terms of long-term course requiring personalized treatment and obviously close follow-up of these women.

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

The last 15 years have brought increased effort to screen for postpartum psychiatric illness. That’s exceedingly welcome given the morbidity and potential mortality associated with postpartum psychiatric disorders across the country.

From small community hospitals to major academic centers, screening for postpartum depression is part of the clinical fabric of routine obstetrical care. There is a growing appreciation for the complexity of perinatal psychiatric illness, particularly with respect to the commingling of both mood and anxiety disorders during the postpartum period. However, willingness to treat and appreciation of the urgency to treat with both pharmacologic and nonpharmacologic interventions can vary. For women who suffer from postpartum depression and their families, there are real-world implications of both treating and failing to treat this illness, and there is an urgent need to really help these women “climb out of the darkness” that is and defines postpartum depression.

Cohen_Lee_S_BOSTON_web.jpg

Less common but of great clinical importance is postpartum psychosis, which occurs in approximately 1 in 1,000-2,000 women based on estimates from several studies. As noted in previous columns, the presentation is a dramatic one, with the typical onset of psychotic symptoms in the first days to weeks post partum. The disorder typically has a mood component and is not an exacerbation of underlying chronic psychotic illness. While there have been few systematic treatment studies, the clinical consensus is treatment usually includes hospitalization to ensure the safety of both the patient and infant. Use of medications, including mood stabilizers, antipsychotics, and benzodiazepines may be appropriate when expeditious treatment is needed.

Appropriate treatment by informed clinical staff is essential, as untreated or incompletely treated postpartum psychosis with its attendant morbidity and potential mortality is a very real concern. As I speak with women across the country with histories of postpartum psychosis, I’m often told of the difficult exchanges that women and their partners have at EDs in various clinical settings where diagnosis was delayed, or treatment was incomplete because of staff without expertise in postpartum psychosis management.

Another dilemma that patients and clinicians face after acute treatment is treatment duration, which is derived from how we conceptualize the illness. Even for experts in the area, there is not a consensus on whether postpartum psychosis should be considered as bipolar disorder or whether it is a circumscribed diagnostic entity. This issue has been hotly debated for many years and is one of the reasons why the illness is not included in the DSM classification system.

At Massachusetts General Hospital, we are systematically studying a large cohort of women with histories of postpartum psychosis as part of the MGH Postpartum Psychosis Project to better understand the phenomenology of postpartum psychosis, and also to understand the possible genomic underpinning of the illness. Most recently, we are conducting a neuroimaging study of women with histories of postpartum psychosis, compared with women in a healthy control group. We hope the results of this novel investigation will help to answer whether there is a neural signature identifiable with neuroimaging techniques such as functional MRI, if those findings are similar to other findings of neural circuitry we see in other forms of psychotic illness, or if the illness has a more distinct neural signature.

A question patients and colleagues often ask is what is the long-term nature of postpartum psychosis. If one considers it clearly to be bipolar disorder, the most intuitive approach would be long-term treatment with mood stabilizers. We now have a growing amount of data on the longitudinal course of postpartum psychosis. In one meta-analysis, 64% of women who had an episode of postpartum psychosis developed episodes of recurrent psychiatric disorder mostly consistent with bipolar illness. However, 36% of women appear to have more circumscribed illness without recurrence. In those women with recurrent disease, the presumption was those patients who had bipolar disorder and their presentation postpartum was simply their index episode of bipolar illness. However, there were other women who looked as if they had developed subsequent illness over the 11-26 years of follow-up, and those women did not receive long-term treatment.

A more recent prospective study of 106 women with postpartum psychosis who had their medication tapered and discontinued showed that 32% of women went on to have recurrent disease with a median time to illness of 20.3 months, and those patients presented primarily with illness that looked like bipolar disorder.

These accumulating data support the impression we’ve had for years that there’s a very strong relationship between bipolar disorder and postpartum psychiatric illness. Regardless of what side of the debate you fall on, the acute treatment is really the same. The real question for the clinician is what to do over the long term. Frequently, patients feel very strongly about a taper and discontinuation of medicine, and even the data show between 30% and 45% of women seem to have relatively circumscribed disease. There may be an issue in terms of prophylaxis if a patient gets pregnant and delivers another child, but that’s a separate issue. The issue is really whether there is a way to “thread the clinical needle” and meet patients where they are who do not want to continue long-term treatment.

I think we are at a point where we could argue the clinical treatment algorithm for patients who present with a new-onset manic-like psychosis postpartum is clear: initial treatment to stabilize, and then treatment with mood stabilizers for at least 12 months to follow is indicated. However, it may also be reasonable to taper treatment at 12-18 months, particularly for patients who have discussed this option with their clinician and who have been totally well for a year. (Women with previously documented bipolar disorder who have episodes of postpartum psychosis should obviously be treated with longer-term treatment aimed at maintenance of euthymia, as discontinuation of mood stabilizer is well known to be associated with risk for relapse.)

It should be noted that the longitudinal course and the treatment implications for women with postpartum psychosis are not etched in stone absent a clear evidence base driving care guidelines. Treatment must still be individualized. Women with underlying mood diatheses will typically declare themselves over time, and others may do well if they discontinue treatment, particularly if they are followed closely and instructed to present to a clinician at the earliest symptoms of mood dysregulation. The good news is we’ve seen an evolution of both interest and expertise in acute management of postpartum psychosis and a richer appreciation of the potential heterogeneity of this sample of women. There may be some variability in terms of long-term course requiring personalized treatment and obviously close follow-up of these women.

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

The last 15 years have brought increased effort to screen for postpartum psychiatric illness. That’s exceedingly welcome given the morbidity and potential mortality associated with postpartum psychiatric disorders across the country.

From small community hospitals to major academic centers, screening for postpartum depression is part of the clinical fabric of routine obstetrical care. There is a growing appreciation for the complexity of perinatal psychiatric illness, particularly with respect to the commingling of both mood and anxiety disorders during the postpartum period. However, willingness to treat and appreciation of the urgency to treat with both pharmacologic and nonpharmacologic interventions can vary. For women who suffer from postpartum depression and their families, there are real-world implications of both treating and failing to treat this illness, and there is an urgent need to really help these women “climb out of the darkness” that is and defines postpartum depression.

Less common but of great clinical importance is postpartum psychosis, which occurs in approximately 1 in 1,000-2,000 women based on estimates from several studies. As noted in previous columns, the presentation is a dramatic one, with the typical onset of psychotic symptoms in the first days to weeks post partum. The disorder typically has a mood component and is not an exacerbation of underlying chronic psychotic illness. While there have been few systematic treatment studies, the clinical consensus is treatment usually includes hospitalization to ensure the safety of both the patient and infant. Use of medications, including mood stabilizers, antipsychotics, and benzodiazepines may be appropriate when expeditious treatment is needed.

Appropriate treatment by informed clinical staff is essential, as untreated or incompletely treated postpartum psychosis with its attendant morbidity and potential mortality is a very real concern. As I speak with women across the country with histories of postpartum psychosis, I’m often told of the difficult exchanges that women and their partners have at EDs in various clinical settings where diagnosis was delayed, or treatment was incomplete because of staff without expertise in postpartum psychosis management.

Another dilemma that patients and clinicians face after acute treatment is treatment duration, which is derived from how we conceptualize the illness. Even for experts in the area, there is not a consensus on whether postpartum psychosis should be considered as bipolar disorder or whether it is a circumscribed diagnostic entity. This issue has been hotly debated for many years and is one of the reasons why the illness is not included in the DSM classification system.

At Massachusetts General Hospital, we are systematically studying a large cohort of women with histories of postpartum psychosis as part of the MGH Postpartum Psychosis Project to better understand the phenomenology of postpartum psychosis, and also to understand the possible genomic underpinning of the illness. Most recently, we are conducting a neuroimaging study of women with histories of postpartum psychosis, compared with women in a healthy control group. We hope the results of this novel investigation will help to answer whether there is a neural signature identifiable with neuroimaging techniques such as functional MRI, if those findings are similar to other findings of neural circuitry we see in other forms of psychotic illness, or if the illness has a more distinct neural signature.

A question patients and colleagues often ask is what is the long-term nature of postpartum psychosis. If one considers it clearly to be bipolar disorder, the most intuitive approach would be long-term treatment with mood stabilizers. We now have a growing amount of data on the longitudinal course of postpartum psychosis. In one meta-analysis, 64% of women who had an episode of postpartum psychosis developed episodes of recurrent psychiatric disorder mostly consistent with bipolar illness. However, 36% of women appear to have more circumscribed illness without recurrence. In those women with recurrent disease, the presumption was those patients who had bipolar disorder and their presentation postpartum was simply their index episode of bipolar illness. However, there were other women who looked as if they had developed subsequent illness over the 11-26 years of follow-up, and those women did not receive long-term treatment.

A more recent prospective study of 106 women with postpartum psychosis who had their medication tapered and discontinued showed that 32% of women went on to have recurrent disease with a median time to illness of 20.3 months, and those patients presented primarily with illness that looked like bipolar disorder.

These accumulating data support the impression we’ve had for years that there’s a very strong relationship between bipolar disorder and postpartum psychiatric illness. Regardless of what side of the debate you fall on, the acute treatment is really the same. The real question for the clinician is what to do over the long term. Frequently, patients feel very strongly about a taper and discontinuation of medicine, and even the data show between 30% and 45% of women seem to have relatively circumscribed disease. There may be an issue in terms of prophylaxis if a patient gets pregnant and delivers another child, but that’s a separate issue. The issue is really whether there is a way to “thread the clinical needle” and meet patients where they are who do not want to continue long-term treatment.

I think we are at a point where we could argue the clinical treatment algorithm for patients who present with a new-onset manic-like psychosis postpartum is clear: initial treatment to stabilize, and then treatment with mood stabilizers for at least 12 months to follow is indicated. However, it may also be reasonable to taper treatment at 12-18 months, particularly for patients who have discussed this option with their clinician and who have been totally well for a year. (Women with previously documented bipolar disorder who have episodes of postpartum psychosis should obviously be treated with longer-term treatment aimed at maintenance of euthymia, as discontinuation of mood stabilizer is well known to be associated with risk for relapse.)

It should be noted that the longitudinal course and the treatment implications for women with postpartum psychosis are not etched in stone absent a clear evidence base driving care guidelines. Treatment must still be individualized. Women with underlying mood diatheses will typically declare themselves over time, and others may do well if they discontinue treatment, particularly if they are followed closely and instructed to present to a clinician at the earliest symptoms of mood dysregulation. The good news is we’ve seen an evolution of both interest and expertise in acute management of postpartum psychosis and a richer appreciation of the potential heterogeneity of this sample of women. There may be some variability in terms of long-term course requiring personalized treatment and obviously close follow-up of these women.

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

The last 15-20 years have brought enormous attention to the relevant clinical issues regarding prescribing antidepressants during pregnancy. Concern about the effects of fetal exposure to selective serotonin reuptake inhibitors (SSRIs) is appropriate given the consistent data that approximately 7% of women use antidepressants during pregnancy, and that risk for relapse of depression during pregnancy in women who have stopped antidepressants during pregnancy is very high.

We have learned so much from studies of relevant questions regarding SSRI exposure. Concerns about increased risk for organ malformation have been set aside. An extraordinary number of studies across a broad range of patients around the globe looked at the issue of risk for organ malformation following in utero SSRI exposure – even looking specifically at risk for cardiac malformations, which had been an earlier concern in the literature – with the evidence supporting absence of increased risk. Also clarified has been, first, the absence of risk of complications such as persistent pulmonary hypertension of the newborn (PPHN) and, second, a delineation of the prevalence and clinical implications of transient neonatal symptoms such as jitteriness and tachypnea in offspring of women who used antidepressants during pregnancy – so-called “poor neonatal adaptation syndrome.”

However, for so many clinicians and for patients, the missing piece in the risk-benefit equation has been the issue of long-term neurodevelopmental sequelae in children whose mothers used antidepressants during pregnancy. While the accumulated data have shown sparse evidence linking SSRI exposure with autism or attention-deficit/hyperactivity disorder (ADHD), the evidence has been mixed regarding neurobehavioral sequelae associated with fetal exposure using developmental outcomes such as language ability, cognition, academic performance, language, math, and other cognitive outcomes. As far back as the 1990s, colleagues in Canada failed to show a difference in neurobehavioral outcomes in 5- to 7-year-old children whose mothers used SSRIs or older tricyclic antidepressants during pregnancy compared to nonexposed women (N Engl J Med. 1997 Jan 23;336[4]:258-62). Even early on, it was noted that one of the strongest predictors of neurodevelopmental outcome was untreated maternal psychiatric illness.

Since those early studies and over the last decade, there have been numerous small studies with conflicting data regarding a whole host of neurodevelopmental outcomes with inconsistent methodologies, different assessments, and failure to control for the presence or absence of maternal psychiatric illness during pregnancy – one of the most critical predictors of neurodevelopmental outcome and one we are beginning to appreciate plays a very significant role.

Most recently, the authors of a very large population-based retrospective cohort study in Denmark linked population-based registries with obstetrical data and examined language and math performance among 575,369 public schoolchildren whose mothers used or didn’t use antidepressants during pregnancy (JAMA. 2021 Nov 2;326[17]:1725-35). These investigators found a decrease in mean test scores for language (53.4 vs. 56.6) and math (52.1 vs. 57.4) in children whose mothers received antidepressant prescriptions during pregnancy compared with children who did not have that exposure. However, when they adjusted for maternal psychiatric illness and other relevant confounders, the finding went to null for language (adjusted difference, –0.1; 95% confidence interval, –0.6 to 0.3), but did not for math (adjusted difference, −2.2; 95% CI, −2.7 to −1.6). The results ultimately showed a modest finding for exposure and a small decrement in mathematical performance. The takeaway is that antidepressant use may be a proxy for neurodevelopmental deficit but is unlikely to be the etiology or direct cause of that deficit.

With that said, patients and their doctors can be reassured with respect to how much we have learned about SSRIs during pregnancy across the last decade. Yet there are appropriate concerns about long-term neurodevelopmental sequelae in this patient population. I think that what we can say in 2022 is that there is a growing appreciation for the effect of maternal psychiatric illness on long-term outcomes in children and the effect of maternal psychiatric illness on risk for postpartum depression, which we know influences long-term neurodevelopmental outcomes in children. Perhaps more than in years past, there is now also an appreciation of the effect of a dysregulated stress axis on the intrauterine fetal neuronal programming, which is perhaps the newest frontier, and which may hold the answers with respect to how to weigh the effect of maternal psychiatric illness on decisions about psychotropic use during pregnancy. But for today, there is an appreciation that exposure to maternal psychopathology is not a benign exposure.

Although some of the data remain incomplete, in 2022, patients will continue to make individual decisions based on the available data, factoring in the effect of maternal adversity in a more deliberate way and with a refined lens through with which to see their options with respect to using or not using SSRIs during pregnancy.

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

The last 15-20 years have brought enormous attention to the relevant clinical issues regarding prescribing antidepressants during pregnancy. Concern about the effects of fetal exposure to selective serotonin reuptake inhibitors (SSRIs) is appropriate given the consistent data that approximately 7% of women use antidepressants during pregnancy, and that risk for relapse of depression during pregnancy in women who have stopped antidepressants during pregnancy is very high.

We have learned so much from studies of relevant questions regarding SSRI exposure. Concerns about increased risk for organ malformation have been set aside. An extraordinary number of studies across a broad range of patients around the globe looked at the issue of risk for organ malformation following in utero SSRI exposure – even looking specifically at risk for cardiac malformations, which had been an earlier concern in the literature – with the evidence supporting absence of increased risk. Also clarified has been, first, the absence of risk of complications such as persistent pulmonary hypertension of the newborn (PPHN) and, second, a delineation of the prevalence and clinical implications of transient neonatal symptoms such as jitteriness and tachypnea in offspring of women who used antidepressants during pregnancy – so-called “poor neonatal adaptation syndrome.”

However, for so many clinicians and for patients, the missing piece in the risk-benefit equation has been the issue of long-term neurodevelopmental sequelae in children whose mothers used antidepressants during pregnancy. While the accumulated data have shown sparse evidence linking SSRI exposure with autism or attention-deficit/hyperactivity disorder (ADHD), the evidence has been mixed regarding neurobehavioral sequelae associated with fetal exposure using developmental outcomes such as language ability, cognition, academic performance, language, math, and other cognitive outcomes. As far back as the 1990s, colleagues in Canada failed to show a difference in neurobehavioral outcomes in 5- to 7-year-old children whose mothers used SSRIs or older tricyclic antidepressants during pregnancy compared to nonexposed women (N Engl J Med. 1997 Jan 23;336[4]:258-62). Even early on, it was noted that one of the strongest predictors of neurodevelopmental outcome was untreated maternal psychiatric illness.

Since those early studies and over the last decade, there have been numerous small studies with conflicting data regarding a whole host of neurodevelopmental outcomes with inconsistent methodologies, different assessments, and failure to control for the presence or absence of maternal psychiatric illness during pregnancy – one of the most critical predictors of neurodevelopmental outcome and one we are beginning to appreciate plays a very significant role.

Most recently, the authors of a very large population-based retrospective cohort study in Denmark linked population-based registries with obstetrical data and examined language and math performance among 575,369 public schoolchildren whose mothers used or didn’t use antidepressants during pregnancy (JAMA. 2021 Nov 2;326[17]:1725-35). These investigators found a decrease in mean test scores for language (53.4 vs. 56.6) and math (52.1 vs. 57.4) in children whose mothers received antidepressant prescriptions during pregnancy compared with children who did not have that exposure. However, when they adjusted for maternal psychiatric illness and other relevant confounders, the finding went to null for language (adjusted difference, –0.1; 95% confidence interval, –0.6 to 0.3), but did not for math (adjusted difference, −2.2; 95% CI, −2.7 to −1.6). The results ultimately showed a modest finding for exposure and a small decrement in mathematical performance. The takeaway is that antidepressant use may be a proxy for neurodevelopmental deficit but is unlikely to be the etiology or direct cause of that deficit.

With that said, patients and their doctors can be reassured with respect to how much we have learned about SSRIs during pregnancy across the last decade. Yet there are appropriate concerns about long-term neurodevelopmental sequelae in this patient population. I think that what we can say in 2022 is that there is a growing appreciation for the effect of maternal psychiatric illness on long-term outcomes in children and the effect of maternal psychiatric illness on risk for postpartum depression, which we know influences long-term neurodevelopmental outcomes in children. Perhaps more than in years past, there is now also an appreciation of the effect of a dysregulated stress axis on the intrauterine fetal neuronal programming, which is perhaps the newest frontier, and which may hold the answers with respect to how to weigh the effect of maternal psychiatric illness on decisions about psychotropic use during pregnancy. But for today, there is an appreciation that exposure to maternal psychopathology is not a benign exposure.

Although some of the data remain incomplete, in 2022, patients will continue to make individual decisions based on the available data, factoring in the effect of maternal adversity in a more deliberate way and with a refined lens through with which to see their options with respect to using or not using SSRIs during pregnancy.

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

The last 15-20 years have brought enormous attention to the relevant clinical issues regarding prescribing antidepressants during pregnancy. Concern about the effects of fetal exposure to selective serotonin reuptake inhibitors (SSRIs) is appropriate given the consistent data that approximately 7% of women use antidepressants during pregnancy, and that risk for relapse of depression during pregnancy in women who have stopped antidepressants during pregnancy is very high.

We have learned so much from studies of relevant questions regarding SSRI exposure. Concerns about increased risk for organ malformation have been set aside. An extraordinary number of studies across a broad range of patients around the globe looked at the issue of risk for organ malformation following in utero SSRI exposure – even looking specifically at risk for cardiac malformations, which had been an earlier concern in the literature – with the evidence supporting absence of increased risk. Also clarified has been, first, the absence of risk of complications such as persistent pulmonary hypertension of the newborn (PPHN) and, second, a delineation of the prevalence and clinical implications of transient neonatal symptoms such as jitteriness and tachypnea in offspring of women who used antidepressants during pregnancy – so-called “poor neonatal adaptation syndrome.”

However, for so many clinicians and for patients, the missing piece in the risk-benefit equation has been the issue of long-term neurodevelopmental sequelae in children whose mothers used antidepressants during pregnancy. While the accumulated data have shown sparse evidence linking SSRI exposure with autism or attention-deficit/hyperactivity disorder (ADHD), the evidence has been mixed regarding neurobehavioral sequelae associated with fetal exposure using developmental outcomes such as language ability, cognition, academic performance, language, math, and other cognitive outcomes. As far back as the 1990s, colleagues in Canada failed to show a difference in neurobehavioral outcomes in 5- to 7-year-old children whose mothers used SSRIs or older tricyclic antidepressants during pregnancy compared to nonexposed women (N Engl J Med. 1997 Jan 23;336[4]:258-62). Even early on, it was noted that one of the strongest predictors of neurodevelopmental outcome was untreated maternal psychiatric illness.

Since those early studies and over the last decade, there have been numerous small studies with conflicting data regarding a whole host of neurodevelopmental outcomes with inconsistent methodologies, different assessments, and failure to control for the presence or absence of maternal psychiatric illness during pregnancy – one of the most critical predictors of neurodevelopmental outcome and one we are beginning to appreciate plays a very significant role.

Most recently, the authors of a very large population-based retrospective cohort study in Denmark linked population-based registries with obstetrical data and examined language and math performance among 575,369 public schoolchildren whose mothers used or didn’t use antidepressants during pregnancy (JAMA. 2021 Nov 2;326[17]:1725-35). These investigators found a decrease in mean test scores for language (53.4 vs. 56.6) and math (52.1 vs. 57.4) in children whose mothers received antidepressant prescriptions during pregnancy compared with children who did not have that exposure. However, when they adjusted for maternal psychiatric illness and other relevant confounders, the finding went to null for language (adjusted difference, –0.1; 95% confidence interval, –0.6 to 0.3), but did not for math (adjusted difference, −2.2; 95% CI, −2.7 to −1.6). The results ultimately showed a modest finding for exposure and a small decrement in mathematical performance. The takeaway is that antidepressant use may be a proxy for neurodevelopmental deficit but is unlikely to be the etiology or direct cause of that deficit.

With that said, patients and their doctors can be reassured with respect to how much we have learned about SSRIs during pregnancy across the last decade. Yet there are appropriate concerns about long-term neurodevelopmental sequelae in this patient population. I think that what we can say in 2022 is that there is a growing appreciation for the effect of maternal psychiatric illness on long-term outcomes in children and the effect of maternal psychiatric illness on risk for postpartum depression, which we know influences long-term neurodevelopmental outcomes in children. Perhaps more than in years past, there is now also an appreciation of the effect of a dysregulated stress axis on the intrauterine fetal neuronal programming, which is perhaps the newest frontier, and which may hold the answers with respect to how to weigh the effect of maternal psychiatric illness on decisions about psychotropic use during pregnancy. But for today, there is an appreciation that exposure to maternal psychopathology is not a benign exposure.

Although some of the data remain incomplete, in 2022, patients will continue to make individual decisions based on the available data, factoring in the effect of maternal adversity in a more deliberate way and with a refined lens through with which to see their options with respect to using or not using SSRIs during pregnancy.

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

The experience of practicing reproductive psychiatry in the context of the pandemic has highlighted unique situations I’ve written about in previous columns that have affected pregnant and postpartum women during the pandemic, such as the management of anxiety and insomnia.

The pandemic has also seen a shift to telemedicine and an opportunity to use virtual platforms to engage with colleagues in our subspecialty across the country. These forums of engagement, which we realize virtually with so many of our colleagues, has prompted me to refine and galvanize what I consider to be some principles that guide frequently encountered clinical scenarios in reproductive psychiatry.

To open 2022, I wanted to revisit the practices I nearly “always” (or conversely, “never”) follow as a reproductive psychiatrist across the numerous clinical situations and variations on the associated clinical themes encountered as we see patients during pregnancy and the postpartum period.
 

Things we ‘always’ do

1. I continue to make maternal euthymia the North Star of treatment before, during, and after pregnancy.

Before pregnancy, maternal euthymia may be realized through optimization of pharmacologic and nonpharmacologic treatments and waiting to conceive until patients are emotionally well. Sustaining euthymia during pregnancy is a critical issue because of the extent to which euthymia during pregnancy predicts postpartum course. According to many studies, postpartum euthymia is the strongest predictor of long-term neurobehavioral outcome and risk for later child psychopathology. At the end of the day, there are few things I would not do with respect to treatment of maternal psychiatric disorder if the upside afforded maternal euthymia.

2. I almost always treat with consistency of medication across the peripartum period.

Although there have been discussions about the wisdom of changing medications, such as antidepressants, benzodiazepines, and mood stabilizers, that have afforded euthymia during pregnancy as patients approach their delivery date, the evidence base supporting switching medications at that time is exceedingly sparse. The time to adjust or to modify is typically not just prior to delivery unless it is to prevent postpartum psychiatric disorder (see below).

3. I simplify regimens before pregnancy if it’s unclear which medications have afforded patients euthymia.

We have a growing appreciation that polypharmacy is the rule in treatment of affective disorder for both unipolar and bipolar illness. Consultation before pregnancy is the ideal time to take a particularly careful history and think about simplifying regimens where adding medicines hasn’t clearly provided enhanced clinical benefit to the patient.

4. When making a treatment plan for psychiatric disorder during pregnancy, I consider the impact of untreated psychiatric disorder (even if not absolutely quantifiable) on fetal, neonatal, and maternal well-being.

Perhaps now more than even 5-10 years ago, we have better data describing the adverse effects of untreated psychiatric illness on fetal, neonatal, and maternal well-being.

We always try to deliberately consider the effect of a specific treatment on fetal well-being. Less attention (and science) has focused on the effect on pregnancy of deferring treatment; historically, this has not been adequately quantified in the risk-benefit decision. Yet, there is growing evidence of the increased adverse effects of activating the stress axis on everything from intrauterine fetal programming in the brain to effects on obstetrical outcomes such as preterm labor and delivery.

5. I appreciate the value of postpartum prophylaxis for pregnant women with bipolar disorder to mitigate risk of relapse.

We have spoken over the last 20 months of the pandemic, particularly in reproductive psychiatry circles, about the importance of keeping reproductive-age women with bipolar disorder emotionally well as they plan to conceive, during pregnancy, and in the postpartum period. The management of bipolar disorder during this time can be a humbling experience. Clinical roughening can be quick and severe, and so we do everything that we can for these women.

The area in which we have the strongest evidence base for mitigating risk with bipolar women is the value of postpartum prophylaxis during the peripartum period, regardless of what patients have done with their mood-stabilizing medications during pregnancy. Given the risk for postpartum disease, even though there are varying amounts of evidence on prophylactic benefit of specific mood stabilizers (i.e., lithium vs. atypical antipsychotics), the value of prophylaxis against worsening of bipolar disorder postpartum is widely accepted.

The importance of this has been particularly underscored during the pandemic where postpartum support, although available, has been more tenuous given the fluctuations in COVID-19 status around the country. The availability of friends and loved ones as support during the postpartum period has become less reliable in certain circumstances during the pandemic. In some cases, COVID-19 surges have wreaked havoc on travel plans and support persons have contracted the virus, rendering on-site support nonviable given safety concerns. Last-minute shifts of support plans have been responsible for disruption of care plans for new moms and by extension, have affected the ability to protect the sleep of bipolar women, which is critical. Keeping bipolar women well during the postpartum period with plans and backup plans for management remains critical.
 

Things we ‘never’ do

1. I never taper antidepressants (just prior to delivery), I never check plasma levels of selective serotonin reuptake inhibitors (across pregnancy, or just prior to labor and delivery), and I never use sodium valproate (during pregnancy).

Although there has been some discussion about the potential to mitigate risk for maternal or neonatal toxicity with lowering of agents such as lithium or lamotrigine during pregnancy, I do not routinely check plasma levels or arbitrarily change the dose of antidepressants, lithium, or lamotrigine during pregnancy in the absence of clinical symptoms.

We know full well that plasma levels of medications decline during pregnancy because of hemodilution with lithium and antidepressants and, in the case of lamotrigine, the effects of rising estrogen concentration during pregnancy on the metabolism of lamotrigine. While several studies have shown the decrease of SSRI concentration during pregnancy absent a change in dose of medication, these data have not correlated changes in plasma concentration of SSRI with a frank change in clinical status across pregnancy. Unlike what we see in conditions like epilepsy, where doses are increased to maintain therapeutic plasma levels to mitigate risk for seizure, those therapeutic plasma levels do not clearly exist for the psychiatric medications most widely used to treat psychiatric disorders.

We also almost never use sodium valproate in reproductive-age women despite its efficacy in both the acute and maintenance treatment of bipolar disorder given the risk of both major malformations associated with first-trimester fetal exposure to valproate and the data suggesting longer-term adverse neurobehavioral effects associated with its use during pregnancy.

2. We never suggest patients defer pregnancy based on their underlying psychiatric disorder.

Our role is to provide the best information regarding reproductive safety of psychiatric medications and risks of untreated psychiatric disorder to patients as they and relevant parties weigh the risks of pursuing one treatment or another. Those are private choices, and women and their partners make private decisions applying their own calculus with respect to moving forward with plans to conceive.

3. We never switch antidepressants once a woman has become pregnant.

Although we continue to see patients switched to older SSRIs such as sertraline with documentation of pregnancy, a patient’s road to getting well is sometimes very lengthy. In the absence of indicting reproductive safety data for any particular antidepressant, for patients who have gotten well on an antidepressant, even one for which we have less information, we stay the course and do not switch arbitrarily to an older SSRI for which we may have more reproductive safety data.

If we have the luxury prior to pregnancy to switch a patient to an untried and better studied antidepressant with more data supporting safety, we do so. But this is rarely the case. More often, we see women presenting with a newly documented pregnancy (frequently unplanned, with half of pregnancies across the country still being unplanned across sociodemographic lines) on an antidepressant with varying amounts of reproductive safety information available for the medicine being taken, and frequently after failed previous trials of other antidepressants. In this scenario, we rarely see the time of a newly documented pregnancy as an opportunity to pursue a new trial of an antidepressant without known efficacy for that patient; we stay the course and hope for sustained euthymia on the drug which has afforded euthymia to date.
 

Final thoughts

Dos and don’ts are relative in reproductive psychiatry. We tend to apply available data and clinical experience as we guide patients on a case-by-case basis, considering the most currently available rigorous reproductive safety data, as well as the individual patient’s clinical status and her personal wishes.

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

The experience of practicing reproductive psychiatry in the context of the pandemic has highlighted unique situations I’ve written about in previous columns that have affected pregnant and postpartum women during the pandemic, such as the management of anxiety and insomnia.

The pandemic has also seen a shift to telemedicine and an opportunity to use virtual platforms to engage with colleagues in our subspecialty across the country. These forums of engagement, which we realize virtually with so many of our colleagues, has prompted me to refine and galvanize what I consider to be some principles that guide frequently encountered clinical scenarios in reproductive psychiatry.

To open 2022, I wanted to revisit the practices I nearly “always” (or conversely, “never”) follow as a reproductive psychiatrist across the numerous clinical situations and variations on the associated clinical themes encountered as we see patients during pregnancy and the postpartum period.
 

Things we ‘always’ do

1. I continue to make maternal euthymia the North Star of treatment before, during, and after pregnancy.

Before pregnancy, maternal euthymia may be realized through optimization of pharmacologic and nonpharmacologic treatments and waiting to conceive until patients are emotionally well. Sustaining euthymia during pregnancy is a critical issue because of the extent to which euthymia during pregnancy predicts postpartum course. According to many studies, postpartum euthymia is the strongest predictor of long-term neurobehavioral outcome and risk for later child psychopathology. At the end of the day, there are few things I would not do with respect to treatment of maternal psychiatric disorder if the upside afforded maternal euthymia.

2. I almost always treat with consistency of medication across the peripartum period.

Although there have been discussions about the wisdom of changing medications, such as antidepressants, benzodiazepines, and mood stabilizers, that have afforded euthymia during pregnancy as patients approach their delivery date, the evidence base supporting switching medications at that time is exceedingly sparse. The time to adjust or to modify is typically not just prior to delivery unless it is to prevent postpartum psychiatric disorder (see below).

3. I simplify regimens before pregnancy if it’s unclear which medications have afforded patients euthymia.

We have a growing appreciation that polypharmacy is the rule in treatment of affective disorder for both unipolar and bipolar illness. Consultation before pregnancy is the ideal time to take a particularly careful history and think about simplifying regimens where adding medicines hasn’t clearly provided enhanced clinical benefit to the patient.

4. When making a treatment plan for psychiatric disorder during pregnancy, I consider the impact of untreated psychiatric disorder (even if not absolutely quantifiable) on fetal, neonatal, and maternal well-being.

Perhaps now more than even 5-10 years ago, we have better data describing the adverse effects of untreated psychiatric illness on fetal, neonatal, and maternal well-being.

We always try to deliberately consider the effect of a specific treatment on fetal well-being. Less attention (and science) has focused on the effect on pregnancy of deferring treatment; historically, this has not been adequately quantified in the risk-benefit decision. Yet, there is growing evidence of the increased adverse effects of activating the stress axis on everything from intrauterine fetal programming in the brain to effects on obstetrical outcomes such as preterm labor and delivery.

5. I appreciate the value of postpartum prophylaxis for pregnant women with bipolar disorder to mitigate risk of relapse.

We have spoken over the last 20 months of the pandemic, particularly in reproductive psychiatry circles, about the importance of keeping reproductive-age women with bipolar disorder emotionally well as they plan to conceive, during pregnancy, and in the postpartum period. The management of bipolar disorder during this time can be a humbling experience. Clinical roughening can be quick and severe, and so we do everything that we can for these women.

The area in which we have the strongest evidence base for mitigating risk with bipolar women is the value of postpartum prophylaxis during the peripartum period, regardless of what patients have done with their mood-stabilizing medications during pregnancy. Given the risk for postpartum disease, even though there are varying amounts of evidence on prophylactic benefit of specific mood stabilizers (i.e., lithium vs. atypical antipsychotics), the value of prophylaxis against worsening of bipolar disorder postpartum is widely accepted.

The importance of this has been particularly underscored during the pandemic where postpartum support, although available, has been more tenuous given the fluctuations in COVID-19 status around the country. The availability of friends and loved ones as support during the postpartum period has become less reliable in certain circumstances during the pandemic. In some cases, COVID-19 surges have wreaked havoc on travel plans and support persons have contracted the virus, rendering on-site support nonviable given safety concerns. Last-minute shifts of support plans have been responsible for disruption of care plans for new moms and by extension, have affected the ability to protect the sleep of bipolar women, which is critical. Keeping bipolar women well during the postpartum period with plans and backup plans for management remains critical.
 

Things we ‘never’ do

1. I never taper antidepressants (just prior to delivery), I never check plasma levels of selective serotonin reuptake inhibitors (across pregnancy, or just prior to labor and delivery), and I never use sodium valproate (during pregnancy).

Although there has been some discussion about the potential to mitigate risk for maternal or neonatal toxicity with lowering of agents such as lithium or lamotrigine during pregnancy, I do not routinely check plasma levels or arbitrarily change the dose of antidepressants, lithium, or lamotrigine during pregnancy in the absence of clinical symptoms.

We know full well that plasma levels of medications decline during pregnancy because of hemodilution with lithium and antidepressants and, in the case of lamotrigine, the effects of rising estrogen concentration during pregnancy on the metabolism of lamotrigine. While several studies have shown the decrease of SSRI concentration during pregnancy absent a change in dose of medication, these data have not correlated changes in plasma concentration of SSRI with a frank change in clinical status across pregnancy. Unlike what we see in conditions like epilepsy, where doses are increased to maintain therapeutic plasma levels to mitigate risk for seizure, those therapeutic plasma levels do not clearly exist for the psychiatric medications most widely used to treat psychiatric disorders.

We also almost never use sodium valproate in reproductive-age women despite its efficacy in both the acute and maintenance treatment of bipolar disorder given the risk of both major malformations associated with first-trimester fetal exposure to valproate and the data suggesting longer-term adverse neurobehavioral effects associated with its use during pregnancy.

2. We never suggest patients defer pregnancy based on their underlying psychiatric disorder.

Our role is to provide the best information regarding reproductive safety of psychiatric medications and risks of untreated psychiatric disorder to patients as they and relevant parties weigh the risks of pursuing one treatment or another. Those are private choices, and women and their partners make private decisions applying their own calculus with respect to moving forward with plans to conceive.

3. We never switch antidepressants once a woman has become pregnant.

Although we continue to see patients switched to older SSRIs such as sertraline with documentation of pregnancy, a patient’s road to getting well is sometimes very lengthy. In the absence of indicting reproductive safety data for any particular antidepressant, for patients who have gotten well on an antidepressant, even one for which we have less information, we stay the course and do not switch arbitrarily to an older SSRI for which we may have more reproductive safety data.

If we have the luxury prior to pregnancy to switch a patient to an untried and better studied antidepressant with more data supporting safety, we do so. But this is rarely the case. More often, we see women presenting with a newly documented pregnancy (frequently unplanned, with half of pregnancies across the country still being unplanned across sociodemographic lines) on an antidepressant with varying amounts of reproductive safety information available for the medicine being taken, and frequently after failed previous trials of other antidepressants. In this scenario, we rarely see the time of a newly documented pregnancy as an opportunity to pursue a new trial of an antidepressant without known efficacy for that patient; we stay the course and hope for sustained euthymia on the drug which has afforded euthymia to date.
 

Final thoughts

Dos and don’ts are relative in reproductive psychiatry. We tend to apply available data and clinical experience as we guide patients on a case-by-case basis, considering the most currently available rigorous reproductive safety data, as well as the individual patient’s clinical status and her personal wishes.

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

The experience of practicing reproductive psychiatry in the context of the pandemic has highlighted unique situations I’ve written about in previous columns that have affected pregnant and postpartum women during the pandemic, such as the management of anxiety and insomnia.

The pandemic has also seen a shift to telemedicine and an opportunity to use virtual platforms to engage with colleagues in our subspecialty across the country. These forums of engagement, which we realize virtually with so many of our colleagues, has prompted me to refine and galvanize what I consider to be some principles that guide frequently encountered clinical scenarios in reproductive psychiatry.

To open 2022, I wanted to revisit the practices I nearly “always” (or conversely, “never”) follow as a reproductive psychiatrist across the numerous clinical situations and variations on the associated clinical themes encountered as we see patients during pregnancy and the postpartum period.
 

Things we ‘always’ do

1. I continue to make maternal euthymia the North Star of treatment before, during, and after pregnancy.

Before pregnancy, maternal euthymia may be realized through optimization of pharmacologic and nonpharmacologic treatments and waiting to conceive until patients are emotionally well. Sustaining euthymia during pregnancy is a critical issue because of the extent to which euthymia during pregnancy predicts postpartum course. According to many studies, postpartum euthymia is the strongest predictor of long-term neurobehavioral outcome and risk for later child psychopathology. At the end of the day, there are few things I would not do with respect to treatment of maternal psychiatric disorder if the upside afforded maternal euthymia.

2. I almost always treat with consistency of medication across the peripartum period.

Although there have been discussions about the wisdom of changing medications, such as antidepressants, benzodiazepines, and mood stabilizers, that have afforded euthymia during pregnancy as patients approach their delivery date, the evidence base supporting switching medications at that time is exceedingly sparse. The time to adjust or to modify is typically not just prior to delivery unless it is to prevent postpartum psychiatric disorder (see below).

3. I simplify regimens before pregnancy if it’s unclear which medications have afforded patients euthymia.

We have a growing appreciation that polypharmacy is the rule in treatment of affective disorder for both unipolar and bipolar illness. Consultation before pregnancy is the ideal time to take a particularly careful history and think about simplifying regimens where adding medicines hasn’t clearly provided enhanced clinical benefit to the patient.

4. When making a treatment plan for psychiatric disorder during pregnancy, I consider the impact of untreated psychiatric disorder (even if not absolutely quantifiable) on fetal, neonatal, and maternal well-being.

Perhaps now more than even 5-10 years ago, we have better data describing the adverse effects of untreated psychiatric illness on fetal, neonatal, and maternal well-being.

We always try to deliberately consider the effect of a specific treatment on fetal well-being. Less attention (and science) has focused on the effect on pregnancy of deferring treatment; historically, this has not been adequately quantified in the risk-benefit decision. Yet, there is growing evidence of the increased adverse effects of activating the stress axis on everything from intrauterine fetal programming in the brain to effects on obstetrical outcomes such as preterm labor and delivery.

5. I appreciate the value of postpartum prophylaxis for pregnant women with bipolar disorder to mitigate risk of relapse.

We have spoken over the last 20 months of the pandemic, particularly in reproductive psychiatry circles, about the importance of keeping reproductive-age women with bipolar disorder emotionally well as they plan to conceive, during pregnancy, and in the postpartum period. The management of bipolar disorder during this time can be a humbling experience. Clinical roughening can be quick and severe, and so we do everything that we can for these women.

The area in which we have the strongest evidence base for mitigating risk with bipolar women is the value of postpartum prophylaxis during the peripartum period, regardless of what patients have done with their mood-stabilizing medications during pregnancy. Given the risk for postpartum disease, even though there are varying amounts of evidence on prophylactic benefit of specific mood stabilizers (i.e., lithium vs. atypical antipsychotics), the value of prophylaxis against worsening of bipolar disorder postpartum is widely accepted.

The importance of this has been particularly underscored during the pandemic where postpartum support, although available, has been more tenuous given the fluctuations in COVID-19 status around the country. The availability of friends and loved ones as support during the postpartum period has become less reliable in certain circumstances during the pandemic. In some cases, COVID-19 surges have wreaked havoc on travel plans and support persons have contracted the virus, rendering on-site support nonviable given safety concerns. Last-minute shifts of support plans have been responsible for disruption of care plans for new moms and by extension, have affected the ability to protect the sleep of bipolar women, which is critical. Keeping bipolar women well during the postpartum period with plans and backup plans for management remains critical.
 

Things we ‘never’ do

1. I never taper antidepressants (just prior to delivery), I never check plasma levels of selective serotonin reuptake inhibitors (across pregnancy, or just prior to labor and delivery), and I never use sodium valproate (during pregnancy).

Although there has been some discussion about the potential to mitigate risk for maternal or neonatal toxicity with lowering of agents such as lithium or lamotrigine during pregnancy, I do not routinely check plasma levels or arbitrarily change the dose of antidepressants, lithium, or lamotrigine during pregnancy in the absence of clinical symptoms.

We know full well that plasma levels of medications decline during pregnancy because of hemodilution with lithium and antidepressants and, in the case of lamotrigine, the effects of rising estrogen concentration during pregnancy on the metabolism of lamotrigine. While several studies have shown the decrease of SSRI concentration during pregnancy absent a change in dose of medication, these data have not correlated changes in plasma concentration of SSRI with a frank change in clinical status across pregnancy. Unlike what we see in conditions like epilepsy, where doses are increased to maintain therapeutic plasma levels to mitigate risk for seizure, those therapeutic plasma levels do not clearly exist for the psychiatric medications most widely used to treat psychiatric disorders.

We also almost never use sodium valproate in reproductive-age women despite its efficacy in both the acute and maintenance treatment of bipolar disorder given the risk of both major malformations associated with first-trimester fetal exposure to valproate and the data suggesting longer-term adverse neurobehavioral effects associated with its use during pregnancy.

2. We never suggest patients defer pregnancy based on their underlying psychiatric disorder.

Our role is to provide the best information regarding reproductive safety of psychiatric medications and risks of untreated psychiatric disorder to patients as they and relevant parties weigh the risks of pursuing one treatment or another. Those are private choices, and women and their partners make private decisions applying their own calculus with respect to moving forward with plans to conceive.

3. We never switch antidepressants once a woman has become pregnant.

Although we continue to see patients switched to older SSRIs such as sertraline with documentation of pregnancy, a patient’s road to getting well is sometimes very lengthy. In the absence of indicting reproductive safety data for any particular antidepressant, for patients who have gotten well on an antidepressant, even one for which we have less information, we stay the course and do not switch arbitrarily to an older SSRI for which we may have more reproductive safety data.

If we have the luxury prior to pregnancy to switch a patient to an untried and better studied antidepressant with more data supporting safety, we do so. But this is rarely the case. More often, we see women presenting with a newly documented pregnancy (frequently unplanned, with half of pregnancies across the country still being unplanned across sociodemographic lines) on an antidepressant with varying amounts of reproductive safety information available for the medicine being taken, and frequently after failed previous trials of other antidepressants. In this scenario, we rarely see the time of a newly documented pregnancy as an opportunity to pursue a new trial of an antidepressant without known efficacy for that patient; we stay the course and hope for sustained euthymia on the drug which has afforded euthymia to date.
 

Final thoughts

Dos and don’ts are relative in reproductive psychiatry. We tend to apply available data and clinical experience as we guide patients on a case-by-case basis, considering the most currently available rigorous reproductive safety data, as well as the individual patient’s clinical status and her personal wishes.

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