Lee S. Cohen, MD

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 [email protected].

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 [email protected].

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 [email protected].

Postpartum depression, in many respects, has become a household term. Over the last decade, there has been increasing awareness of the importance of screening for postpartum depression, with increased systematic screening across clinical settings where care is delivered to women during pregnancy and the postpartum period. There have also been greater efforts to identify women who are suffering postpartum depression and to support them with appropriate clinical interventions, whether through psychotherapy and/or pharmacologic therapy. Clinical interventions are supplemented by the increasing awareness of the value of community-based support groups for women who are suffering from postpartum mood and anxiety disorders.

Despite the growing, appropriate focus on recognition and acute treatment of postpartum depression as well as assessing clinical outcomes for those who suffer from postpartum mood and anxiety disorders, less attention has been given to postpartum psychosis, the most severe form of postpartum depression. It is indeed, the least common postpartum psychiatric syndrome (1 in 1,000 births) and comes to public attention when there has been a tragedy during the acute postpartum period such as maternal suicide or infanticide. In this sense, postpartum psychosis is ironically an underappreciated clinical entity across America given its severity, the effect it has on longer-term psychiatric morbidity, and its effect on children and families.

Our group at the Center for Women’s Mental Health has been interested in postpartum psychosis for years and started the Postpartum Psychosis Project in an effort to better understand the phenomenology, course, treatment, outcome, and genomic underpinnings of postpartum psychosis. Risk factors that are well established for postpartum psychosis have been described and overwhelmingly include patients with bipolar disorder. The risk for recurrent postpartum psychosis in women who have had a previous episode is as great as 75%-90% in the absence of prophylactic intervention. With that said, we are extremely interested in understanding the etiology of postpartum psychosis. Various studies over the last 5 years have looked at a whole host of psychosocial as well as neurobiologic variables that may contribute to risk for postpartum psychosis, including dysregulation of the stress axis, heightened inflammation as well as a history of child adversity and heightened experience of stress during the perinatal period.

There have also been anecdotal reports during Virtual Rounds at the Center for Women’s Mental Health of higher recent rates of postpartum psychosis manifesting during the postpartum period. This is a clinical observation and has not been systematically studied. However, one can wonder whether the experience of the pandemic has constituted a stressor for at-risk women, tipping the scales toward women becoming ill, or whether clinicians are seeing this finding more because of our ability to observe it more within the context of the pandemic.

Precise quantification of risk for postpartum psychosis is complicated; as noted, women with bipolar disorder have a predictably high risk for getting ill during the postpartum period and many go on to have clinical courses consistent with recurrent bipolar disorder. However, there are other women who have circumscribed episodes of psychotic illness in the postpartum period who recover and are totally well without any evidence of psychiatric disorder until they have another child, at which time the risk for recurrence of postpartum psychosis is very high. Interest in developing a model of risk that could reliably predict an illness as serious as postpartum psychosis is on the minds of researchers around the world.

One recent study that highlights the multiple factors involved in risk of postpartum psychosis involved a prospective longitudinal study of a group of women who were followed across the peripartum period from the third trimester until 4 weeks postpartum. In this group, 51 women were at increased risk for postpartum psychosis based on their diagnosis of bipolar disorder, schizoaffective disorder, or a previous episode of postpartum psychosis. These women were matched with a control group with no past or current diagnosis of psychiatric disorder or family history of postpartum psychosis. The findings suggested that women at risk for postpartum psychosis who experienced a psychiatric relapse during the first 4 weeks postpartum relative to women at risk who remained well had histories of severe childhood adversity as well as biomarkers consistent with a dysregulated stress axis (a statistically higher daily cortisol level). This is consistent with other data that have implicated the complex role between psychosocial variables as well as neurobiologic variables, such as a dysregulation in the hypothalamic pituitary adrenal axis and other studies that suggest that dysregulated inflammatory status may also drive risk for postpartum psychosis (Hazelgrove K et al. Psychoneuroendocrinology. 2021 Jun. doi: 10.1016/j.psyneuen.2021.105218).

At the end of the day, postpartum psychosis is a psychiatric and obstetrical emergency. In our center, it is rare for women not to be hospitalized with this condition to ensure the safety of the mother as well as her newborn, and to also get her recompensated and functioning as quickly and as significantly as possible. However, an interesting extrapolation of the findings noted by Hazelgrove and colleagues is that it raises the question of what effective treatments might be used to mitigate risk for those at greatest risk for postpartum psychosis. For example, are there other treatments over and above the few effective ones that have been studied as prophylactic pharmacologic interventions that might mitigate risk for recurrence of an illness as serious as postpartum psychosis?

The data suggesting dysregulation of the stress axis as a predictor variable for risk in women vulnerable to postpartum psychosis opens an array of opportunities that are nonpharmacologic, such as mindfulness-based cognitive therapy or other interventions that help to modulate the stress axis. This is a terrific opportunity to have pharmacologic intervention meet nonpharmacologic intervention to potentially mitigate risk for postpartum psychosis with its attendant serious sequelae.

In our own work, where we are evaluating genomic data in an extremely well-characterized group of women with known histories of postpartum psychosis, we are interested to see if we can enhance understanding of the model of risk for postpartum psychosis by factoring in genomic underpinning, history of diagnosis, and psychosocial variables to optimally craft interventions for this population of at-risk women. This brings us one step closer to the future in women’s mental health, to the practice of “precision reproductive psychiatry,” matching interventions to specific presentations across perinatal populations.
 

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 [email protected].

Postpartum depression, in many respects, has become a household term. Over the last decade, there has been increasing awareness of the importance of screening for postpartum depression, with increased systematic screening across clinical settings where care is delivered to women during pregnancy and the postpartum period. There have also been greater efforts to identify women who are suffering postpartum depression and to support them with appropriate clinical interventions, whether through psychotherapy and/or pharmacologic therapy. Clinical interventions are supplemented by the increasing awareness of the value of community-based support groups for women who are suffering from postpartum mood and anxiety disorders.

Despite the growing, appropriate focus on recognition and acute treatment of postpartum depression as well as assessing clinical outcomes for those who suffer from postpartum mood and anxiety disorders, less attention has been given to postpartum psychosis, the most severe form of postpartum depression. It is indeed, the least common postpartum psychiatric syndrome (1 in 1,000 births) and comes to public attention when there has been a tragedy during the acute postpartum period such as maternal suicide or infanticide. In this sense, postpartum psychosis is ironically an underappreciated clinical entity across America given its severity, the effect it has on longer-term psychiatric morbidity, and its effect on children and families.

Our group at the Center for Women’s Mental Health has been interested in postpartum psychosis for years and started the Postpartum Psychosis Project in an effort to better understand the phenomenology, course, treatment, outcome, and genomic underpinnings of postpartum psychosis. Risk factors that are well established for postpartum psychosis have been described and overwhelmingly include patients with bipolar disorder. The risk for recurrent postpartum psychosis in women who have had a previous episode is as great as 75%-90% in the absence of prophylactic intervention. With that said, we are extremely interested in understanding the etiology of postpartum psychosis. Various studies over the last 5 years have looked at a whole host of psychosocial as well as neurobiologic variables that may contribute to risk for postpartum psychosis, including dysregulation of the stress axis, heightened inflammation as well as a history of child adversity and heightened experience of stress during the perinatal period.

There have also been anecdotal reports during Virtual Rounds at the Center for Women’s Mental Health of higher recent rates of postpartum psychosis manifesting during the postpartum period. This is a clinical observation and has not been systematically studied. However, one can wonder whether the experience of the pandemic has constituted a stressor for at-risk women, tipping the scales toward women becoming ill, or whether clinicians are seeing this finding more because of our ability to observe it more within the context of the pandemic.

Precise quantification of risk for postpartum psychosis is complicated; as noted, women with bipolar disorder have a predictably high risk for getting ill during the postpartum period and many go on to have clinical courses consistent with recurrent bipolar disorder. However, there are other women who have circumscribed episodes of psychotic illness in the postpartum period who recover and are totally well without any evidence of psychiatric disorder until they have another child, at which time the risk for recurrence of postpartum psychosis is very high. Interest in developing a model of risk that could reliably predict an illness as serious as postpartum psychosis is on the minds of researchers around the world.

One recent study that highlights the multiple factors involved in risk of postpartum psychosis involved a prospective longitudinal study of a group of women who were followed across the peripartum period from the third trimester until 4 weeks postpartum. In this group, 51 women were at increased risk for postpartum psychosis based on their diagnosis of bipolar disorder, schizoaffective disorder, or a previous episode of postpartum psychosis. These women were matched with a control group with no past or current diagnosis of psychiatric disorder or family history of postpartum psychosis. The findings suggested that women at risk for postpartum psychosis who experienced a psychiatric relapse during the first 4 weeks postpartum relative to women at risk who remained well had histories of severe childhood adversity as well as biomarkers consistent with a dysregulated stress axis (a statistically higher daily cortisol level). This is consistent with other data that have implicated the complex role between psychosocial variables as well as neurobiologic variables, such as a dysregulation in the hypothalamic pituitary adrenal axis and other studies that suggest that dysregulated inflammatory status may also drive risk for postpartum psychosis (Hazelgrove K et al. Psychoneuroendocrinology. 2021 Jun. doi: 10.1016/j.psyneuen.2021.105218).

At the end of the day, postpartum psychosis is a psychiatric and obstetrical emergency. In our center, it is rare for women not to be hospitalized with this condition to ensure the safety of the mother as well as her newborn, and to also get her recompensated and functioning as quickly and as significantly as possible. However, an interesting extrapolation of the findings noted by Hazelgrove and colleagues is that it raises the question of what effective treatments might be used to mitigate risk for those at greatest risk for postpartum psychosis. For example, are there other treatments over and above the few effective ones that have been studied as prophylactic pharmacologic interventions that might mitigate risk for recurrence of an illness as serious as postpartum psychosis?

The data suggesting dysregulation of the stress axis as a predictor variable for risk in women vulnerable to postpartum psychosis opens an array of opportunities that are nonpharmacologic, such as mindfulness-based cognitive therapy or other interventions that help to modulate the stress axis. This is a terrific opportunity to have pharmacologic intervention meet nonpharmacologic intervention to potentially mitigate risk for postpartum psychosis with its attendant serious sequelae.

In our own work, where we are evaluating genomic data in an extremely well-characterized group of women with known histories of postpartum psychosis, we are interested to see if we can enhance understanding of the model of risk for postpartum psychosis by factoring in genomic underpinning, history of diagnosis, and psychosocial variables to optimally craft interventions for this population of at-risk women. This brings us one step closer to the future in women’s mental health, to the practice of “precision reproductive psychiatry,” matching interventions to specific presentations across perinatal populations.
 

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 [email protected].

Postpartum depression, in many respects, has become a household term. Over the last decade, there has been increasing awareness of the importance of screening for postpartum depression, with increased systematic screening across clinical settings where care is delivered to women during pregnancy and the postpartum period. There have also been greater efforts to identify women who are suffering postpartum depression and to support them with appropriate clinical interventions, whether through psychotherapy and/or pharmacologic therapy. Clinical interventions are supplemented by the increasing awareness of the value of community-based support groups for women who are suffering from postpartum mood and anxiety disorders.

Despite the growing, appropriate focus on recognition and acute treatment of postpartum depression as well as assessing clinical outcomes for those who suffer from postpartum mood and anxiety disorders, less attention has been given to postpartum psychosis, the most severe form of postpartum depression. It is indeed, the least common postpartum psychiatric syndrome (1 in 1,000 births) and comes to public attention when there has been a tragedy during the acute postpartum period such as maternal suicide or infanticide. In this sense, postpartum psychosis is ironically an underappreciated clinical entity across America given its severity, the effect it has on longer-term psychiatric morbidity, and its effect on children and families.

Our group at the Center for Women’s Mental Health has been interested in postpartum psychosis for years and started the Postpartum Psychosis Project in an effort to better understand the phenomenology, course, treatment, outcome, and genomic underpinnings of postpartum psychosis. Risk factors that are well established for postpartum psychosis have been described and overwhelmingly include patients with bipolar disorder. The risk for recurrent postpartum psychosis in women who have had a previous episode is as great as 75%-90% in the absence of prophylactic intervention. With that said, we are extremely interested in understanding the etiology of postpartum psychosis. Various studies over the last 5 years have looked at a whole host of psychosocial as well as neurobiologic variables that may contribute to risk for postpartum psychosis, including dysregulation of the stress axis, heightened inflammation as well as a history of child adversity and heightened experience of stress during the perinatal period.

There have also been anecdotal reports during Virtual Rounds at the Center for Women’s Mental Health of higher recent rates of postpartum psychosis manifesting during the postpartum period. This is a clinical observation and has not been systematically studied. However, one can wonder whether the experience of the pandemic has constituted a stressor for at-risk women, tipping the scales toward women becoming ill, or whether clinicians are seeing this finding more because of our ability to observe it more within the context of the pandemic.

Precise quantification of risk for postpartum psychosis is complicated; as noted, women with bipolar disorder have a predictably high risk for getting ill during the postpartum period and many go on to have clinical courses consistent with recurrent bipolar disorder. However, there are other women who have circumscribed episodes of psychotic illness in the postpartum period who recover and are totally well without any evidence of psychiatric disorder until they have another child, at which time the risk for recurrence of postpartum psychosis is very high. Interest in developing a model of risk that could reliably predict an illness as serious as postpartum psychosis is on the minds of researchers around the world.

One recent study that highlights the multiple factors involved in risk of postpartum psychosis involved a prospective longitudinal study of a group of women who were followed across the peripartum period from the third trimester until 4 weeks postpartum. In this group, 51 women were at increased risk for postpartum psychosis based on their diagnosis of bipolar disorder, schizoaffective disorder, or a previous episode of postpartum psychosis. These women were matched with a control group with no past or current diagnosis of psychiatric disorder or family history of postpartum psychosis. The findings suggested that women at risk for postpartum psychosis who experienced a psychiatric relapse during the first 4 weeks postpartum relative to women at risk who remained well had histories of severe childhood adversity as well as biomarkers consistent with a dysregulated stress axis (a statistically higher daily cortisol level). This is consistent with other data that have implicated the complex role between psychosocial variables as well as neurobiologic variables, such as a dysregulation in the hypothalamic pituitary adrenal axis and other studies that suggest that dysregulated inflammatory status may also drive risk for postpartum psychosis (Hazelgrove K et al. Psychoneuroendocrinology. 2021 Jun. doi: 10.1016/j.psyneuen.2021.105218).

At the end of the day, postpartum psychosis is a psychiatric and obstetrical emergency. In our center, it is rare for women not to be hospitalized with this condition to ensure the safety of the mother as well as her newborn, and to also get her recompensated and functioning as quickly and as significantly as possible. However, an interesting extrapolation of the findings noted by Hazelgrove and colleagues is that it raises the question of what effective treatments might be used to mitigate risk for those at greatest risk for postpartum psychosis. For example, are there other treatments over and above the few effective ones that have been studied as prophylactic pharmacologic interventions that might mitigate risk for recurrence of an illness as serious as postpartum psychosis?

The data suggesting dysregulation of the stress axis as a predictor variable for risk in women vulnerable to postpartum psychosis opens an array of opportunities that are nonpharmacologic, such as mindfulness-based cognitive therapy or other interventions that help to modulate the stress axis. This is a terrific opportunity to have pharmacologic intervention meet nonpharmacologic intervention to potentially mitigate risk for postpartum psychosis with its attendant serious sequelae.

In our own work, where we are evaluating genomic data in an extremely well-characterized group of women with known histories of postpartum psychosis, we are interested to see if we can enhance understanding of the model of risk for postpartum psychosis by factoring in genomic underpinning, history of diagnosis, and psychosocial variables to optimally craft interventions for this population of at-risk women. This brings us one step closer to the future in women’s mental health, to the practice of “precision reproductive psychiatry,” matching interventions to specific presentations across perinatal populations.
 

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 [email protected].

Since March 2020, my colleagues and I have conducted Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital. It has been an opportunity to review the basic tenets of care for reproductive age women before, during, and after pregnancy, and also to learn of extraordinary cases being managed both in the outpatient setting and in the context of the COVID-19 pandemic.

As I’ve noted in previous columns, we have seen a heightening of symptoms of anxiety and insomnia during the pandemic in women who visit our center, and at the centers of the more than 100 clinicians who join Virtual Rounds each week. These colleagues represent people in rural areas, urban environments, and underserved communities across America that have been severely affected by the pandemic. It is clear that the stress of the pandemic is undeniable for patients both with and without psychiatric or mental health issues. We have also seen clinical roughening in women who have been well for a long period of time. In particular, we have noticed that postpartum women are struggling with the stressors of the postpartum period, such as figuring out the logistics of support with respect to childcare, managing maternity leave, and adapting to shifting of anticipated support systems.

Hundreds of women with bipolar disorder come to see us each year about the reproductive safety of the medicines on which they are maintained. Those patients are typically well, and we collaborate with them and their doctors about the safest treatment recommendations. With that said, women with bipolar disorder are at particular risk for postpartum worsening of their mood. The management of their medications during pregnancy requires extremely careful attention because relapse of psychiatric disorder during pregnancy is the strongest predictor of postpartum worsening of underlying psychiatric illness.

This is an opportunity to briefly review the reproductive safety of treatments for these women. We know through initiatives such as the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications that the most widely used medicines for bipolar women during pregnancy include lamotrigine, atypical antipsychotics, and lithium carbonate.
 

Lamotrigine

The last 15 years have generated the most consistent data on the reproductive safety of lamotrigine. One of the issues, however, with respect to lamotrigine is that its use requires very careful and slow titration and it is also more effective in patients who are well and in the maintenance phase of the illness versus those who are more acutely manic or who are suffering from frank bipolar depression.

Critically, the literature does not support the use of lamotrigine for patients with bipolar I or with more manic symptoms. That being said, it remains a mainstay of treatment for many patients with bipolar disorder, is easy to use across pregnancy, and has an attractive side-effect profile and a very strong reproductive safety profile, suggesting the absence of an increased risk for major malformations.
 

Atypical antipsychotics

We have less information but have a growing body of evidence about atypical antipsychotics. Both data from administrative databases as well a growing literature from pregnancy registries, such as the National Pregnancy Registry for Atypical Antipsychotics, fail to show a signal for teratogenicity with respect to use of the medicines as a class, and also with specific reference to some of the most widely used atypical antipsychotics, particularly quetiapine and aripiprazole. Our comfort level, compared with a decade ago, with using the second-generation antipsychotics is much greater. That’s a good thing considering the extent to which patients presenting on a combination of, for example, lamotrigine and atypical antipsychotics.

Lithium carbonate

Another mainstay of treatment for women with bipolar I disorder and prominent symptoms of mania is lithium carbonate. The data for efficacy of lithium carbonate used both acutely and for maintenance treatment of bipolar disorder has been unequivocal. Concerns about the teratogenicity of lithium go back to the 1970s and indicate a small increased absolute and relative risk for cardiovascular malformations. More recently, a meta-analysis of lithium exposure during pregnancy and the postpartum period supports this older data, which suggests this increased risk, and examines other outcomes concerning to women with bipolar disorder who use lithium, such as preterm labor, low birth weight, miscarriage, and other adverse neonatal outcomes.

In 2021, with the backdrop of the pandemic, what we actually see is that, for our pregnant and postpartum patients with bipolar disorder, the imperative to keep them well, keep them out of the hospital, and keep them safe has often required careful coadministration of drugs like lamotrigine, lithium, and atypical antipsychotics (and even benzodiazepines). Keeping this population well during the perinatal period is so critical. We were all trained to use the least number of medications when possible across psychiatric illnesses. But the years, data, and clinical experience have shown that polypharmacy may be required to sustain euthymia in many patients with bipolar disorder. The reflex historically has been to stop medications during pregnancy. We take pause, particularly during the pandemic, before reverting back to the practice of 25 years ago of abruptly stopping medicines such as lithium or atypical antipsychotics in patients with bipolar disorder because we know that the risk for relapse is very high following a shift from the regimen that got the patient well.

The COVID-19 pandemic in many respects has highlighted a need to clinically thread the needle with respect to developing a regimen that minimizes risk of reproductive safety concerns but maximizes the likelihood that we can sustain the emotional well-being of these women across pregnancy and into the postpartum period.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, 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 [email protected].

Since March 2020, my colleagues and I have conducted Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital. It has been an opportunity to review the basic tenets of care for reproductive age women before, during, and after pregnancy, and also to learn of extraordinary cases being managed both in the outpatient setting and in the context of the COVID-19 pandemic.

As I’ve noted in previous columns, we have seen a heightening of symptoms of anxiety and insomnia during the pandemic in women who visit our center, and at the centers of the more than 100 clinicians who join Virtual Rounds each week. These colleagues represent people in rural areas, urban environments, and underserved communities across America that have been severely affected by the pandemic. It is clear that the stress of the pandemic is undeniable for patients both with and without psychiatric or mental health issues. We have also seen clinical roughening in women who have been well for a long period of time. In particular, we have noticed that postpartum women are struggling with the stressors of the postpartum period, such as figuring out the logistics of support with respect to childcare, managing maternity leave, and adapting to shifting of anticipated support systems.

Hundreds of women with bipolar disorder come to see us each year about the reproductive safety of the medicines on which they are maintained. Those patients are typically well, and we collaborate with them and their doctors about the safest treatment recommendations. With that said, women with bipolar disorder are at particular risk for postpartum worsening of their mood. The management of their medications during pregnancy requires extremely careful attention because relapse of psychiatric disorder during pregnancy is the strongest predictor of postpartum worsening of underlying psychiatric illness.

This is an opportunity to briefly review the reproductive safety of treatments for these women. We know through initiatives such as the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications that the most widely used medicines for bipolar women during pregnancy include lamotrigine, atypical antipsychotics, and lithium carbonate.
 

Lamotrigine

The last 15 years have generated the most consistent data on the reproductive safety of lamotrigine. One of the issues, however, with respect to lamotrigine is that its use requires very careful and slow titration and it is also more effective in patients who are well and in the maintenance phase of the illness versus those who are more acutely manic or who are suffering from frank bipolar depression.

Critically, the literature does not support the use of lamotrigine for patients with bipolar I or with more manic symptoms. That being said, it remains a mainstay of treatment for many patients with bipolar disorder, is easy to use across pregnancy, and has an attractive side-effect profile and a very strong reproductive safety profile, suggesting the absence of an increased risk for major malformations.
 

Atypical antipsychotics

We have less information but have a growing body of evidence about atypical antipsychotics. Both data from administrative databases as well a growing literature from pregnancy registries, such as the National Pregnancy Registry for Atypical Antipsychotics, fail to show a signal for teratogenicity with respect to use of the medicines as a class, and also with specific reference to some of the most widely used atypical antipsychotics, particularly quetiapine and aripiprazole. Our comfort level, compared with a decade ago, with using the second-generation antipsychotics is much greater. That’s a good thing considering the extent to which patients presenting on a combination of, for example, lamotrigine and atypical antipsychotics.

Lithium carbonate

Another mainstay of treatment for women with bipolar I disorder and prominent symptoms of mania is lithium carbonate. The data for efficacy of lithium carbonate used both acutely and for maintenance treatment of bipolar disorder has been unequivocal. Concerns about the teratogenicity of lithium go back to the 1970s and indicate a small increased absolute and relative risk for cardiovascular malformations. More recently, a meta-analysis of lithium exposure during pregnancy and the postpartum period supports this older data, which suggests this increased risk, and examines other outcomes concerning to women with bipolar disorder who use lithium, such as preterm labor, low birth weight, miscarriage, and other adverse neonatal outcomes.

In 2021, with the backdrop of the pandemic, what we actually see is that, for our pregnant and postpartum patients with bipolar disorder, the imperative to keep them well, keep them out of the hospital, and keep them safe has often required careful coadministration of drugs like lamotrigine, lithium, and atypical antipsychotics (and even benzodiazepines). Keeping this population well during the perinatal period is so critical. We were all trained to use the least number of medications when possible across psychiatric illnesses. But the years, data, and clinical experience have shown that polypharmacy may be required to sustain euthymia in many patients with bipolar disorder. The reflex historically has been to stop medications during pregnancy. We take pause, particularly during the pandemic, before reverting back to the practice of 25 years ago of abruptly stopping medicines such as lithium or atypical antipsychotics in patients with bipolar disorder because we know that the risk for relapse is very high following a shift from the regimen that got the patient well.

The COVID-19 pandemic in many respects has highlighted a need to clinically thread the needle with respect to developing a regimen that minimizes risk of reproductive safety concerns but maximizes the likelihood that we can sustain the emotional well-being of these women across pregnancy and into the postpartum period.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, 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 [email protected].

Since March 2020, my colleagues and I have conducted Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital. It has been an opportunity to review the basic tenets of care for reproductive age women before, during, and after pregnancy, and also to learn of extraordinary cases being managed both in the outpatient setting and in the context of the COVID-19 pandemic.

As I’ve noted in previous columns, we have seen a heightening of symptoms of anxiety and insomnia during the pandemic in women who visit our center, and at the centers of the more than 100 clinicians who join Virtual Rounds each week. These colleagues represent people in rural areas, urban environments, and underserved communities across America that have been severely affected by the pandemic. It is clear that the stress of the pandemic is undeniable for patients both with and without psychiatric or mental health issues. We have also seen clinical roughening in women who have been well for a long period of time. In particular, we have noticed that postpartum women are struggling with the stressors of the postpartum period, such as figuring out the logistics of support with respect to childcare, managing maternity leave, and adapting to shifting of anticipated support systems.

Hundreds of women with bipolar disorder come to see us each year about the reproductive safety of the medicines on which they are maintained. Those patients are typically well, and we collaborate with them and their doctors about the safest treatment recommendations. With that said, women with bipolar disorder are at particular risk for postpartum worsening of their mood. The management of their medications during pregnancy requires extremely careful attention because relapse of psychiatric disorder during pregnancy is the strongest predictor of postpartum worsening of underlying psychiatric illness.

This is an opportunity to briefly review the reproductive safety of treatments for these women. We know through initiatives such as the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications that the most widely used medicines for bipolar women during pregnancy include lamotrigine, atypical antipsychotics, and lithium carbonate.
 

Lamotrigine

The last 15 years have generated the most consistent data on the reproductive safety of lamotrigine. One of the issues, however, with respect to lamotrigine is that its use requires very careful and slow titration and it is also more effective in patients who are well and in the maintenance phase of the illness versus those who are more acutely manic or who are suffering from frank bipolar depression.

Critically, the literature does not support the use of lamotrigine for patients with bipolar I or with more manic symptoms. That being said, it remains a mainstay of treatment for many patients with bipolar disorder, is easy to use across pregnancy, and has an attractive side-effect profile and a very strong reproductive safety profile, suggesting the absence of an increased risk for major malformations.
 

Atypical antipsychotics

We have less information but have a growing body of evidence about atypical antipsychotics. Both data from administrative databases as well a growing literature from pregnancy registries, such as the National Pregnancy Registry for Atypical Antipsychotics, fail to show a signal for teratogenicity with respect to use of the medicines as a class, and also with specific reference to some of the most widely used atypical antipsychotics, particularly quetiapine and aripiprazole. Our comfort level, compared with a decade ago, with using the second-generation antipsychotics is much greater. That’s a good thing considering the extent to which patients presenting on a combination of, for example, lamotrigine and atypical antipsychotics.

Lithium carbonate

Another mainstay of treatment for women with bipolar I disorder and prominent symptoms of mania is lithium carbonate. The data for efficacy of lithium carbonate used both acutely and for maintenance treatment of bipolar disorder has been unequivocal. Concerns about the teratogenicity of lithium go back to the 1970s and indicate a small increased absolute and relative risk for cardiovascular malformations. More recently, a meta-analysis of lithium exposure during pregnancy and the postpartum period supports this older data, which suggests this increased risk, and examines other outcomes concerning to women with bipolar disorder who use lithium, such as preterm labor, low birth weight, miscarriage, and other adverse neonatal outcomes.

In 2021, with the backdrop of the pandemic, what we actually see is that, for our pregnant and postpartum patients with bipolar disorder, the imperative to keep them well, keep them out of the hospital, and keep them safe has often required careful coadministration of drugs like lamotrigine, lithium, and atypical antipsychotics (and even benzodiazepines). Keeping this population well during the perinatal period is so critical. We were all trained to use the least number of medications when possible across psychiatric illnesses. But the years, data, and clinical experience have shown that polypharmacy may be required to sustain euthymia in many patients with bipolar disorder. The reflex historically has been to stop medications during pregnancy. We take pause, particularly during the pandemic, before reverting back to the practice of 25 years ago of abruptly stopping medicines such as lithium or atypical antipsychotics in patients with bipolar disorder because we know that the risk for relapse is very high following a shift from the regimen that got the patient well.

The COVID-19 pandemic in many respects has highlighted a need to clinically thread the needle with respect to developing a regimen that minimizes risk of reproductive safety concerns but maximizes the likelihood that we can sustain the emotional well-being of these women across pregnancy and into the postpartum period.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, 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 [email protected].

Across this period of the pandemic, we’ve spent considerable attention focusing on adaptations to clinical care for pregnant and postpartum women across the board. From the start, this has included a shift to telemedicine for the majority of our patients who come to see us with psychiatric disorders either before, during, or after pregnancy.

Specific issues for perinatal patients since the early days of COVID-19 have included the shifts in women’s plans with respect to delivery as well as the limitation on women’s ability to configure the types of support that they had originally planned on with family, friends, and others during delivery. Telemedicine again helped, at least in part, to fill that void by having online digital support by individuals or groups for both pregnant and postpartum women. These supports were always available, but quickly scaled up during the first 6-9 months of the pandemic and have likely seen their greatest increase in participation in the history of support groups for pregnant and postpartum women.

Similarly, at our own center, we have seen a dramatic increase across the last 10 months in requests for consultation by women with psychiatric disorders who have hopes and plans to conceive, to those who are pregnant or post partum and who are trying to sustain emotional well-being despite the added burden of the pandemic. As we heard similar stories regarding interactions with perinatal patients from reproductive psychiatrists across the country, my colleagues and I had to set up an additional resource, Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital, Boston, which has been mentioned in previous columns, which has only grown during the last 6 months of the pandemic. We have colleagues across the country joining us from 2 p.m. to 3 p.m. on Wednesdays after our own faculty rounds, where we perform case reviews of our own patients, and invite our colleagues to share cases that are then reviewed with expert panelists together with our own faculty in a collaborative environment. Feedback from the community of clinicians has indicated that these virtual rounds have been invaluable to their efforts in taking care of women with perinatal psychiatric issues, particularly during the pandemic.

Of particular note during consultations on our service is the number of women coming to see us for questions about the reproductive safety of the medications on which they are maintained. Hundreds of women present to the center each year for the most up-to-date information regarding the reproductive safety of the most commonly used psychiatric medications in reproductive-age women, including antidepressants (SSRIs, serotonin norepinephrine reuptake inhibitor), mood stabilizers, lithium, lamotrigine, and atypical antipsychotics, as well as other medicines used to treat symptoms that have been a particular issue during the pandemic, such as insomnia and anxiety (benzodiazepines, nonbenzodiazepines, sedative hypnotics, and medicines such as gabapentin).

While consultation regarding risk of fetal exposure to psychotropics has been the cornerstone of our clinical work for 25 years, it has taken on a particularly critical dimension during the pandemic given the wish that women stay euthymic during the pandemic to limit the possibility of patients needing to present in a clinical space that would increase their risk for COVID-19, and to also minimize their risk for postpartum depression. (Psychiatric disorder during pregnancy remains the strongest predictor of emergence or worsening of underlying illness during the postpartum period.)

It is also noteworthy that, during a pandemic year, publications in reproductive psychiatry have been numerous, and we continue to make an effort at our own center to keep up with this and to share with our colleagues our impression of that literature using the weekly blog at womensmentalhealth.org. Last year brought the largest audience to the blog and visits to womensmentalhealth.org in the history of our center.

A case recently at our center presents a unique opportunity to review a confusing question in reproductive psychiatry over the last 15 years. A woman with a longstanding history of mixed anxiety and depression recently came to see us on a regimen of escitalopram and low-dose benzodiazepine. She was doing well, and she and her husband of 4 years were hopeful about starting to try to conceive despite the pandemic. We reviewed the reproductive safety data of the medicines on which she was maintained and made plans to follow-up as her plans galvanized. She notified me several months later that she had become pregnant but had experienced an early miscarriage. The patient was obviously upset and, as she reflected on her decision to maintain treatment with SSRI during her attempts to conceive and across a very early pregnancy, she queried about the extent to which her SSRI use might have contributed to her miscarriage.

The question about the possible association of antidepressant use during pregnancy and increased risk for miscarriage goes back at least 15 years when there were reports of an increased risk of miscarriage in women taking SSRIs during pregnancy. In that early work, there was an apparent increase in miscarriage in women taking SSRIs relative to a control group, but the rate did not exceed the prevalence of miscarriage in the general population. Since those early reports, we are lucky to have had multiple investigators look very closely at this issue, including one meta-analysis of 11 studies done approximately 8 years ago that failed to show an increased risk of miscarriage in the setting of first trimester exposure to SSRIs.

What has been most problematic methodologically, however, has been the failure to account for the potential role of depression in models that predict risk. A subsequent large epidemiologic study from Denmark evaluating over a million women has looked at this question further. The authors found a slightly increased risk of spontaneous abortion associated with the use of antidepressants (12.0% in women with antidepressant exposure vs. 11.1% in women with no exposure). However, looking only at women with a diagnosis of depression, the adjusted risk ratio for spontaneous abortion after any antidepressant exposure was 1.00 (95% confidence interval, 0.80-1.24). Thus, the researchers concluded that exposure to depression – but not exposure to antidepressant – is associated with a slightly higher risk of miscarriage.

Even more recently, a follow-up study examining this question supports the large epidemiologic study by Kjaersgaard and colleagues. For most readers, this effectively answers this very important question for women about rates of miscarriage associated with fetal exposure to SSRIs.

For the patient who presented at the center, reassuring her with this information felt particularly good, especially within the context of the pandemic. After several months of trying to conceive, she again became pregnant and delivered without difficulty. What was palpable in that clinical scenario, as it relates to the practice of reproductive psychiatry during the pandemic, is the even-greater emotional valence that questions about using psychiatric medications during pregnancy has taken on across these past months. While attention and thoughtful consideration about the relative risks of using psychiatric medications during pregnancy should be standard clinical practice, the level of anxiety associated with decisions to sustain or to discontinue treatment during pregnancy seems to have increased for some patients during the pandemic.

Even as the COVID-19 vaccine initiative across the United States is rolled out, 2021 will continue to be a complicated time for women and families. We still need to be vigilant. In addition to screening for perinatal depression during pregnancy and the postpartum period, we should be equally mindful of screening and treating perinatal anxiety, particularly during this challenging time. The challenge to keep pregnant and postpartum women well is perhaps even greater now, 10 months into the pandemic, than it was when we were in crisis mode in March 2020. As clinicians, we need to mobilize the spectrum of both pharmacologic and nonpharmacologic treatment options to sustain emotional well-being among women planning to conceive as well as those who are pregnant or postpartum as we navigate our way to safer times.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, 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 [email protected].

Across this period of the pandemic, we’ve spent considerable attention focusing on adaptations to clinical care for pregnant and postpartum women across the board. From the start, this has included a shift to telemedicine for the majority of our patients who come to see us with psychiatric disorders either before, during, or after pregnancy.

Specific issues for perinatal patients since the early days of COVID-19 have included the shifts in women’s plans with respect to delivery as well as the limitation on women’s ability to configure the types of support that they had originally planned on with family, friends, and others during delivery. Telemedicine again helped, at least in part, to fill that void by having online digital support by individuals or groups for both pregnant and postpartum women. These supports were always available, but quickly scaled up during the first 6-9 months of the pandemic and have likely seen their greatest increase in participation in the history of support groups for pregnant and postpartum women.

Similarly, at our own center, we have seen a dramatic increase across the last 10 months in requests for consultation by women with psychiatric disorders who have hopes and plans to conceive, to those who are pregnant or post partum and who are trying to sustain emotional well-being despite the added burden of the pandemic. As we heard similar stories regarding interactions with perinatal patients from reproductive psychiatrists across the country, my colleagues and I had to set up an additional resource, Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital, Boston, which has been mentioned in previous columns, which has only grown during the last 6 months of the pandemic. We have colleagues across the country joining us from 2 p.m. to 3 p.m. on Wednesdays after our own faculty rounds, where we perform case reviews of our own patients, and invite our colleagues to share cases that are then reviewed with expert panelists together with our own faculty in a collaborative environment. Feedback from the community of clinicians has indicated that these virtual rounds have been invaluable to their efforts in taking care of women with perinatal psychiatric issues, particularly during the pandemic.

Of particular note during consultations on our service is the number of women coming to see us for questions about the reproductive safety of the medications on which they are maintained. Hundreds of women present to the center each year for the most up-to-date information regarding the reproductive safety of the most commonly used psychiatric medications in reproductive-age women, including antidepressants (SSRIs, serotonin norepinephrine reuptake inhibitor), mood stabilizers, lithium, lamotrigine, and atypical antipsychotics, as well as other medicines used to treat symptoms that have been a particular issue during the pandemic, such as insomnia and anxiety (benzodiazepines, nonbenzodiazepines, sedative hypnotics, and medicines such as gabapentin).

While consultation regarding risk of fetal exposure to psychotropics has been the cornerstone of our clinical work for 25 years, it has taken on a particularly critical dimension during the pandemic given the wish that women stay euthymic during the pandemic to limit the possibility of patients needing to present in a clinical space that would increase their risk for COVID-19, and to also minimize their risk for postpartum depression. (Psychiatric disorder during pregnancy remains the strongest predictor of emergence or worsening of underlying illness during the postpartum period.)

It is also noteworthy that, during a pandemic year, publications in reproductive psychiatry have been numerous, and we continue to make an effort at our own center to keep up with this and to share with our colleagues our impression of that literature using the weekly blog at womensmentalhealth.org. Last year brought the largest audience to the blog and visits to womensmentalhealth.org in the history of our center.

A case recently at our center presents a unique opportunity to review a confusing question in reproductive psychiatry over the last 15 years. A woman with a longstanding history of mixed anxiety and depression recently came to see us on a regimen of escitalopram and low-dose benzodiazepine. She was doing well, and she and her husband of 4 years were hopeful about starting to try to conceive despite the pandemic. We reviewed the reproductive safety data of the medicines on which she was maintained and made plans to follow-up as her plans galvanized. She notified me several months later that she had become pregnant but had experienced an early miscarriage. The patient was obviously upset and, as she reflected on her decision to maintain treatment with SSRI during her attempts to conceive and across a very early pregnancy, she queried about the extent to which her SSRI use might have contributed to her miscarriage.

The question about the possible association of antidepressant use during pregnancy and increased risk for miscarriage goes back at least 15 years when there were reports of an increased risk of miscarriage in women taking SSRIs during pregnancy. In that early work, there was an apparent increase in miscarriage in women taking SSRIs relative to a control group, but the rate did not exceed the prevalence of miscarriage in the general population. Since those early reports, we are lucky to have had multiple investigators look very closely at this issue, including one meta-analysis of 11 studies done approximately 8 years ago that failed to show an increased risk of miscarriage in the setting of first trimester exposure to SSRIs.

What has been most problematic methodologically, however, has been the failure to account for the potential role of depression in models that predict risk. A subsequent large epidemiologic study from Denmark evaluating over a million women has looked at this question further. The authors found a slightly increased risk of spontaneous abortion associated with the use of antidepressants (12.0% in women with antidepressant exposure vs. 11.1% in women with no exposure). However, looking only at women with a diagnosis of depression, the adjusted risk ratio for spontaneous abortion after any antidepressant exposure was 1.00 (95% confidence interval, 0.80-1.24). Thus, the researchers concluded that exposure to depression – but not exposure to antidepressant – is associated with a slightly higher risk of miscarriage.

Even more recently, a follow-up study examining this question supports the large epidemiologic study by Kjaersgaard and colleagues. For most readers, this effectively answers this very important question for women about rates of miscarriage associated with fetal exposure to SSRIs.

For the patient who presented at the center, reassuring her with this information felt particularly good, especially within the context of the pandemic. After several months of trying to conceive, she again became pregnant and delivered without difficulty. What was palpable in that clinical scenario, as it relates to the practice of reproductive psychiatry during the pandemic, is the even-greater emotional valence that questions about using psychiatric medications during pregnancy has taken on across these past months. While attention and thoughtful consideration about the relative risks of using psychiatric medications during pregnancy should be standard clinical practice, the level of anxiety associated with decisions to sustain or to discontinue treatment during pregnancy seems to have increased for some patients during the pandemic.

Even as the COVID-19 vaccine initiative across the United States is rolled out, 2021 will continue to be a complicated time for women and families. We still need to be vigilant. In addition to screening for perinatal depression during pregnancy and the postpartum period, we should be equally mindful of screening and treating perinatal anxiety, particularly during this challenging time. The challenge to keep pregnant and postpartum women well is perhaps even greater now, 10 months into the pandemic, than it was when we were in crisis mode in March 2020. As clinicians, we need to mobilize the spectrum of both pharmacologic and nonpharmacologic treatment options to sustain emotional well-being among women planning to conceive as well as those who are pregnant or postpartum as we navigate our way to safer times.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, 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 [email protected].

Across this period of the pandemic, we’ve spent considerable attention focusing on adaptations to clinical care for pregnant and postpartum women across the board. From the start, this has included a shift to telemedicine for the majority of our patients who come to see us with psychiatric disorders either before, during, or after pregnancy.

Specific issues for perinatal patients since the early days of COVID-19 have included the shifts in women’s plans with respect to delivery as well as the limitation on women’s ability to configure the types of support that they had originally planned on with family, friends, and others during delivery. Telemedicine again helped, at least in part, to fill that void by having online digital support by individuals or groups for both pregnant and postpartum women. These supports were always available, but quickly scaled up during the first 6-9 months of the pandemic and have likely seen their greatest increase in participation in the history of support groups for pregnant and postpartum women.

Similarly, at our own center, we have seen a dramatic increase across the last 10 months in requests for consultation by women with psychiatric disorders who have hopes and plans to conceive, to those who are pregnant or post partum and who are trying to sustain emotional well-being despite the added burden of the pandemic. As we heard similar stories regarding interactions with perinatal patients from reproductive psychiatrists across the country, my colleagues and I had to set up an additional resource, Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital, Boston, which has been mentioned in previous columns, which has only grown during the last 6 months of the pandemic. We have colleagues across the country joining us from 2 p.m. to 3 p.m. on Wednesdays after our own faculty rounds, where we perform case reviews of our own patients, and invite our colleagues to share cases that are then reviewed with expert panelists together with our own faculty in a collaborative environment. Feedback from the community of clinicians has indicated that these virtual rounds have been invaluable to their efforts in taking care of women with perinatal psychiatric issues, particularly during the pandemic.

Of particular note during consultations on our service is the number of women coming to see us for questions about the reproductive safety of the medications on which they are maintained. Hundreds of women present to the center each year for the most up-to-date information regarding the reproductive safety of the most commonly used psychiatric medications in reproductive-age women, including antidepressants (SSRIs, serotonin norepinephrine reuptake inhibitor), mood stabilizers, lithium, lamotrigine, and atypical antipsychotics, as well as other medicines used to treat symptoms that have been a particular issue during the pandemic, such as insomnia and anxiety (benzodiazepines, nonbenzodiazepines, sedative hypnotics, and medicines such as gabapentin).

While consultation regarding risk of fetal exposure to psychotropics has been the cornerstone of our clinical work for 25 years, it has taken on a particularly critical dimension during the pandemic given the wish that women stay euthymic during the pandemic to limit the possibility of patients needing to present in a clinical space that would increase their risk for COVID-19, and to also minimize their risk for postpartum depression. (Psychiatric disorder during pregnancy remains the strongest predictor of emergence or worsening of underlying illness during the postpartum period.)

It is also noteworthy that, during a pandemic year, publications in reproductive psychiatry have been numerous, and we continue to make an effort at our own center to keep up with this and to share with our colleagues our impression of that literature using the weekly blog at womensmentalhealth.org. Last year brought the largest audience to the blog and visits to womensmentalhealth.org in the history of our center.

A case recently at our center presents a unique opportunity to review a confusing question in reproductive psychiatry over the last 15 years. A woman with a longstanding history of mixed anxiety and depression recently came to see us on a regimen of escitalopram and low-dose benzodiazepine. She was doing well, and she and her husband of 4 years were hopeful about starting to try to conceive despite the pandemic. We reviewed the reproductive safety data of the medicines on which she was maintained and made plans to follow-up as her plans galvanized. She notified me several months later that she had become pregnant but had experienced an early miscarriage. The patient was obviously upset and, as she reflected on her decision to maintain treatment with SSRI during her attempts to conceive and across a very early pregnancy, she queried about the extent to which her SSRI use might have contributed to her miscarriage.

The question about the possible association of antidepressant use during pregnancy and increased risk for miscarriage goes back at least 15 years when there were reports of an increased risk of miscarriage in women taking SSRIs during pregnancy. In that early work, there was an apparent increase in miscarriage in women taking SSRIs relative to a control group, but the rate did not exceed the prevalence of miscarriage in the general population. Since those early reports, we are lucky to have had multiple investigators look very closely at this issue, including one meta-analysis of 11 studies done approximately 8 years ago that failed to show an increased risk of miscarriage in the setting of first trimester exposure to SSRIs.

What has been most problematic methodologically, however, has been the failure to account for the potential role of depression in models that predict risk. A subsequent large epidemiologic study from Denmark evaluating over a million women has looked at this question further. The authors found a slightly increased risk of spontaneous abortion associated with the use of antidepressants (12.0% in women with antidepressant exposure vs. 11.1% in women with no exposure). However, looking only at women with a diagnosis of depression, the adjusted risk ratio for spontaneous abortion after any antidepressant exposure was 1.00 (95% confidence interval, 0.80-1.24). Thus, the researchers concluded that exposure to depression – but not exposure to antidepressant – is associated with a slightly higher risk of miscarriage.

Even more recently, a follow-up study examining this question supports the large epidemiologic study by Kjaersgaard and colleagues. For most readers, this effectively answers this very important question for women about rates of miscarriage associated with fetal exposure to SSRIs.

For the patient who presented at the center, reassuring her with this information felt particularly good, especially within the context of the pandemic. After several months of trying to conceive, she again became pregnant and delivered without difficulty. What was palpable in that clinical scenario, as it relates to the practice of reproductive psychiatry during the pandemic, is the even-greater emotional valence that questions about using psychiatric medications during pregnancy has taken on across these past months. While attention and thoughtful consideration about the relative risks of using psychiatric medications during pregnancy should be standard clinical practice, the level of anxiety associated with decisions to sustain or to discontinue treatment during pregnancy seems to have increased for some patients during the pandemic.

Even as the COVID-19 vaccine initiative across the United States is rolled out, 2021 will continue to be a complicated time for women and families. We still need to be vigilant. In addition to screening for perinatal depression during pregnancy and the postpartum period, we should be equally mindful of screening and treating perinatal anxiety, particularly during this challenging time. The challenge to keep pregnant and postpartum women well is perhaps even greater now, 10 months into the pandemic, than it was when we were in crisis mode in March 2020. As clinicians, we need to mobilize the spectrum of both pharmacologic and nonpharmacologic treatment options to sustain emotional well-being among women planning to conceive as well as those who are pregnant or postpartum as we navigate our way to safer times.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, 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 [email protected].

Since the start of the pandemic, we have been conducting an extra hour of Virtual Rounds at the Center for Women’s Mental Health. Virtual Rounds has been an opportunity to discuss cases around a spectrum of clinical management issues with respect to depression, bipolar disorder, and a spectrum of anxiety disorders like obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and generalized anxiety disorder. How to apply the calculus of risk-benefit decision-making around management of psychiatric disorder during pregnancy and the postpartum period has been the cornerstone of the work at our center for over 2 decades.

When we went virtual at our center in the early Spring, we decided to keep the format of our faculty rounds the way they have been for years and to sustain cohesiveness of our program during the pandemic. But we thought the needs of pregnant and postpartum women warranted being addressed in a context more specific to COVID-19, and also that reproductive psychiatrists and other clinicians could learn from each other about novel issues coming up for this group of patients during the pandemic. With that backdrop, Marlene Freeman, MD, and I founded “Virtual Rounds at the Center” to respond to queries from our colleagues across the country; we do this just after our own rounds on Wednesdays at 2:00 p.m.

As the pandemic has progressed, Virtual Rounds has blossomed into a virtual community on the Zoom platform, where social workers, psychologists, nurse prescribers, psychiatrists, and obstetricians discuss the needs of pregnant and postpartum women specific to COVID-19. Frequently, our discussions involve a review of the risks and benefits of treatment before, during, and after pregnancy.

Seemingly, week to week, more and more colleagues raise questions about the treatment of anxiety and insomnia during pregnancy and the postpartum period. I’ve spoken in previous columns about the enhanced use of telemedicine. Telemedicine not only facilitates efforts like Virtual Rounds and our ability to reach out to colleagues across the country and share cases, but also has allowed us to keep even closer tabs on the emotional well-being of our pregnant and postpartum women during COVID-19.

The question is not just about the effects of a medicine that a woman might take to treat anxiety or insomnia during pregnancy, but the experience of the pandemic per se, which we are measuring in multiple studies now using a variety of psychological instruments that patients complete. The pandemic is unequivocally taking a still unquantified toll on the mental health of Americans and potentially on the next generation to come.

Midcycle awakening during pregnancy

Complaints of insomnia and midcycle awakening during pregnancy are not new – it is the rule, rather than the exception for many pregnant women, particularly later in pregnancy. We have unequivocally seen a worsening of complaints of sleep disruption including insomnia and midcycle awakening during the pandemic that is greater than what we have seen previously. Both patients and colleagues have asked us the safest ways to manage it. One of the first things we consider when we hear about insomnia is whether it is part of an underlying mood disorder. While we see primary insomnia clinically, it really is important to remember that insomnia can be part and parcel of an underlying mood disorder.

With that in mind, what are the options? During the pandemic, we’ve seen an increased use of digital cognitive behavioral therapy for insomnia (CBT-I) for patients who cannot initiate sleep, which has a very strong evidence base for effectiveness as a first-line intervention for many.

If a patient has an incomplete response to CBT-I, what might be pursued next? In our center, we have a low threshold for using low doses of benzodiazepines, such as lorazepam or clonazepam, because the majority of data do not support an increased risk of major congenital malformations even when used in the first trimester. It is quite common to see medicines such as newer nonbenzodiazepine sedative hypnotics such as Ambien CR (zolpidem) or Lunesta (eszopiclone) used by our colleagues in ob.gyn. The reproductive safety data on those medicines are particularly sparse, and they may have greater risk of cognitive side effects the next day, so we tend to avoid them.

Another sometimes-forgotten option to consider is using low doses of tricyclic antidepressants (i.e., 10-25 mg of nortriptyline at bedtime), with tricyclics having a 40-year history and at least one pooled analysis showing the absence of increased risk for major congenital malformations when used. This may be a very easy way of managing insomnia, with low-dose tricyclics having an anxiolytic effect as well.

Anxiety during pregnancy

The most common rise in symptoms during COVID-19 for women who are pregnant or post partum has been an increase in anxiety. Women present with a spectrum of concerns leading to anxiety symptoms in the context of the pandemic. Earlier on in the pandemic, concerns focused mostly on how to stay healthy, and how to mitigate risk and not catch SARS-CoV-2 during pregnancy, as well as the very complex issues that were playing out in real time as hospital systems were figuring out how to manage pregnant women in labor and to keep both them and staff safe. Over time, anxiety has shifted to still staying safe during the pandemic and the potential impact of SARS-CoV-2 infection on pregnancy outcomes. The No. 1 concern is what the implications of COVID-19 disease are on mother and child. New mothers also are anxious about how they will practically navigate life with a newborn in the postpartum setting.

Early on in the pandemic, some hospital systems severely limited who was in the room with a woman during labor, potentially impeding the wishes of women during delivery who would have wanted their loved ones and/or a doula present, as an example. With enhanced testing available now, protocols have since relaxed in many hospitals to allow partners – but not a team – to remain in the hospital during the labor process. Still, the prospect of delivering during a pandemic is undoubtedly a source of anxiety for some women.

This sort of anxiety, particularly in patients with preexisting anxiety disorders, can be particularly challenging. Fortunately, there has been a rapid increase over the last several years of digital apps to mitigate anxiety. While many of them have not been systematically studied, the data on biobehavioral intervention for anxiety is enormous, and this should be used as first-line treatment for patients with mild to moderate symptoms; so many women would prefer to avoid pharmacological intervention during pregnancy, if possible, to avoid fetal drug exposure. For patients who meet criteria for frank anxiety disorder, other nonpharmacologic interventions such as CBT have been shown to be effective.

Frequently, we see women who are experiencing levels of anxiety where nonpharmacological interventions have an incomplete response, and colleagues have asked about the safest way to treat these patients. As has been discussed in multiple previous columns, selective serotonin reuptake inhibitors (SSRIs) should be thought of sooner rather than later, particularly with medicines with good reproductive safety data such as sertraline, citalopram, or fluoxetine.

We also reported over 15 years ago that at least 30%-40% of women presenting with histories of recurrent major depression at the beginning of pregnancy had comorbid anxiety disorders, and that the use of benzodiazepines in that population in addition to SSRIs was exceedingly common, with doses of approximately 0.5-1.5 mg of clonazepam or lorazepam being standard fare. Again, this is very appropriate treatment to mitigate anxiety symptoms because now have enough data as a field that support the existence of adverse outcomes associated with untreated anxiety during pregnancy in terms of both adverse obstetric and neonatal outcomes, higher rates of preterm birth, and other obstetric complications. Hence, managing anxiety during pregnancy should be considered like managing a toxic exposure – the same way that one would be concerned about anything else that a pregnant woman could be exposed to.

Lastly, although no atypical antipsychotic has been approved for the treatment of anxiety, its use off label is extremely common. More and more data support the absence of a signal of teratogenicity across the family of molecules including atypical antipsychotics. Beyond potential use of atypical antipsychotics, at Virtual Rounds last week, a colleague asked about the use of gabapentin in a patient who was diagnosed with substance use disorder and who had inadvertently conceived on gabapentin, which was being used to treat both anxiety and insomnia. We have typically avoided the use of gabapentin during pregnancy because prospective data have been limited to relatively small case series and one report, with a total of exposures in roughly the 300 range.

However, our colleagues at the Harvard School of Public Health have recently published an article that looked at the United States Medicaid Analytic eXtract (MAX) dataset, which has been used to publish other articles addressing atypical antipsychotics, SSRIs, lithium, and pharmacovigilance investigations among other important topics. In this study, the database was used to look specifically at 4,642 pregnancies with gabapentin exposure relative to 1,744,447 unexposed pregnancies, without a significant finding for increased risk for major congenital malformations.

The question of an increased risk of cardiac malformations and of increased risk for obstetric complications are difficult to untangle from anxiety and depression, as they also are associated with those same outcomes. With that said, the analysis is a welcome addition to our knowledge base for a medicine used more widely to treat symptoms such as anxiety and insomnia in the general population, with a question mark around where it may fit into the algorithm during pregnancy.

In our center, gabapentin still would not be used as a first-line treatment for the management of anxiety or insomnia during pregnancy. But these new data still are reassuring for patients who come in, frequently with unplanned pregnancies. It is an important reminder to those of us taking care of patients during the pandemic to review use of contraception, because although data are unavailable specific to the period of the pandemic, what is clear is that, even prior to COVID-19, 50% of pregnancies in America were unplanned. Addressing issues of reliable use of contraception, particularly during the pandemic, is that much more important.

In this particular case, our clinician colleague in Virtual Rounds decided to continue gabapentin across pregnancy in the context of these reassuring data, but others may choose to discontinue or pursue some of the other treatment options noted above.
 

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 [email protected].

Since the start of the pandemic, we have been conducting an extra hour of Virtual Rounds at the Center for Women’s Mental Health. Virtual Rounds has been an opportunity to discuss cases around a spectrum of clinical management issues with respect to depression, bipolar disorder, and a spectrum of anxiety disorders like obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and generalized anxiety disorder. How to apply the calculus of risk-benefit decision-making around management of psychiatric disorder during pregnancy and the postpartum period has been the cornerstone of the work at our center for over 2 decades.

When we went virtual at our center in the early Spring, we decided to keep the format of our faculty rounds the way they have been for years and to sustain cohesiveness of our program during the pandemic. But we thought the needs of pregnant and postpartum women warranted being addressed in a context more specific to COVID-19, and also that reproductive psychiatrists and other clinicians could learn from each other about novel issues coming up for this group of patients during the pandemic. With that backdrop, Marlene Freeman, MD, and I founded “Virtual Rounds at the Center” to respond to queries from our colleagues across the country; we do this just after our own rounds on Wednesdays at 2:00 p.m.

As the pandemic has progressed, Virtual Rounds has blossomed into a virtual community on the Zoom platform, where social workers, psychologists, nurse prescribers, psychiatrists, and obstetricians discuss the needs of pregnant and postpartum women specific to COVID-19. Frequently, our discussions involve a review of the risks and benefits of treatment before, during, and after pregnancy.

Seemingly, week to week, more and more colleagues raise questions about the treatment of anxiety and insomnia during pregnancy and the postpartum period. I’ve spoken in previous columns about the enhanced use of telemedicine. Telemedicine not only facilitates efforts like Virtual Rounds and our ability to reach out to colleagues across the country and share cases, but also has allowed us to keep even closer tabs on the emotional well-being of our pregnant and postpartum women during COVID-19.

The question is not just about the effects of a medicine that a woman might take to treat anxiety or insomnia during pregnancy, but the experience of the pandemic per se, which we are measuring in multiple studies now using a variety of psychological instruments that patients complete. The pandemic is unequivocally taking a still unquantified toll on the mental health of Americans and potentially on the next generation to come.

Midcycle awakening during pregnancy

Complaints of insomnia and midcycle awakening during pregnancy are not new – it is the rule, rather than the exception for many pregnant women, particularly later in pregnancy. We have unequivocally seen a worsening of complaints of sleep disruption including insomnia and midcycle awakening during the pandemic that is greater than what we have seen previously. Both patients and colleagues have asked us the safest ways to manage it. One of the first things we consider when we hear about insomnia is whether it is part of an underlying mood disorder. While we see primary insomnia clinically, it really is important to remember that insomnia can be part and parcel of an underlying mood disorder.

With that in mind, what are the options? During the pandemic, we’ve seen an increased use of digital cognitive behavioral therapy for insomnia (CBT-I) for patients who cannot initiate sleep, which has a very strong evidence base for effectiveness as a first-line intervention for many.

If a patient has an incomplete response to CBT-I, what might be pursued next? In our center, we have a low threshold for using low doses of benzodiazepines, such as lorazepam or clonazepam, because the majority of data do not support an increased risk of major congenital malformations even when used in the first trimester. It is quite common to see medicines such as newer nonbenzodiazepine sedative hypnotics such as Ambien CR (zolpidem) or Lunesta (eszopiclone) used by our colleagues in ob.gyn. The reproductive safety data on those medicines are particularly sparse, and they may have greater risk of cognitive side effects the next day, so we tend to avoid them.

Another sometimes-forgotten option to consider is using low doses of tricyclic antidepressants (i.e., 10-25 mg of nortriptyline at bedtime), with tricyclics having a 40-year history and at least one pooled analysis showing the absence of increased risk for major congenital malformations when used. This may be a very easy way of managing insomnia, with low-dose tricyclics having an anxiolytic effect as well.

Anxiety during pregnancy

The most common rise in symptoms during COVID-19 for women who are pregnant or post partum has been an increase in anxiety. Women present with a spectrum of concerns leading to anxiety symptoms in the context of the pandemic. Earlier on in the pandemic, concerns focused mostly on how to stay healthy, and how to mitigate risk and not catch SARS-CoV-2 during pregnancy, as well as the very complex issues that were playing out in real time as hospital systems were figuring out how to manage pregnant women in labor and to keep both them and staff safe. Over time, anxiety has shifted to still staying safe during the pandemic and the potential impact of SARS-CoV-2 infection on pregnancy outcomes. The No. 1 concern is what the implications of COVID-19 disease are on mother and child. New mothers also are anxious about how they will practically navigate life with a newborn in the postpartum setting.

Early on in the pandemic, some hospital systems severely limited who was in the room with a woman during labor, potentially impeding the wishes of women during delivery who would have wanted their loved ones and/or a doula present, as an example. With enhanced testing available now, protocols have since relaxed in many hospitals to allow partners – but not a team – to remain in the hospital during the labor process. Still, the prospect of delivering during a pandemic is undoubtedly a source of anxiety for some women.

This sort of anxiety, particularly in patients with preexisting anxiety disorders, can be particularly challenging. Fortunately, there has been a rapid increase over the last several years of digital apps to mitigate anxiety. While many of them have not been systematically studied, the data on biobehavioral intervention for anxiety is enormous, and this should be used as first-line treatment for patients with mild to moderate symptoms; so many women would prefer to avoid pharmacological intervention during pregnancy, if possible, to avoid fetal drug exposure. For patients who meet criteria for frank anxiety disorder, other nonpharmacologic interventions such as CBT have been shown to be effective.

Frequently, we see women who are experiencing levels of anxiety where nonpharmacological interventions have an incomplete response, and colleagues have asked about the safest way to treat these patients. As has been discussed in multiple previous columns, selective serotonin reuptake inhibitors (SSRIs) should be thought of sooner rather than later, particularly with medicines with good reproductive safety data such as sertraline, citalopram, or fluoxetine.

We also reported over 15 years ago that at least 30%-40% of women presenting with histories of recurrent major depression at the beginning of pregnancy had comorbid anxiety disorders, and that the use of benzodiazepines in that population in addition to SSRIs was exceedingly common, with doses of approximately 0.5-1.5 mg of clonazepam or lorazepam being standard fare. Again, this is very appropriate treatment to mitigate anxiety symptoms because now have enough data as a field that support the existence of adverse outcomes associated with untreated anxiety during pregnancy in terms of both adverse obstetric and neonatal outcomes, higher rates of preterm birth, and other obstetric complications. Hence, managing anxiety during pregnancy should be considered like managing a toxic exposure – the same way that one would be concerned about anything else that a pregnant woman could be exposed to.

Lastly, although no atypical antipsychotic has been approved for the treatment of anxiety, its use off label is extremely common. More and more data support the absence of a signal of teratogenicity across the family of molecules including atypical antipsychotics. Beyond potential use of atypical antipsychotics, at Virtual Rounds last week, a colleague asked about the use of gabapentin in a patient who was diagnosed with substance use disorder and who had inadvertently conceived on gabapentin, which was being used to treat both anxiety and insomnia. We have typically avoided the use of gabapentin during pregnancy because prospective data have been limited to relatively small case series and one report, with a total of exposures in roughly the 300 range.

However, our colleagues at the Harvard School of Public Health have recently published an article that looked at the United States Medicaid Analytic eXtract (MAX) dataset, which has been used to publish other articles addressing atypical antipsychotics, SSRIs, lithium, and pharmacovigilance investigations among other important topics. In this study, the database was used to look specifically at 4,642 pregnancies with gabapentin exposure relative to 1,744,447 unexposed pregnancies, without a significant finding for increased risk for major congenital malformations.

The question of an increased risk of cardiac malformations and of increased risk for obstetric complications are difficult to untangle from anxiety and depression, as they also are associated with those same outcomes. With that said, the analysis is a welcome addition to our knowledge base for a medicine used more widely to treat symptoms such as anxiety and insomnia in the general population, with a question mark around where it may fit into the algorithm during pregnancy.

In our center, gabapentin still would not be used as a first-line treatment for the management of anxiety or insomnia during pregnancy. But these new data still are reassuring for patients who come in, frequently with unplanned pregnancies. It is an important reminder to those of us taking care of patients during the pandemic to review use of contraception, because although data are unavailable specific to the period of the pandemic, what is clear is that, even prior to COVID-19, 50% of pregnancies in America were unplanned. Addressing issues of reliable use of contraception, particularly during the pandemic, is that much more important.

In this particular case, our clinician colleague in Virtual Rounds decided to continue gabapentin across pregnancy in the context of these reassuring data, but others may choose to discontinue or pursue some of the other treatment options noted above.
 

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 [email protected].

Since the start of the pandemic, we have been conducting an extra hour of Virtual Rounds at the Center for Women’s Mental Health. Virtual Rounds has been an opportunity to discuss cases around a spectrum of clinical management issues with respect to depression, bipolar disorder, and a spectrum of anxiety disorders like obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and generalized anxiety disorder. How to apply the calculus of risk-benefit decision-making around management of psychiatric disorder during pregnancy and the postpartum period has been the cornerstone of the work at our center for over 2 decades.

When we went virtual at our center in the early Spring, we decided to keep the format of our faculty rounds the way they have been for years and to sustain cohesiveness of our program during the pandemic. But we thought the needs of pregnant and postpartum women warranted being addressed in a context more specific to COVID-19, and also that reproductive psychiatrists and other clinicians could learn from each other about novel issues coming up for this group of patients during the pandemic. With that backdrop, Marlene Freeman, MD, and I founded “Virtual Rounds at the Center” to respond to queries from our colleagues across the country; we do this just after our own rounds on Wednesdays at 2:00 p.m.

As the pandemic has progressed, Virtual Rounds has blossomed into a virtual community on the Zoom platform, where social workers, psychologists, nurse prescribers, psychiatrists, and obstetricians discuss the needs of pregnant and postpartum women specific to COVID-19. Frequently, our discussions involve a review of the risks and benefits of treatment before, during, and after pregnancy.

Seemingly, week to week, more and more colleagues raise questions about the treatment of anxiety and insomnia during pregnancy and the postpartum period. I’ve spoken in previous columns about the enhanced use of telemedicine. Telemedicine not only facilitates efforts like Virtual Rounds and our ability to reach out to colleagues across the country and share cases, but also has allowed us to keep even closer tabs on the emotional well-being of our pregnant and postpartum women during COVID-19.

The question is not just about the effects of a medicine that a woman might take to treat anxiety or insomnia during pregnancy, but the experience of the pandemic per se, which we are measuring in multiple studies now using a variety of psychological instruments that patients complete. The pandemic is unequivocally taking a still unquantified toll on the mental health of Americans and potentially on the next generation to come.

Midcycle awakening during pregnancy

Complaints of insomnia and midcycle awakening during pregnancy are not new – it is the rule, rather than the exception for many pregnant women, particularly later in pregnancy. We have unequivocally seen a worsening of complaints of sleep disruption including insomnia and midcycle awakening during the pandemic that is greater than what we have seen previously. Both patients and colleagues have asked us the safest ways to manage it. One of the first things we consider when we hear about insomnia is whether it is part of an underlying mood disorder. While we see primary insomnia clinically, it really is important to remember that insomnia can be part and parcel of an underlying mood disorder.

With that in mind, what are the options? During the pandemic, we’ve seen an increased use of digital cognitive behavioral therapy for insomnia (CBT-I) for patients who cannot initiate sleep, which has a very strong evidence base for effectiveness as a first-line intervention for many.

If a patient has an incomplete response to CBT-I, what might be pursued next? In our center, we have a low threshold for using low doses of benzodiazepines, such as lorazepam or clonazepam, because the majority of data do not support an increased risk of major congenital malformations even when used in the first trimester. It is quite common to see medicines such as newer nonbenzodiazepine sedative hypnotics such as Ambien CR (zolpidem) or Lunesta (eszopiclone) used by our colleagues in ob.gyn. The reproductive safety data on those medicines are particularly sparse, and they may have greater risk of cognitive side effects the next day, so we tend to avoid them.

Another sometimes-forgotten option to consider is using low doses of tricyclic antidepressants (i.e., 10-25 mg of nortriptyline at bedtime), with tricyclics having a 40-year history and at least one pooled analysis showing the absence of increased risk for major congenital malformations when used. This may be a very easy way of managing insomnia, with low-dose tricyclics having an anxiolytic effect as well.

Anxiety during pregnancy

The most common rise in symptoms during COVID-19 for women who are pregnant or post partum has been an increase in anxiety. Women present with a spectrum of concerns leading to anxiety symptoms in the context of the pandemic. Earlier on in the pandemic, concerns focused mostly on how to stay healthy, and how to mitigate risk and not catch SARS-CoV-2 during pregnancy, as well as the very complex issues that were playing out in real time as hospital systems were figuring out how to manage pregnant women in labor and to keep both them and staff safe. Over time, anxiety has shifted to still staying safe during the pandemic and the potential impact of SARS-CoV-2 infection on pregnancy outcomes. The No. 1 concern is what the implications of COVID-19 disease are on mother and child. New mothers also are anxious about how they will practically navigate life with a newborn in the postpartum setting.

Early on in the pandemic, some hospital systems severely limited who was in the room with a woman during labor, potentially impeding the wishes of women during delivery who would have wanted their loved ones and/or a doula present, as an example. With enhanced testing available now, protocols have since relaxed in many hospitals to allow partners – but not a team – to remain in the hospital during the labor process. Still, the prospect of delivering during a pandemic is undoubtedly a source of anxiety for some women.

This sort of anxiety, particularly in patients with preexisting anxiety disorders, can be particularly challenging. Fortunately, there has been a rapid increase over the last several years of digital apps to mitigate anxiety. While many of them have not been systematically studied, the data on biobehavioral intervention for anxiety is enormous, and this should be used as first-line treatment for patients with mild to moderate symptoms; so many women would prefer to avoid pharmacological intervention during pregnancy, if possible, to avoid fetal drug exposure. For patients who meet criteria for frank anxiety disorder, other nonpharmacologic interventions such as CBT have been shown to be effective.

Frequently, we see women who are experiencing levels of anxiety where nonpharmacological interventions have an incomplete response, and colleagues have asked about the safest way to treat these patients. As has been discussed in multiple previous columns, selective serotonin reuptake inhibitors (SSRIs) should be thought of sooner rather than later, particularly with medicines with good reproductive safety data such as sertraline, citalopram, or fluoxetine.

We also reported over 15 years ago that at least 30%-40% of women presenting with histories of recurrent major depression at the beginning of pregnancy had comorbid anxiety disorders, and that the use of benzodiazepines in that population in addition to SSRIs was exceedingly common, with doses of approximately 0.5-1.5 mg of clonazepam or lorazepam being standard fare. Again, this is very appropriate treatment to mitigate anxiety symptoms because now have enough data as a field that support the existence of adverse outcomes associated with untreated anxiety during pregnancy in terms of both adverse obstetric and neonatal outcomes, higher rates of preterm birth, and other obstetric complications. Hence, managing anxiety during pregnancy should be considered like managing a toxic exposure – the same way that one would be concerned about anything else that a pregnant woman could be exposed to.

Lastly, although no atypical antipsychotic has been approved for the treatment of anxiety, its use off label is extremely common. More and more data support the absence of a signal of teratogenicity across the family of molecules including atypical antipsychotics. Beyond potential use of atypical antipsychotics, at Virtual Rounds last week, a colleague asked about the use of gabapentin in a patient who was diagnosed with substance use disorder and who had inadvertently conceived on gabapentin, which was being used to treat both anxiety and insomnia. We have typically avoided the use of gabapentin during pregnancy because prospective data have been limited to relatively small case series and one report, with a total of exposures in roughly the 300 range.

However, our colleagues at the Harvard School of Public Health have recently published an article that looked at the United States Medicaid Analytic eXtract (MAX) dataset, which has been used to publish other articles addressing atypical antipsychotics, SSRIs, lithium, and pharmacovigilance investigations among other important topics. In this study, the database was used to look specifically at 4,642 pregnancies with gabapentin exposure relative to 1,744,447 unexposed pregnancies, without a significant finding for increased risk for major congenital malformations.

The question of an increased risk of cardiac malformations and of increased risk for obstetric complications are difficult to untangle from anxiety and depression, as they also are associated with those same outcomes. With that said, the analysis is a welcome addition to our knowledge base for a medicine used more widely to treat symptoms such as anxiety and insomnia in the general population, with a question mark around where it may fit into the algorithm during pregnancy.

In our center, gabapentin still would not be used as a first-line treatment for the management of anxiety or insomnia during pregnancy. But these new data still are reassuring for patients who come in, frequently with unplanned pregnancies. It is an important reminder to those of us taking care of patients during the pandemic to review use of contraception, because although data are unavailable specific to the period of the pandemic, what is clear is that, even prior to COVID-19, 50% of pregnancies in America were unplanned. Addressing issues of reliable use of contraception, particularly during the pandemic, is that much more important.

In this particular case, our clinician colleague in Virtual Rounds decided to continue gabapentin across pregnancy in the context of these reassuring data, but others may choose to discontinue or pursue some of the other treatment options noted above.
 

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 [email protected].

In a previous column, I addressed some of the issues that quickly arose in the context of the COVID-19 pandemic and their implications for reproductive psychiatry. These issues ranged from the importance of sustaining well-being in pregnant and postpartum women during the pandemic, to temporary restrictions that were in place during the early part of the pandemic with respect to performing infertility procedures, to the practical issues of limiting the number of people who could attend to women during labor and delivery in the hospital.

lechatnoir/E+

Five months later, we’ve learned a great deal about trying to sustain emotional well-being among pregnant women during COVID-19. There is a high rate of anxiety among women who are pregnant and women who have particularly young children around the various issues of juggling activities of daily living during the pandemic, including switching to remote work and homeschooling children. There is fear of contracting COVID-19 during pregnancy, the exact effects of which are still somewhat unknown. We have seen a shift to telemedicine for prenatal and postpartum obstetrics visits, and a change with respect to visitors and even in-home nurses that would help during the first weeks of life for some couples.

We wondered whether we would see a falloff in the numbers of women presenting to our clinic with questions about the reproductive safety of taking psychiatric medications during pregnancy. We were unclear as to whether women would defer plans to get pregnant given some of the uncertainties that have come with COVID-19. What we’ve seen, at least early on in the pandemic in Massachusetts, has been the opposite. More women during the first 4 months of the pandemic have been seen in our center compared with the same corresponding period over the last 5 years. The precise reasons for this are unclear, but one reason may be that shifting the practice of reproductive psychiatry and pregnancy planning for reproductive-age women to full virtual care has dropped the number of missed appointments to essentially zero. Women perhaps feel an urgency to have a plan for using psychiatric medication during pregnancy. They may also see the benefit of being able to have extended telemedicine consultations that frequently involve their partners, a practice we have always supported, but posed logistical challenges for some.

As our colleagues learned that we had shifted our clinical rounds at the Center for Women’s Mental Health, which we’ve been doing for 25 years, to a virtual format, we began offering a free 1-hour forum to discuss relevant issues around caring for psychiatrically ill women, with a focus on some of the issues that were particularly relevant during the pandemic. The most common reasons for consultation on our service are the appropriate, safest use of antidepressants and mood stabilizers during pregnancy, and that continues to be the case.

If there has been one guiding principle in treating perinatal depression during pregnancy, it has been our long-standing, laser-like focus on keeping women emotionally well during pregnancy, and to highlight the importance of this with women during consultations prior to and during pregnancy. Relapse of psychiatric disorder during pregnancy is one the strongest predictors of postpartum depression, and the impact of untreated depression during pregnancy has been described in the literature and over the years in this column. However, the implications of having severe relapse of a mood disorder, for example, such as depression or bipolar disorder during the pandemic, takes on a new context where we want to minimize, if possible, severe onset of illness requiring hospitalization or emergent attention considering it may make social distancing and some of the other mitigating factors vis-à-vis COVID-19 more challenging.

Despite the accumulated data over the last 2 decades on the reproductive safety of antidepressants, women continue to have questions about the safety of these medications during pregnancy. Studies show now that many women would prefer, if at all possible, to defer treatment with antidepressants, and so they come to us with questions about their reproductive safety, the potential of switching to nonpharmacologic interventions, and the use of alternative interventions that might be used to treat their underlying mood disorder.

Investigators at the University of British Columbia recently have tried to inform the field with still another look, not at reproductive safety per se, but at risk of relapse of depression if women discontinue those medicines during pregnancy.¹ There is a timeliness to this investigation, which was a systematic review and meta-analysis of studies that met a priori criteria for inclusion. Since some of our own group’s early work over 15 years ago on relapse of psychiatric disorder during pregnancy,² which indicated a substantial difference in risk of relapse between women who continued versus who discontinued antidepressants, other investigators have showed the difference in risk for relapse is not as substantial, and that continuation of medication did not appear to mitigate risk for relapse. In fact, in the systematic review, the investigators demonstrated that as a group, maintaining medicine did not appear to confer particular benefit to patients relative to risk for relapse compared to discontinuation of antidepressants.

However, looking more closely, Bayrampour and colleagues note for women with histories of more severe recurrent, major depression, relapse did in fact appear to be greater in women who discontinued compared with those with cases of mild to moderate depression. It is noteworthy that in both our early and later work, and certainly dovetailing with our clinical practice, we have noted severity of illness does not appear to correlate with the actual decisions women ultimately make regarding what they will do with antidepressants. Specifically, some women with very severe illness histories will discontinue antidepressants regardless of their risk for relapse. Alternatively, women with mild to moderate illness will sometimes elect to stay on antidepressant therapy. With all the information that we have about fetal exposure to antidepressants on one hand, the “unknown unknowns” are an understandable concern to both patients and clinicians. Clinicians are faced with the dilemma of how to best counsel women on continuing or discontinuing antidepressants as they plan to conceive or during pregnancy and in the postpartum period.

The literature cited and clinical experience over the last 3 decades suggests rather strongly that there is a relatively low likelihood women with histories of severe recurrent disease will be able to successfully discontinue antidepressants in the absence of relapse. A greater question is, what is the best way to proceed for women who have been on maintenance therapy and had more moderate symptoms?

I am inspired by some of the more recent literature that has tried to elucidate the role of nonpharmacologic interventions such as mindfulness-based cognitive therapy (MBCT) in an effort to mitigate risk for depressive relapse in pregnant women who are well with histories of depression. To date, data do not inform the question as to whether MBCT can be used to mitigate risk of depressive relapse in pregnant women who continue or discontinue antidepressants. That research question is actively being studied by several investigators, including ourselves.

Of particular interest is whether the addition of mindfulness practices such as MBCT in treatment could mitigate risk for depressive relapse in pregnant women who continue or discontinue antidepressant treatment, as that would certainly be a no-harm intervention that could mitigate risk even in a lower risk sample of patients. The question of how to “thread the needle” during the pandemic and best approach woman with a history of recurrent major depression on antidepressants is particularly timely and critical.

Regardless, we make clinical decisions collaboratively with patients based on their histories and individual wishes, and perhaps what we have learned over the last 5 months is the use of telemedicine does afford us the opportunity, regardless of the decisions that patients make, to more closely follow the clinical trajectory of women during pregnancy and the postpartum period so that regardless of treatment, we have an opportunity to intervene early when needed and to ascertain changes in clinical status early to mitigate the risk of frank relapse. From a reproductive psychiatric point of view, that is a silver lining with respect to the associated challenges that have come along with the pandemic.
 

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 [email protected].

References

1. J Clin Psychiatry 2020;81(4):19r13134.

2. JAMA. 2006 Feb 1;295(5):499-507.

In a previous column, I addressed some of the issues that quickly arose in the context of the COVID-19 pandemic and their implications for reproductive psychiatry. These issues ranged from the importance of sustaining well-being in pregnant and postpartum women during the pandemic, to temporary restrictions that were in place during the early part of the pandemic with respect to performing infertility procedures, to the practical issues of limiting the number of people who could attend to women during labor and delivery in the hospital.

lechatnoir/E+

Five months later, we’ve learned a great deal about trying to sustain emotional well-being among pregnant women during COVID-19. There is a high rate of anxiety among women who are pregnant and women who have particularly young children around the various issues of juggling activities of daily living during the pandemic, including switching to remote work and homeschooling children. There is fear of contracting COVID-19 during pregnancy, the exact effects of which are still somewhat unknown. We have seen a shift to telemedicine for prenatal and postpartum obstetrics visits, and a change with respect to visitors and even in-home nurses that would help during the first weeks of life for some couples.

We wondered whether we would see a falloff in the numbers of women presenting to our clinic with questions about the reproductive safety of taking psychiatric medications during pregnancy. We were unclear as to whether women would defer plans to get pregnant given some of the uncertainties that have come with COVID-19. What we’ve seen, at least early on in the pandemic in Massachusetts, has been the opposite. More women during the first 4 months of the pandemic have been seen in our center compared with the same corresponding period over the last 5 years. The precise reasons for this are unclear, but one reason may be that shifting the practice of reproductive psychiatry and pregnancy planning for reproductive-age women to full virtual care has dropped the number of missed appointments to essentially zero. Women perhaps feel an urgency to have a plan for using psychiatric medication during pregnancy. They may also see the benefit of being able to have extended telemedicine consultations that frequently involve their partners, a practice we have always supported, but posed logistical challenges for some.

As our colleagues learned that we had shifted our clinical rounds at the Center for Women’s Mental Health, which we’ve been doing for 25 years, to a virtual format, we began offering a free 1-hour forum to discuss relevant issues around caring for psychiatrically ill women, with a focus on some of the issues that were particularly relevant during the pandemic. The most common reasons for consultation on our service are the appropriate, safest use of antidepressants and mood stabilizers during pregnancy, and that continues to be the case.

If there has been one guiding principle in treating perinatal depression during pregnancy, it has been our long-standing, laser-like focus on keeping women emotionally well during pregnancy, and to highlight the importance of this with women during consultations prior to and during pregnancy. Relapse of psychiatric disorder during pregnancy is one the strongest predictors of postpartum depression, and the impact of untreated depression during pregnancy has been described in the literature and over the years in this column. However, the implications of having severe relapse of a mood disorder, for example, such as depression or bipolar disorder during the pandemic, takes on a new context where we want to minimize, if possible, severe onset of illness requiring hospitalization or emergent attention considering it may make social distancing and some of the other mitigating factors vis-à-vis COVID-19 more challenging.

Despite the accumulated data over the last 2 decades on the reproductive safety of antidepressants, women continue to have questions about the safety of these medications during pregnancy. Studies show now that many women would prefer, if at all possible, to defer treatment with antidepressants, and so they come to us with questions about their reproductive safety, the potential of switching to nonpharmacologic interventions, and the use of alternative interventions that might be used to treat their underlying mood disorder.

Investigators at the University of British Columbia recently have tried to inform the field with still another look, not at reproductive safety per se, but at risk of relapse of depression if women discontinue those medicines during pregnancy.¹ There is a timeliness to this investigation, which was a systematic review and meta-analysis of studies that met a priori criteria for inclusion. Since some of our own group’s early work over 15 years ago on relapse of psychiatric disorder during pregnancy,² which indicated a substantial difference in risk of relapse between women who continued versus who discontinued antidepressants, other investigators have showed the difference in risk for relapse is not as substantial, and that continuation of medication did not appear to mitigate risk for relapse. In fact, in the systematic review, the investigators demonstrated that as a group, maintaining medicine did not appear to confer particular benefit to patients relative to risk for relapse compared to discontinuation of antidepressants.

However, looking more closely, Bayrampour and colleagues note for women with histories of more severe recurrent, major depression, relapse did in fact appear to be greater in women who discontinued compared with those with cases of mild to moderate depression. It is noteworthy that in both our early and later work, and certainly dovetailing with our clinical practice, we have noted severity of illness does not appear to correlate with the actual decisions women ultimately make regarding what they will do with antidepressants. Specifically, some women with very severe illness histories will discontinue antidepressants regardless of their risk for relapse. Alternatively, women with mild to moderate illness will sometimes elect to stay on antidepressant therapy. With all the information that we have about fetal exposure to antidepressants on one hand, the “unknown unknowns” are an understandable concern to both patients and clinicians. Clinicians are faced with the dilemma of how to best counsel women on continuing or discontinuing antidepressants as they plan to conceive or during pregnancy and in the postpartum period.

The literature cited and clinical experience over the last 3 decades suggests rather strongly that there is a relatively low likelihood women with histories of severe recurrent disease will be able to successfully discontinue antidepressants in the absence of relapse. A greater question is, what is the best way to proceed for women who have been on maintenance therapy and had more moderate symptoms?

I am inspired by some of the more recent literature that has tried to elucidate the role of nonpharmacologic interventions such as mindfulness-based cognitive therapy (MBCT) in an effort to mitigate risk for depressive relapse in pregnant women who are well with histories of depression. To date, data do not inform the question as to whether MBCT can be used to mitigate risk of depressive relapse in pregnant women who continue or discontinue antidepressants. That research question is actively being studied by several investigators, including ourselves.

Of particular interest is whether the addition of mindfulness practices such as MBCT in treatment could mitigate risk for depressive relapse in pregnant women who continue or discontinue antidepressant treatment, as that would certainly be a no-harm intervention that could mitigate risk even in a lower risk sample of patients. The question of how to “thread the needle” during the pandemic and best approach woman with a history of recurrent major depression on antidepressants is particularly timely and critical.

Regardless, we make clinical decisions collaboratively with patients based on their histories and individual wishes, and perhaps what we have learned over the last 5 months is the use of telemedicine does afford us the opportunity, regardless of the decisions that patients make, to more closely follow the clinical trajectory of women during pregnancy and the postpartum period so that regardless of treatment, we have an opportunity to intervene early when needed and to ascertain changes in clinical status early to mitigate the risk of frank relapse. From a reproductive psychiatric point of view, that is a silver lining with respect to the associated challenges that have come along with the pandemic.
 

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 [email protected].

References

1. J Clin Psychiatry 2020;81(4):19r13134.

2. JAMA. 2006 Feb 1;295(5):499-507.

In a previous column, I addressed some of the issues that quickly arose in the context of the COVID-19 pandemic and their implications for reproductive psychiatry. These issues ranged from the importance of sustaining well-being in pregnant and postpartum women during the pandemic, to temporary restrictions that were in place during the early part of the pandemic with respect to performing infertility procedures, to the practical issues of limiting the number of people who could attend to women during labor and delivery in the hospital.

lechatnoir/E+

Five months later, we’ve learned a great deal about trying to sustain emotional well-being among pregnant women during COVID-19. There is a high rate of anxiety among women who are pregnant and women who have particularly young children around the various issues of juggling activities of daily living during the pandemic, including switching to remote work and homeschooling children. There is fear of contracting COVID-19 during pregnancy, the exact effects of which are still somewhat unknown. We have seen a shift to telemedicine for prenatal and postpartum obstetrics visits, and a change with respect to visitors and even in-home nurses that would help during the first weeks of life for some couples.

We wondered whether we would see a falloff in the numbers of women presenting to our clinic with questions about the reproductive safety of taking psychiatric medications during pregnancy. We were unclear as to whether women would defer plans to get pregnant given some of the uncertainties that have come with COVID-19. What we’ve seen, at least early on in the pandemic in Massachusetts, has been the opposite. More women during the first 4 months of the pandemic have been seen in our center compared with the same corresponding period over the last 5 years. The precise reasons for this are unclear, but one reason may be that shifting the practice of reproductive psychiatry and pregnancy planning for reproductive-age women to full virtual care has dropped the number of missed appointments to essentially zero. Women perhaps feel an urgency to have a plan for using psychiatric medication during pregnancy. They may also see the benefit of being able to have extended telemedicine consultations that frequently involve their partners, a practice we have always supported, but posed logistical challenges for some.

As our colleagues learned that we had shifted our clinical rounds at the Center for Women’s Mental Health, which we’ve been doing for 25 years, to a virtual format, we began offering a free 1-hour forum to discuss relevant issues around caring for psychiatrically ill women, with a focus on some of the issues that were particularly relevant during the pandemic. The most common reasons for consultation on our service are the appropriate, safest use of antidepressants and mood stabilizers during pregnancy, and that continues to be the case.

If there has been one guiding principle in treating perinatal depression during pregnancy, it has been our long-standing, laser-like focus on keeping women emotionally well during pregnancy, and to highlight the importance of this with women during consultations prior to and during pregnancy. Relapse of psychiatric disorder during pregnancy is one the strongest predictors of postpartum depression, and the impact of untreated depression during pregnancy has been described in the literature and over the years in this column. However, the implications of having severe relapse of a mood disorder, for example, such as depression or bipolar disorder during the pandemic, takes on a new context where we want to minimize, if possible, severe onset of illness requiring hospitalization or emergent attention considering it may make social distancing and some of the other mitigating factors vis-à-vis COVID-19 more challenging.

Despite the accumulated data over the last 2 decades on the reproductive safety of antidepressants, women continue to have questions about the safety of these medications during pregnancy. Studies show now that many women would prefer, if at all possible, to defer treatment with antidepressants, and so they come to us with questions about their reproductive safety, the potential of switching to nonpharmacologic interventions, and the use of alternative interventions that might be used to treat their underlying mood disorder.

Investigators at the University of British Columbia recently have tried to inform the field with still another look, not at reproductive safety per se, but at risk of relapse of depression if women discontinue those medicines during pregnancy.¹ There is a timeliness to this investigation, which was a systematic review and meta-analysis of studies that met a priori criteria for inclusion. Since some of our own group’s early work over 15 years ago on relapse of psychiatric disorder during pregnancy,² which indicated a substantial difference in risk of relapse between women who continued versus who discontinued antidepressants, other investigators have showed the difference in risk for relapse is not as substantial, and that continuation of medication did not appear to mitigate risk for relapse. In fact, in the systematic review, the investigators demonstrated that as a group, maintaining medicine did not appear to confer particular benefit to patients relative to risk for relapse compared to discontinuation of antidepressants.

However, looking more closely, Bayrampour and colleagues note for women with histories of more severe recurrent, major depression, relapse did in fact appear to be greater in women who discontinued compared with those with cases of mild to moderate depression. It is noteworthy that in both our early and later work, and certainly dovetailing with our clinical practice, we have noted severity of illness does not appear to correlate with the actual decisions women ultimately make regarding what they will do with antidepressants. Specifically, some women with very severe illness histories will discontinue antidepressants regardless of their risk for relapse. Alternatively, women with mild to moderate illness will sometimes elect to stay on antidepressant therapy. With all the information that we have about fetal exposure to antidepressants on one hand, the “unknown unknowns” are an understandable concern to both patients and clinicians. Clinicians are faced with the dilemma of how to best counsel women on continuing or discontinuing antidepressants as they plan to conceive or during pregnancy and in the postpartum period.

The literature cited and clinical experience over the last 3 decades suggests rather strongly that there is a relatively low likelihood women with histories of severe recurrent disease will be able to successfully discontinue antidepressants in the absence of relapse. A greater question is, what is the best way to proceed for women who have been on maintenance therapy and had more moderate symptoms?

I am inspired by some of the more recent literature that has tried to elucidate the role of nonpharmacologic interventions such as mindfulness-based cognitive therapy (MBCT) in an effort to mitigate risk for depressive relapse in pregnant women who are well with histories of depression. To date, data do not inform the question as to whether MBCT can be used to mitigate risk of depressive relapse in pregnant women who continue or discontinue antidepressants. That research question is actively being studied by several investigators, including ourselves.

Of particular interest is whether the addition of mindfulness practices such as MBCT in treatment could mitigate risk for depressive relapse in pregnant women who continue or discontinue antidepressant treatment, as that would certainly be a no-harm intervention that could mitigate risk even in a lower risk sample of patients. The question of how to “thread the needle” during the pandemic and best approach woman with a history of recurrent major depression on antidepressants is particularly timely and critical.

Regardless, we make clinical decisions collaboratively with patients based on their histories and individual wishes, and perhaps what we have learned over the last 5 months is the use of telemedicine does afford us the opportunity, regardless of the decisions that patients make, to more closely follow the clinical trajectory of women during pregnancy and the postpartum period so that regardless of treatment, we have an opportunity to intervene early when needed and to ascertain changes in clinical status early to mitigate the risk of frank relapse. From a reproductive psychiatric point of view, that is a silver lining with respect to the associated challenges that have come along with the pandemic.
 

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 [email protected].

References

1. J Clin Psychiatry 2020;81(4):19r13134.

2. JAMA. 2006 Feb 1;295(5):499-507.

When last I wrote this column, I was preparing for travel to professional meetings in the spring, planning a presentation for an upcoming grand rounds, and readying to host a scientific advisory board meeting as part of a large scientific project we conduct in Center for Women’s Mental Health. We were also awaiting the relocation of several junior faculty and research staff to Boston this spring and summer as we build our team.

JarekJoepera/iStock/Getty Images

It is now obvious that the COVID-19 pandemic is not a passing squall, but rather a persistent gale that has placed our collective sails in the water. It has not capsized the boat, however, thanks in part to the actions of courageous frontline caregivers and first responders who have mobilized in the wake of this recent public health crisis. From doctors, nurses, and hospital staff to grocery store clerks, home health aides, and neighbors checking in on the elderly – to name just a few – a whole crew of members across society have helped buoy our collective ship. Resilience also is required by all of us who are managing the array of feelings brought about by the day-in, day-out challenges of living life with restricted movement and freedom to engage in pre-COVID-19 activities we took for granted. What seemed like a temporary workaround is now becoming the “new normal” for an unknown amount of time looking forward.

For over 3 decades, my colleagues and I have worked with women who suffer from serious psychiatric disorders and whose treatment has required psychiatric medications such as antidepressants, mood stabilizers, and anxiolytics. The challenge of our work with women who are pregnant or planning pregnancy has been the configuration of the safest ways to navigate treatment on an individual basis for these women across pregnancy and post partum, with continual assessments of how to minimize the risk to fetus from in utero exposure to medications that have been instrumental in the treatment of psychiatric disorders on one hand versus the risks of untreated psychiatric disorder on the other. This work has been the essence of the clinical mission and the cornerstone of the research conducted at the Center for Women’s Mental Health since its inception.

While I have worked shoulder to shoulder with obstetricians for years, my respect for these colleagues during these past weeks has only grown as they have instituted the swiftest protocols to mitigate risk associated with COVID-19 for our pregnant patients, some of whom have tested positive for COVID-19, all in an effort to keep both mother, fetus, and newborn as safe as possible.

For those of us providing mental health services to pregnant women during this time, certain clinical situations have arisen in the context of the COVID-19 pandemic which require particular attention and discussion.
 

Planned pregnancy and contraception during the COVID-19 pandemic

Half of the pregnancies in this country are unplanned. Now more than ever, it is critical that decisions about moving forward with a plan to conceive be deliberate. These considerations range from the existential to the most concrete. For example, during these last weeks, we have consulted on cases where couples on the cusp of attempts to conceive face concerns about COVID-19, hence making more complicated their timeline with respect to actual plans to get pregnant. These are complicated decisions, particularly for women who may be slightly older and at the reproductive age where delaying pregnancy may have an adverse effect on fertility.

A concrete example of how the pandemic has affected fertility is evident as we encounter situations where women may defer starting a prescription oral contraceptive or lapse in its use because they have had difficulty coordinating visits with health care providers and may fear picking up prescriptions from pharmacies. We also have seen that procedures such as IUD placements have been deferred or canceled, or that some patients decline trips to the hospital or clinic to receive this type of service. These new barriers to access of contraception may require more planning at this time so that decisions about family planning are by design and not default during a time as complicated as the current public health crisis.
 

Telemedicine: telepsychiatry and obstetrics virtual visits

While wide-scale use of telemedicine platforms was not the standard day-to-day practice in either obstetrics or psychiatry prior to the pandemic, telepsychiatry has come up to speed within a short number of weeks. At our institution, 85% of outpatient visits are being conducted remotely, with in-person visits being reserved for only urgent or emergent visits. Our inpatient psychiatry service remains a setting where psychiatric patients, regardless of their COVID-19 status, can receive necessary care.

The use of telemedicine and specifically telepsychiatry is critical to mitigate the likelihood of exposure to SARS-CoV-2. On our reproductive psychiatry service, it has actually been an opportunity to engage with patients for comprehensive initial consults about reproductive safety of psychiatric medications currently being taken, or for ongoing consultation and direct patient care during follow-up visits during pregnancy to see that patients are sustaining emotional well-being or have changes for treatment implemented if they are not well. An increased frequency of visits allows us more opportunity to capture any signs of early clinical worsening of symptoms that might have been missed previously using the more traditional in-person setting.

Telepsychiatry and “virtual visits” have allowed us to do real-time, nimble modifications of treatment regimens with both pharmacologic and nonpharmacologic interventions to keep women well and to keep them out of the hospital for psychiatric care as often as possible. It also has facilitated a closer collaboration with our colleagues in obstetrics. In a way, the team of providers, including psychiatrists, obstetrical providers, social workers, and therapists can more easily communicate virtually than has sometimes been the case previously, when day-to-day use of telemedicine and virtual team meetings was less common.
 

Recognition and treatment of anxiety in perinatal patients

Even pregnant women without preexisting anxiety disorders may have heightened anxiety during usual times, and women and their partners cope with this typically in numerous ways including participation in peer-support opportunities, wellness and self-care activities, leveraging support from care providers, and engaging with family. But the previously “typical pregnancy experience” has shifted in the context of COVID-19. Specifically, added concerns of pregnant women about becoming infected, of potential separation from family if they do become ill, or of separation from partners or support systems during labor and delivery (an issue that has been largely resolved in many hospitals), as well as the possibility that a neonate might become ill with exposure to the coronavirus are obviously understandable and real. Such contingencies are unsettling, even for the most settled of our patients. Labor and delivery plans, and plans for outside help from family or others with the baby and older children in the postpartum period, have been upended for many patients.

These are anxious times. The number of nonpharmacologic virtual interventions available to mitigate anxiety are filling email inboxes daily. Curating these options can be a challenge, although several resources are worth noting, such as our department’s page on mental health resources.

During these past weeks, we have seen growing numbers of women for whom the normative anxiety of pregnancy is increasing to the point of causing distress to the level of functional impairment. Many patients for the first time meet criteria for frank anxiety disorders. These patients deserve prompt evaluation by mental health professionals and treatment with evidence-based therapies for anxiety disorders whether nonpharmacologic or pharmacologic so as to mitigate the risk of untreated anxiety on maternal and fetal well-being and also to limit risk for postpartum depression and postpartum anxiety disorders.

Miscarriage and infertility

A 36-year-old patient came to see me in clinic in late January following a miscarriage. She had a history of a previous miscarriage a year before and had an episode of major depression to follow for which she received treatment with an antidepressant and cognitive-behavioral therapy; she also attended a perinatal loss support group. She saw me in early March, anxious to try to conceive but extremely concerned about the risks associated with becoming pregnant at this point in time. Following a lengthy discussion with me and her obstetrician, the patient decided to wait until “the curve flattened” in Boston in terms of new cases of COVID-19, and then start trying to conceive. The case of another patient with a very similar history was presented at our rounds a few weeks ago; she also elected to defer attempts to conceive until life is more settled.

Perhaps one of the most dramatic examples of the impact of COVID-19 on fertility has been for those women with plans to pursue treatment with one of the assisted reproductive technologies. They have been told that professional societies have made recommendations regarding use of assisted reproductive technologies that are not entirely consistent across the country, but where in many places such interventions have been suspended during the COVID-19 pandemic. For many women near the end of their reproductive years, delays in trying to conceive either with or without the aid of fertility treatments may indelibly shape their plans to have children.
 

Sustaining emotional well-being across pregnancy

Because most psychiatric disorders are chronic in course, it is often the situation where women are treated to wellness for serious psychiatric disorders, with the goal of maintaining wellness across pregnancy and the post partum. One of the most critical takeaway points from 30 years of working with psychiatrically ill pregnant women is the maxim that keeping women well during pregnancy is simply imperative. Maternal psychiatric well-being during pregnancy is a strong predictor of obstetrical and neonatal outcomes, postpartum mental health, and longer-term neurobehavioral outcomes in children. Critically, in the context of the pandemic, keeping women out of psychiatric crises mitigates the necessity of visits to urgent clinical settings such as EDs and psychiatric inpatient units, which can increase the likelihood of exposure to the coronavirus.

Preservation of sleep

Disruption in sleep (duration and quality) can be seen in well over half of women during pregnancy with and without psychiatric disorders, and our experience has been that this has been exacerbated for many women during the COVID-19 crisis. Yet there are very rich data showing that sleep deprivation or sleep dysregulation in women, for example, who suffer from bipolar disorder or major depression can be a strong trigger for psychiatric relapse of underlying illness during pregnancy and the postpartum period.

During a time when normal rhythms of day-to-day life have been shifted – if not frankly disrupted – by swift transitions to remote work, cancellation of school and associated school activities across the country, complaints of insomnia and non-restorative sleep have been exceedingly common. Relevant to all but particularly for pregnant women with histories of psychiatric disorder, attention to sleep hygiene, moderation of caffeine use (if any), and use of any number of biobehavioral interventions to enhance relaxation and modulate stress may be of great value.

Cognitive-behavioral therapy for insomnia (CBT-I) has been demonstrated to be effective in pregnant women. Fortunately, there are user-friendly options on digital platforms that can be used during the pandemic that may play an important role in sustaining emotional well-being for pregnant women who have frank symptoms of insomnia.
 

Maintenance of ongoing antidepressant treatment during pregnancy among women with histories of mood disorder

Over a decade ago, my colleagues and I wrote about the comparison of outcomes for women with histories of recurrent major depression, demonstrating the value of maintenance treatment with antidepressants, compared with discontinuation of these medications during pregnancy (JAMA. 2006 Feb 1;295[5]:499-507). Recently, I was asked if maintenance antidepressant use in women with histories of recurrent depression was still our clinical recommendation. Over the last decade, we have noted that nearly half of women treated with antidepressants, regardless of illness severity, will discontinue their use of these medications prior to or early on in pregnancy given concerns about potential unknown effects of fetal exposure to medications, even medications for which there are robust data supporting reproductive safety regarding risk of congenital malformations. Routine discontinuation of antidepressants prior to or during pregnancy continues, despite the fact that we showed nearly 70% of those women with past histories of depression on maintenance antidepressant treatment relapsed shortly after discontinuing medication.

While we do not dictate the decisions women make about antidepressant use before, during, or after pregnancy, women with the same severity of illness will frequently make different decisions (a good thing) but we are now having very frank discussions about the particular need during a pandemic to avoid the relapse of serious psychiatric disorders. We typically endorse maintenance medication use with all but a very few number of psychotropic medications for which benefit may not outweigh risk to the fetus. However, for women who have decided nonetheless to discontinue antidepressants or other psychotropics during pregnancy despite the known risk of relapse, we strongly advise that they initiate treatment with evidence-based nonpharmacologic intervention such as CBT or mindfulness-based cognitive therapy (MBCT).

As in other areas of medicine, the pandemic is prompting we professionals in psychiatry, and specifically in perinatal psychiatry, to use all of our tools to keep pregnant and postpartum women well. The availability of digital tools to deliver MBCT and CBT has made the use of such interventions particularly viable at a time of social distancing. That being said, for patients with highly recurrent affective disorder with histories of previous recurrence when they stop their antidepressants, we are more strongly recommending serious consideration of maintenance medication treatment.
 

Virtual rounds in reproductive psychiatry and women’s mental health

The use of virtual platforms to connect with both patients and colleagues also has provided new opportunities for interaction with the reproductive psychiatry community as a whole. Peer teaching and peer support has been a critical part of our mission, and we decided 1 month ago to establish Virtual Rounds at the Center for Women’s Mental Health. This is a free digital platform, held on a weekly basis with our colleagues from across the country, where we discuss cases that come up in our own clinical rounds and also questions that get put forth by our colleagues in the area of reproductive psychiatry as they manage patients during the pandemic.

Changes in the postpartum experience

The last decade has brought a growing appreciation of postpartum depression and the need to screen and treat postpartum psychiatric disorders, such as postpartum mood and anxiety disorders. Yet in the era of this pandemic, the postpartum experience is itself is changing. Changes in carefully configured plans for the postpartum period – from family coming and going to mobilizing extra support at home and to now having new moms having to manage families and their other children at home – has been an enormous stressor for many women. Plans to have more elderly parents visit during the acute postpartum period, and the increased concerns about people traveling to and from a home where there is a newborn and the need to quarantine, has made the transition to motherhood much more complicated for all postpartum women, let alone for those postpartum women who have histories of psychiatric disorder.

There is a risk of social isolation for postpartum women even under normal circumstances, and this is profoundly more likely during this pandemic. We are actively working with our postpartum patients and optimizing treatment, brainstorming options in terms of using both virtual and real-time support to the extent that it is safe in order to keep women healthy during such a stressful and critical time.

I am heartened by the efforts on the part of organizations such as Postpartum Support International to make available virtually their resources with respect to community-based support and education for women who feel increasingly isolated during the postpartum period, a time where connectedness is so critical.

Summarily, these have been challenging times, but also times of opportunity. The COVID-19 pandemic has prompted us to get even more creative as we configure ways to optimize the emotional well-being of our patients who are planning to get pregnant, who are pregnant, or who are post partum.

The current time, while challenging in so many ways and a time of great pain, loss, and grief for far too many, has also provided an opportunity to work even more collaboratively with our colleagues, coming up with new paradigms of treatments as we weather this historic challenge.

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 him at [email protected].

When last I wrote this column, I was preparing for travel to professional meetings in the spring, planning a presentation for an upcoming grand rounds, and readying to host a scientific advisory board meeting as part of a large scientific project we conduct in Center for Women’s Mental Health. We were also awaiting the relocation of several junior faculty and research staff to Boston this spring and summer as we build our team.

JarekJoepera/iStock/Getty Images

It is now obvious that the COVID-19 pandemic is not a passing squall, but rather a persistent gale that has placed our collective sails in the water. It has not capsized the boat, however, thanks in part to the actions of courageous frontline caregivers and first responders who have mobilized in the wake of this recent public health crisis. From doctors, nurses, and hospital staff to grocery store clerks, home health aides, and neighbors checking in on the elderly – to name just a few – a whole crew of members across society have helped buoy our collective ship. Resilience also is required by all of us who are managing the array of feelings brought about by the day-in, day-out challenges of living life with restricted movement and freedom to engage in pre-COVID-19 activities we took for granted. What seemed like a temporary workaround is now becoming the “new normal” for an unknown amount of time looking forward.

For over 3 decades, my colleagues and I have worked with women who suffer from serious psychiatric disorders and whose treatment has required psychiatric medications such as antidepressants, mood stabilizers, and anxiolytics. The challenge of our work with women who are pregnant or planning pregnancy has been the configuration of the safest ways to navigate treatment on an individual basis for these women across pregnancy and post partum, with continual assessments of how to minimize the risk to fetus from in utero exposure to medications that have been instrumental in the treatment of psychiatric disorders on one hand versus the risks of untreated psychiatric disorder on the other. This work has been the essence of the clinical mission and the cornerstone of the research conducted at the Center for Women’s Mental Health since its inception.

While I have worked shoulder to shoulder with obstetricians for years, my respect for these colleagues during these past weeks has only grown as they have instituted the swiftest protocols to mitigate risk associated with COVID-19 for our pregnant patients, some of whom have tested positive for COVID-19, all in an effort to keep both mother, fetus, and newborn as safe as possible.

For those of us providing mental health services to pregnant women during this time, certain clinical situations have arisen in the context of the COVID-19 pandemic which require particular attention and discussion.
 

Planned pregnancy and contraception during the COVID-19 pandemic

Half of the pregnancies in this country are unplanned. Now more than ever, it is critical that decisions about moving forward with a plan to conceive be deliberate. These considerations range from the existential to the most concrete. For example, during these last weeks, we have consulted on cases where couples on the cusp of attempts to conceive face concerns about COVID-19, hence making more complicated their timeline with respect to actual plans to get pregnant. These are complicated decisions, particularly for women who may be slightly older and at the reproductive age where delaying pregnancy may have an adverse effect on fertility.

A concrete example of how the pandemic has affected fertility is evident as we encounter situations where women may defer starting a prescription oral contraceptive or lapse in its use because they have had difficulty coordinating visits with health care providers and may fear picking up prescriptions from pharmacies. We also have seen that procedures such as IUD placements have been deferred or canceled, or that some patients decline trips to the hospital or clinic to receive this type of service. These new barriers to access of contraception may require more planning at this time so that decisions about family planning are by design and not default during a time as complicated as the current public health crisis.
 

Telemedicine: telepsychiatry and obstetrics virtual visits

While wide-scale use of telemedicine platforms was not the standard day-to-day practice in either obstetrics or psychiatry prior to the pandemic, telepsychiatry has come up to speed within a short number of weeks. At our institution, 85% of outpatient visits are being conducted remotely, with in-person visits being reserved for only urgent or emergent visits. Our inpatient psychiatry service remains a setting where psychiatric patients, regardless of their COVID-19 status, can receive necessary care.

The use of telemedicine and specifically telepsychiatry is critical to mitigate the likelihood of exposure to SARS-CoV-2. On our reproductive psychiatry service, it has actually been an opportunity to engage with patients for comprehensive initial consults about reproductive safety of psychiatric medications currently being taken, or for ongoing consultation and direct patient care during follow-up visits during pregnancy to see that patients are sustaining emotional well-being or have changes for treatment implemented if they are not well. An increased frequency of visits allows us more opportunity to capture any signs of early clinical worsening of symptoms that might have been missed previously using the more traditional in-person setting.

Telepsychiatry and “virtual visits” have allowed us to do real-time, nimble modifications of treatment regimens with both pharmacologic and nonpharmacologic interventions to keep women well and to keep them out of the hospital for psychiatric care as often as possible. It also has facilitated a closer collaboration with our colleagues in obstetrics. In a way, the team of providers, including psychiatrists, obstetrical providers, social workers, and therapists can more easily communicate virtually than has sometimes been the case previously, when day-to-day use of telemedicine and virtual team meetings was less common.
 

Recognition and treatment of anxiety in perinatal patients

Even pregnant women without preexisting anxiety disorders may have heightened anxiety during usual times, and women and their partners cope with this typically in numerous ways including participation in peer-support opportunities, wellness and self-care activities, leveraging support from care providers, and engaging with family. But the previously “typical pregnancy experience” has shifted in the context of COVID-19. Specifically, added concerns of pregnant women about becoming infected, of potential separation from family if they do become ill, or of separation from partners or support systems during labor and delivery (an issue that has been largely resolved in many hospitals), as well as the possibility that a neonate might become ill with exposure to the coronavirus are obviously understandable and real. Such contingencies are unsettling, even for the most settled of our patients. Labor and delivery plans, and plans for outside help from family or others with the baby and older children in the postpartum period, have been upended for many patients.

These are anxious times. The number of nonpharmacologic virtual interventions available to mitigate anxiety are filling email inboxes daily. Curating these options can be a challenge, although several resources are worth noting, such as our department’s page on mental health resources.

During these past weeks, we have seen growing numbers of women for whom the normative anxiety of pregnancy is increasing to the point of causing distress to the level of functional impairment. Many patients for the first time meet criteria for frank anxiety disorders. These patients deserve prompt evaluation by mental health professionals and treatment with evidence-based therapies for anxiety disorders whether nonpharmacologic or pharmacologic so as to mitigate the risk of untreated anxiety on maternal and fetal well-being and also to limit risk for postpartum depression and postpartum anxiety disorders.

Miscarriage and infertility

A 36-year-old patient came to see me in clinic in late January following a miscarriage. She had a history of a previous miscarriage a year before and had an episode of major depression to follow for which she received treatment with an antidepressant and cognitive-behavioral therapy; she also attended a perinatal loss support group. She saw me in early March, anxious to try to conceive but extremely concerned about the risks associated with becoming pregnant at this point in time. Following a lengthy discussion with me and her obstetrician, the patient decided to wait until “the curve flattened” in Boston in terms of new cases of COVID-19, and then start trying to conceive. The case of another patient with a very similar history was presented at our rounds a few weeks ago; she also elected to defer attempts to conceive until life is more settled.

Perhaps one of the most dramatic examples of the impact of COVID-19 on fertility has been for those women with plans to pursue treatment with one of the assisted reproductive technologies. They have been told that professional societies have made recommendations regarding use of assisted reproductive technologies that are not entirely consistent across the country, but where in many places such interventions have been suspended during the COVID-19 pandemic. For many women near the end of their reproductive years, delays in trying to conceive either with or without the aid of fertility treatments may indelibly shape their plans to have children.
 

Sustaining emotional well-being across pregnancy

Because most psychiatric disorders are chronic in course, it is often the situation where women are treated to wellness for serious psychiatric disorders, with the goal of maintaining wellness across pregnancy and the post partum. One of the most critical takeaway points from 30 years of working with psychiatrically ill pregnant women is the maxim that keeping women well during pregnancy is simply imperative. Maternal psychiatric well-being during pregnancy is a strong predictor of obstetrical and neonatal outcomes, postpartum mental health, and longer-term neurobehavioral outcomes in children. Critically, in the context of the pandemic, keeping women out of psychiatric crises mitigates the necessity of visits to urgent clinical settings such as EDs and psychiatric inpatient units, which can increase the likelihood of exposure to the coronavirus.

Preservation of sleep

Disruption in sleep (duration and quality) can be seen in well over half of women during pregnancy with and without psychiatric disorders, and our experience has been that this has been exacerbated for many women during the COVID-19 crisis. Yet there are very rich data showing that sleep deprivation or sleep dysregulation in women, for example, who suffer from bipolar disorder or major depression can be a strong trigger for psychiatric relapse of underlying illness during pregnancy and the postpartum period.

During a time when normal rhythms of day-to-day life have been shifted – if not frankly disrupted – by swift transitions to remote work, cancellation of school and associated school activities across the country, complaints of insomnia and non-restorative sleep have been exceedingly common. Relevant to all but particularly for pregnant women with histories of psychiatric disorder, attention to sleep hygiene, moderation of caffeine use (if any), and use of any number of biobehavioral interventions to enhance relaxation and modulate stress may be of great value.

Cognitive-behavioral therapy for insomnia (CBT-I) has been demonstrated to be effective in pregnant women. Fortunately, there are user-friendly options on digital platforms that can be used during the pandemic that may play an important role in sustaining emotional well-being for pregnant women who have frank symptoms of insomnia.
 

Maintenance of ongoing antidepressant treatment during pregnancy among women with histories of mood disorder

Over a decade ago, my colleagues and I wrote about the comparison of outcomes for women with histories of recurrent major depression, demonstrating the value of maintenance treatment with antidepressants, compared with discontinuation of these medications during pregnancy (JAMA. 2006 Feb 1;295[5]:499-507). Recently, I was asked if maintenance antidepressant use in women with histories of recurrent depression was still our clinical recommendation. Over the last decade, we have noted that nearly half of women treated with antidepressants, regardless of illness severity, will discontinue their use of these medications prior to or early on in pregnancy given concerns about potential unknown effects of fetal exposure to medications, even medications for which there are robust data supporting reproductive safety regarding risk of congenital malformations. Routine discontinuation of antidepressants prior to or during pregnancy continues, despite the fact that we showed nearly 70% of those women with past histories of depression on maintenance antidepressant treatment relapsed shortly after discontinuing medication.

While we do not dictate the decisions women make about antidepressant use before, during, or after pregnancy, women with the same severity of illness will frequently make different decisions (a good thing) but we are now having very frank discussions about the particular need during a pandemic to avoid the relapse of serious psychiatric disorders. We typically endorse maintenance medication use with all but a very few number of psychotropic medications for which benefit may not outweigh risk to the fetus. However, for women who have decided nonetheless to discontinue antidepressants or other psychotropics during pregnancy despite the known risk of relapse, we strongly advise that they initiate treatment with evidence-based nonpharmacologic intervention such as CBT or mindfulness-based cognitive therapy (MBCT).

As in other areas of medicine, the pandemic is prompting we professionals in psychiatry, and specifically in perinatal psychiatry, to use all of our tools to keep pregnant and postpartum women well. The availability of digital tools to deliver MBCT and CBT has made the use of such interventions particularly viable at a time of social distancing. That being said, for patients with highly recurrent affective disorder with histories of previous recurrence when they stop their antidepressants, we are more strongly recommending serious consideration of maintenance medication treatment.
 

Virtual rounds in reproductive psychiatry and women’s mental health

The use of virtual platforms to connect with both patients and colleagues also has provided new opportunities for interaction with the reproductive psychiatry community as a whole. Peer teaching and peer support has been a critical part of our mission, and we decided 1 month ago to establish Virtual Rounds at the Center for Women’s Mental Health. This is a free digital platform, held on a weekly basis with our colleagues from across the country, where we discuss cases that come up in our own clinical rounds and also questions that get put forth by our colleagues in the area of reproductive psychiatry as they manage patients during the pandemic.

Changes in the postpartum experience

The last decade has brought a growing appreciation of postpartum depression and the need to screen and treat postpartum psychiatric disorders, such as postpartum mood and anxiety disorders. Yet in the era of this pandemic, the postpartum experience is itself is changing. Changes in carefully configured plans for the postpartum period – from family coming and going to mobilizing extra support at home and to now having new moms having to manage families and their other children at home – has been an enormous stressor for many women. Plans to have more elderly parents visit during the acute postpartum period, and the increased concerns about people traveling to and from a home where there is a newborn and the need to quarantine, has made the transition to motherhood much more complicated for all postpartum women, let alone for those postpartum women who have histories of psychiatric disorder.

There is a risk of social isolation for postpartum women even under normal circumstances, and this is profoundly more likely during this pandemic. We are actively working with our postpartum patients and optimizing treatment, brainstorming options in terms of using both virtual and real-time support to the extent that it is safe in order to keep women healthy during such a stressful and critical time.

I am heartened by the efforts on the part of organizations such as Postpartum Support International to make available virtually their resources with respect to community-based support and education for women who feel increasingly isolated during the postpartum period, a time where connectedness is so critical.

Summarily, these have been challenging times, but also times of opportunity. The COVID-19 pandemic has prompted us to get even more creative as we configure ways to optimize the emotional well-being of our patients who are planning to get pregnant, who are pregnant, or who are post partum.

The current time, while challenging in so many ways and a time of great pain, loss, and grief for far too many, has also provided an opportunity to work even more collaboratively with our colleagues, coming up with new paradigms of treatments as we weather this historic challenge.

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 him at [email protected].

When last I wrote this column, I was preparing for travel to professional meetings in the spring, planning a presentation for an upcoming grand rounds, and readying to host a scientific advisory board meeting as part of a large scientific project we conduct in Center for Women’s Mental Health. We were also awaiting the relocation of several junior faculty and research staff to Boston this spring and summer as we build our team.

JarekJoepera/iStock/Getty Images

It is now obvious that the COVID-19 pandemic is not a passing squall, but rather a persistent gale that has placed our collective sails in the water. It has not capsized the boat, however, thanks in part to the actions of courageous frontline caregivers and first responders who have mobilized in the wake of this recent public health crisis. From doctors, nurses, and hospital staff to grocery store clerks, home health aides, and neighbors checking in on the elderly – to name just a few – a whole crew of members across society have helped buoy our collective ship. Resilience also is required by all of us who are managing the array of feelings brought about by the day-in, day-out challenges of living life with restricted movement and freedom to engage in pre-COVID-19 activities we took for granted. What seemed like a temporary workaround is now becoming the “new normal” for an unknown amount of time looking forward.

For over 3 decades, my colleagues and I have worked with women who suffer from serious psychiatric disorders and whose treatment has required psychiatric medications such as antidepressants, mood stabilizers, and anxiolytics. The challenge of our work with women who are pregnant or planning pregnancy has been the configuration of the safest ways to navigate treatment on an individual basis for these women across pregnancy and post partum, with continual assessments of how to minimize the risk to fetus from in utero exposure to medications that have been instrumental in the treatment of psychiatric disorders on one hand versus the risks of untreated psychiatric disorder on the other. This work has been the essence of the clinical mission and the cornerstone of the research conducted at the Center for Women’s Mental Health since its inception.

While I have worked shoulder to shoulder with obstetricians for years, my respect for these colleagues during these past weeks has only grown as they have instituted the swiftest protocols to mitigate risk associated with COVID-19 for our pregnant patients, some of whom have tested positive for COVID-19, all in an effort to keep both mother, fetus, and newborn as safe as possible.

For those of us providing mental health services to pregnant women during this time, certain clinical situations have arisen in the context of the COVID-19 pandemic which require particular attention and discussion.
 

Planned pregnancy and contraception during the COVID-19 pandemic

Half of the pregnancies in this country are unplanned. Now more than ever, it is critical that decisions about moving forward with a plan to conceive be deliberate. These considerations range from the existential to the most concrete. For example, during these last weeks, we have consulted on cases where couples on the cusp of attempts to conceive face concerns about COVID-19, hence making more complicated their timeline with respect to actual plans to get pregnant. These are complicated decisions, particularly for women who may be slightly older and at the reproductive age where delaying pregnancy may have an adverse effect on fertility.

A concrete example of how the pandemic has affected fertility is evident as we encounter situations where women may defer starting a prescription oral contraceptive or lapse in its use because they have had difficulty coordinating visits with health care providers and may fear picking up prescriptions from pharmacies. We also have seen that procedures such as IUD placements have been deferred or canceled, or that some patients decline trips to the hospital or clinic to receive this type of service. These new barriers to access of contraception may require more planning at this time so that decisions about family planning are by design and not default during a time as complicated as the current public health crisis.
 

Telemedicine: telepsychiatry and obstetrics virtual visits

While wide-scale use of telemedicine platforms was not the standard day-to-day practice in either obstetrics or psychiatry prior to the pandemic, telepsychiatry has come up to speed within a short number of weeks. At our institution, 85% of outpatient visits are being conducted remotely, with in-person visits being reserved for only urgent or emergent visits. Our inpatient psychiatry service remains a setting where psychiatric patients, regardless of their COVID-19 status, can receive necessary care.

The use of telemedicine and specifically telepsychiatry is critical to mitigate the likelihood of exposure to SARS-CoV-2. On our reproductive psychiatry service, it has actually been an opportunity to engage with patients for comprehensive initial consults about reproductive safety of psychiatric medications currently being taken, or for ongoing consultation and direct patient care during follow-up visits during pregnancy to see that patients are sustaining emotional well-being or have changes for treatment implemented if they are not well. An increased frequency of visits allows us more opportunity to capture any signs of early clinical worsening of symptoms that might have been missed previously using the more traditional in-person setting.

Telepsychiatry and “virtual visits” have allowed us to do real-time, nimble modifications of treatment regimens with both pharmacologic and nonpharmacologic interventions to keep women well and to keep them out of the hospital for psychiatric care as often as possible. It also has facilitated a closer collaboration with our colleagues in obstetrics. In a way, the team of providers, including psychiatrists, obstetrical providers, social workers, and therapists can more easily communicate virtually than has sometimes been the case previously, when day-to-day use of telemedicine and virtual team meetings was less common.
 

Recognition and treatment of anxiety in perinatal patients

Even pregnant women without preexisting anxiety disorders may have heightened anxiety during usual times, and women and their partners cope with this typically in numerous ways including participation in peer-support opportunities, wellness and self-care activities, leveraging support from care providers, and engaging with family. But the previously “typical pregnancy experience” has shifted in the context of COVID-19. Specifically, added concerns of pregnant women about becoming infected, of potential separation from family if they do become ill, or of separation from partners or support systems during labor and delivery (an issue that has been largely resolved in many hospitals), as well as the possibility that a neonate might become ill with exposure to the coronavirus are obviously understandable and real. Such contingencies are unsettling, even for the most settled of our patients. Labor and delivery plans, and plans for outside help from family or others with the baby and older children in the postpartum period, have been upended for many patients.

These are anxious times. The number of nonpharmacologic virtual interventions available to mitigate anxiety are filling email inboxes daily. Curating these options can be a challenge, although several resources are worth noting, such as our department’s page on mental health resources.

During these past weeks, we have seen growing numbers of women for whom the normative anxiety of pregnancy is increasing to the point of causing distress to the level of functional impairment. Many patients for the first time meet criteria for frank anxiety disorders. These patients deserve prompt evaluation by mental health professionals and treatment with evidence-based therapies for anxiety disorders whether nonpharmacologic or pharmacologic so as to mitigate the risk of untreated anxiety on maternal and fetal well-being and also to limit risk for postpartum depression and postpartum anxiety disorders.

Miscarriage and infertility

A 36-year-old patient came to see me in clinic in late January following a miscarriage. She had a history of a previous miscarriage a year before and had an episode of major depression to follow for which she received treatment with an antidepressant and cognitive-behavioral therapy; she also attended a perinatal loss support group. She saw me in early March, anxious to try to conceive but extremely concerned about the risks associated with becoming pregnant at this point in time. Following a lengthy discussion with me and her obstetrician, the patient decided to wait until “the curve flattened” in Boston in terms of new cases of COVID-19, and then start trying to conceive. The case of another patient with a very similar history was presented at our rounds a few weeks ago; she also elected to defer attempts to conceive until life is more settled.

Perhaps one of the most dramatic examples of the impact of COVID-19 on fertility has been for those women with plans to pursue treatment with one of the assisted reproductive technologies. They have been told that professional societies have made recommendations regarding use of assisted reproductive technologies that are not entirely consistent across the country, but where in many places such interventions have been suspended during the COVID-19 pandemic. For many women near the end of their reproductive years, delays in trying to conceive either with or without the aid of fertility treatments may indelibly shape their plans to have children.
 

Sustaining emotional well-being across pregnancy

Because most psychiatric disorders are chronic in course, it is often the situation where women are treated to wellness for serious psychiatric disorders, with the goal of maintaining wellness across pregnancy and the post partum. One of the most critical takeaway points from 30 years of working with psychiatrically ill pregnant women is the maxim that keeping women well during pregnancy is simply imperative. Maternal psychiatric well-being during pregnancy is a strong predictor of obstetrical and neonatal outcomes, postpartum mental health, and longer-term neurobehavioral outcomes in children. Critically, in the context of the pandemic, keeping women out of psychiatric crises mitigates the necessity of visits to urgent clinical settings such as EDs and psychiatric inpatient units, which can increase the likelihood of exposure to the coronavirus.

Preservation of sleep

Disruption in sleep (duration and quality) can be seen in well over half of women during pregnancy with and without psychiatric disorders, and our experience has been that this has been exacerbated for many women during the COVID-19 crisis. Yet there are very rich data showing that sleep deprivation or sleep dysregulation in women, for example, who suffer from bipolar disorder or major depression can be a strong trigger for psychiatric relapse of underlying illness during pregnancy and the postpartum period.

During a time when normal rhythms of day-to-day life have been shifted – if not frankly disrupted – by swift transitions to remote work, cancellation of school and associated school activities across the country, complaints of insomnia and non-restorative sleep have been exceedingly common. Relevant to all but particularly for pregnant women with histories of psychiatric disorder, attention to sleep hygiene, moderation of caffeine use (if any), and use of any number of biobehavioral interventions to enhance relaxation and modulate stress may be of great value.

Cognitive-behavioral therapy for insomnia (CBT-I) has been demonstrated to be effective in pregnant women. Fortunately, there are user-friendly options on digital platforms that can be used during the pandemic that may play an important role in sustaining emotional well-being for pregnant women who have frank symptoms of insomnia.
 

Maintenance of ongoing antidepressant treatment during pregnancy among women with histories of mood disorder

Over a decade ago, my colleagues and I wrote about the comparison of outcomes for women with histories of recurrent major depression, demonstrating the value of maintenance treatment with antidepressants, compared with discontinuation of these medications during pregnancy (JAMA. 2006 Feb 1;295[5]:499-507). Recently, I was asked if maintenance antidepressant use in women with histories of recurrent depression was still our clinical recommendation. Over the last decade, we have noted that nearly half of women treated with antidepressants, regardless of illness severity, will discontinue their use of these medications prior to or early on in pregnancy given concerns about potential unknown effects of fetal exposure to medications, even medications for which there are robust data supporting reproductive safety regarding risk of congenital malformations. Routine discontinuation of antidepressants prior to or during pregnancy continues, despite the fact that we showed nearly 70% of those women with past histories of depression on maintenance antidepressant treatment relapsed shortly after discontinuing medication.

While we do not dictate the decisions women make about antidepressant use before, during, or after pregnancy, women with the same severity of illness will frequently make different decisions (a good thing) but we are now having very frank discussions about the particular need during a pandemic to avoid the relapse of serious psychiatric disorders. We typically endorse maintenance medication use with all but a very few number of psychotropic medications for which benefit may not outweigh risk to the fetus. However, for women who have decided nonetheless to discontinue antidepressants or other psychotropics during pregnancy despite the known risk of relapse, we strongly advise that they initiate treatment with evidence-based nonpharmacologic intervention such as CBT or mindfulness-based cognitive therapy (MBCT).

As in other areas of medicine, the pandemic is prompting we professionals in psychiatry, and specifically in perinatal psychiatry, to use all of our tools to keep pregnant and postpartum women well. The availability of digital tools to deliver MBCT and CBT has made the use of such interventions particularly viable at a time of social distancing. That being said, for patients with highly recurrent affective disorder with histories of previous recurrence when they stop their antidepressants, we are more strongly recommending serious consideration of maintenance medication treatment.
 

Virtual rounds in reproductive psychiatry and women’s mental health

The use of virtual platforms to connect with both patients and colleagues also has provided new opportunities for interaction with the reproductive psychiatry community as a whole. Peer teaching and peer support has been a critical part of our mission, and we decided 1 month ago to establish Virtual Rounds at the Center for Women’s Mental Health. This is a free digital platform, held on a weekly basis with our colleagues from across the country, where we discuss cases that come up in our own clinical rounds and also questions that get put forth by our colleagues in the area of reproductive psychiatry as they manage patients during the pandemic.

Changes in the postpartum experience

The last decade has brought a growing appreciation of postpartum depression and the need to screen and treat postpartum psychiatric disorders, such as postpartum mood and anxiety disorders. Yet in the era of this pandemic, the postpartum experience is itself is changing. Changes in carefully configured plans for the postpartum period – from family coming and going to mobilizing extra support at home and to now having new moms having to manage families and their other children at home – has been an enormous stressor for many women. Plans to have more elderly parents visit during the acute postpartum period, and the increased concerns about people traveling to and from a home where there is a newborn and the need to quarantine, has made the transition to motherhood much more complicated for all postpartum women, let alone for those postpartum women who have histories of psychiatric disorder.

There is a risk of social isolation for postpartum women even under normal circumstances, and this is profoundly more likely during this pandemic. We are actively working with our postpartum patients and optimizing treatment, brainstorming options in terms of using both virtual and real-time support to the extent that it is safe in order to keep women healthy during such a stressful and critical time.

I am heartened by the efforts on the part of organizations such as Postpartum Support International to make available virtually their resources with respect to community-based support and education for women who feel increasingly isolated during the postpartum period, a time where connectedness is so critical.

Summarily, these have been challenging times, but also times of opportunity. The COVID-19 pandemic has prompted us to get even more creative as we configure ways to optimize the emotional well-being of our patients who are planning to get pregnant, who are pregnant, or who are post partum.

The current time, while challenging in so many ways and a time of great pain, loss, and grief for far too many, has also provided an opportunity to work even more collaboratively with our colleagues, coming up with new paradigms of treatments as we weather this historic challenge.

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 him at [email protected].

Although the last decade has brought appropriate increased interest in the diagnosis and treatment of postpartum depression, with screening initiatives across more than 40 states in place and even new medications being brought to market for treatment, far less attention has been given to diagnosis and treatment of a particularly serious psychiatric illness: postpartum psychosis.

Postpartum psychosis is relatively rare, with an incidence of 1 in 1,000 births, but it is one of the most serious complications of modern obstetrics. Clinically, women can experience rapid mood changes, most often with the presentation that is consistent with a manic-like psychosis, with associated symptoms of delusional thinking, hallucinations, paranoia and either depression or elation, or an amalgam of these so-called “mixed symptoms.” Onset of symptoms typically is early, within 72 hours as is classically described, but may have a somewhat later time of onset in some women.

Many investigators have studied risk factors for postpartum psychosis, and it has been well established that a history of mood disorder, particularly bipolar disorder, is one of the strongest predictors of risk for postpartum psychosis. Women with histories of postpartum psychosis are at very high risk of recurrence, with as many as 70%-90% of women experiencing recurrence if not prophylaxed with an appropriate agent. From a clinical point of view, women with postpartum psychosis typically are hospitalized, given that this is both a psychiatric and potential obstetrical emergency. In fact, the data would suggest that although postpartum suicide and infanticide are not common, they can be a tragic concomitant of postpartum psychosis (Am J Psychiatry. 2016 Dec 1;173[12]:1179-88).

A great amount of interest has been placed on the etiology of postpartum psychosis, as it’s a dramatic presentation with very rapid onset in the acute postpartum period. A rich evidence base with respect to an algorithm of treatment that maximizes likelihood of full recovery or sustaining of euthymia after recovery is limited. Few studies have looked systematically at the optimum way to treat postpartum psychosis. Clinical wisdom has dictated that, given the dramatic symptoms with which these patients present, most patients are treated with lithium and an antipsychotic medication as if they have a manic-like psychosis. It may take brief or extended periods of time for patients to stabilize. Once they are stabilized, one of the most challenging questions for clinicians is how long to treat. Again, an evidence base clearly informing this question is lacking.

Over the years, many clinicians have treated patients with postpartum psychosis as if they have bipolar disorder, given the index presentation of the illness, so some of these patients are treated with antimanic drugs indefinitely. However, clinical experience from several centers that treat women with postpartum psychosis suggests that in remitted patients, a proportion of them may be able to taper and discontinue treatment, then sustain well-being for protracted periods.

One obstacle with respect to treatment of postpartum psychosis derives from the short length of stay after delivery for many women. Some women who present with symptoms of postpartum psychosis in the first 24-48 hours frequently are managed with direct admission to an inpatient psychiatric service. But others may not develop symptoms until they are home, which may place both mother and newborn at risk.

Given that the risk for recurrent postpartum psychosis is so great (70%-90%), women with histories of postpartum psychosis invariably are prophylaxed with mood stabilizer prior to delivery in a subsequent pregnancy. In our own center, we have published on the value of such prophylactic intervention, not just in women with postpartum psychosis, but in women with bipolar disorder, who are, as noted, at great risk for developing postpartum psychotic symptoms (Am J Psychiatry. 1995 Nov;152[11]:1641-5.)

Although postpartum psychosis may be rare, over the last 3 decades we have seen a substantial number of women with postpartum psychosis and have been fascinated with the spectrum of symptoms with which some women with postpartum psychotic illness present. We also have been impressed with the time required for some women to recompensate from their illness and the course of their disorder after they have seemingly remitted. Some women appear to be able to discontinue treatment as noted above; others, particularly if there is any history of bipolar disorder, need to be maintained on treatment with mood stabilizer indefinitely.

To better understand the phenomenology of postpartum psychosis, as well as the longitudinal course of the illness, in 2019, the Mass General Hospital Postpartum Psychosis Project (MGHP3) was established. The project is conducted as a hospital-based registry where women with histories of postpartum psychosis over the last decade are invited to participate in an in-depth interview to understand both symptoms and course of underlying illness. This is complemented by obtaining a sample of saliva, which is used for genetic testing to try to identify a genetic underpinning associated with postpartum psychosis, as the question of genetic etiology of postpartum psychosis is still an open one.

As part of the MGHP3 project, clinicians across the country are able to contact perinatal psychiatrists in our center with expertise in the treatment of postpartum psychosis. Our psychiatrists also can counsel clinicians on issues regarding long-term management of postpartum psychosis because for many, knowledge of precisely how to manage this disorder or the follow-up treatment may be incomplete.

From a clinical point of view, the relevant questions really include not only acute treatment, which has already been outlined, but also the issue of duration of treatment. While some patients may be able to taper and discontinue treatment after, for example, a year of being totally well, to date we are unable to know who those patients are. We tend to be more conservative in our own center and treat patients with puerperal psychosis for a more protracted period of time, usually over several years. We also ask women about their family history of bipolar disorder or postpartum psychosis. Depending on the clinical course (if the patient really has sustained euthymia), we consider slow taper and ultimate discontinuation. As always, treatment decisions are tailored to individual clinical history, course, and patient wishes.

Postpartum psychosis remains one of the most serious illnesses that we find in reproductive psychiatry, and incomplete attention has been given to this devastating illness, which we read about periodically in newspapers and magazines. Greater understanding of postpartum psychosis will lead to a more precision-like psychiatric approach, tailoring treatment to the invariable heterogeneity of this illness.

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 [email protected].

Although the last decade has brought appropriate increased interest in the diagnosis and treatment of postpartum depression, with screening initiatives across more than 40 states in place and even new medications being brought to market for treatment, far less attention has been given to diagnosis and treatment of a particularly serious psychiatric illness: postpartum psychosis.

Postpartum psychosis is relatively rare, with an incidence of 1 in 1,000 births, but it is one of the most serious complications of modern obstetrics. Clinically, women can experience rapid mood changes, most often with the presentation that is consistent with a manic-like psychosis, with associated symptoms of delusional thinking, hallucinations, paranoia and either depression or elation, or an amalgam of these so-called “mixed symptoms.” Onset of symptoms typically is early, within 72 hours as is classically described, but may have a somewhat later time of onset in some women.

Many investigators have studied risk factors for postpartum psychosis, and it has been well established that a history of mood disorder, particularly bipolar disorder, is one of the strongest predictors of risk for postpartum psychosis. Women with histories of postpartum psychosis are at very high risk of recurrence, with as many as 70%-90% of women experiencing recurrence if not prophylaxed with an appropriate agent. From a clinical point of view, women with postpartum psychosis typically are hospitalized, given that this is both a psychiatric and potential obstetrical emergency. In fact, the data would suggest that although postpartum suicide and infanticide are not common, they can be a tragic concomitant of postpartum psychosis (Am J Psychiatry. 2016 Dec 1;173[12]:1179-88).

A great amount of interest has been placed on the etiology of postpartum psychosis, as it’s a dramatic presentation with very rapid onset in the acute postpartum period. A rich evidence base with respect to an algorithm of treatment that maximizes likelihood of full recovery or sustaining of euthymia after recovery is limited. Few studies have looked systematically at the optimum way to treat postpartum psychosis. Clinical wisdom has dictated that, given the dramatic symptoms with which these patients present, most patients are treated with lithium and an antipsychotic medication as if they have a manic-like psychosis. It may take brief or extended periods of time for patients to stabilize. Once they are stabilized, one of the most challenging questions for clinicians is how long to treat. Again, an evidence base clearly informing this question is lacking.

Over the years, many clinicians have treated patients with postpartum psychosis as if they have bipolar disorder, given the index presentation of the illness, so some of these patients are treated with antimanic drugs indefinitely. However, clinical experience from several centers that treat women with postpartum psychosis suggests that in remitted patients, a proportion of them may be able to taper and discontinue treatment, then sustain well-being for protracted periods.

One obstacle with respect to treatment of postpartum psychosis derives from the short length of stay after delivery for many women. Some women who present with symptoms of postpartum psychosis in the first 24-48 hours frequently are managed with direct admission to an inpatient psychiatric service. But others may not develop symptoms until they are home, which may place both mother and newborn at risk.

Given that the risk for recurrent postpartum psychosis is so great (70%-90%), women with histories of postpartum psychosis invariably are prophylaxed with mood stabilizer prior to delivery in a subsequent pregnancy. In our own center, we have published on the value of such prophylactic intervention, not just in women with postpartum psychosis, but in women with bipolar disorder, who are, as noted, at great risk for developing postpartum psychotic symptoms (Am J Psychiatry. 1995 Nov;152[11]:1641-5.)

Although postpartum psychosis may be rare, over the last 3 decades we have seen a substantial number of women with postpartum psychosis and have been fascinated with the spectrum of symptoms with which some women with postpartum psychotic illness present. We also have been impressed with the time required for some women to recompensate from their illness and the course of their disorder after they have seemingly remitted. Some women appear to be able to discontinue treatment as noted above; others, particularly if there is any history of bipolar disorder, need to be maintained on treatment with mood stabilizer indefinitely.

To better understand the phenomenology of postpartum psychosis, as well as the longitudinal course of the illness, in 2019, the Mass General Hospital Postpartum Psychosis Project (MGHP3) was established. The project is conducted as a hospital-based registry where women with histories of postpartum psychosis over the last decade are invited to participate in an in-depth interview to understand both symptoms and course of underlying illness. This is complemented by obtaining a sample of saliva, which is used for genetic testing to try to identify a genetic underpinning associated with postpartum psychosis, as the question of genetic etiology of postpartum psychosis is still an open one.

As part of the MGHP3 project, clinicians across the country are able to contact perinatal psychiatrists in our center with expertise in the treatment of postpartum psychosis. Our psychiatrists also can counsel clinicians on issues regarding long-term management of postpartum psychosis because for many, knowledge of precisely how to manage this disorder or the follow-up treatment may be incomplete.

From a clinical point of view, the relevant questions really include not only acute treatment, which has already been outlined, but also the issue of duration of treatment. While some patients may be able to taper and discontinue treatment after, for example, a year of being totally well, to date we are unable to know who those patients are. We tend to be more conservative in our own center and treat patients with puerperal psychosis for a more protracted period of time, usually over several years. We also ask women about their family history of bipolar disorder or postpartum psychosis. Depending on the clinical course (if the patient really has sustained euthymia), we consider slow taper and ultimate discontinuation. As always, treatment decisions are tailored to individual clinical history, course, and patient wishes.

Postpartum psychosis remains one of the most serious illnesses that we find in reproductive psychiatry, and incomplete attention has been given to this devastating illness, which we read about periodically in newspapers and magazines. Greater understanding of postpartum psychosis will lead to a more precision-like psychiatric approach, tailoring treatment to the invariable heterogeneity of this illness.

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 [email protected].

Although the last decade has brought appropriate increased interest in the diagnosis and treatment of postpartum depression, with screening initiatives across more than 40 states in place and even new medications being brought to market for treatment, far less attention has been given to diagnosis and treatment of a particularly serious psychiatric illness: postpartum psychosis.

Postpartum psychosis is relatively rare, with an incidence of 1 in 1,000 births, but it is one of the most serious complications of modern obstetrics. Clinically, women can experience rapid mood changes, most often with the presentation that is consistent with a manic-like psychosis, with associated symptoms of delusional thinking, hallucinations, paranoia and either depression or elation, or an amalgam of these so-called “mixed symptoms.” Onset of symptoms typically is early, within 72 hours as is classically described, but may have a somewhat later time of onset in some women.

Many investigators have studied risk factors for postpartum psychosis, and it has been well established that a history of mood disorder, particularly bipolar disorder, is one of the strongest predictors of risk for postpartum psychosis. Women with histories of postpartum psychosis are at very high risk of recurrence, with as many as 70%-90% of women experiencing recurrence if not prophylaxed with an appropriate agent. From a clinical point of view, women with postpartum psychosis typically are hospitalized, given that this is both a psychiatric and potential obstetrical emergency. In fact, the data would suggest that although postpartum suicide and infanticide are not common, they can be a tragic concomitant of postpartum psychosis (Am J Psychiatry. 2016 Dec 1;173[12]:1179-88).

A great amount of interest has been placed on the etiology of postpartum psychosis, as it’s a dramatic presentation with very rapid onset in the acute postpartum period. A rich evidence base with respect to an algorithm of treatment that maximizes likelihood of full recovery or sustaining of euthymia after recovery is limited. Few studies have looked systematically at the optimum way to treat postpartum psychosis. Clinical wisdom has dictated that, given the dramatic symptoms with which these patients present, most patients are treated with lithium and an antipsychotic medication as if they have a manic-like psychosis. It may take brief or extended periods of time for patients to stabilize. Once they are stabilized, one of the most challenging questions for clinicians is how long to treat. Again, an evidence base clearly informing this question is lacking.

Over the years, many clinicians have treated patients with postpartum psychosis as if they have bipolar disorder, given the index presentation of the illness, so some of these patients are treated with antimanic drugs indefinitely. However, clinical experience from several centers that treat women with postpartum psychosis suggests that in remitted patients, a proportion of them may be able to taper and discontinue treatment, then sustain well-being for protracted periods.

One obstacle with respect to treatment of postpartum psychosis derives from the short length of stay after delivery for many women. Some women who present with symptoms of postpartum psychosis in the first 24-48 hours frequently are managed with direct admission to an inpatient psychiatric service. But others may not develop symptoms until they are home, which may place both mother and newborn at risk.

Given that the risk for recurrent postpartum psychosis is so great (70%-90%), women with histories of postpartum psychosis invariably are prophylaxed with mood stabilizer prior to delivery in a subsequent pregnancy. In our own center, we have published on the value of such prophylactic intervention, not just in women with postpartum psychosis, but in women with bipolar disorder, who are, as noted, at great risk for developing postpartum psychotic symptoms (Am J Psychiatry. 1995 Nov;152[11]:1641-5.)

Although postpartum psychosis may be rare, over the last 3 decades we have seen a substantial number of women with postpartum psychosis and have been fascinated with the spectrum of symptoms with which some women with postpartum psychotic illness present. We also have been impressed with the time required for some women to recompensate from their illness and the course of their disorder after they have seemingly remitted. Some women appear to be able to discontinue treatment as noted above; others, particularly if there is any history of bipolar disorder, need to be maintained on treatment with mood stabilizer indefinitely.

To better understand the phenomenology of postpartum psychosis, as well as the longitudinal course of the illness, in 2019, the Mass General Hospital Postpartum Psychosis Project (MGHP3) was established. The project is conducted as a hospital-based registry where women with histories of postpartum psychosis over the last decade are invited to participate in an in-depth interview to understand both symptoms and course of underlying illness. This is complemented by obtaining a sample of saliva, which is used for genetic testing to try to identify a genetic underpinning associated with postpartum psychosis, as the question of genetic etiology of postpartum psychosis is still an open one.

As part of the MGHP3 project, clinicians across the country are able to contact perinatal psychiatrists in our center with expertise in the treatment of postpartum psychosis. Our psychiatrists also can counsel clinicians on issues regarding long-term management of postpartum psychosis because for many, knowledge of precisely how to manage this disorder or the follow-up treatment may be incomplete.

From a clinical point of view, the relevant questions really include not only acute treatment, which has already been outlined, but also the issue of duration of treatment. While some patients may be able to taper and discontinue treatment after, for example, a year of being totally well, to date we are unable to know who those patients are. We tend to be more conservative in our own center and treat patients with puerperal psychosis for a more protracted period of time, usually over several years. We also ask women about their family history of bipolar disorder or postpartum psychosis. Depending on the clinical course (if the patient really has sustained euthymia), we consider slow taper and ultimate discontinuation. As always, treatment decisions are tailored to individual clinical history, course, and patient wishes.

Postpartum psychosis remains one of the most serious illnesses that we find in reproductive psychiatry, and incomplete attention has been given to this devastating illness, which we read about periodically in newspapers and magazines. Greater understanding of postpartum psychosis will lead to a more precision-like psychiatric approach, tailoring treatment to the invariable heterogeneity of this illness.

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 [email protected].

The last decade has brought increasing awareness of the need to effectively screen for postpartum depression, with a majority of states across the country now having some sort of formal program by which women are screened for mood disorder during the postnatal period, typically with scales such as the Edinburgh Postnatal Depression Scale (EPDS).

monkeybusinessimages/Thinkstock

In addition to effective screening is a pressing need for effective referral networks of clinicians who have both the expertise and time to manage the 10%-15% of women who have been identified and who suffer from postpartum psychiatric disorders – both postpartum mood and anxiety disorders. Several studies have suggested that only a small percentage of postpartum women who score with clinically significant level of depressive symptoms actually get to a clinician or, if they do get to a clinician, receive adequate treatment restoring their emotional well-being (J Clin Psychiatry. 2016 Sep;77[9]:1189-200).

Zulresso (brexanolone), a novel new antidepressant medication which recently received Food and Drug Administration approval for the treatment of postpartum depression, is a first-in-class molecule to get such approval. Zulresso is a neurosteroid, an analogue of allopregnanolone and a GABA_A receptor–positive allosteric modulator, a primary inhibitory neurotransmitter in the brain.

Zulresso, an IV infusion, was developed by its manufacturer Sage Therapeutics specifically for moderate to severe postpartum depression. There is every reason to believe that, as a class, this group of neurosteroid molecules are effective in treating depression in other populations aside from women with postpartum depression and hence may not be specific to the postpartum period. For example, recent presentations of preliminary data suggest other neurosteroids such as zuranolone (an oral medication also developed by Sage Therapeutics) is effective for both men and women who have major depression in addition to women suffering from postpartum depression.

Zulresso is approved through a Risk Evaluation and Mitigation Strategy–restricted program and, per that protocol, needs to be administered by a health care provider in a recognized health care setting intravenously over 2.5 days (60 hours). Because of concerns regarding increased sedation, continuous pulse oximetry is required, and this is outlined in a boxed warning in the prescribing information. Zulresso has been classified by the Drug Enforcement Administration (DEA) as a Schedule IV injection and is subject to the prescribing regulations for a controlled substance.

Since Zulresso’s approval, my colleagues and I at the Center for Women’s Mental Health have received numerous queries from patients and colleagues about our clinical impression of this new molecule with a different mechanism of action – a welcome addition to the antidepressant pharmacopeia. The question posed to us essentially is: Where does brexanolone fit into our algorithm for treating women who suffer from postpartum depression? And frequently, the follow-up query is: Because subjects in the clinical trials for this medication included women who had onset of depression either late in pregnancy or during the postpartum period, how specific is brexanolone with respect to being a targeted therapy for postpartum depression, compared with depression encountered in other clinical settings.

What clearly can be stated is that Zulresso has a rapid onset of action and was demonstrated across clinical trials to have sustained benefit up to 30 days after IV administration. The question is whether patients have sustained benefit after 30 days or if this is a medicine to be considered as a “bridge” to other treatment. Data answering that critical clinical question are unavailable at this time. From a clinical standpoint, do patients receive this treatment and get sent home on antidepressants, as we would for patients who receive ECT, often discharging them with prophylactic antidepressants to sustain the benefit of the treatment? Or do patients receive this new medicine with the clinician providing close follow-up, assuming a wait-and-see approach? Because data informing the answer to that question are not available, this decision will be made empirically, frequently factoring in the patient’s past clinical history where presumably more liberal use of antidepressant immediately after the administration of Zulresso will be pursued in those with histories of highly recurrent major depression.

So where might this new medicine fit into the treatment of postpartum depression of moderate severity, or modest to moderate severity? It should be kept in mind that for patients with mild to moderate postpartum depression, there are data supporting the efficacy of cognitive-behavioral therapy (CBT). CBT frequently is pursued with concurrent mobilization of substantial social support with good outcomes. In patients with more severe postpartum depression, there are data supporting the use of antidepressants, and in these patients as well, use of established support from the ever-growing network of community-based support groups and services can be particularly helpful. It is unlikely that Zulresso will be a first-line medication for the treatment of postpartum depression, but it may be particularly appropriate for patients with severe illness who have not responded to other interventions.

Other practical considerations regarding use of Zulresso include the requirement that the medicine be administered in hospitals that have established clinical infrastructure to accommodate this particular population of patients and where pharmacists and other relevant parties in hospitals have accepted the medicine into its drug formulary. While coverage by various insurance policies may vary, the cost of this new medication is substantial, between $24,000 and $34,000 per treatment, according to reports.

Where Zulresso fits into the pharmacopeia for treating postpartum depression may fall well beyond the issues of efficacy. Given all of the attention to this first-in-class medicine, Zulresso has reinforced the growing interest in the substantial prevalence and the morbidity associated with postpartum depression. It is hard to imagine Zulresso being used in cases of more mild to moderate depression, in which there is nonemergent opportunity to pursue options that do not require a new mom to absent herself from homelife with a newborn. However, in picking cases of severe new onset or recurrence of depression in postpartum women, the rapid onset of benefit that was noted within days could be an extraordinary relief and be the beginning of a road to wellness for some women.

Ultimately, the collaboration of patients with their doctors, the realities of cost, and the acceptability of use in various clinical settings will determine how Zulresso is incorporated into seeking treatment to mitigate the suffering associated with postpartum depression. We at the Center for Women’s Mental Health are interested in user experience with respect to this medicine and welcome comments from both patients and their doctors at [email protected].
 

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. This center was an investigator site for one of the studies supported by Sage Therapeutics, the manufacturer of Zulresso. Dr. Cohen is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School, also in Boston. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

The last decade has brought increasing awareness of the need to effectively screen for postpartum depression, with a majority of states across the country now having some sort of formal program by which women are screened for mood disorder during the postnatal period, typically with scales such as the Edinburgh Postnatal Depression Scale (EPDS).

monkeybusinessimages/Thinkstock

In addition to effective screening is a pressing need for effective referral networks of clinicians who have both the expertise and time to manage the 10%-15% of women who have been identified and who suffer from postpartum psychiatric disorders – both postpartum mood and anxiety disorders. Several studies have suggested that only a small percentage of postpartum women who score with clinically significant level of depressive symptoms actually get to a clinician or, if they do get to a clinician, receive adequate treatment restoring their emotional well-being (J Clin Psychiatry. 2016 Sep;77[9]:1189-200).

Zulresso (brexanolone), a novel new antidepressant medication which recently received Food and Drug Administration approval for the treatment of postpartum depression, is a first-in-class molecule to get such approval. Zulresso is a neurosteroid, an analogue of allopregnanolone and a GABA_A receptor–positive allosteric modulator, a primary inhibitory neurotransmitter in the brain.

Zulresso, an IV infusion, was developed by its manufacturer Sage Therapeutics specifically for moderate to severe postpartum depression. There is every reason to believe that, as a class, this group of neurosteroid molecules are effective in treating depression in other populations aside from women with postpartum depression and hence may not be specific to the postpartum period. For example, recent presentations of preliminary data suggest other neurosteroids such as zuranolone (an oral medication also developed by Sage Therapeutics) is effective for both men and women who have major depression in addition to women suffering from postpartum depression.

Zulresso is approved through a Risk Evaluation and Mitigation Strategy–restricted program and, per that protocol, needs to be administered by a health care provider in a recognized health care setting intravenously over 2.5 days (60 hours). Because of concerns regarding increased sedation, continuous pulse oximetry is required, and this is outlined in a boxed warning in the prescribing information. Zulresso has been classified by the Drug Enforcement Administration (DEA) as a Schedule IV injection and is subject to the prescribing regulations for a controlled substance.

Since Zulresso’s approval, my colleagues and I at the Center for Women’s Mental Health have received numerous queries from patients and colleagues about our clinical impression of this new molecule with a different mechanism of action – a welcome addition to the antidepressant pharmacopeia. The question posed to us essentially is: Where does brexanolone fit into our algorithm for treating women who suffer from postpartum depression? And frequently, the follow-up query is: Because subjects in the clinical trials for this medication included women who had onset of depression either late in pregnancy or during the postpartum period, how specific is brexanolone with respect to being a targeted therapy for postpartum depression, compared with depression encountered in other clinical settings.

What clearly can be stated is that Zulresso has a rapid onset of action and was demonstrated across clinical trials to have sustained benefit up to 30 days after IV administration. The question is whether patients have sustained benefit after 30 days or if this is a medicine to be considered as a “bridge” to other treatment. Data answering that critical clinical question are unavailable at this time. From a clinical standpoint, do patients receive this treatment and get sent home on antidepressants, as we would for patients who receive ECT, often discharging them with prophylactic antidepressants to sustain the benefit of the treatment? Or do patients receive this new medicine with the clinician providing close follow-up, assuming a wait-and-see approach? Because data informing the answer to that question are not available, this decision will be made empirically, frequently factoring in the patient’s past clinical history where presumably more liberal use of antidepressant immediately after the administration of Zulresso will be pursued in those with histories of highly recurrent major depression.

So where might this new medicine fit into the treatment of postpartum depression of moderate severity, or modest to moderate severity? It should be kept in mind that for patients with mild to moderate postpartum depression, there are data supporting the efficacy of cognitive-behavioral therapy (CBT). CBT frequently is pursued with concurrent mobilization of substantial social support with good outcomes. In patients with more severe postpartum depression, there are data supporting the use of antidepressants, and in these patients as well, use of established support from the ever-growing network of community-based support groups and services can be particularly helpful. It is unlikely that Zulresso will be a first-line medication for the treatment of postpartum depression, but it may be particularly appropriate for patients with severe illness who have not responded to other interventions.

Other practical considerations regarding use of Zulresso include the requirement that the medicine be administered in hospitals that have established clinical infrastructure to accommodate this particular population of patients and where pharmacists and other relevant parties in hospitals have accepted the medicine into its drug formulary. While coverage by various insurance policies may vary, the cost of this new medication is substantial, between $24,000 and $34,000 per treatment, according to reports.

Where Zulresso fits into the pharmacopeia for treating postpartum depression may fall well beyond the issues of efficacy. Given all of the attention to this first-in-class medicine, Zulresso has reinforced the growing interest in the substantial prevalence and the morbidity associated with postpartum depression. It is hard to imagine Zulresso being used in cases of more mild to moderate depression, in which there is nonemergent opportunity to pursue options that do not require a new mom to absent herself from homelife with a newborn. However, in picking cases of severe new onset or recurrence of depression in postpartum women, the rapid onset of benefit that was noted within days could be an extraordinary relief and be the beginning of a road to wellness for some women.

Ultimately, the collaboration of patients with their doctors, the realities of cost, and the acceptability of use in various clinical settings will determine how Zulresso is incorporated into seeking treatment to mitigate the suffering associated with postpartum depression. We at the Center for Women’s Mental Health are interested in user experience with respect to this medicine and welcome comments from both patients and their doctors at [email protected].
 

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. This center was an investigator site for one of the studies supported by Sage Therapeutics, the manufacturer of Zulresso. Dr. Cohen is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School, also in Boston. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

The last decade has brought increasing awareness of the need to effectively screen for postpartum depression, with a majority of states across the country now having some sort of formal program by which women are screened for mood disorder during the postnatal period, typically with scales such as the Edinburgh Postnatal Depression Scale (EPDS).

monkeybusinessimages/Thinkstock

In addition to effective screening is a pressing need for effective referral networks of clinicians who have both the expertise and time to manage the 10%-15% of women who have been identified and who suffer from postpartum psychiatric disorders – both postpartum mood and anxiety disorders. Several studies have suggested that only a small percentage of postpartum women who score with clinically significant level of depressive symptoms actually get to a clinician or, if they do get to a clinician, receive adequate treatment restoring their emotional well-being (J Clin Psychiatry. 2016 Sep;77[9]:1189-200).

Zulresso (brexanolone), a novel new antidepressant medication which recently received Food and Drug Administration approval for the treatment of postpartum depression, is a first-in-class molecule to get such approval. Zulresso is a neurosteroid, an analogue of allopregnanolone and a GABA_A receptor–positive allosteric modulator, a primary inhibitory neurotransmitter in the brain.

Zulresso, an IV infusion, was developed by its manufacturer Sage Therapeutics specifically for moderate to severe postpartum depression. There is every reason to believe that, as a class, this group of neurosteroid molecules are effective in treating depression in other populations aside from women with postpartum depression and hence may not be specific to the postpartum period. For example, recent presentations of preliminary data suggest other neurosteroids such as zuranolone (an oral medication also developed by Sage Therapeutics) is effective for both men and women who have major depression in addition to women suffering from postpartum depression.

Zulresso is approved through a Risk Evaluation and Mitigation Strategy–restricted program and, per that protocol, needs to be administered by a health care provider in a recognized health care setting intravenously over 2.5 days (60 hours). Because of concerns regarding increased sedation, continuous pulse oximetry is required, and this is outlined in a boxed warning in the prescribing information. Zulresso has been classified by the Drug Enforcement Administration (DEA) as a Schedule IV injection and is subject to the prescribing regulations for a controlled substance.

Since Zulresso’s approval, my colleagues and I at the Center for Women’s Mental Health have received numerous queries from patients and colleagues about our clinical impression of this new molecule with a different mechanism of action – a welcome addition to the antidepressant pharmacopeia. The question posed to us essentially is: Where does brexanolone fit into our algorithm for treating women who suffer from postpartum depression? And frequently, the follow-up query is: Because subjects in the clinical trials for this medication included women who had onset of depression either late in pregnancy or during the postpartum period, how specific is brexanolone with respect to being a targeted therapy for postpartum depression, compared with depression encountered in other clinical settings.

What clearly can be stated is that Zulresso has a rapid onset of action and was demonstrated across clinical trials to have sustained benefit up to 30 days after IV administration. The question is whether patients have sustained benefit after 30 days or if this is a medicine to be considered as a “bridge” to other treatment. Data answering that critical clinical question are unavailable at this time. From a clinical standpoint, do patients receive this treatment and get sent home on antidepressants, as we would for patients who receive ECT, often discharging them with prophylactic antidepressants to sustain the benefit of the treatment? Or do patients receive this new medicine with the clinician providing close follow-up, assuming a wait-and-see approach? Because data informing the answer to that question are not available, this decision will be made empirically, frequently factoring in the patient’s past clinical history where presumably more liberal use of antidepressant immediately after the administration of Zulresso will be pursued in those with histories of highly recurrent major depression.

So where might this new medicine fit into the treatment of postpartum depression of moderate severity, or modest to moderate severity? It should be kept in mind that for patients with mild to moderate postpartum depression, there are data supporting the efficacy of cognitive-behavioral therapy (CBT). CBT frequently is pursued with concurrent mobilization of substantial social support with good outcomes. In patients with more severe postpartum depression, there are data supporting the use of antidepressants, and in these patients as well, use of established support from the ever-growing network of community-based support groups and services can be particularly helpful. It is unlikely that Zulresso will be a first-line medication for the treatment of postpartum depression, but it may be particularly appropriate for patients with severe illness who have not responded to other interventions.

Other practical considerations regarding use of Zulresso include the requirement that the medicine be administered in hospitals that have established clinical infrastructure to accommodate this particular population of patients and where pharmacists and other relevant parties in hospitals have accepted the medicine into its drug formulary. While coverage by various insurance policies may vary, the cost of this new medication is substantial, between $24,000 and $34,000 per treatment, according to reports.

Where Zulresso fits into the pharmacopeia for treating postpartum depression may fall well beyond the issues of efficacy. Given all of the attention to this first-in-class medicine, Zulresso has reinforced the growing interest in the substantial prevalence and the morbidity associated with postpartum depression. It is hard to imagine Zulresso being used in cases of more mild to moderate depression, in which there is nonemergent opportunity to pursue options that do not require a new mom to absent herself from homelife with a newborn. However, in picking cases of severe new onset or recurrence of depression in postpartum women, the rapid onset of benefit that was noted within days could be an extraordinary relief and be the beginning of a road to wellness for some women.

Ultimately, the collaboration of patients with their doctors, the realities of cost, and the acceptability of use in various clinical settings will determine how Zulresso is incorporated into seeking treatment to mitigate the suffering associated with postpartum depression. We at the Center for Women’s Mental Health are interested in user experience with respect to this medicine and welcome comments from both patients and their doctors at [email protected].
 

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. This center was an investigator site for one of the studies supported by Sage Therapeutics, the manufacturer of Zulresso. Dr. Cohen is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School, also in Boston. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Careful management of bipolar disorder during pregnancy is critical because for so many patients with this illness, the road to emotional well-being has been a long one, requiring a combination of careful pharmacologic and nonpharmacologic strategies.

KatarzynaBialasiewicz/thinkstockphotos

Half of referrals to our Center for Women’s Mental Health – where we evaluate and treat women before, during, and after pregnancy – are for women who have histories of bipolar disorder. My colleagues and I are asked at continuing medical education programs what we “always do” and “never do” with respect to the treatment of these patients.
 

What about discontinuation of mood stabilizers during pregnancy and risk of relapse?

We never abruptly stop mood stabilizers if a patient has an unplanned pregnancy – a common scenario, with 50% of pregnancies across the country being unplanned across sociodemographic lines – save for sodium valproate, which is a clearly a documented teratogen; it increases risk for organ malformation and behavioral difficulties in exposed offspring. In our center, we typically view the use of sodium valproate in reproductive age women as contraindicated.

One may then question the circumstances under which lithium might be used during pregnancy, because many clinicians are faced with patients who have been exquisite responders to lithium. Such a patient may present with a history of mania, but there are obvious concerns given the historical literature, and even some more recent reports, that describe an increased risk of teratogenicity with fetal exposure to lithium.

Maintenance pharmacotherapy for women with bipolar disorder during pregnancy is so important, not only to decrease the risk of relapse following discontinuation of mood stabilizers, but because recurrence of illness during pregnancy for these patients is a very strong predictor of risk for postpartum depression. Women with bipolar disorder already are at a fivefold increased risk for postpartum depression, so discussion of sustaining euthymia during pregnancy for bipolar women is particularly timely given the focus nationally on treatment and prevention of postpartum depression.
 

In patients with history of mania, what about stopping treatment with lithium and other effective treatments during pregnancy?

Historically, we sometimes divided patients with bipolar disorder into those with “more severe recurrent disease” compared with those with more distant, circumscribed disease. In patients with more remote histories of mood dysregulation, we tended to discontinue treatment with mood stabilizers such as lithium or even newer second-generation atypical antipsychotics to see if patients could at least get through earlier stages of pregnancy before going back on anti-manic treatment.

Our experience now over several decades has revealed that this can be a risky clinical move. What we see is that even in patients with histories of mania years in the past (i.e., a circumscribed episode of mania during college in a woman now 35 years old with intervening sustained well-being), discontinuation of treatment that got patients well can lead to recurrence. Hence, we should not confuse an exquisite response to treatment with long periods of well-being as suggesting that the patient has a less severe form of bipolar disorder and hence the capacity to sustain that well-being when treatment is removed.
 

What about increasing/decreasing lithium dose during pregnancy and around time of delivery?

Select patients may be sensitive to changes in plasma levels of lithium, but the literature suggests that the clinical utility of arbitrarily sustaining plasma levels at the upper limit of the accepted range may be of only modest advantage, if any. With this as a backdrop and even while knowing that increased plasma volume of pregnancy is associated with a fall in plasma level of most medications, we do not arbitrarily increase the dose of lithium across pregnancy merely to sustain a level in the absence of a change in clinical symptoms. Indeed, to my knowledge, currently available data supporting a clear correlation of decline in plasma levels and frank change in symptoms during pregnancy are very sparse, if existent.

Earlier work had suggested that lithium dosage should be reduced proximate to delivery, a period characterized by rapid shifts in plasma volume during the acute peripartum period. Because physicians in our center do not alter lithium dose across pregnancy, we never reduce the dose of lithium proximate to delivery because of a theoretical concern for increased risk of either neonatal toxicity or maternal lithium toxicity, which is essentially nonexistent in terms of systematic reports in the literature.

Obvious concerns about lithium during pregnancy have focused on increased risk of teratogenesis, with the earliest reports supporting an increased risk of Epstein’s anomaly (0.05%-0.1%). More recent reports suggest an increased risk of cardiovascular malformations, which according to some investigators may be dose dependent.

For those patients who are exquisitely responsive to lithium, we typically leave them on the medicine and avail ourselves of current fetal echocardiographic evaluation at 16 weeks to 18 weeks to document the integrity of the fetal cardiac anatomy. Although the risk for cardiac malformations associated with lithium exposure during the first trimester is still exceedingly small, it is still extremely reassuring to patients to know that they are safely on the other side of a teratogenic window.
 

What about lamotrigine levels across pregnancy?

The last decade has seen a dramatic decrease in the administration of lithium to women with bipolar disorder, and growing use of both lamotrigine and second-generation atypical antipsychotics (frequently in combination) as an alternative. The changes in plasma level of lamotrigine across pregnancy are being increasingly well documented based on rigorous studies (Obstet Gynecol Clin North Am. 2018 Sep;45[3]:403-17).

These are welcome data, but the correlation between plasma concentration of lamotrigine and clinical response is a poor one. To date, there are sparse data to suggest that maintaining plasma levels of lithium or lamotrigine at a certain level during pregnancy changes clinical outcome. Following lamotrigine plasma levels during pregnancy seems more like an academic exercise than a procedure associated with particular clinical value.

As in the case of lithium, we never change lamotrigine doses proximate to pregnancy because of the absence of reports of neonatal toxicity associated with using lamotrigine during the peripartum period. The rationale for removing or minimizing the use of an effective medicine proximate to delivery, a period of risk for bipolar women, is lacking.

In 2019, we clearly are seeing a growing use of atypical antipsychotics for the treatment of bipolar disorder during pregnancy frequently coadministered with medicines such as lamotrigine as opposed to lithium. The accumulated data to date on second-generation atypical antipsychotics are not definitive, but increasingly are reassuring in terms of absence of a clear signal for teratogenicity; hence, our comfort in using this class of medicines is only growing, which is important given the prevalence of use of these agents in reproductive-age women.

If there is a single critical guiding principle for the clinician when it comes to managing bipolar women during pregnancy and the postpartum period, it is sustaining euthymia. With the recent focus of the U.S. Preventive Services Task Force on prevention of postpartum depression, nothing is more helpful perhaps than keeping women with bipolar disorder well, both proximate to pregnancy and during an actual pregnancy. Keeping those patients well maximizes the likelihood that they will proceed across the peripartum and into the postpartum period with a level of emotional well-being that optimizes and maximizes positive long-term outcomes for both patients and families.
 

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 is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Careful management of bipolar disorder during pregnancy is critical because for so many patients with this illness, the road to emotional well-being has been a long one, requiring a combination of careful pharmacologic and nonpharmacologic strategies.

KatarzynaBialasiewicz/thinkstockphotos

Half of referrals to our Center for Women’s Mental Health – where we evaluate and treat women before, during, and after pregnancy – are for women who have histories of bipolar disorder. My colleagues and I are asked at continuing medical education programs what we “always do” and “never do” with respect to the treatment of these patients.
 

What about discontinuation of mood stabilizers during pregnancy and risk of relapse?

We never abruptly stop mood stabilizers if a patient has an unplanned pregnancy – a common scenario, with 50% of pregnancies across the country being unplanned across sociodemographic lines – save for sodium valproate, which is a clearly a documented teratogen; it increases risk for organ malformation and behavioral difficulties in exposed offspring. In our center, we typically view the use of sodium valproate in reproductive age women as contraindicated.

One may then question the circumstances under which lithium might be used during pregnancy, because many clinicians are faced with patients who have been exquisite responders to lithium. Such a patient may present with a history of mania, but there are obvious concerns given the historical literature, and even some more recent reports, that describe an increased risk of teratogenicity with fetal exposure to lithium.

Maintenance pharmacotherapy for women with bipolar disorder during pregnancy is so important, not only to decrease the risk of relapse following discontinuation of mood stabilizers, but because recurrence of illness during pregnancy for these patients is a very strong predictor of risk for postpartum depression. Women with bipolar disorder already are at a fivefold increased risk for postpartum depression, so discussion of sustaining euthymia during pregnancy for bipolar women is particularly timely given the focus nationally on treatment and prevention of postpartum depression.
 

In patients with history of mania, what about stopping treatment with lithium and other effective treatments during pregnancy?

Historically, we sometimes divided patients with bipolar disorder into those with “more severe recurrent disease” compared with those with more distant, circumscribed disease. In patients with more remote histories of mood dysregulation, we tended to discontinue treatment with mood stabilizers such as lithium or even newer second-generation atypical antipsychotics to see if patients could at least get through earlier stages of pregnancy before going back on anti-manic treatment.

Our experience now over several decades has revealed that this can be a risky clinical move. What we see is that even in patients with histories of mania years in the past (i.e., a circumscribed episode of mania during college in a woman now 35 years old with intervening sustained well-being), discontinuation of treatment that got patients well can lead to recurrence. Hence, we should not confuse an exquisite response to treatment with long periods of well-being as suggesting that the patient has a less severe form of bipolar disorder and hence the capacity to sustain that well-being when treatment is removed.
 

What about increasing/decreasing lithium dose during pregnancy and around time of delivery?

Select patients may be sensitive to changes in plasma levels of lithium, but the literature suggests that the clinical utility of arbitrarily sustaining plasma levels at the upper limit of the accepted range may be of only modest advantage, if any. With this as a backdrop and even while knowing that increased plasma volume of pregnancy is associated with a fall in plasma level of most medications, we do not arbitrarily increase the dose of lithium across pregnancy merely to sustain a level in the absence of a change in clinical symptoms. Indeed, to my knowledge, currently available data supporting a clear correlation of decline in plasma levels and frank change in symptoms during pregnancy are very sparse, if existent.

Earlier work had suggested that lithium dosage should be reduced proximate to delivery, a period characterized by rapid shifts in plasma volume during the acute peripartum period. Because physicians in our center do not alter lithium dose across pregnancy, we never reduce the dose of lithium proximate to delivery because of a theoretical concern for increased risk of either neonatal toxicity or maternal lithium toxicity, which is essentially nonexistent in terms of systematic reports in the literature.

Obvious concerns about lithium during pregnancy have focused on increased risk of teratogenesis, with the earliest reports supporting an increased risk of Epstein’s anomaly (0.05%-0.1%). More recent reports suggest an increased risk of cardiovascular malformations, which according to some investigators may be dose dependent.

For those patients who are exquisitely responsive to lithium, we typically leave them on the medicine and avail ourselves of current fetal echocardiographic evaluation at 16 weeks to 18 weeks to document the integrity of the fetal cardiac anatomy. Although the risk for cardiac malformations associated with lithium exposure during the first trimester is still exceedingly small, it is still extremely reassuring to patients to know that they are safely on the other side of a teratogenic window.
 

What about lamotrigine levels across pregnancy?

The last decade has seen a dramatic decrease in the administration of lithium to women with bipolar disorder, and growing use of both lamotrigine and second-generation atypical antipsychotics (frequently in combination) as an alternative. The changes in plasma level of lamotrigine across pregnancy are being increasingly well documented based on rigorous studies (Obstet Gynecol Clin North Am. 2018 Sep;45[3]:403-17).

These are welcome data, but the correlation between plasma concentration of lamotrigine and clinical response is a poor one. To date, there are sparse data to suggest that maintaining plasma levels of lithium or lamotrigine at a certain level during pregnancy changes clinical outcome. Following lamotrigine plasma levels during pregnancy seems more like an academic exercise than a procedure associated with particular clinical value.

As in the case of lithium, we never change lamotrigine doses proximate to pregnancy because of the absence of reports of neonatal toxicity associated with using lamotrigine during the peripartum period. The rationale for removing or minimizing the use of an effective medicine proximate to delivery, a period of risk for bipolar women, is lacking.

In 2019, we clearly are seeing a growing use of atypical antipsychotics for the treatment of bipolar disorder during pregnancy frequently coadministered with medicines such as lamotrigine as opposed to lithium. The accumulated data to date on second-generation atypical antipsychotics are not definitive, but increasingly are reassuring in terms of absence of a clear signal for teratogenicity; hence, our comfort in using this class of medicines is only growing, which is important given the prevalence of use of these agents in reproductive-age women.

If there is a single critical guiding principle for the clinician when it comes to managing bipolar women during pregnancy and the postpartum period, it is sustaining euthymia. With the recent focus of the U.S. Preventive Services Task Force on prevention of postpartum depression, nothing is more helpful perhaps than keeping women with bipolar disorder well, both proximate to pregnancy and during an actual pregnancy. Keeping those patients well maximizes the likelihood that they will proceed across the peripartum and into the postpartum period with a level of emotional well-being that optimizes and maximizes positive long-term outcomes for both patients and families.
 

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 is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

Careful management of bipolar disorder during pregnancy is critical because for so many patients with this illness, the road to emotional well-being has been a long one, requiring a combination of careful pharmacologic and nonpharmacologic strategies.

KatarzynaBialasiewicz/thinkstockphotos

Half of referrals to our Center for Women’s Mental Health – where we evaluate and treat women before, during, and after pregnancy – are for women who have histories of bipolar disorder. My colleagues and I are asked at continuing medical education programs what we “always do” and “never do” with respect to the treatment of these patients.
 

What about discontinuation of mood stabilizers during pregnancy and risk of relapse?

We never abruptly stop mood stabilizers if a patient has an unplanned pregnancy – a common scenario, with 50% of pregnancies across the country being unplanned across sociodemographic lines – save for sodium valproate, which is a clearly a documented teratogen; it increases risk for organ malformation and behavioral difficulties in exposed offspring. In our center, we typically view the use of sodium valproate in reproductive age women as contraindicated.

One may then question the circumstances under which lithium might be used during pregnancy, because many clinicians are faced with patients who have been exquisite responders to lithium. Such a patient may present with a history of mania, but there are obvious concerns given the historical literature, and even some more recent reports, that describe an increased risk of teratogenicity with fetal exposure to lithium.

Maintenance pharmacotherapy for women with bipolar disorder during pregnancy is so important, not only to decrease the risk of relapse following discontinuation of mood stabilizers, but because recurrence of illness during pregnancy for these patients is a very strong predictor of risk for postpartum depression. Women with bipolar disorder already are at a fivefold increased risk for postpartum depression, so discussion of sustaining euthymia during pregnancy for bipolar women is particularly timely given the focus nationally on treatment and prevention of postpartum depression.
 

In patients with history of mania, what about stopping treatment with lithium and other effective treatments during pregnancy?

Historically, we sometimes divided patients with bipolar disorder into those with “more severe recurrent disease” compared with those with more distant, circumscribed disease. In patients with more remote histories of mood dysregulation, we tended to discontinue treatment with mood stabilizers such as lithium or even newer second-generation atypical antipsychotics to see if patients could at least get through earlier stages of pregnancy before going back on anti-manic treatment.

Our experience now over several decades has revealed that this can be a risky clinical move. What we see is that even in patients with histories of mania years in the past (i.e., a circumscribed episode of mania during college in a woman now 35 years old with intervening sustained well-being), discontinuation of treatment that got patients well can lead to recurrence. Hence, we should not confuse an exquisite response to treatment with long periods of well-being as suggesting that the patient has a less severe form of bipolar disorder and hence the capacity to sustain that well-being when treatment is removed.
 

What about increasing/decreasing lithium dose during pregnancy and around time of delivery?

Select patients may be sensitive to changes in plasma levels of lithium, but the literature suggests that the clinical utility of arbitrarily sustaining plasma levels at the upper limit of the accepted range may be of only modest advantage, if any. With this as a backdrop and even while knowing that increased plasma volume of pregnancy is associated with a fall in plasma level of most medications, we do not arbitrarily increase the dose of lithium across pregnancy merely to sustain a level in the absence of a change in clinical symptoms. Indeed, to my knowledge, currently available data supporting a clear correlation of decline in plasma levels and frank change in symptoms during pregnancy are very sparse, if existent.

Earlier work had suggested that lithium dosage should be reduced proximate to delivery, a period characterized by rapid shifts in plasma volume during the acute peripartum period. Because physicians in our center do not alter lithium dose across pregnancy, we never reduce the dose of lithium proximate to delivery because of a theoretical concern for increased risk of either neonatal toxicity or maternal lithium toxicity, which is essentially nonexistent in terms of systematic reports in the literature.

Obvious concerns about lithium during pregnancy have focused on increased risk of teratogenesis, with the earliest reports supporting an increased risk of Epstein’s anomaly (0.05%-0.1%). More recent reports suggest an increased risk of cardiovascular malformations, which according to some investigators may be dose dependent.

For those patients who are exquisitely responsive to lithium, we typically leave them on the medicine and avail ourselves of current fetal echocardiographic evaluation at 16 weeks to 18 weeks to document the integrity of the fetal cardiac anatomy. Although the risk for cardiac malformations associated with lithium exposure during the first trimester is still exceedingly small, it is still extremely reassuring to patients to know that they are safely on the other side of a teratogenic window.
 

What about lamotrigine levels across pregnancy?

The last decade has seen a dramatic decrease in the administration of lithium to women with bipolar disorder, and growing use of both lamotrigine and second-generation atypical antipsychotics (frequently in combination) as an alternative. The changes in plasma level of lamotrigine across pregnancy are being increasingly well documented based on rigorous studies (Obstet Gynecol Clin North Am. 2018 Sep;45[3]:403-17).

These are welcome data, but the correlation between plasma concentration of lamotrigine and clinical response is a poor one. To date, there are sparse data to suggest that maintaining plasma levels of lithium or lamotrigine at a certain level during pregnancy changes clinical outcome. Following lamotrigine plasma levels during pregnancy seems more like an academic exercise than a procedure associated with particular clinical value.

As in the case of lithium, we never change lamotrigine doses proximate to pregnancy because of the absence of reports of neonatal toxicity associated with using lamotrigine during the peripartum period. The rationale for removing or minimizing the use of an effective medicine proximate to delivery, a period of risk for bipolar women, is lacking.

In 2019, we clearly are seeing a growing use of atypical antipsychotics for the treatment of bipolar disorder during pregnancy frequently coadministered with medicines such as lamotrigine as opposed to lithium. The accumulated data to date on second-generation atypical antipsychotics are not definitive, but increasingly are reassuring in terms of absence of a clear signal for teratogenicity; hence, our comfort in using this class of medicines is only growing, which is important given the prevalence of use of these agents in reproductive-age women.

If there is a single critical guiding principle for the clinician when it comes to managing bipolar women during pregnancy and the postpartum period, it is sustaining euthymia. With the recent focus of the U.S. Preventive Services Task Force on prevention of postpartum depression, nothing is more helpful perhaps than keeping women with bipolar disorder well, both proximate to pregnancy and during an actual pregnancy. Keeping those patients well maximizes the likelihood that they will proceed across the peripartum and into the postpartum period with a level of emotional well-being that optimizes and maximizes positive long-term outcomes for both patients and families.
 

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 is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].