User login
Lessons in perinatal psychiatry after 19 months of COVID-19*
For the last 25 years, my colleagues have spent midday on Wednesdays at clinical rounds as a group – a time spent reviewing cases in perinatal psychiatry and important new scientific findings in the literature that inform patient care. At the start of the pandemic, my colleague Marlene Freeman, MD, and I started Virtual Rounds at the Center for Women’s Mental Health to open our rounds to colleagues involved in multiple aspects of perinatal psychiatric care.
In my last column of 2021, I wanted to take the opportunity to reflect on some of what we have learned from 19 months of virtual rounding as a community of clinicians during the pandemic.
Telemedicine
Telemedicine allows us to see into the homes, relationships, and environments of our pregnant and postpartum women in a way we could never have imagined. It’s an opportunity to follow patients closely and intervene sooner rather than later, which might have been constrained by pre–COVID-19 typical scheduled office appointments. Telemedicine also gives us a clearer sense of some of the issues faced by underserved and marginalized populations of patients as we look to increase outreach to those groups.
COVID-19 vaccines in pregnancy
We now know much more about the potential for COVID-19 to cause complications during pregnancy than we did earlier in the pandemic. Although there may be a variety of factors fueling whether those in the general population decide to get vaccinated or not, there is no ambiguity in the message from our colleagues in obstetrics about the importance of vaccination for pregnant and postpartum women.
Bipolar disorder
Appropriate treatment for the spectrum of subtypes of bipolar disorder during pregnancy in the postpartum period is a frequent topic of discussion that colleagues raise. The pandemic has kindled clinical worsening for women with mood and anxiety disorders presumably driven by a host of factors ranging from shifts in medication adherence to sleep dysregulation to name just a few. Bipolar II disorder is underdiagnosed, yet there’s a growing appreciation of the morbidity associated with this subtype of bipolar disorder, which probably equals that of other groups on the bipolar spectrum such as those with bipolar I disorder.
Sustaining emotional well-being for bipolar women during pregnancy has never been more important than during the pandemic since psychiatric illness during pregnancy is the strongest predictor of risk for postpartum psychiatric disorder and the literature demonstrates that bipolar women are at particular risk for postpartum mood disorder. Historically, treatment of bipolar disorder during pregnancy was particularly problematic for clinicians and patients deciding about potential use of pharmacotherapy because options were finite; some treatments were known teratogens (valproate and to a far less extent lithium) and other newer treatments for bipolar disorder had sparse reproductive safety data (second-generation antipsychotics).
The message today is we have tools to safely treat bipolar disorder during pregnancy and the postpartum period not available 10 years ago. Lithium is likely underused and can be safely used during pregnancy; we have vast data on the effectiveness of lithium in bipolar disorder. Clinicians should also know that lamotrigine is safe to use for pregnant women with bipolar disorder and the data show no increased risk for major malformations associated with first trimester exposure. In the case of atypical antipsychotics, which increasingly are used in the treatment of bipolar disorder, the take-home message is our comfort level using these medicines during pregnancy is growing given more data supporting that atypical antipsychotics are not major teratogens.
We’ve also learned polytherapy is the rule, not the exception. As my colleague Adele Viguera, MD, recently referenced in Virtual Rounds: Polytherapy is a small price to pay when the other side is sustaining euthymia in bipolar disorder.
What we’ve learned about treating perinatal mood disorder is it takes a village of clinicians and resources to treat and mitigate risk for recurrence. Nothing is more important than either ensuring or recapturing maternal euthymia. The flip side is a recent report that maternal self-harm/suicide is the leading cause of death in the first year postpartum. It is a charge to the medical community at large to screen for maternal psychiatric illness and, more importantly, to refer patients and ensure they receive adequate care during the postpartum period.
Anxiety
Anxiety and insomnia have been prevalent during the pandemic. Pregnancy-associated and postpartum anxiety have been underappreciated in lieu of focusing on perinatal depression, and we lack consensus regarding the most appropriate treatment of perinatal anxiety. Nonpharmacologic interventions have been extremely helpful for women whose anxiety is mild to moderate or as an adjunct to pharmacologic intervention for patients with more severe anxiety disorders.
Robust data on untreated anxiety during pregnancy suggest it leads to adverse outcomes. The reproductive safety rules above for depression also apply for anxiety. Here, we find a multimodal approach, both nonpharmacologic and pharmacologic, optimizes treatment for that population.
Clinicians have asked about other medicines many women take to treat anxiety including gabapentin, hydroxyzine, and benzodiazepines. Because of concerns about dependence and about using benzodiazepines during pregnancy, hydroxyzine is frequently used despite sparse reproductive safety data. Data on the effectiveness of hydroxyzine is even smaller and tends to be incomplete for patients with more moderate to severe anxiety.
Our comfort level in our center is greater for using benzodiazepines in patients who are clearly not at risk for substance use disorder because particularly when used with selective serotonin reuptake inhibitors, we find it optimizes treatment, mitigates symptoms, and attenuates suffering.
Insomnia
For insomnia, cognitive behavioral therapy for insomnia (CBTI) has the most data for effectiveness. Pharmacologic interventions such as gabapentin and benzodiazepines are also frequently used as therapies for insomnia.
Concern about treating insomnia by perinatal psychiatrists comes from the knowledge that insomnia is so often comorbid with anxiety and depression. Psychiatrists must consider the possibility that complaints of insomnia are part of an underlying mood or anxiety disorder; it would be unfortunate to miss the underlying illness and only treat just symptoms of insomnia. That being said, circumscribed insomnia is not uncommon during pregnancy and needs to be managed accordingly.
Postpartum psychosis
It’s been noteworthy the extent to which rare cases of postpartum psychosis have been presented in our Virtual Round meetings during the pandemic. As discussed previously, postpartum psychosis is one of the most serious illnesses we treat in reproductive psychiatry.
The debate as to whether postpartum psychosis is a discrete circumscribed illness or an illness that recurs over time won’t be answered without better longitudinal data. What we can say is there is no role, particularly during the pandemic, for outpatient management of postpartum psychosis. The waxing and waning of psychotic symptoms, while reassuring when patients are compensated, are of great concern when patients are psychotic and not in a safe environment.
While there are no consensus guidelines for postpartum psychosis treatment, the data support use of agents such as lithium. Growing data exist on the use of atypical antipsychotics to ameliorate psychotic symptoms and get patients functioning as quickly as possible. Resolution of postpartum psychosis may take a considerable amount of time. During the pandemic, it is critical that appropriate resources be managed before patients leave the hospital, including support by family, open communication with community-based providers, and support groups.
Nineteen months into the pandemic, it seems we’ve learned much: how to leverage technology like telemedicine, and the upsides of folding in our multidisciplinary colleagues to reduce barriers around collaboration and learn from one another to provide the best care for our shared patients.
*This column was updated on Jan. 11. 2022.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at obnews@mdedge.com.
For the last 25 years, my colleagues have spent midday on Wednesdays at clinical rounds as a group – a time spent reviewing cases in perinatal psychiatry and important new scientific findings in the literature that inform patient care. At the start of the pandemic, my colleague Marlene Freeman, MD, and I started Virtual Rounds at the Center for Women’s Mental Health to open our rounds to colleagues involved in multiple aspects of perinatal psychiatric care.
In my last column of 2021, I wanted to take the opportunity to reflect on some of what we have learned from 19 months of virtual rounding as a community of clinicians during the pandemic.
Telemedicine
Telemedicine allows us to see into the homes, relationships, and environments of our pregnant and postpartum women in a way we could never have imagined. It’s an opportunity to follow patients closely and intervene sooner rather than later, which might have been constrained by pre–COVID-19 typical scheduled office appointments. Telemedicine also gives us a clearer sense of some of the issues faced by underserved and marginalized populations of patients as we look to increase outreach to those groups.
COVID-19 vaccines in pregnancy
We now know much more about the potential for COVID-19 to cause complications during pregnancy than we did earlier in the pandemic. Although there may be a variety of factors fueling whether those in the general population decide to get vaccinated or not, there is no ambiguity in the message from our colleagues in obstetrics about the importance of vaccination for pregnant and postpartum women.
Bipolar disorder
Appropriate treatment for the spectrum of subtypes of bipolar disorder during pregnancy in the postpartum period is a frequent topic of discussion that colleagues raise. The pandemic has kindled clinical worsening for women with mood and anxiety disorders presumably driven by a host of factors ranging from shifts in medication adherence to sleep dysregulation to name just a few. Bipolar II disorder is underdiagnosed, yet there’s a growing appreciation of the morbidity associated with this subtype of bipolar disorder, which probably equals that of other groups on the bipolar spectrum such as those with bipolar I disorder.
Sustaining emotional well-being for bipolar women during pregnancy has never been more important than during the pandemic since psychiatric illness during pregnancy is the strongest predictor of risk for postpartum psychiatric disorder and the literature demonstrates that bipolar women are at particular risk for postpartum mood disorder. Historically, treatment of bipolar disorder during pregnancy was particularly problematic for clinicians and patients deciding about potential use of pharmacotherapy because options were finite; some treatments were known teratogens (valproate and to a far less extent lithium) and other newer treatments for bipolar disorder had sparse reproductive safety data (second-generation antipsychotics).
The message today is we have tools to safely treat bipolar disorder during pregnancy and the postpartum period not available 10 years ago. Lithium is likely underused and can be safely used during pregnancy; we have vast data on the effectiveness of lithium in bipolar disorder. Clinicians should also know that lamotrigine is safe to use for pregnant women with bipolar disorder and the data show no increased risk for major malformations associated with first trimester exposure. In the case of atypical antipsychotics, which increasingly are used in the treatment of bipolar disorder, the take-home message is our comfort level using these medicines during pregnancy is growing given more data supporting that atypical antipsychotics are not major teratogens.
We’ve also learned polytherapy is the rule, not the exception. As my colleague Adele Viguera, MD, recently referenced in Virtual Rounds: Polytherapy is a small price to pay when the other side is sustaining euthymia in bipolar disorder.
What we’ve learned about treating perinatal mood disorder is it takes a village of clinicians and resources to treat and mitigate risk for recurrence. Nothing is more important than either ensuring or recapturing maternal euthymia. The flip side is a recent report that maternal self-harm/suicide is the leading cause of death in the first year postpartum. It is a charge to the medical community at large to screen for maternal psychiatric illness and, more importantly, to refer patients and ensure they receive adequate care during the postpartum period.
Anxiety
Anxiety and insomnia have been prevalent during the pandemic. Pregnancy-associated and postpartum anxiety have been underappreciated in lieu of focusing on perinatal depression, and we lack consensus regarding the most appropriate treatment of perinatal anxiety. Nonpharmacologic interventions have been extremely helpful for women whose anxiety is mild to moderate or as an adjunct to pharmacologic intervention for patients with more severe anxiety disorders.
Robust data on untreated anxiety during pregnancy suggest it leads to adverse outcomes. The reproductive safety rules above for depression also apply for anxiety. Here, we find a multimodal approach, both nonpharmacologic and pharmacologic, optimizes treatment for that population.
Clinicians have asked about other medicines many women take to treat anxiety including gabapentin, hydroxyzine, and benzodiazepines. Because of concerns about dependence and about using benzodiazepines during pregnancy, hydroxyzine is frequently used despite sparse reproductive safety data. Data on the effectiveness of hydroxyzine is even smaller and tends to be incomplete for patients with more moderate to severe anxiety.
Our comfort level in our center is greater for using benzodiazepines in patients who are clearly not at risk for substance use disorder because particularly when used with selective serotonin reuptake inhibitors, we find it optimizes treatment, mitigates symptoms, and attenuates suffering.
Insomnia
For insomnia, cognitive behavioral therapy for insomnia (CBTI) has the most data for effectiveness. Pharmacologic interventions such as gabapentin and benzodiazepines are also frequently used as therapies for insomnia.
Concern about treating insomnia by perinatal psychiatrists comes from the knowledge that insomnia is so often comorbid with anxiety and depression. Psychiatrists must consider the possibility that complaints of insomnia are part of an underlying mood or anxiety disorder; it would be unfortunate to miss the underlying illness and only treat just symptoms of insomnia. That being said, circumscribed insomnia is not uncommon during pregnancy and needs to be managed accordingly.
Postpartum psychosis
It’s been noteworthy the extent to which rare cases of postpartum psychosis have been presented in our Virtual Round meetings during the pandemic. As discussed previously, postpartum psychosis is one of the most serious illnesses we treat in reproductive psychiatry.
The debate as to whether postpartum psychosis is a discrete circumscribed illness or an illness that recurs over time won’t be answered without better longitudinal data. What we can say is there is no role, particularly during the pandemic, for outpatient management of postpartum psychosis. The waxing and waning of psychotic symptoms, while reassuring when patients are compensated, are of great concern when patients are psychotic and not in a safe environment.
While there are no consensus guidelines for postpartum psychosis treatment, the data support use of agents such as lithium. Growing data exist on the use of atypical antipsychotics to ameliorate psychotic symptoms and get patients functioning as quickly as possible. Resolution of postpartum psychosis may take a considerable amount of time. During the pandemic, it is critical that appropriate resources be managed before patients leave the hospital, including support by family, open communication with community-based providers, and support groups.
Nineteen months into the pandemic, it seems we’ve learned much: how to leverage technology like telemedicine, and the upsides of folding in our multidisciplinary colleagues to reduce barriers around collaboration and learn from one another to provide the best care for our shared patients.
*This column was updated on Jan. 11. 2022.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at obnews@mdedge.com.
For the last 25 years, my colleagues have spent midday on Wednesdays at clinical rounds as a group – a time spent reviewing cases in perinatal psychiatry and important new scientific findings in the literature that inform patient care. At the start of the pandemic, my colleague Marlene Freeman, MD, and I started Virtual Rounds at the Center for Women’s Mental Health to open our rounds to colleagues involved in multiple aspects of perinatal psychiatric care.
In my last column of 2021, I wanted to take the opportunity to reflect on some of what we have learned from 19 months of virtual rounding as a community of clinicians during the pandemic.
Telemedicine
Telemedicine allows us to see into the homes, relationships, and environments of our pregnant and postpartum women in a way we could never have imagined. It’s an opportunity to follow patients closely and intervene sooner rather than later, which might have been constrained by pre–COVID-19 typical scheduled office appointments. Telemedicine also gives us a clearer sense of some of the issues faced by underserved and marginalized populations of patients as we look to increase outreach to those groups.
COVID-19 vaccines in pregnancy
We now know much more about the potential for COVID-19 to cause complications during pregnancy than we did earlier in the pandemic. Although there may be a variety of factors fueling whether those in the general population decide to get vaccinated or not, there is no ambiguity in the message from our colleagues in obstetrics about the importance of vaccination for pregnant and postpartum women.
Bipolar disorder
Appropriate treatment for the spectrum of subtypes of bipolar disorder during pregnancy in the postpartum period is a frequent topic of discussion that colleagues raise. The pandemic has kindled clinical worsening for women with mood and anxiety disorders presumably driven by a host of factors ranging from shifts in medication adherence to sleep dysregulation to name just a few. Bipolar II disorder is underdiagnosed, yet there’s a growing appreciation of the morbidity associated with this subtype of bipolar disorder, which probably equals that of other groups on the bipolar spectrum such as those with bipolar I disorder.
Sustaining emotional well-being for bipolar women during pregnancy has never been more important than during the pandemic since psychiatric illness during pregnancy is the strongest predictor of risk for postpartum psychiatric disorder and the literature demonstrates that bipolar women are at particular risk for postpartum mood disorder. Historically, treatment of bipolar disorder during pregnancy was particularly problematic for clinicians and patients deciding about potential use of pharmacotherapy because options were finite; some treatments were known teratogens (valproate and to a far less extent lithium) and other newer treatments for bipolar disorder had sparse reproductive safety data (second-generation antipsychotics).
The message today is we have tools to safely treat bipolar disorder during pregnancy and the postpartum period not available 10 years ago. Lithium is likely underused and can be safely used during pregnancy; we have vast data on the effectiveness of lithium in bipolar disorder. Clinicians should also know that lamotrigine is safe to use for pregnant women with bipolar disorder and the data show no increased risk for major malformations associated with first trimester exposure. In the case of atypical antipsychotics, which increasingly are used in the treatment of bipolar disorder, the take-home message is our comfort level using these medicines during pregnancy is growing given more data supporting that atypical antipsychotics are not major teratogens.
We’ve also learned polytherapy is the rule, not the exception. As my colleague Adele Viguera, MD, recently referenced in Virtual Rounds: Polytherapy is a small price to pay when the other side is sustaining euthymia in bipolar disorder.
What we’ve learned about treating perinatal mood disorder is it takes a village of clinicians and resources to treat and mitigate risk for recurrence. Nothing is more important than either ensuring or recapturing maternal euthymia. The flip side is a recent report that maternal self-harm/suicide is the leading cause of death in the first year postpartum. It is a charge to the medical community at large to screen for maternal psychiatric illness and, more importantly, to refer patients and ensure they receive adequate care during the postpartum period.
Anxiety
Anxiety and insomnia have been prevalent during the pandemic. Pregnancy-associated and postpartum anxiety have been underappreciated in lieu of focusing on perinatal depression, and we lack consensus regarding the most appropriate treatment of perinatal anxiety. Nonpharmacologic interventions have been extremely helpful for women whose anxiety is mild to moderate or as an adjunct to pharmacologic intervention for patients with more severe anxiety disorders.
Robust data on untreated anxiety during pregnancy suggest it leads to adverse outcomes. The reproductive safety rules above for depression also apply for anxiety. Here, we find a multimodal approach, both nonpharmacologic and pharmacologic, optimizes treatment for that population.
Clinicians have asked about other medicines many women take to treat anxiety including gabapentin, hydroxyzine, and benzodiazepines. Because of concerns about dependence and about using benzodiazepines during pregnancy, hydroxyzine is frequently used despite sparse reproductive safety data. Data on the effectiveness of hydroxyzine is even smaller and tends to be incomplete for patients with more moderate to severe anxiety.
Our comfort level in our center is greater for using benzodiazepines in patients who are clearly not at risk for substance use disorder because particularly when used with selective serotonin reuptake inhibitors, we find it optimizes treatment, mitigates symptoms, and attenuates suffering.
Insomnia
For insomnia, cognitive behavioral therapy for insomnia (CBTI) has the most data for effectiveness. Pharmacologic interventions such as gabapentin and benzodiazepines are also frequently used as therapies for insomnia.
Concern about treating insomnia by perinatal psychiatrists comes from the knowledge that insomnia is so often comorbid with anxiety and depression. Psychiatrists must consider the possibility that complaints of insomnia are part of an underlying mood or anxiety disorder; it would be unfortunate to miss the underlying illness and only treat just symptoms of insomnia. That being said, circumscribed insomnia is not uncommon during pregnancy and needs to be managed accordingly.
Postpartum psychosis
It’s been noteworthy the extent to which rare cases of postpartum psychosis have been presented in our Virtual Round meetings during the pandemic. As discussed previously, postpartum psychosis is one of the most serious illnesses we treat in reproductive psychiatry.
The debate as to whether postpartum psychosis is a discrete circumscribed illness or an illness that recurs over time won’t be answered without better longitudinal data. What we can say is there is no role, particularly during the pandemic, for outpatient management of postpartum psychosis. The waxing and waning of psychotic symptoms, while reassuring when patients are compensated, are of great concern when patients are psychotic and not in a safe environment.
While there are no consensus guidelines for postpartum psychosis treatment, the data support use of agents such as lithium. Growing data exist on the use of atypical antipsychotics to ameliorate psychotic symptoms and get patients functioning as quickly as possible. Resolution of postpartum psychosis may take a considerable amount of time. During the pandemic, it is critical that appropriate resources be managed before patients leave the hospital, including support by family, open communication with community-based providers, and support groups.
Nineteen months into the pandemic, it seems we’ve learned much: how to leverage technology like telemedicine, and the upsides of folding in our multidisciplinary colleagues to reduce barriers around collaboration and learn from one another to provide the best care for our shared patients.
*This column was updated on Jan. 11. 2022.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at obnews@mdedge.com.
Weighing New Evidence on SSRI Use
Until fairly recently, studies and reviews of global teratovigilance data have been relatively reassuring that SSRIs were particularly safe, especially with regard to their teratogenicity. In fact, there are more reproductive safety data available for SSRIs than for many medicines women take during pregnancy. However, new reports have raised concerns regarding the teratogenicity of paroxetine, which we have previously discussed (INTERNAL MEDICINE NEWS, Nov. 15, 2005, p. 24), as well as risk for putative neonatal distress syndromes and, most recently, possible increased rates of persistent pulmonary hypertension of the newborn (PPHN) following late-pregnancy exposure to SSRIs.
What do the new reports describe and how do the findings inform clinical care? One study supports previous reports of a “neonatal abstinence syndrome” with characteristic symptoms of jitteriness, sleep disturbance, dysregulation, tachypnea, and myoclonus in infants whose mothers used antidepressants during pregnancy. In this prospective cohort study of 120 infants, examiners used a systematic scale to assess full-term SSRI-exposed newborns with respect to presence or absence of a wide range of previously reported symptoms.
Of the 60 infants exposed in utero to various SSRIs for a mean of 35.5 weeks, 8 had severe symptoms and 10 had mild symptoms, compared with none of the 60 infants who had not been exposed in utero to these drugs (Arch. Pediatr. Adolesc. Med. 2006;160:173–6). A particularly noteworthy finding is that no infant with symptoms required treatment intervention; symptoms were transient and of little if any clinical significance.
In the second study, investigators using a case-control design described an elevated risk for PPHN, a far more serious syndrome associated with severe respiratory failure, in newborns with in utero exposure to SSRIs late in pregnancy. In this study, which enrolled almost 400 women whose infants had PPHN, matching them to more than 800 control mothers and infants, the use of SSRIs at any point during pregnancy was not associated with PPHN, but there was a significant association between PPHN and in utero exposure to an SSRI after 20 weeks' gestation (N. Engl. J. Med. 2006;354:579–87).
The study describes a very disturbing and striking finding. But an accompanying editorial points out that the number of cases reported is small (N. Engl. J. Med. 2006;354:636–8). And though not mentioned in the editorial, the vulnerability to reporting bias in such a study is great. One wonders whether women without an adverse outcome may be reluctant to disclose use of an antidepressant during pregnancy, compared with those with an adverse outcome as serious as PPHN. Because the conclusions are based on a small number of PPHN cases, a difference of a small number of cases in either direction can strengthen or attenuate a positive finding.
The authors of the second study suggest that the incidence of PPHN associated with SSRI exposure in late pregnancy approaches 1%. But because hundreds of women have used SSRIs during late pregnancy, it is unlikely that such a dramatic clinical finding would not have been reported prior to this study—the first of such reports. These studies understandably alarmed women who are taking antidepressants. In fact, they were published just weeks after we reported the results of a prospective study of 201 women with a history of major depression who were prospectively followed during pregnancy. Women who discontinued their antidepressant medication proximate to conception were at a fivefold greater risk for depressive relapse during pregnancy, compared with those who continued with an antidepressant (JAMA 2006;295:499–507).
These data certainly suggest that pregnancy is not protective with respect to depression and that many women who stop antidepressants will relapse during pregnancy.
Although some women will still stop antidepressant therapy during pregnancy, patients should be informed that depression during pregnancy can increase the risk for other neonatal complications and can substantially increase their risk for postpartum depression. Other women will choose to continue antidepressant use during pregnancy, regardless of the findings of some of these more recent studies, given what some patients will view as a modest risk for the neonatal outcomes described.
Regardless of individual choices, which will be extremely variable, it is crucial to present all available information to reproductive-age women on antidepressants who plan to conceive or who are pregnant, so that collaborative decisions can be made based on these data and personal wishes. No decision is perfect or risk free. Interestingly, women provided with the same information may make very different decisions.
Until fairly recently, studies and reviews of global teratovigilance data have been relatively reassuring that SSRIs were particularly safe, especially with regard to their teratogenicity. In fact, there are more reproductive safety data available for SSRIs than for many medicines women take during pregnancy. However, new reports have raised concerns regarding the teratogenicity of paroxetine, which we have previously discussed (INTERNAL MEDICINE NEWS, Nov. 15, 2005, p. 24), as well as risk for putative neonatal distress syndromes and, most recently, possible increased rates of persistent pulmonary hypertension of the newborn (PPHN) following late-pregnancy exposure to SSRIs.
What do the new reports describe and how do the findings inform clinical care? One study supports previous reports of a “neonatal abstinence syndrome” with characteristic symptoms of jitteriness, sleep disturbance, dysregulation, tachypnea, and myoclonus in infants whose mothers used antidepressants during pregnancy. In this prospective cohort study of 120 infants, examiners used a systematic scale to assess full-term SSRI-exposed newborns with respect to presence or absence of a wide range of previously reported symptoms.
Of the 60 infants exposed in utero to various SSRIs for a mean of 35.5 weeks, 8 had severe symptoms and 10 had mild symptoms, compared with none of the 60 infants who had not been exposed in utero to these drugs (Arch. Pediatr. Adolesc. Med. 2006;160:173–6). A particularly noteworthy finding is that no infant with symptoms required treatment intervention; symptoms were transient and of little if any clinical significance.
In the second study, investigators using a case-control design described an elevated risk for PPHN, a far more serious syndrome associated with severe respiratory failure, in newborns with in utero exposure to SSRIs late in pregnancy. In this study, which enrolled almost 400 women whose infants had PPHN, matching them to more than 800 control mothers and infants, the use of SSRIs at any point during pregnancy was not associated with PPHN, but there was a significant association between PPHN and in utero exposure to an SSRI after 20 weeks' gestation (N. Engl. J. Med. 2006;354:579–87).
The study describes a very disturbing and striking finding. But an accompanying editorial points out that the number of cases reported is small (N. Engl. J. Med. 2006;354:636–8). And though not mentioned in the editorial, the vulnerability to reporting bias in such a study is great. One wonders whether women without an adverse outcome may be reluctant to disclose use of an antidepressant during pregnancy, compared with those with an adverse outcome as serious as PPHN. Because the conclusions are based on a small number of PPHN cases, a difference of a small number of cases in either direction can strengthen or attenuate a positive finding.
The authors of the second study suggest that the incidence of PPHN associated with SSRI exposure in late pregnancy approaches 1%. But because hundreds of women have used SSRIs during late pregnancy, it is unlikely that such a dramatic clinical finding would not have been reported prior to this study—the first of such reports. These studies understandably alarmed women who are taking antidepressants. In fact, they were published just weeks after we reported the results of a prospective study of 201 women with a history of major depression who were prospectively followed during pregnancy. Women who discontinued their antidepressant medication proximate to conception were at a fivefold greater risk for depressive relapse during pregnancy, compared with those who continued with an antidepressant (JAMA 2006;295:499–507).
These data certainly suggest that pregnancy is not protective with respect to depression and that many women who stop antidepressants will relapse during pregnancy.
Although some women will still stop antidepressant therapy during pregnancy, patients should be informed that depression during pregnancy can increase the risk for other neonatal complications and can substantially increase their risk for postpartum depression. Other women will choose to continue antidepressant use during pregnancy, regardless of the findings of some of these more recent studies, given what some patients will view as a modest risk for the neonatal outcomes described.
Regardless of individual choices, which will be extremely variable, it is crucial to present all available information to reproductive-age women on antidepressants who plan to conceive or who are pregnant, so that collaborative decisions can be made based on these data and personal wishes. No decision is perfect or risk free. Interestingly, women provided with the same information may make very different decisions.
Until fairly recently, studies and reviews of global teratovigilance data have been relatively reassuring that SSRIs were particularly safe, especially with regard to their teratogenicity. In fact, there are more reproductive safety data available for SSRIs than for many medicines women take during pregnancy. However, new reports have raised concerns regarding the teratogenicity of paroxetine, which we have previously discussed (INTERNAL MEDICINE NEWS, Nov. 15, 2005, p. 24), as well as risk for putative neonatal distress syndromes and, most recently, possible increased rates of persistent pulmonary hypertension of the newborn (PPHN) following late-pregnancy exposure to SSRIs.
What do the new reports describe and how do the findings inform clinical care? One study supports previous reports of a “neonatal abstinence syndrome” with characteristic symptoms of jitteriness, sleep disturbance, dysregulation, tachypnea, and myoclonus in infants whose mothers used antidepressants during pregnancy. In this prospective cohort study of 120 infants, examiners used a systematic scale to assess full-term SSRI-exposed newborns with respect to presence or absence of a wide range of previously reported symptoms.
Of the 60 infants exposed in utero to various SSRIs for a mean of 35.5 weeks, 8 had severe symptoms and 10 had mild symptoms, compared with none of the 60 infants who had not been exposed in utero to these drugs (Arch. Pediatr. Adolesc. Med. 2006;160:173–6). A particularly noteworthy finding is that no infant with symptoms required treatment intervention; symptoms were transient and of little if any clinical significance.
In the second study, investigators using a case-control design described an elevated risk for PPHN, a far more serious syndrome associated with severe respiratory failure, in newborns with in utero exposure to SSRIs late in pregnancy. In this study, which enrolled almost 400 women whose infants had PPHN, matching them to more than 800 control mothers and infants, the use of SSRIs at any point during pregnancy was not associated with PPHN, but there was a significant association between PPHN and in utero exposure to an SSRI after 20 weeks' gestation (N. Engl. J. Med. 2006;354:579–87).
The study describes a very disturbing and striking finding. But an accompanying editorial points out that the number of cases reported is small (N. Engl. J. Med. 2006;354:636–8). And though not mentioned in the editorial, the vulnerability to reporting bias in such a study is great. One wonders whether women without an adverse outcome may be reluctant to disclose use of an antidepressant during pregnancy, compared with those with an adverse outcome as serious as PPHN. Because the conclusions are based on a small number of PPHN cases, a difference of a small number of cases in either direction can strengthen or attenuate a positive finding.
The authors of the second study suggest that the incidence of PPHN associated with SSRI exposure in late pregnancy approaches 1%. But because hundreds of women have used SSRIs during late pregnancy, it is unlikely that such a dramatic clinical finding would not have been reported prior to this study—the first of such reports. These studies understandably alarmed women who are taking antidepressants. In fact, they were published just weeks after we reported the results of a prospective study of 201 women with a history of major depression who were prospectively followed during pregnancy. Women who discontinued their antidepressant medication proximate to conception were at a fivefold greater risk for depressive relapse during pregnancy, compared with those who continued with an antidepressant (JAMA 2006;295:499–507).
These data certainly suggest that pregnancy is not protective with respect to depression and that many women who stop antidepressants will relapse during pregnancy.
Although some women will still stop antidepressant therapy during pregnancy, patients should be informed that depression during pregnancy can increase the risk for other neonatal complications and can substantially increase their risk for postpartum depression. Other women will choose to continue antidepressant use during pregnancy, regardless of the findings of some of these more recent studies, given what some patients will view as a modest risk for the neonatal outcomes described.
Regardless of individual choices, which will be extremely variable, it is crucial to present all available information to reproductive-age women on antidepressants who plan to conceive or who are pregnant, so that collaborative decisions can be made based on these data and personal wishes. No decision is perfect or risk free. Interestingly, women provided with the same information may make very different decisions.
Weighing New Evidence on SSRI Use
Until fairly recently, studies and reviews of global teratovigilance data have been relatively reassuring that SSRIs were particularly safe, especially with regard to their teratogenicity. In fact, there are more reproductive safety data available for SSRIs than for many medicines women take during pregnancy. But new reports have raised concerns about the teratogenicity of paroxetine, which we have previously discussed (FAMILY PRACTICE NEWS, Nov. 1, 2005, p. 41), as well as risk for putative neonatal distress syndromes and, most recently, possible increased rates of persistent pulmonary hypertension of the newborn (PPHN) following late-pregnancy exposure to SSRIs.
What do the new reports describe and how do the findings inform clinical care? One study supports previous reports of a “neonatal abstinence syndrome” with characteristic symptoms of jitteriness, sleep disturbance, dysregulation, tachypnea, and myoclonus in infants whose mothers used antidepressants during pregnancy. In this prospective cohort study of 120 infants, examiners used a systematic scale to assess full-term SSRI-exposed newborns with respect to the presence or absence of a wide range of previously reported symptoms.
Of the 60 infants exposed in utero to various SSRIs for a mean of 35.5 weeks, 8 had severe symptoms and 10 had mild symptoms, compared with none of the 60 infants who had not been exposed in utero to these drugs (Arch. Pediatr. Adolesc. Med. 2006;160:173–6). A particularly noteworthy finding is that no infant with symptoms required treatment intervention; symptoms were transient and of little if any clinical significance.
In the second study, investigators using a case-control design described an elevated risk for PPHN, a far more serious syndrome associated with severe respiratory failure, in newborns with in utero exposure to SSRIs late in pregnancy. In this study, which enrolled almost 400 women whose infants had PPHN, matching them to more than 800 control mothers and infants, the use of SSRIs at any point during pregnancy was not associated with PPHN, but there was a significant association between PPHN and in utero exposure to an SSRI after 20 weeks' gestation (N. Engl. J. Med. 2006;354:579–87).
The study describes a very disturbing and striking finding. But an accompanying editorial points out that the number of cases reported is small (N. Engl. J. Med. 2006;354:636–8). And though not mentioned in the editorial, the vulnerability to reporting bias in such a study is great. One wonders whether women without an adverse outcome may be reluctant to disclose use of an antidepressant during pregnancy, compared with those with an adverse outcome as serious as PPHN. Because the conclusions are based on a small number of PPHN cases, a difference of a small number of cases in either direction can strengthen or attenuate a positive finding.
The authors of the second study suggest that the incidence of PPHN associated with SSRI exposure in late pregnancy approaches 1%. However, given the hundreds of women who have used SSRIs during late pregnancy, it is unlikely such a dramatic clinical finding would not have been reported, even anecdotally, before this study—the first of such reports.
These studies, which have had considerable media attention, have alarmed women who are taking antidepressants. In fact, they were published just weeks after we reported the results of a prospective study of 201 women with a history of major depression who were prospectively followed during pregnancy. Women who discontinued their antidepressant medication proximate to conception were at a fivefold greater risk for depressive relapse during pregnancy, compared with those who continued with an antidepressant (JAMA 2006;295:499–507). These data certainly suggest pregnancy is not protective with respect to depression and many women who stop antidepressants will relapse during pregnancy.
Although some women will still stop antidepressant therapy during pregnancy, patients should be informed that depression during pregnancy can increase the risk for other neonatal complications and substantially increase the risk for postpartum depression. Other women will choose to continue antidepressant use during pregnancy, regardless of the findings of these more recent studies, given what for some patients will be viewed as a modest risk for the neonatal outcomes described. Regardless of individual choices, which can vary greatly, it is crucial to present all available information to reproductive-age women on antidepressants who plan to conceive or who are pregnant, so collaborative decisions can be made based on the data and personal wishes. No decision is perfect or risk free. Women provided with the same information may make very different decisions.
Until fairly recently, studies and reviews of global teratovigilance data have been relatively reassuring that SSRIs were particularly safe, especially with regard to their teratogenicity. In fact, there are more reproductive safety data available for SSRIs than for many medicines women take during pregnancy. But new reports have raised concerns about the teratogenicity of paroxetine, which we have previously discussed (FAMILY PRACTICE NEWS, Nov. 1, 2005, p. 41), as well as risk for putative neonatal distress syndromes and, most recently, possible increased rates of persistent pulmonary hypertension of the newborn (PPHN) following late-pregnancy exposure to SSRIs.
What do the new reports describe and how do the findings inform clinical care? One study supports previous reports of a “neonatal abstinence syndrome” with characteristic symptoms of jitteriness, sleep disturbance, dysregulation, tachypnea, and myoclonus in infants whose mothers used antidepressants during pregnancy. In this prospective cohort study of 120 infants, examiners used a systematic scale to assess full-term SSRI-exposed newborns with respect to the presence or absence of a wide range of previously reported symptoms.
Of the 60 infants exposed in utero to various SSRIs for a mean of 35.5 weeks, 8 had severe symptoms and 10 had mild symptoms, compared with none of the 60 infants who had not been exposed in utero to these drugs (Arch. Pediatr. Adolesc. Med. 2006;160:173–6). A particularly noteworthy finding is that no infant with symptoms required treatment intervention; symptoms were transient and of little if any clinical significance.
In the second study, investigators using a case-control design described an elevated risk for PPHN, a far more serious syndrome associated with severe respiratory failure, in newborns with in utero exposure to SSRIs late in pregnancy. In this study, which enrolled almost 400 women whose infants had PPHN, matching them to more than 800 control mothers and infants, the use of SSRIs at any point during pregnancy was not associated with PPHN, but there was a significant association between PPHN and in utero exposure to an SSRI after 20 weeks' gestation (N. Engl. J. Med. 2006;354:579–87).
The study describes a very disturbing and striking finding. But an accompanying editorial points out that the number of cases reported is small (N. Engl. J. Med. 2006;354:636–8). And though not mentioned in the editorial, the vulnerability to reporting bias in such a study is great. One wonders whether women without an adverse outcome may be reluctant to disclose use of an antidepressant during pregnancy, compared with those with an adverse outcome as serious as PPHN. Because the conclusions are based on a small number of PPHN cases, a difference of a small number of cases in either direction can strengthen or attenuate a positive finding.
The authors of the second study suggest that the incidence of PPHN associated with SSRI exposure in late pregnancy approaches 1%. However, given the hundreds of women who have used SSRIs during late pregnancy, it is unlikely such a dramatic clinical finding would not have been reported, even anecdotally, before this study—the first of such reports.
These studies, which have had considerable media attention, have alarmed women who are taking antidepressants. In fact, they were published just weeks after we reported the results of a prospective study of 201 women with a history of major depression who were prospectively followed during pregnancy. Women who discontinued their antidepressant medication proximate to conception were at a fivefold greater risk for depressive relapse during pregnancy, compared with those who continued with an antidepressant (JAMA 2006;295:499–507). These data certainly suggest pregnancy is not protective with respect to depression and many women who stop antidepressants will relapse during pregnancy.
Although some women will still stop antidepressant therapy during pregnancy, patients should be informed that depression during pregnancy can increase the risk for other neonatal complications and substantially increase the risk for postpartum depression. Other women will choose to continue antidepressant use during pregnancy, regardless of the findings of these more recent studies, given what for some patients will be viewed as a modest risk for the neonatal outcomes described. Regardless of individual choices, which can vary greatly, it is crucial to present all available information to reproductive-age women on antidepressants who plan to conceive or who are pregnant, so collaborative decisions can be made based on the data and personal wishes. No decision is perfect or risk free. Women provided with the same information may make very different decisions.
Until fairly recently, studies and reviews of global teratovigilance data have been relatively reassuring that SSRIs were particularly safe, especially with regard to their teratogenicity. In fact, there are more reproductive safety data available for SSRIs than for many medicines women take during pregnancy. But new reports have raised concerns about the teratogenicity of paroxetine, which we have previously discussed (FAMILY PRACTICE NEWS, Nov. 1, 2005, p. 41), as well as risk for putative neonatal distress syndromes and, most recently, possible increased rates of persistent pulmonary hypertension of the newborn (PPHN) following late-pregnancy exposure to SSRIs.
What do the new reports describe and how do the findings inform clinical care? One study supports previous reports of a “neonatal abstinence syndrome” with characteristic symptoms of jitteriness, sleep disturbance, dysregulation, tachypnea, and myoclonus in infants whose mothers used antidepressants during pregnancy. In this prospective cohort study of 120 infants, examiners used a systematic scale to assess full-term SSRI-exposed newborns with respect to the presence or absence of a wide range of previously reported symptoms.
Of the 60 infants exposed in utero to various SSRIs for a mean of 35.5 weeks, 8 had severe symptoms and 10 had mild symptoms, compared with none of the 60 infants who had not been exposed in utero to these drugs (Arch. Pediatr. Adolesc. Med. 2006;160:173–6). A particularly noteworthy finding is that no infant with symptoms required treatment intervention; symptoms were transient and of little if any clinical significance.
In the second study, investigators using a case-control design described an elevated risk for PPHN, a far more serious syndrome associated with severe respiratory failure, in newborns with in utero exposure to SSRIs late in pregnancy. In this study, which enrolled almost 400 women whose infants had PPHN, matching them to more than 800 control mothers and infants, the use of SSRIs at any point during pregnancy was not associated with PPHN, but there was a significant association between PPHN and in utero exposure to an SSRI after 20 weeks' gestation (N. Engl. J. Med. 2006;354:579–87).
The study describes a very disturbing and striking finding. But an accompanying editorial points out that the number of cases reported is small (N. Engl. J. Med. 2006;354:636–8). And though not mentioned in the editorial, the vulnerability to reporting bias in such a study is great. One wonders whether women without an adverse outcome may be reluctant to disclose use of an antidepressant during pregnancy, compared with those with an adverse outcome as serious as PPHN. Because the conclusions are based on a small number of PPHN cases, a difference of a small number of cases in either direction can strengthen or attenuate a positive finding.
The authors of the second study suggest that the incidence of PPHN associated with SSRI exposure in late pregnancy approaches 1%. However, given the hundreds of women who have used SSRIs during late pregnancy, it is unlikely such a dramatic clinical finding would not have been reported, even anecdotally, before this study—the first of such reports.
These studies, which have had considerable media attention, have alarmed women who are taking antidepressants. In fact, they were published just weeks after we reported the results of a prospective study of 201 women with a history of major depression who were prospectively followed during pregnancy. Women who discontinued their antidepressant medication proximate to conception were at a fivefold greater risk for depressive relapse during pregnancy, compared with those who continued with an antidepressant (JAMA 2006;295:499–507). These data certainly suggest pregnancy is not protective with respect to depression and many women who stop antidepressants will relapse during pregnancy.
Although some women will still stop antidepressant therapy during pregnancy, patients should be informed that depression during pregnancy can increase the risk for other neonatal complications and substantially increase the risk for postpartum depression. Other women will choose to continue antidepressant use during pregnancy, regardless of the findings of these more recent studies, given what for some patients will be viewed as a modest risk for the neonatal outcomes described. Regardless of individual choices, which can vary greatly, it is crucial to present all available information to reproductive-age women on antidepressants who plan to conceive or who are pregnant, so collaborative decisions can be made based on the data and personal wishes. No decision is perfect or risk free. Women provided with the same information may make very different decisions.