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.
Dr. Lee S. Cohen
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 obnews@mdedge.com.