Lauren Osborne, MD.
Vice Chair of Clinical Research, Department of Obstetrics & Gynecology, Weill Cornell Medicine, New York, NY.
Dr. Osborne has no financial relationships with companies related to this material.
CHPR: Dr. Osborne, please tell us a little about yourself.
Dr. Osborne: I’m a reproductive psychiatrist. I conduct research on the biological mechanisms of mental illness in pregnancy and postpartum and on quality of care delivery for pregnant and postpartum patients. I am also the education chair of the Marcé Society of North America, a perinatal mental health research society. In that role, I’ve created a residency curriculum in reproductive psychiatry and have produced a textbook on this topic (Hutner LA et al. Textbook of Women’s Reproductive Mental Health. Washington, DC: American Psychiatric Association Publishing; 2022).
CHPR: We couldn’t have asked for a more perfect person for this interview! Can you start by describing the natural course of bipolar disorder (BD) over pregnancy?
Dr. Osborne: Sure. There doesn’t appear to be any increased risk for the development of symptoms of BD during pregnancy, but patients are at risk of relapsing if they stop medications, which many patients do when they find out they’re pregnant. If a patient discontinues mood stabilizers, they face about an 85% chance of relapse into a mood episode over a nine-month period, whether they’re pregnant or not (Viguera AC et al, Am J Psychiatry 2007;164(12):1817–1824).
CHPR: How do you educate patients about the pros and cons of taking medications during pregnancy?
Dr. Osborne: It’s a discussion about the risks of medication versus the risks of untreated illness. I review all the data with patients and help them come to a decision. Some patients choose to not take medication, even in cases where the risks of untreated illness are greater than the risks of medication, and of course it’s their body and their choice. Nonpharmacologic treatments can be helpful, like family support and psychotherapy, but anyone with a chronic illness like BD is at significant risk of relapsing if they stop their medications.
CHPR: What do you tell patients about the safety of lithium in pregnancy?
Dr. Osborne: I explain that, with lithium, there is a small risk of cardiac defects in exposed babies, but the risk is much smaller than we used to think, and I tell them that we’ll obtain a high-resolution fetal echocardiogram at around 20 weeks of gestation to check for heart defects. I’ll also point out that the risk of relapse into a mood episode is about 85%, and we must weigh that risk against the much smaller risk of cardiac defects. We’ll talk about what happens when they do become ill and review the risks that those mood symptoms might pose to their health and the health of the fetus. We have good data showing that untreated depression in pregnancy is associated with deficits in child development and increased risk of psychiatric disorders in the child—and of course with a risk for worsening of symptoms and even suicide in the parent.
CHPR: Do you dose lithium differently in pregnant patients?
Dr. Osborne: Yes, the dose of lithium in pregnancy is very different because there’s an increase in lithium excretion during pregnancy. You need higher doses in pregnancy and must then adjust the dose back down when they deliver. I get lithium levels at least monthly, then weekly as we get toward the end of pregnancy, and then right after delivery because there’s a huge fluid shift at that point. Then I get another lithium level about five days after delivery once I’ve put them back on their pre-pregnancy dose.
CHPR: What about valproic acid and carbamazepine in pregnancy?
Dr. Osborne: In cases of fetal exposure to valproic acid, we worry about neural tube defects, like spina bifida. Valproic acid is the one medication that I really try not to use in pregnancy and that, in fact, I don’t ever prescribe to patients of childbearing age if possible because it is associated with such a high risk of neural tube defects and IQ deficits. Carbamazepine also increases the risk of neural tube defects. Very occasionally I’ll encounter a patient for whom I must use one of those meds: for example, a patient whose illness is well controlled on valproic acid, who has already tried—and not responded to—multiple other mood stabilizers, and who has very severe life-threatening symptoms when they relapse. In those cases, I add high-dose folic acid supplementation to try to protect against neural tube defects. I usually recommend 4 mg of folic acid daily, which is about four times above the usual recommendation for prenatal vitamins.
CHPR: For patients who are already being treated for BD with valproic acid or carbamazepine, what medications do you switch to when they want to get pregnant?
Dr. Osborne: It’s a case-by-case question, depending on their history of other medication trials and the severity of their illness. I’m also going to hope they come see me well before pregnancy, so we have time for a proper trial of something else to ensure they are stable prior to attempting to conceive. I typically switch to lithium or lamotrigine. Lamotrigine has relatively few risks in pregnancy, fewer than lithium, but it’s a less powerful mood stabilizer and will not work for everyone. Something to keep in mind is that blood levels of lamotrigine drop considerably during pregnancy because the high estrogen levels in pregnancy speed up its metabolism. The therapeutic range for lamotrigine levels is very broad, and while we don’t typically dose by level outside of pregnancy, the levels can be very helpful in pregnancy. Ideally, I’ll get a lamotrigine level when the patient is stable and not pregnant, so I know that for this patient, whatever their dose is, this is the level that keeps them stable—their “reference concentration.” I check lamotrigine levels every month early in the pregnancy and then more frequently as they get into the third trimester, and I raise the dose relatively aggressively to keep the patient at their reference concentration. I derived this approach from the neurology literature and some great papers about the pharmacokinetics and pharmacodynamics associated with the drug, but there are no published clinical guidelines for how to manage lamotrigine across pregnancy when used for mood stabilization.
CHPR: Going back to what you said about valproic acid, some countries, like France and England, place restrictions on the prescription of valproic acid to patients of reproductive age, like the restrictions the FDA places on isotretinoin (Accutane) prescriptions.
Dr. Osborne: I think we should have those stricter guidelines here also. Valproic acid can be teratogenic early in a patient’s pregnancy before they might even know they’re pregnant. Patients of childbearing age should not be using it as a maintenance medication because many people will get pregnant. Nearly 50% of the pregnancies in this country are unplanned, and 80% of patients of childbearing age will have a pregnancy at some point (www.tinyurl.com/4rzah6kd). Particularly in somebody with an illness like BD, which can be associated with risky behavior, unintended pregnancies are relatively common. But I also think any guidelines we develop should apply whether the drug is used for a psychiatric or a neurologic reason; it doesn’t make sense to ban the drug for BD but allow it for epilepsy, as some countries have done.
CHPR: Do you ever prescribe hormonal contraceptives to your patients?
Dr. Osborne: All the time. I feel strongly that it should be in the psychiatrist’s mandate to prescribe hormonal contraception. We use medications that affect the health of the fetus, and agency over fertility is an important part of managing mental health. It’s often hard for patients to get appointments to see their gynecologists. If a patient tells me they want contraception and haven’t been able to obtain it, I will absolutely prescribe an oral contraceptive. There’s a great chart on the CDC’s website that covers the risk factors for different types of contraceptives so you can easily work out which ones will be right and safe for your patient (www.tinyurl.com/43v5fehu).
CHPR: When prescribing antipsychotic medications for a pregnant patient, which are your go-to drugs?
Dr. Osborne: Almost all antipsychotics are compatible with pregnancy. We have pretty good information now about whether there are connections with birth defects or with longer-term developmental effects in babies, and almost all the antipsychotics are low risk. When I choose antipsychotic medications, I look at what works for that patient, because the goal is to keep the patient well. We have a lot of information about first-generation antipsychotics, like haloperidol, and there’s a growing body of information about second-generation antipsychotics, like olanzapine, risperidone, and quetiapine (Editor’s note: For patients who want to contribute to research, see “Patient Registry for Second-Generation Antipsychotic Medications” box on page 4). I am hesitant about using clozapine during breastfeeding because of the agranulocytosis risk to the infant (though the data supporting this are weak), and I try to avoid newer medications because we don’t have the data built up about them. Aripiprazole can be problematic in the postpartum because it’s a partial dopamine agonist and may reduce the secretion of prolactin and impair a new mother’s ability to produce breast milk.
CHPR: What potential adverse effects do you watch for when infants are exposed to antipsychotics during pregnancy?
Dr. Osborne: There’s a theoretical risk of transient extrapyramidal symptoms in the child, and there can be a risk of gestational diabetes with some of the second-generation agents. Increased maternal blood sugars can lead to fetal macrosomia, meaning the baby is large for its gestational age.
CHPR: You mentioned you don’t feel comfortable prescribing clozapine to a pregnant patient, and yet it’s listed in the B category for the FDA’s use-in-pregnancy ratings.
Dr. Osborne: The old FDA categories were really misleading. People thought it was a graded system; they thought that A was good and X was bad, and that B was better than C. But often, category B medications just have fewer data, and as more data become available, a drug can get pushed to category C. So, it’s not true that a category B drug would be safer. But I’ve encountered many patients who were on a category C medication, like citalopram, and their doctor said “Oh, you’re going to get pregnant; I’m going to switch you to vortioxetine because it’s category B.” Well, it’s category B because it’s new; we don’t know anything about it.
CHPR: I myself encountered a patient who had been stable on olanzapine, which falls into category C in pregnancy, and her doctor switched her to clozapine because clozapine is listed as category B—even though there are far fewer data on clozapine than olanzapine in pregnancy!
Dr. Osborne: Right; I’m glad the FDA changed its use-in-pregnancy categories and now instead includes a detailed narrative for each medication. It’s a better system, but it’s very long and many doctors might not have time to read through it. And the A, B, C, D, and X categories still apply to medications that received FDA approval before 2001.
CHPR: How do you handle situations where the patient receives conflicting information from their OB/GYN or pediatrician compared to what you’re recommending?
Dr. Osborne: That’s tough and unfortunately very common. We don’t require obstetricians to learn much about mental health (or psychiatrists to learn anything about pregnancy), and pediatricians also may not be up to date on the literature. Remember that this is a team sport—I try to reach out to the other clinician and provide some education (even sending papers or citations) to try to get us on the same page. Very often the other clinician will be grateful for the education and glad to change their point of view, but sometimes even good evidence will not convince someone. In those cases, I try to give the patient as much of the evidence as possible to assure them that my answer is evidence-based and that I’m happy to review any evidence the other clinician wants to provide to support that position.
CHPR: Moving on to the postpartum, please describe the course of BD after delivery.
Dr. Osborne: There is an increased risk of mental health symptoms in the postpartum. A patient with BD is 23 times more likely to be hospitalized psychiatrically in the first month postpartum than at any other time point in her life (Munk-Olsen T et al, JAMA 2006;296:2582–2589). Patients with BD have an extremely high risk of postpartum psychosis.
CHPR: Do some patients experience postpartum psychosis, but no other symptoms of BD outside of the postpartum period?
Dr. Osborne: The research doesn’t have a clear answer yet. We used to think that if a patient presented with postpartum psychosis, they had BD. Most cases of postpartum psychosis, and many cases of postpartum depression, who present in the early postpartum period go on to be diagnosed with BD (Wisner KL et al, JAMA Psychiatry 2013;70(5):490–498). But a significant number of patients who present with mood episodes after childbirth do not experience symptoms outside of the postpartum. We don’t know the exact percentage—studies have shown somewhere around 20%–50%. There’s a lot of controversy about whether to categorize postpartum psychosis as part of the BD spectrum, given that some patients end up never having an episode outside of the postpartum.
CHPR: For a patient who’s had a previous postpartum psychotic episode but no other signs of BD outside of the postpartum period, do you start them on prophylactic medication if they have another pregnancy?
Dr. Osborne: Yes, I do. We know that patients with postpartum psychosis are unusually responsive to lithium. A study found that lithium led to complete remission in over 98% of the patients with postpartum psychosis (Bergink V et al, Am J Psychiatry 2015;172(2):115–123). So, if I have a patient with postpartum psychosis and no prior psychiatric history, I will usually treat them with lithium for nine months to a year after the episode of postpartum psychosis and then gradually taper down the medication. If the patient does not self-declare as having BD before the next pregnancy, I watch them very carefully during pregnancy and then start lithium prophylactically toward the end of pregnancy, around 32-36 weeks of gestation. Sometimes I’ll wait until after delivery, but that’s tricky because postpartum psychosis can present within days, and you want the lithium to be up to a steady-state level.
CHPR: Do you ever use ECT for pregnant or postpartum patients who experience BD relapses?
Dr. Osborne: Absolutely. There are good data for the use of ECT in pregnancy and the postpartum—and again, not that it’s completely benign, but usually the risks of ECT are outweighed by the risks of the illness. So, I do use it, but I’ll use it on a case-by-case basis. For example, in postpartum psychosis, I wouldn’t go first to ECT; instead, I’d give the patient lithium because they’re probably going to respond to lithium. But for somebody who hasn’t responded to medication, I would absolutely go to ECT.
CHPR: Thank you for your time, Dr. Osborne.
PO Box 626, Newburyport MA 01950