TCPR: The FDA is considering stricter warnings on antidepressants in pregnancy. Any thoughts on that?
Dr. Bhat: Yes. The FDA panel on antidepressants in pregnancy did not provide balance. They paid little attention to the risks of not treating psychiatric disorders during pregnancy. In practice, the question is not “Is this medication safe or not?” but “What is the risk of the medication vs leaving the psychiatric disorder untreated?” Depression both during and after pregnancy has negative effects on child development and behavior. There’s also the mother’s suffering, the risk of suicide, and instability in the family. 

TCPR: Is medication the only solution?
Dr. Bhat: No. Light therapy, aerobic exercise, and psychotherapy are also effective—but when they don’t work, or the symptoms are severe, antidepressants are often needed. Many women are already on an antidepressant, and stopping it during pregnancy raises the risk of relapse, approximately doubling the risk (Bayrampour H et al, J Clin Psychiatry 2020;81(4):19r13134).

TCPR: What are the risks with antidepressants in pregnancy?
Dr. Bhat: About 25% of babies exposed in utero to selective serotonin reuptake inhibitors (SSRIs) develop poor neonatal adaptation syndrome, which is a self-limited syndrome of abnormal tone, jitteriness, and irritability (Cornet MC et al, Arch Dis Child Fetal Neonatal Ed 2024;109(3)). More controversial is the risk of persistent pulmonary hypertension of the newborn with SSRIs, which may occur in less than 1% of exposed newborns, but some studies find no risk. On the other hand, commonly used antidepressants (SSRIs, serotonin/norepinephrine reuptake inhibitors [SNRIs], and bupropion) are not associated with an increased risk of congenital malformations or autism (Editor’s note: Early studies suggested an association with autism, but newer ones with better designs have refuted that association.) (Mezzacappa A et al, JAMA Pediatr 2017;171(6):555–563).

TCPR: Which antidepressant is safest in pregnancy?
Dr. Bhat: Sertraline is considered the safest, but the real goal in safety is to minimize the number of medication exposures, so I will usually go with an antidepressant the patient responded to in the past. 

TCPR: Are there any antidepressants you’d avoid in pregnancy altogether?
Dr. Bhat: Not really. The newer ones have fewer data (vortioxetine, vilazodone), so I wouldn’t start with those. Paroxetine has a warning about heart defects, but more recent studies do not indicate an increased risk of any congenital malformations with paroxetine, so I would not consider it absolutely contraindicated in pregnancy, especially if it is the only antidepressant someone responds to (Einarson A et al, Am J Psychiatry 2008;165(6):749–752). The rule of thumb is to prefer antidepressants with more available reproductive safety data, prioritizing those that patients have responded to in the past. Zuranolone (Zurzuvae) is a new option for postpartum depression, but it is not studied or indicated during pregnancy. Keep in mind that DSM-5 now uses “peripartum” to describe these disorders, which includes depression that begin during pregnancy or within four weeks of delivery (although the risk period continues up to about one year postpartum, so many experts use that cutoff).

TCPR: How does zuranolone work? 
Dr. Bhat: It is an analogue of allopregnanolone, a neurosteroid hormone that modulates the GABA-A receptor. Allopregnanolone levels rise during pregnancy and fall after delivery. That’s not to say that zuranolone is only useful for depressions that start after delivery—the studies included women whose depressions started in pregnancy (Oliveira JA et al, Rev Bras Ginecol Obstet 2024;46:e-rbgo79). But it may be particularly effective for women who are sensitive to hormonal fluctuations. These women often report that they had depression around puberty, or that their mood worsened before menses as in premenstrual dysphoric disorder. 

TCPR: How do you dose zuranolone?
Dr. Bhat: We start at the target dose (50 mg QHS), taken with a high-fat meal to improve absorption. It works quickly, within a few days. It is a Schedule IV controlled drug and is only indicated for a two-week course. The main risk is sedation and driving impairment, so we give it before bed. Zuranolone hasn’t been studied adequately in breastfeeding yet, and some women continue to pump (and discard the milk) while taking it, but that’s a personal decision that I discuss with patients. Waking up to pump is stressful for anyone, let alone someone struggling with postpartum depression!

TCPR: How do you prevent relapse after the two-week course?
Dr. Bhat: That’s a concern for a lot of patients, especially if they have recurrent depression or risk factors for relapse like chronic PTSD, anxiety, or major stress. The studies didn’t enroll a lot of women with recurrent depression, and they only followed participants for a month after the zuranolone was stopped. If I’m worried about relapse, I’ll start an antidepressant or psychotherapy, or both. Some psychiatrists start a second course of zuranolone if depression returns, but we have limited data on that approach. 

TCPR: What other peripartum disorders should we look out for?
Dr. Bhat: You can have bipolar disorder, psychosis, OCD, anxiety, PTSD, substance use disorder ... really any diagnosis. In most cases the rates are higher postpartum. During pregnancy, the rates are about the same as in the general population (although risk of relapse increase if medication is stopped abruptly).

TCPR: What about mood problems that start right after childbirth?
Dr. Bhat: That could indicate depression, but may be postpartum blues. That is a transient syndrome of tearfulness, irritability, and anxiety that peaks four to five days after delivery and resolves within two weeks. Medications are not used here—mainly reassurance, education, and close follow-up. Women with postpartum blues are twice as likely to develop full postpartum depression (Landman A et al, Eur Psychiatry 2024;67(1):e30). Mood problems that start right after childbirth could also indicate postpartum psychosis.

TCPR: Is postpartum psychosis a psychotic disorder or mood disorder?
Dr. Bhat: In many cases it is probably a bipolar spectrum disorder. Two-thirds of women who have psychosis in the postpartum period go on to have bipolar disorder (Bergink V et al, Am J Psychiatry 2016;173(12):1179–1188). It’s not actually listed as a separate diagnosis in DSM-5. Rather, it is a specifier for mood episodes—actually two specifiers: peripartum onset and psychotic features. There is a movement to recognize it as a diagnostic category in its own right.

“Stopping an antidepressant during pregnancy roughly doubles the risk of relapse.”

Amritha Bhat, MBBS, MD, MPH

TCPR: What is the advantage of recognizing it in a separate diagnosis?
Dr. Bhat: For one thing, it would support identification and treatment. Although postpartum psychosis is rare (1–2 in 1,000 births), it is a psychiatric emergency that often needs inpatient treatment (Toor R et al, Focus 2024;22(1):44–52). It comes on rapidly and carries a 4% risk of infanticide and a 5% risk of suicide. It does have clinical validity—with the clear biological trigger and temporal onset—and about a third of women who have postpartum psychosis do not go to have a recurrent mood disorder. There are also legal and forensic implications, as a distinct diagnosis could support psychiatric treatment rather than punishment in the rare cases of infanticide due to untreated postpartum psychosis.

TCPR: Are the symptoms different from psychotic mood disorders?
Dr. Bhat: One difference is that the psychotic symptoms wax and wane, and there are cognitive changes. Patients may have periods of lucidity and confusion, and depersonalization, derealization, and disorientation that can resemble delirium. We don’t tend to see that in bipolar disorder. That is the classic presentation, but it can also look like severe depression or mania with psychotic features. 

TCPR: What is the content of the psychotic symptoms? 
Dr. Bhat: The Massachusetts General Hospital Postpartum Psychosis Project released the largest study of that to date, involving 248 women with postpartum psychosis. Delusions were the most common symptom (88%), especially persecutory delusions (75%) and delusions of reference (56%). Half the women had visual hallucinations and half had auditory hallucinations (Cohen LS et al, Mol Psychiatry 2025;30(6):2537–2544). The focus of these delusions varies, but it often revolves around the newborn or paranoia toward their relatives. They might believe their child is possessed and hear voices telling them to kill the child. Or a woman who is depressed may hear voices telling her she is worthless and needs to die and take the child with her. 

TCPR: What are the risk factors?
Dr. Bhat: The main one is having a prior episode of postpartum psychosis. Around 75% will have a repeat episode in a subsequent pregnancy. Bipolar disorder and a family history of bipolar disorder are risks, as are high stress and complications around the pregnancy. 

TCPR: How do you treat postpartum psychosis?
Dr. Bhat: Lithium and antipsychotics such as olanzapine are first line. Either of those can treat postpartum psychosis (as monotherapy or combination), and both have pros and cons. With lithium, we worry about breastfeeding, as it passes into the breast milk, but lithium also has good evidence to prevent postpartum psychosis. Sleep is critical here, and we often use a benzodiazepine like lorazepam, which is the safest among them in breastfeeding (Jairaj C et al, Focus 2024;22(1):131–142). We also provide a lot of guidance on prioritizing sleep over breastfeeding. 

TCPR: What about antidepressants?
Dr. Bhat: We don’t recommend those in postpartum psychosis because of the risk of mania and psychosis. Some women are already on them. We handle that on a case-by-case basis, and may taper off or start a mood stabilizer. In postpartum psychosis, we generally treat depressive symptoms in the same way we would approach bipolar depression.

TCPR: What about mood stabilizers in pregnancy?
Dr. Bhat: Lamotrigine is most commonly used, especially for bipolar II, and it is likely the safest in pregnancy. Second-generation antipsychotics are also frequently used, with emerging data on reproductive safety. We avoid valproate (Depakote). It is absolutely contraindicated in pregnancy because of the risk of neural tube defects and neurodevelopmental delays (Viguera AC et al, J Clin Psychiatry 2021;82(4):20m13745; Andrade C et al, Acta Psychiatr Scand 2025;151(6):668–679).

TCPR: What about lithium?
Dr. Bhat: Lithium has a risk of congenital deficits—especially cardiac (Ebstein’s anomaly). The reported prevalence of any congenital malformations after lithium exposure ranges from 1% to 4%, but that needs to be weighed against the risk of severe postpartum episodes, which is very high for women with bipolar disorder or a history of postpartum psychosis. In the past there was a recommendation to taper off lithium just before the delivery, but we don’t do that anymore because it raises the risk of postpartum relapse. You do have to watch the levels though. Lithium levels tend to drop in the third trimester as the volume of distribution increases, and then they rise after delivery. We see the same fluctuations with lamotrigine, but lithium has a narrow therapeutic index, so there’s greater danger with toxic levels after delivery.

TCPR: Do you ever start lithium to prevent postpartum psychosis?
Dr. Bhat: Yes. Currently the recommendations are to start lithium right after delivery if the patient has had postpartum psychosis in the past, and continue it for at least a year postpartum for prevention. Some start it two to four weeks before delivery. The target level is on the high side (0.8–1.0 mmol/L) at first, and can be tapered to around 0.6 mmol/L after 3 months (Azorin JM et al, J Affect Disord 2012;136(3):710–715). You have to watch the levels after delivery because of the pharmacokinetics shift. Although recommendations are to check lithium levels one to two times a week in the first two weeks postpartum, this can be difficult with new parents! 

TCPR: How do you work with the family? 
Dr. Bhat: I always try to include the family through preconception, pregnancy, and postpartum. The more support they have, the better. They can support the patient with keeping appointments, treatment decisions, and safety planning. Another area where the family can help is with sleep. We’ll talk about what they can do to support sleep, like reducing noise and lights and taking care of the infant so the woman can get a solid 4–5 hours of uninterrupted sleep at night.

TCPR: What hypnotics are appropriate in the peripartum period?
Dr. Bhat: When necessary, I’d stick with one with a shorter half-life. Among benzodiazepines, the best support is for lorazepam (Ativan). But often the mother is waking up to care for the baby, so we’ll focus on behavioral steps to protect sleep and avoid hypnotics.

TCPR: Any other thoughts?
Dr. Bhat: This is a difficult time for pregnant women and new parents. Many are isolated, and don’t have the support or time for even basic self-care. So we don’t want to push unrealistic expectations. We do want to bring the family in to change that system. Treatment decisions in the perinatal period are very difficult. Patients often struggle to balance their mental health, the demands of parenting, and the safety of medications. There’s a lot of guilt around whether it will harm the baby, and there are long wait times to access psychotherapy. Connect women to support organizations like Postpartum Support International, or to other community-based supports like doulas and public health nurses. Pregnancy and postpartum is a time of increased interaction with the health care system. It’s a wonderful opportunity for collaboration between psychiatrics, obstetrics, primary care and pediatric clinicians, and community-based providers to support families through this important milestone of pregnancy, childbirth, and postpartum. 

TCPR: Thank you for your time, Dr. Bhat.