Q&A: Treatment choice for postpartum depression is a ‘complex decision’

Key takeaways:

• Postpartum depression is the most common childbirth complication in the U.S.
• More providers and women are becoming more aware of postpartum depression symptoms and treatment options.

More women and providers in both psychiatry and obstetrics and gynecology are becoming aware of the high prevalence of postpartum depression and treatments available, including recently approved zuranolone.

“Postpartum depression is the most common complication of childbirth with about 10% to 15% of women from the general population experiencing postpartum depression,” Jennifer L. Payne, MD, professor and vice chair of research in the department of psychiatry and neurobehavioral sciences at the University of Virginia, told Healio. “It is really very common. It’s more common than gestational diabetes.”

Healio spoke with Payne about postpartum depression awareness, treatment strategies and use of zuranolone (Zurzuvae; Sage Therapeutics and Biogen), a faster-acting medication approval in August 2023.

Healio: Is there more awareness of postpartum depression today?

Payne: There is more awareness, and this is due to a number of reasons. One is that there’s a growing awareness of psychiatric illness, treatment and need for treatment in general. Secondly, the CDC published data about 2 years ago now showing that there’s a rapid increase in maternal mortality in the U.S., and that maternal mortality in the U.S. is far greater than other developed countries, and the leading cause of maternal mortality is psychiatric in nature. The leading causes are overdose and suicide, and so there’s an increased awareness of postpartum depression and the need to screen for it and treat it.

Healio: How has postpartum depression been treated?
In general, postpartum depression has been treated with standard antidepressant treatments with the selective serotonin reuptake inhibitors like Prozac (fluoxetine, Eli Lilly) or Zoloft (sertraline, Viatris), those are name brands being used preferentially. But, for example, if a woman had a previous history of major depression and responded to a previous trial of a particular antidepressant, we would go back to that antidepressant. The FDA also approved brexanolone (Zulresso, Sage Therapeutics) for the treatment of postpartum depression in 2019, which is an intravenous version of or very similar to zuranolone. Both zuranolone and brexanolone are positive allosteric modulators of the gamma-aminobutyric acid (GABA) type A receptor. The GABAergic system is an inhibitory neurotransmitter system in the brain that calms the brain down and calms what we call the hypothalamic-pituitary-adrenal axis, so it calms down stress and reactions to stress in the brain. Both of these drugs act on the GABAergic system to increase inhibitory activity in the brain.

Healio: Zuranolone was approved for treating postpartum depression last year. Are many prescribers aware of zuranolone and prescribing it?

Payne: Certainly, in my world, everybody’s aware of it. All reproductive psychiatrists are aware of it. If they’re not, they shouldn’t call themselves reproductive psychiatrists. I think the population that’s not as aware are the OB/GYNs. But there’s starting to be growing awareness in the OB/GYN community, and certainly, those of us in reproductive psychiatry have started prescribing zuranolone.

Deciding to use zuranolone is a complex decision because it’s still very early. With insurance companies, we’re getting mixed responses in terms of whether they cover it or not. We also use a patient’s prior history, treatment response and whether they’re already on a medication or not to determine if we’re going to prescribe it. So, I would hesitate to give you statistics in this area, I will say that we are starting to use it and I think the use of zuranolone will grow in the coming years.

My research is really starting to develop a test that is predictive with 80% accuracy of who is at risk for postpartum depression. We might see medications like this used for women who have yet to develop postpartum depression but have a very high likelihood of developing postpartum depression. What I’m hoping is that we’ll be able to prevent postpartum depression onset and perhaps use zuranolone to help prevent onset in women who are at high risk. That would be a huge step forward if we don’t have to let women suffer this complication.

Healio: What kind of questions do patients have about this drug? Are patients themselves aware of postpartum depression and its treatments?

Payne: Women certainly have all the standard questions that patients do when you say, “I really think you need a medication for your psychiatric symptoms.” They want to know how quickly they’ll feel better. They want to know how long they have to stay on the medication. With this particular medication, a lot of women are wondering if they need to be on a standard antidepressant afterward. They want to know if they can breastfeed and what the side effects are.

People are becoming more aware of postpartum depression and sensitive to the fact that they need to get treatment. However, there are other types of postpartum psychiatric illness that most people don’t know about; for example, one very common thing that can happen is that obsessive compulsive disorder can either start or flare in the postpartum period. That is a big surprise to a lot of women, even women with a prior psychiatric history. For the women that I’ve been seeing, the biggest surprises are other types of psychiatric illness. But postpartum depression, luckily, is being talked about enough that at least the women I’m seeing are much more aware of it.

Healio: Whom would you avoid prescribing zuranolone to?

Payne: We are not necessarily prescribing zuranolone for women with preexistent major depression or women with preexisting bipolar disorder. We have not studied zuranolone in bipolar depression, for example, so we are not prescribing it for women with bipolar disorder.

Women with preexisting major depression often have a history of either responding to a particular medication that they went off of — say, for pregnancy, they’re on a low dose of it — or they have a complicated history of medication trials. We’re a little less likely to prescribe zuranolone in those cases simply because we know that they’re going to need to be on a long-standing antidepressant regimen. That’s not to say that zuranolone wouldn’t necessarily be helpful, but if a woman is going to need to be on an antidepressant for the foreseeable future, we’re often more likely to start with that medication.

Healio: How can clinicians initiate conversations with their patients about postpartum depression?

Payne: This conversation needs to start at least during pregnancy, if not prior to pregnancy. Physicians taking care of women who are contemplating pregnancy should talk to them about their psychiatric history — if they’re taking psychiatric meds, what their plans are and whether the medications they’re taking should and could be used during pregnancy and lactation. Then that starts the whole conversation of an increased risk of depression during the postpartum period.

We should be looking for postpartum depression because it’s incredibly important to treat it. When prolonged, postpartum depression has significant effects on the child’s development. When women are depressed postpartum, they don’t interact with their children the way that they would normally, so they don’t talk to them as much and they don’t play with them as much. That can have significant effects on a child’s IQ, language development and, later, behavioral and psychological development. So, the conversation starts preferably prior to pregnancy, but certainly in pregnancy about what the symptoms are, what we’re looking for and why treatment is important.

Healio: Is there anything you’d like to add?

Payne: The one other thing is that probably one of the biggest factors in the development of postpartum depression in women with a preexisting mood or anxiety disorder is stopping medications for pregnancy. We know that when women stop antidepressants for pregnancy, 70% of them will relapse either during pregnancy or during the postpartum period. There are negative repercussions from being depressed during pregnancy and postpartum that affect not only the mother, but the developing child. It’s important to talk to women about continuing psychiatric medications during pregnancy. There are a couple that should not be continued during pregnancy, but most psychiatric medications should be continued during pregnancy to promote the health of the mother as well as the child.