Round 3: To What Extent Does the Timing of Postpartum Depression (PPD) Influence Treatment Decisions?

In the final round of this debate, Nicole Cirino, MD, and Melanie Barrett, MD, provide their perspectives on the following question: To what extent does the timing of PPD influence treatment decisions? 

Nicole Cirino, MD: Hello, and welcome back to our final round in this Great Debate brought to you by Psych Congress Network; we'll end our discussion around this important topic by considering how the timing of onset of postpartum depression influences our treatment decisions in our particular practices. Since Dr Barrett and I have both been treating perinatal patients for many years. How many years roughly? Dr Barrett?

Melanie Barrett, MD: Oh goodness. Let's see. 2010 on.

Nicole Cirono: MD: I've got about 10 years on you. So, I thought what we could do is go together through each stage of the perinatal period and discuss how we approach our patients based on timing. So, I believe this will illustrate both our points that no matter how we clarify the timing of postpartum depression, timing does matter indeed in how we approach treatment. We will divide the periods into first trimester, second and third trimester, the first 8 weeks postpartum, and the first year postpartum. How does that sound?

Melanie Barrett, MD:  That’s great.

Nicole Cirino, MD: Okay, so let's start when someone comes into your office in the first trimester. What history would you want to elicit? What would you be thinking about and why?

Melanie Barrett, MD: So though, most antidepressant medications are not considered teratogenic. There are newer medications that have not been studied in pregnancy, and adjunctive medications that depressed women may be using that we would consider holding in the first trimester. So, things like benzodiazepines, stimulants, MAOIs, and some blood pressure medications like Prazosin and Clonidine.

Nicole Cirino, MD: Thank you. Absolutely. You're correct. And I see, as well, more hyperemesis gravidarum in the hospital setting, which makes me remember that we have to think about side effects during each of these phases, including the side effects of nausea, vomiting, decreased appetite in some of our antidepressants and our SSRIs. But the very important question, can women even keep these medications down? Okay, now let's move to the second and third trimester. I'll tell you some of the things that I think about here, and I want to hear your thoughts as well, Dr Barrett. I'll evaluate did she receive a new diagnosis of gestational diabetes per se, possibly a fetal anomaly. What about some workplace backlash from reporting the pregnancy? I'm thinking about the pharmacokinetic factors and how the pregnancy can affect the bioavailability of her medications. I'm thinking about if she has access to appropriate healthcare with a trusted provider as she nears delivery.

Are the normal physiologic changes in pregnancy that occur naturally, such as dyspnea or sleep architecture changes, those, actually impacting her mood and behavior? Are they worsening her comorbid psychiatric conditions like panic disorder? I'm thinking, will these resolve postpartum, and can they be treated with supportive interventions alone, or do we need to initiate a new treatment? You know that we consider the greatest predictor of postpartum depression to be active depression at the time of delivery. So, I'm also thinking in the second third trimester that I may be more aggressive in achieving euthymia prior to her delivery. I'll use a variety of modalities to do this because I do not want postpartum worsening during the most vulnerable time, which is at and after delivery in those first 8 weeks, as we talked about. Also, at this time, I'm beginning to spend some of my sessions talking about prevention strategies for postpartum depression. I was hoping maybe here, Dr Barrett, you could tell me about the conversation you have with patients, particularly about prevention strategies entering the postpartum period.

Melanie Barrett, MD: So, I really like to discuss sleep preservation, can't emphasize this enough, the importance of thinking about this and logistically what it's potentially going to look like after delivery. I talk about self-care. I find that it's helpful to bring the partner in if this is an option; we may discuss the change in sleep and may need to adjust or hold hypnotics. We discuss breastfeeding, shared feedings at night, connecting with the community.

Nicole Cirino, MD: Absolutely. I know most of us who have been in this field for a while do spend a good deal of time kind of talking about what they could expect in the postpartum period with the hormonal changes on their mood and behavior. So, are there any particular psychopharm considerations you have at this stage, second and third trimester?

Melanie Barrett, MD:  Yeah, I mean, I think we can't forget about the comorbid obstetric conditions. So, things like gestational diabetes, hypertension, and our need to monitor how our psychiatric treatments may be impacting those medical conditions.

Nicole Cirino, MD: Absolutely. Also, remind us it's a good time to reach out to the obstetrician and obstetric providers that are caring for the patient so we can coordinate if we need to.

Melanie Barrett, MD: Yeah, absolutely. Teamwork. Right.

Nicole Cirino, MD: Alright, so now let's move to the first 8 weeks postpartum, and how are we approaching the patient that presents to us in the first 8 weeks of the postpartum period? I'll tell you, these are the women I worry about the most, particularly if the onset or worsening occurs during this timeframe and they've never had depression before, and it's often new to them and can have a rapid onset. We do know that symptoms are more severe during this time period, and we also know that we need to be careful in recognizing differential diagnoses of other psychiatric conditions besides postpartum depression that are more severe in nature that can occur in the first 8 weeks postpartum, such as postpartum psychosis or perinatal OCD. They can also have abrupt onset as well. So, my evaluation during these first 8 weeks will be slightly different as I'm considering the differential diagnosis. What else do you consider in this first 8-week timeframe, Dr Barrett?

Melanie Barrett, MD:  Yeah, so I'm thinking about is the patient, one of the known females that is genetically predisposed to be vulnerable to depression during times of hormonal fluctuation. Did she have a traumatic birth? Was there a new onset in medical condition like postpartum hemorrhage, preeclampsia, thyroid dysfunction? Have there been breastfeeding difficulties? Is she perhaps taking lactogens that may influence her mood? Did her partner get any leave to help her with nighttime feedings, or is she significantly sleep-deprived?

Nicole Cirino, MD: Absolutely. Absolutely. Sleep is such an important topic, as we've mentioned several times that we're going to be discussing in each phase of the perinatal period. Alright, so let's go back a little bit to psychopharmacology in this period. So, what is the first and second line pharmacologic treatment for the women? First, assuming that they are planning on breastfeeding or are breastfeeding?

Melanie Barrett, MD: Yeah, so, SSRIs, SNRIs, I try to avoid sedating medications due to lactation and advise to avoid co-sleeping. If a patient is lactating, we'll often adjust our treatment plan for her, particularly if her infant is preterm or medically fragile. So those are important questions to be asking about. Acute insomnia associated with depression during late pregnancy I might treat and think about that differently than acute insomnia in the immediate postpartum period.

Nicole Cirino, MD: Absolutely. Thank you for going through that. I'm in agreement there as well. Okay. Now, let's move to the first year postpartum. We know that the peak incidence of postpartum depression is week 6 to 8, but what about the women who present to us between week 8 and one year postpartum? I find that these women have similar themes in my experience where I'm looking at psychosocial stressors like returning to work. I'm looking at the increase in social isolation after a lot of friends and family have left after the initial phase. I'm looking at low-grade depression or anxiety that has gradually worsened; perhaps the patient was unable to access care. I'm looking at if these initial mood and anxiety symptoms have led something further, like interpersonal conflict, domestic violence, new substance use or recurrence of substance use, underemployment, food insecurity, and then I'm paying attention to her breastfeeding status.

Is she still breastfeeding? Is she weaning? Because we do know after women weaned breastfeeding, another hormonal change occurs that can give it rise in depression. And then, I'm thinking about my intervention at this stage in terms of psychopharm or psychosocial interventions. Sometimes, when I see a woman who has just weaned breastfeeding, let's say she's 9 months postpartum, I may actually wait to initiate a change in my psychopharm or my medical treatment because, sometimes, these symptoms will self-resolve with psychoeducation and supportive treatment. So, I may change the cadence of my psychopharm interventions to women at this time. Can you tell us a little bit about other things we should be thinking about in the 8-week to one-year postpartum period?

Melanie Barrett, MD: Yeah, I agree that many of these women who had symptoms earlier on really just may not have had adequate access to treatments. Another thing that I think is important to be considering is has she chosen to start a new birth control method that might be influencing mood or behavior.

Nicole Cirino, MD: It also makes me think about the resuming of her sexual activity and how has her sexual function been changed in, influencing her depression and anxiety. Right?

Melanie Barrett, MD: Absolutely. Absolutely

Nicole Cirino, MD: Right. Okay. So then, let's move a little bit forward. I know you've had one of the large active programs for Brexanolone in your clinic for years, and I'm interested in how when we're thinking about which candidates you would choose specifically for your Brexanolone program.

Melanie Barrett, MD: So, clinically, if a patient is pregnant or in the first year postpartum, I'm assessing them for depression, and if not present, then I'm discussing warning signs, and I'm providing my patients with resources should the depression arise. So, in some instances, it's really not the timing of onset as much as the timing of the point of care that's going to impact treatment decisions. So, for example, like you said, Dr CIrino, I've been able to provide alongside my team because it does take a team, been able to provide Brexanolone for a number of patients with postpartum depression. It really does and has represented a breakthrough treatment for postpartum depression. It's not approved for use during pregnancy, though. So, if a patient of mine has onset of depression during the third trimester, and that is when I'm seeing them, I'm going to be considering other treatment modalities. But if the depression persists after delivery or if I'm seeing them for the first time after delivery, I'll be discussing the option of Brexanolone. In the Brexanolone phase 3 studies, patients had onset of depression during the third trimester or up to 4 weeks postpartum, but it also included patients who were up to 6 months postpartum at the time of screening. So, this really supports the idea that the timing of access to care and treatment considerations should not be narrowly defined.

Nicole Cirino, MD:  Right, absolutely. And now, with the new FDA approval of Zuranolone, we obviously don't have access to that yet and don't know yet, but how are you thinking about the use of Zuranolone, particularly as we talk about these stages and these timings?

Melanie Barrett, MD: Yeah, so I think one thing that it brings up, regardless of timing, is kind of our need to quickly get moms feeling back to themselves again as quickly as possible. So, I think that's one thing that these fast-acting treatments bring up. But also looking again at timing of onset and timing of point of care.

Nicole Cirino, MD: Absolutely. As well as breastfeeding.

Melanie Barrett, MD: And…

Nicole Cirino, MD: Lactation data, right?

Melanie Barrett, MD:  Yes. Yes. That is a consideration and an individual discussion that we'll have to have with our patients.

Nicole Cirino, MD: Right, particularly when we're not using SSRIs or SNRIs.

Melanie Barrett, MD: Yes.

Nicole Cirino, MD: Absolutely. Right. Okay, so that's such a great conversation. Thank you so much again, Dr Barrett, and thank you all for watching. This concludes round 3 of this debate. In the next and final installment, we'll provide our concluding statements on the topic that we've covered here and allow you to weigh in on where you fall after watching the conclusion of this debate.