How post is postpartum? And how fast do you need to intervene?

Publication Date: 03/10/2025

Duration: 16 minutes, 31 seconds

KELLIE NEWSOME: Sorry, sertraline. We have a new first-line approach to postpartum depression. Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. 

CHRIS AIKEN: I’m Chris Aiken, the editor-in-chief of the Carlat Psychiatry Report. 

KELLIE NEWSOME: And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue. We began this series on timing treatment with an element that entered the universe in the first few minutes of the Big Bang. Lithium, and we’re going to end it with a different kind of beginning, childbirth. 

CHRIS AIKEN: Postpartum depression affects 1 in 8 new mothers, and early intervention is critical here, not just for the mother but for the infant and the family. The mother’s eyes are the first thing a baby can see at birth, followed later by her face. The baby’s vision is limited in those early days – everything is blurry, and about the only thing they can make out are two black dots about 8-12 inches away, in other words, the mother's eyes, and it’s through that interaction with their mother that development takes place, from attachment to cognition.

KELLIE NEWSOME: Postpartum depression takes a measurable toll on infant health, causing detriments or delays in language, learning, intelligence, self-control, and attachment. Anxiety, depression, ADHD, sleep, and eating problems are all linked to it. It makes intuitive sense that these problems are bigger the longer the depression goes on, but that’s not so easy to study. You can’t exactly randomize it, and chronic depressions tend to be more severe, which complicates the association.

CHRIS AIKEN: A few studies have compared children of mothers with similar severity of depression but different durations, and they confirm the idea that longer durations worsen the outcomes. 

KELLIE NEWSOME: Let’s pause for a preview of the CME quiz for this episode. Earn CME for each episode through the link in the show notes. 

1. Where does DSM-5 place the cut-off for postpartum (or peripartum) depression?

A. 2 weeks after delivery

B. 4 weeks after delivery

C. 8 weeks after delivery

D. 6 months after delivery

The typical treatment for postpartum depression is an antidepressant, usually sertraline because that one has the most favorable breastfeeding effects, and there’s nothing wrong with that approach, but with a small benefit – only 1 in 3 reach remission on it - and a slow onset of 4-6 weeks, there’s a good chance you’re going to shuffle through a few antidepressant trials and waste a lot of precious time if you go this route. Besides, postpartum depression is a risk factor for bipolar disorder, in which case antidepressants can make things worse.

CHRIS AIKEN: This is where zuranolone (Zurzuvae) has an advantage. Zuranolone is a synthetic version of allopregnanolone, a hormone that rises during pregnancy and takes a sharp fall after delivery. It was approved for postpartum depression in 2023, and it works quickly, within a few days. It’s part of a new crop of rapid-acting treatments that have gained FDA approval in recent years, including esketamine (Spravato) and bupropion-dextromethorphan combo (Auvelity), both of which speed up response in depression. The downside of many rapid-acting treatments is that they don’t have a clearly defined end date, and many of them are controlled substances where we worry about long-term effects like tolerance and misuse. 

KELLIE NEWSOME: Actually, the first rapid-acting treatment for depression was alprazolam (Xanax). In the late 1970s, the manufacturer tried to get this benzo approved for depression, and indeed there are over a dozen studies showing it treats depression with a fast onset, independent of its effects on anxiety, but, the FDA wasn’t having it. Probably, they were too concerned about the risks of this controlled substance, and the fact that long-term benzo use can worsen depression. In the end, they approved alprazolam for panic disorder, generalized anxiety disorder, and anxious symptoms during depression…which doesn’t exactly put much limit on its use.

CHRIS AIKEN: Zuranolone acts a lot like a benzo. It modulates the same receptor – GABA-A – and it has similar sedative, anxiolytic, and rewarding qualities as benzos, which is why it is classified as a controlled substance. But, the FDA limits its use to just two weeks, which means we don’t need to worry about long-term use, and we’re going to have to do something to keep depression from coming back after it works.

KELLIE NEWSOME: That may involve psychotherapy, family support, better sleep, and light exercise. A healthy diet – particularly lots of blueberries and fruits – has prevented postpartum depression in some trials, and so has an infant carrier. In a randomized controlled trial from 2023, simply giving low-income mothers an ergonomic infant carrier prevented postpartum depression. It may involve light therapy or an antidepressant, but hopefully, the mother will be in treatment so they can start that antidepressant early when the symptoms are mild if the depression comes back. 

CHRIS AIKEN: In many cultures, healing is a ritual that takes place in a sacred space and time under the direction of the shaman, and if this New Age banter has made you want to skip to the end of the podcast, hear me out, they did this because the format worked, and as we’ve developed more effective therapeutic ingredients we’ve lost that format. But, with zuranolone and brexanolone, the FDA has approved the first time-limited medication for depression, which gives us the opportunity to recreate the sacred time and place idea. That doesn’t mean your patient needs to chant while they take zuranolone, but we can borrow a bit from the traditional healing. Shamanic rituals are one-time events, and they come with instructions to maintain the healing after the ritual has ended. In practice, that means you need to lay out a pathway for prevention with the patient before zuranolone begins, and that may involve bringing the family in so everyone takes part in supporting her recovery and reducing the stress that brought about the episode. Zuranolone works faster than an SSRI, but does it work any better? Maybe. Its effect size is 0.5 (medium), compared to 0.3 (small) for SSRIs, but these aren’t head-to-head studies so we can’t say for sure. But, the IV version, brexanolone, has an ever larger effect size at 1.2, so that might be the route to go if the depression is severe (Kanes S et al, Lancet 2017, 390(10093):480-489). You can find a center that offers brexanolone at the manufacturer’s website, www.zulressorems.com, or by calling 1-844-472-4379. 

KELLIE NEWSOME: But a warning. A lot of times severe postpartum depression is a different illness altogether – it’s postpartum psychosis, a psychiatric emergency that happens at 1 in 1,000 births. The psychosis here usually involves paranoia about their family being out to get them in some way or delusions about the baby’s safety. These women are not likely to respond to zuranolone, and an antidepressant is not a good idea here either as most cases of postpartum psychosis have strong bipolar features. New treatment guidelines recommend lithium and antipsychotics for postpartum psychosis, and you can read more about those guidelines in the March issue of the Carlat Report. 

CHRIS AIKEN: Three other conditions that might rise up in the postpartum period are OCD, PTSD, and bipolar. Around 1 in 6 mothers develop postpartum OCD (Fairbrother N et al, J Clin Psychiatry 2021, 82(2):20m13398). But, this diagnosis is a little tricky because half of women with postpartum depression have obsessive thoughts, usually centered on the child’s health and safety.

KELLIE NEWSOME: Childbirth is often traumatic, particularly if there are medical complications or emergency C-sections is required. If we look at the matter subjectively, 1 in 3 women experience childbirth as a traumatic event, but theDSM only allows these to qualify as a trauma if the mother’s life – or the newborn’s life – was threatened. But, not all that is traumatic leads to PTSD. While, childbirth is traumatic for 30% of women, only 3-6% of women go on to have full PTSD from it.

CHRIS AIKEN: For a woman with bipolar disorder, the postpartum is the highest risk factor for new episode. Actually, it’s a ultrahigh risk period for men as well, with all of the changes in sleep and routines a new baby brings. But, here’s what you really need to know – If you see a woman with postpartum depression, the chance that she is having bipolar depression is 25-50%. The actual rate depends on the setting, but if you are in a psychiatric practice, it trends toward the higher, 50% side. Many women with bipolar disorder have their very first mood episode at this time, so past history is not a reliable guide here, but those who are younger, have a family history of bipolar, or who have mixed or psychotic features are more at risk. 

KELLIE NEWSOME: Psychosis is the more severe side of postpartum psychiatry, and on the milder side is the baby blues, a common brief syndrome of crying irritability, and insomnia that starts within 1-2 days after delivery and resolves within 10 days. Zuranolone is not appropriate here. Most cases don’t go on to postpartum depression, though the baby blues is a risk factor for this mood disorder. So, if the baby blues begins in the first few days after childbirth, when does postpartum depression begin? DSM sets the postpartum cut-off at 4 weeks after delivery, but for ICD-11 it’s 6 weeks, and other groups argue for 6-12 months. Actually, in 2013, DSM-5 changed the definition and the name, from postpartum to peripartum, so the new DSM specifier includes depression that begins during pregnancy or within the first 4 weeks postpartum. 

CHRIS AIKEN: I go with 8 weeks as the cut-off for postpartum depression, which is a little longer than DSM’s 4 weeks, and ICD’s 6 weeks, but it’s based on a more recent study from France where the cases spiked between 2-8 weeks. Afterthat, they started to plateau but still crept up for the full year after delivery.

KELLIE NEWSOME: The zuranolone trials followed the DSM approach, with a 4-week cut-off. They also enrolled whose depression began in the third trimester, although most of the subjects – 2/3 of them – had their onset in the first four weeks after delivery.  This doesn’t mean they gave zuranolone during pregnancy – it is NOT indicated then – but it does mean they gave it after childbirth to women whose depression began late in the course of pregnancy. Another limit: Zuranolone has not been tested during breastfeeding, and women have to stop breastfeeding for the two-week period. That’s a shame because breastfeeding is good for the health of the mother and the baby, and women can lose the ability to lactate if they stop. We recommend a lactation consultant to help here – pumping and disposing of mild while on zuranolone might keep it going.

CHRIS AIKEN: Fun fact. In 1992, Sven Dencker and colleagues in Sweden found naturally occurring benzodiazepines in human breast milk, to our knowledge, the finding has not been replicated, although similar reports exist in cow milk, and researchers have also found naturally occurring benzos very similar to lorazepam in the human brain. Exactly what purpose these low-level anxiolytics serve remains unknown. Rapid detection of bipolar disorder. Lithium for early-phase bipolar, clozapine within 3 years of antipsychotic resistance in schizophrenia, metformin at the first signs of significant weight gain on an antipsychotic, psychoeducation to reverse the phobia after a panic attack, zuranolone for quick relief for postpartum depression, and with that, we close the window on this podcast series, but we aren’t sealing it. These are just the windows of opportunity that we thought of, and we tried to highlight the ones that are underutilized in our field. Maybe you know some more? Write us as asktheeditor@thecarlatreport.com.

KELLIE NEWSOME: Want to keep up with the latest in psychiatric research? We post new studies in the Daily Psych feed – Search for ChrisAikenMD on LinkedIn, Twitter, Facebook, and that new one – BlueSky. It’s a first glimpse of the trials that inform this podcast. Thanks for tuning in and helping us stay free of industry support.