Podcast Summary: Dr. Chapa’s Clinical Pearls

Episode: “New” CPU on Zuranolone? “NOTHING”

Date: October 11, 2025
Host: Dr. Chapa

Episode Overview

This episode critically reviews the new Clinical Practice Update (CPU) from ACOG ("Zuranolone and Brexanolone for the treatment of postpartum depression," released October 9, 2025). Dr. Chapa humorously and candidly explains that, contrary to expectations of groundbreaking changes or insights, the new CPU contains essentially "nothing new"—a point made repeatedly through Seinfeld references. The episode contextualizes the update, reviews key clinical concerns around Zuranolone (brand name: Zurzuve), and highlights ongoing questions about treatment and practical application for postpartum depression.

Key Discussion Points & Insights

1. The Theme of "Nothing New" (00:36, 02:56, 13:03, 23:05)

• Repeated parallels are drawn with Seinfeld's "show about nothing," humorously emphasizing that the new CPU offers minimal new guidance or data.

  "I can sum up the show for you with one word: Nothing."
  — [00:42, 05:13, 23:05]

2. Background on the Clinical Practice Update

• The new CPU replaces the August 2023 advisory on Zuranolone, which responded to its FDA approval as the first US medication for postpartum depression. The main difference: a formal removal of the now-defunct Brexanolone (IV form).

  "This new clinical practice update does update and remove a couple of things...it's pretty much a cut and paste deal."
  — [05:18]

Key Difference

• Brexanolone Withdrawal:
  • Brexanolone pulled from US and UK markets (too costly and impractical at $30k, requiring 60-hour IV).
  • CPU simply reaffirms it's unavailable, and notes Zuranolone is the (oral) alternative.

  "Brexanolone, which was the IV version of zuranolone... no longer available. Not available in the US and not available in the UK. I mean, it's just it's dead and buried."
  — [13:46]

3. Clinical Realities and Questions About Zuranolone

a) Cost & Accessibility (03:01, 04:05, 13:15)

• Zuranolone (Zurzuve): Less than Brexanolone, but still ~$16,000 per course (manufacturer offers patient programs for cost reduction).
• Financial burden remains high, limiting widespread use.

b) Limitations & Safety

• Major CNS depressant effects: somnolence, confusion, “feeling a little wiggy.”
  • Complex safety instructions:

    "Nobody needs to drive after they take this medication...for 12 hours after each dose, they shouldn't drive...or do anything that potentially could put them at risk, quote, including feeding, changing or bathing the child, end quote."
    — [16:24]

• Contraception required during and one week after therapy.
• Breastfeeding: Must pump and discard for one week after finishing; limited data on safety.

c) Gaps in Evidence (06:15, 18:16, 20:28)

• Studies follow outcomes for only up to 4 weeks post-dose:

  "The data followed patients to a max of four weeks. So like, hey, how are you doing four weeks after your last tablet? You good? You're good. Success. And I'm not minimizing. That's fantastic...But what about two months later or three months later?...We just don't know."
  — [06:15]

• No guidance or FDA approval for what to do if symptoms recur—retreatment is unstudied and “off label.”
• Not compared against standard therapies (SSRIs, CBT, EMDR).

d) Practical Use and Recommendations

• Zuranolone can be used as primary or adjunct therapy for postpartum depression within 12 months of delivery; best considered for moderate-to-severe cases.

  "This is not for...postpartum blues. This is the shotgun approach... if a patient has severe limitation from postpartum depression, then I'm all for it—with those limitations that we've already discussed."
  — [20:28]

• Must be taken in the evening with a fatty meal—adds to practical complexity.

4. Seinfeld/Pop Culture References & Tone

• Continual callbacks to Seinfeld’s “about nothing” reinforce both the content’s lack of newness and Dr. Chapa's light-hearted, irreverent approach.
• Repeated jabs at the sameness of the update, with several “I have no beef with anyone” disclaimers.

  "I'm not against Zuranolone, guys. I'm just saying, again, it's very tricky here because it's a tough medication."
  — [16:51]

• Parallels drawn between “Addyi” in female sexual dysfunction (passed due to demand, not strength of data) and Zuranolone’s FDA approval.

  "What Addi is for sexual function is what Zuranolone kind of is for postpartum depression long term. Because we don't have that data short term. Yes... But is that our goal? ...We probably need more information."
  — [21:07]

Notable Quotes & Moments

• Cost context & practical barrier:

  "It's still like 16 grand. You heard right, 16 grand, that's three zeros."
  — [03:01]

• Brexanolone's fate:

  "Not available in the US and not available in the UK. I mean, it's just it's dead and buried. They're like, forget about. Nobody's using that because they had so much pushback. Because it was like 30 grand."
  — [13:46]

• Safety instructions:

  "For at least 12 hours after each dose, patients should avoid driving, operating heavy machinery, engaging in potentially dangerous activities, and importantly, caring for their infant alone, including feeding, changing, or bathing. End quote."
  — [17:58]

• Repeating the central "nothing" motif:

  "I think I can sum up the show for you with one word. Nothing."
  — [23:05]

Key Timestamps

| Timestamp | Segment / Content | |-----------|--------------------------------------------------------------| | 00:36 | Introduction to “nothing“ motif; setup with Seinfeld | | 02:56 | First detailed take on the CPU’s lack of novelty | | 05:13 | Explains the “cut and paste” nature of the updated guidance | | 06:15 | Questions about Zuranolone’s efficacy and follow-up limits | | 13:03 | Again, repeats “nothing new” in the CPU | | 13:46 | Explains Brexanolone’s market withdrawal | | 16:24 | Full safety caveats for Zuranolone | | 17:58 | Direct quote from the manufacturer on safety limitations | | 20:28 | Dr. Chapa’s concluding clinical position/applied context | | 23:05 | Final comedic repetition of “nothing” |

Summary Table

| Drug | Status (US) | Cost | Mode | Key Issues | |-----------------|------------------------|-------------|---------|----------------------------------------------| | Brexanolone | Withdrawn (2025) | ~$30,000 | IV | 60-hr infusion, impractical | | Zuranolone | Available; first oral | ~$16,000 | Oral | Sedation, limited follow-up, costly, safety |

Takeaway

The new ACOG Clinical Practice Update on Zuranolone and Brexanolone for postpartum depression primarily exists to officially retract Brexanolone, which is no longer available. Otherwise, it repeats previous guidance with no substantive updates. Zuranolone remains an option for moderate-to-severe postpartum depression but with major limitations: high cost, significant safety restrictions, limited supporting data for long-term use, and a lack of comparison to standard therapies. Clinicians should be cautious, fully inform patients, and watch for more comprehensive options in the future.

"If we think we got the holy grail here for the medication on postpartum depression, it's probably not it. Plus, a big question that remains is what do you do if a patient...starts feeling depressed again?"
— [19:44]

This episode reaffirms Dr. Chapa’s central tenet: “No Spin”—just clinical pearls, candor, and a dash of Seinfeld.