Espresso: Zuranolone for Postpartum Depression

We’re back! While we’ll operate for a bit on a reduced schedule (new episodes every-other-week), we are so excited to get back to podcasting and covering the need-to-know in OB/GYN. Thanks for all the love and support over the last few months! <3 Nick & Fei

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Reading: Zuranolone for the Treatment of Postpartum Depression (ACOG Practice Advisory)

What is zuranolone and why is it important? 

• We know that postpartum/perinatal mental health conditions and some of the leading causes of preventable maternal mortality 

• PPD affects approximately 14% of women 

• Understanding/discussing/recommending medication and treatment can potentially decrease maternal morbidity and mortality 

• Medication type

• Neuroactive steroid gamma-aminobutyric acid (GABA) A receptor positive modulator 

• Oral medication  

• Recent FDA approval for use in PPD 

Why is zuranolone recommended, and what else is out there? 

• Why is it recommended? 

• Two phase 3 randomized double-blind, placebo-controlled multicenter studies 

• Primary endpoint in both: change in depressive symptoms in the Hamilton depression rating scale (HAMD-17) 

• 17 point scale 

• Assesses somatic (physical ie. loss of appetite), affective (mood ie. sadness), cognitive (thinking, ie. difficulty concentrating), and behavioral (ie. social withdrawal) symptoms of depression 

• Reliable and valid method of assessing and measuring depression 

• In both studies, those on Zuranolone showed significantly more improvement in their symptoms compared those in placebo 

• Treatment effect maintained at day 42 (4 weeks after last dose of zuranolone) 

• Why the HAMD-17? 

• More used in research settings, but anticipated that other validated tools (like EPDS or PHQ9) will be used in clinical settings 

• What else is out there? 

• Brexanolone - first FDA approved medication specifically for postpartum depression

• However, unlike zuranolone which is oral, brexanolone consists of a 60 hour in-hospital IV infusion, which may not be readily accessible 

• May be difficult to arrange inpatient admission 

• May also be difficult for patients to leave their newborns for 60 hours to get infusion 

• SSRIs 

• Not specific for postpartum/perinatal depression 

• Can be effective, but also may be difficult to find the correct SSRI

• Many SSRIs also require uptitration of dosage 

• What to consider when prescribing zuranolone 

• Consideration of zuranolone in the postpartum period (within 12 months postpartum) for depression that has onset in the third trimester or within 4 weeks postpartum

• Benefits: 

• Significantly improved and rapid resolution of symptoms 

• Risks: 

• Potential suicidal thoughts or behavior 

• Sedation - can make it so you can’t drive 

• Lack of efficacy data beyond 42 days 

• How to prescribe and take zuranolone 

• Daily recommended dose is 50 mg 

• Take in evening with fatty meal (400-1000 calories, 25-50% fat) for 14 days 

• Can reduce dose to 40 mg if CNS depression effects occur 

• If hepatic or renal impairment, start dose at 30 mg 

• Can be used alone or as an adjunct to other oral antidepressant therapy like SSRIs 

• Recommendation is to have effective contraception during treatment and for 1 week after final dose. There is a registry if pregnancy occurs 

• Warn patients about adverse reactions 

• Impaired ability to drive 

• CNS depressant effects 

• Increased suicidal thoughts and behaviors 

• Zuranolone does pass into breastmilk, but relative infant dose is smaller than that of SSRIs 

Physiologic Changes of Pregnancy: Part 2

10/08/2023
As part of our brief break for parental leave, we’re revisiting some of our most popular episodes! Today we’re revisiting Physiologic Changes of Pregnancy, part II.

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We’re continuing “Fei and Nick’s Fabulous Adventure Through Pregnancy” today!

Need a refresher on all those lung volumes? So did we. There are a number of resources online to review them, however a nice quick video review can be found here.

These two episodes have covered a lot of ground on a lot of systems. We tried to come up with a quick-view table encompassing all of these changes. Let us know what you think!

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Physiologic Changes of Pregnancy: Part 1

10/01/2023
As part of our brief break for parental leave, we’re revisiting some of our most popular episodes! Today we’re revisiting Physiologic Changes of Pregnancy - almost five years to the day since we released it! Check out our reprisal of part II next week with the all-encompassing table of changes.

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As promised, our first episode on pregnancy! Join us on “Fei and Nick’s Fabulous Adventure Through Pregnancy!”

Today we tackled the changes of the immunologic and hematologic systems seen in pregnancy. There’s quite a bit of information there! If you feel like we’ve missed anything, feel free to reach out via email or social media.

Next week, we’ll release Part 2 and have some more resources ready for your studying!

Third Stage of Labor, feat. Dr. Alyssa Hersh

Today we are joined by Dr. Alyssa Hersh, a resident at Oregon Health and Sciences University (OHSU) who is the lead author on a new Gray Journal (AJOG) review on the third stage of labor.

Check out the paper for all the good stuff, but here are the highlights of the podcast:

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• The third stage of labor occurs between fetal and placental delivery. It typically lasts 4-10 minutes, with complications starting to increase after 30 minutes.

• WThe ACOG definition of postpartum hemorrhage is blood loss ≥1,000 milliliters regardless of mode of delivery, or blood loss along with signs of excessive blood loss.

  • Remember the 4 T’s of etiologies of postpartum hemorrhage, including tone, tissue, trauma and thrombin.

• The original components of active management of the third stage of labor include:

  • Uterotonic, namely oxytocin;

  • Early cord clamping;

  • Controlled cord traction;

  • External uterine massage.

    • However, not all of these components are still evidence-based.

• There may be more effective uterotonic regimens than oxytocin alone for preventing postpartum hemorrhage.

• While TXA may be an effective adjunct to a uterotonic for prevention of postpartum hemorrhage, current evidence is conflicting and there is insufficient evidence to support its broad use at this time after all births.

• There is evidence supporting the use of controlled cord traction, particularly for reducing the need for manual extraction of the placenta.

  • External uterine massage is not effective for preventing postpartum hemorrhage.

• Early cord clamping has largely been replaced with delayed cord clamping due to the known benefits for both preterm and term infants.

• Cord milking may be harmful for very preterm neonates without sufficient data to support using it for neonates at higher gestational ages.

Viral Hepatitis in Pregnancy, with Dr. Brenna Hughes

We were lucky enough to get a sneak peak at ACOG’s newest Clinical Practice Guideline #6 on Viral Hepatitis in Pregnancy. We sat down with co-author Dr. Brenna Hughes, professor of obstetrics and gynecology and Vice Chair of Obstetrics and Quality at Duke University, to get highlights of the newest updates and changes concerning hepatitis in pregnancy.

Background

• There are five types of viral hepatitis: A, B, C, D, E

  • A and B are preventable through vaccination

  • B and C are recommended for screening in pregnancy.

• Screening and vaccination is important, as these infections cause morbidity for pregnant folks.

  • Recall we reviewed some of this in our prior podcast on hepatitis.

• Hepatitis A — small case-fatality and rare complications

  • Associated with food-borne outbreaks

  • Fecal-oral contamination or foodborne outbreaks related to contaminated food/water

• Hepatitis B — highly pathogenic and infectious

  • Perinatal transmission is single largest cause of chronic infection worldwide.

  • Also associated with sexual contact, IV drug use, contaminated blood product.

  • Mortality 1%

    • 85-90% of adults will experience resolution of physical findings and develop antibody.

    • 10-15% will develop chronic infection, with a minority of those continuing with viral replication and active viral DNA synthesis.

• Hepatitis C

  • Most commonly reported bloodborne infection in the US

    • Principal risk factor: IV drug use

  • 75% of individuals are asymptomatic with infection

  • Can be concomitantly spread with HIV

• Hepatitis D

  • Incomplete viral particle that exists only in presence of hepatitis B

  • Transmission primarily blood borne

  • Produces more severe disease than other forms of chronic hepatitis

    • 70-80% develop cirrhosis and portal hypertension, 15% within 2 years of initial onset of acute illness

      • This is compared to just 15-30% of patients with Hep B alone who develop cirrhosis and portal hypertension over time.

• Hepatitis E

  • Similarly to hepatitis A, associated with fecal-oral transmission

  • Generally self-limited viral illness

    • In pregnant persons, higher risk of fulminant hepatitis E with 20-35% fetal mortality and significant maternal morbidity (including need for transplant).

    • Rare in US

New Updates in Screening for Hepatitis B

• ACOG recommends triple panel screening for all pregnant patients without documented negative triple screen after age 18, or haven't completed HepB vaccine series, or who have ongoing risk for HepB infection regardless of prior vaccination / testing.

  • This encompasses obtaining a:

    • HepB surface antigen (Hep B sAg)

    • HepB anti-surface antibody (anti-HBs)

    • HepB total core antibody (total anti-HBc)

  • A triple panel provides opportunity to inform decisions regarding treatment (if needed) or vaccination.

  • If positive surface antigen — additional testing will help determine type of infection and chronicity.

• ACOG still recommends early universal prenatal screening for HepB sAg in all pregnancies regardless of testing and vaccination status.

  • 12-18% of patients still don’t receive even this baseline level of screening.

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ACOG CPG 6

Managing Hepatitis B in Pregnancy

• Pregnancy is well tolerated in those with hepatitis B infection without advanced liver disease.

  • There is a risk of hepatitis flare, particularly postpartum.

• Those with chronic hepB and a viral load of > 200,000 IU/mL should be on antiviral therapy in the third trimester to reduce risk of perinatal transmission.

  • Some patients with lower VL may also be on antivirals if indicated for their own risk/health.

• Vertical transmission is low with amniocentesis and shared-decision making can be employed when making decisions on this.

• There is insufficient evidence to suggest invasive obstetric procedures (FSE, episiotomy, operative delivery) increase transmission risk, but there are some reports of increased risk with neonate coming to contact with infected blood.

• All neonates of individuals with HBsAg-positive status or unknown status should receive HBIG and hepatitis B vaccine within 12 hours of birth.

• Breastfeeding can proceed unless there are other contraindications.

  • Tenofovir can be continued during breastfeeding.

Hepatitis C: Screening, Treatment, and Pregnancy Pearls

• ACOG recommends pre-pregnancy screening for hepatitis C virus infection and treatment.

  • Ideally, pregnant folks will get screened for hepatitis C antibody at the first prenatal visit of each pregnancy.

    • If positive —> assess hepatitis C viral PCR testing to confirm active infection vs cleared infection or false positive.

  • There are no treatment options for hepatitis C diagnosed in pregnancy — but there are really successful treatment options outside of pregnancy.

    • OB/GYNs can help get these patients to successful treatment in the postpartum period with prenatal screening.

  • Ribavirin achieves virology cure in large proportion of patients.

    • If patients are taking prior to pregnancy, couples should wait 6 months after completion of therapy due to possible teratogenic effects.

• In pregnancy, there are no known preventive measures to reduce risk of vertical transmission.

  • Risk is generally low for amniocentesis and CVS: use shared decision making in decision to proceed.

  • There is insufficient evidence to suggest routine invasive obstetric procedures should be avoided (internal monitoring, episiotomy, operative delivery) but can be considered/minimized when possible.

    • No evidence pre labor cesarean decreases transmission risk.

  • Breastfeeding is not discouraged in patients with active hepatitis C.

    • Not enough data on cracked/bleeding nipples.

Immunization in Pregnancy

• Both hepatitis A and hepatitis B vaccination are safe in pregnancy!

  • Newer hepatitis B vaccines do not have sufficient data (HepBZ-CpG and Hepb Vaccine Recombinant) — so need to know your manufacturer.

  • There is a combination vaccination for adults that can be used in pregnancy as well!