Espresso: Zuranolone for Postpartum Depression

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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

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