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From the Family Practice Inquiries Network

Zuranolone (Zurzuvae) for Treatment of Severe Postpartum Depression in Adults

Serena Fang, MD
Roya Sharifian, MD
Vivian Cheng, PharmD
Jon O. Neher, MD

American Family Physician. 2025;111(3):265-266.

Author disclosure: No relevant financial relationships.

CLINICAL QUESTION

How effective is the gamma-aminobutyric acid type A (GABA-A) receptor modulator zuranolone (Zurzuvae) for treatment of severe postpartum depression in adults?

EVIDENCE-BASED ANSWER

Zuranolone is an effective treatment for adults with severe postpartum depression. (Strength of Recommendation: A, meta-analysis of randomized controlled trials [RCTs].)

EVIDENCE SUMMARY

A 2023 systematic review and meta-analysis evaluated nine double-blind RCTs assessing the effectiveness and safety of GABA-A receptor modulators such as zuranolone in female patients with major depressive disorder or postpartum depression (defined as major depression with onset within 4 weeks of delivery).1 Of the nine studies, two assessed zuranolone for postpartum depression (N = 346). The studies examined changes in the Hamilton Depression Rating Scale (HAM-D) score (scoring range = 0–54; higher score indicates more severe depression) with a 14-day course of zuranolone. Secondary outcomes included a more than 50% reduction in HAM-D score (response) or HAM-D score ≤ 7 (remission) and were measured up to day 45.

In patients with postpartum depression, treatment with oral zuranolone for 14 days improved depression scores compared with placebo. HAM-D scores were approximately 4 points lower with zuranolone vs placebo at day 15 (least squares mean difference = 4.2; 95% CI, 1.5–6.9; P = .003 and least squares mean difference = 4.0; 95% CI, 1.7–6.3; P < .001, respectively).2,3 The least squares mean difference is that between the predicted average values of the two groups. Patients taking zuranolone are more likely to achieve remission as defined by HAM-D score at day 15 compared with patients taking placebo. Postpartum depression response and remission rates were greater in the zuranolone group compared with the placebo group at all time points (Table 1).1

TABLE 1. Meta-Analysis of Hamilton Depression Rating Scale Response and Remission With Zuranolone (Zurzuvae) Compared With Placebo in Adults With Postpartum Depression

Time pointRelative risk (95% CI)P value
Zuranolone (2 studies, N = 346)
HAM-D response
Day 31.70 (1.170–2.465).005
Day 81.64 (1.289–2.089)< .001
Day 151.48 (1.203–1.824)< .001
Day 211.33 (1.094–1.610).004
Day 451.24 (1.038–1.481).018
HAM-D remission
Day 32.36 (1.105–5.033).027
Day 81.65 (1.054–2.568).028
Day 151.78 (1.229–2.581).002
Day 211.46 (1.031–2.054).033
Day 451.62 (1.210–2.166).001

Note: Response is defined as a 50% decrease in HAM-D score. Remission is defined as a HAM-D score ≤ 7.

HAM-D = Hamilton Depression Rating Scale (scoring range = 0–54).

Information from reference 1.

Zuranolone was associated with an increased risk of adverse effects (relative risk [RR] = 1.19; 95% CI, 1.07–1.31; P = .001), particularly somnolence (RR = 2.82; 95% CI, 1.79–4.44; P < .001), dizziness (RR = 3.02; 95% CI, 1.83–4.98; P < .001), and sedation (RR = 2.14; 95% CI, 1.03–4.44; P = .042).1

SERENA FANG, MD; ROYA SHARIFIAN, MD; VIVIAN CHENG, PHARMD; and JON O. NEHER, MD Valley Family Medicine, Renton, Washington

Address correspondence to Vivian Cheng, PharmD, at vivian_cheng@valleymed.org.

Author disclosure: No relevant financial relationships.

  1. 1.Zou J, Yang L, Yang G, et al. The efficacy and safety of some new GABAkines for treatment of depression: a systematic review and meta-analysis from randomized controlled trials. Psychiatry Res. 2023;328:115450.
  2. 2.Deligiannidis KM, Meltzer-Brody S, Gunduz-Bruce H, et al. Effect of zuranolone vs placebo in postpartum depression: a randomized clinical trial. JAMA Psychiatry. 2021;78(9):951-959.
  3. 3.Deligiannidis KM, Meltzer-Brody S, Maximos B, et al. Zuranolone for the treatment of postpartum depression. Am J Psychiatry. 2023;180(9):668-675.
  4. 4.American College of Obstetricians and Gynecologists. Practice advisory: zuranolone for the treatment of postpartum depression. August 2023. Updated January 30, 2024. Accessed January 6, 2025. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2023/08/zuranolone-for-the-treatment-of-postpartum-depression
  5. 5.US Food and Drug Administration. Highlights of prescribing information. Zurzuvae (zuranolone) capsules, for oral use. July 2024. Accessed January 9, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217369s001lbl.pdf

Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (https://www.cebm.net).

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to https://www.fpin.org or email questions@fpin.org.

Copyright © Family Physicians Inquiries Network. Used with permission.

This series is coordinated by John E. Delzell Jr., MD, MSPH, associate medical editor.

A collection of FPIN’s Clinical Inquiries published in AFP is available at https://www.aafp.org/afp/fpin.

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