Frequently Asked Questions

Yes. In women with postpartum depression, zuranolone was associated with higher rates of concurrent remission of depressive and anxiety symptoms than placebo as early as day 3, and this advantage was maintained through day 45.

• Using HDRS-17 total score ≤ 7 plus HARS total score ≤ 7, concurrent remission rates were 18.9% vs 2.7% at day 3 (P=.003), 40.5% vs 19.2% at day 15 (P=.007), and 52.1% vs 23.2% at day 45 (P<.001).
• Using MADRS total score ≤ 10 plus HARS total score ≤ 7, rates were 23.0% vs 6.8% at day 3 (P=.010), 43.2% vs 23.3% at day 15 (P=.014), and 53.4% vs 26.1% at day 45 (P=.001).

Zuranolone showed early improvement in anxiety symptoms by day 3 on clinician-rated measures. On the HDRS-17 Anxiety/Somatization subscale, the LS mean change from baseline was −3.8 with zuranolone versus −2.7 with placebo at day 3 (P=.007), and the between-group difference remained significant through day 45, when changes were −5.7 vs −4.3 (P=.003).

Reductions on the patient-reported EPDS-3A anxiety subscale were also greater with zuranolone beginning at day 8 (−2.2 vs −1.5, P=.032) and continued through day 45 (−3.6 vs −2.1, P<.001).

At day 15, anxiety response rates were higher with zuranolone than with placebo. HARS response, defined as at least 50% reduction from baseline, occurred in 71.6% of women receiving zuranolone versus 49.3% receiving placebo (P=.007), and HDRS-17 Anxiety/Somatization response occurred in 68.9% vs 46.6% (P=.008).

These higher response rates continued at all measured time points through day 45. EPDS-3A response rates were numerically higher with zuranolone from day 8 through day 45, with a nominally significant difference at day 45 (56.2% vs 26.1%, P<.001).

Yes. Women receiving zuranolone had numerically greater improvement in insomnia symptoms than women receiving placebo across 3 sleep-related measures: the HDRS-17 insomnia subscale, MADRS item 4 for reduced sleep, and EPDS item 7 for difficulty sleeping.

Nominally significant benefits for zuranolone versus placebo were seen at all measured time points on the HDRS-17 insomnia subscale, at all time points except day 21 on the MADRS reduced sleep item, and at day 45 on the EPDS difficulty sleeping item.

Yes. Although zuranolone was given once daily for 14 days, benefits remained evident at the day 45 follow-up, which was 30 days after treatment ended. For example, concurrent remission using HDRS-17 plus HARS criteria was 52.1% with zuranolone versus 23.2% with placebo at day 45 (P<.001).

Sustained concurrent remission at both days 15 and 45 also favored zuranolone, with an odds ratio of 6.2 (95% CI, 2.2 to 17.4; P<.001) using HDRS-17/HARS criteria and 3.7 (95% CI, 1.5 to 8.9; P=.003) using MADRS/HARS criteria.

Yes. At day 45, women receiving zuranolone reported greater improvement than placebo in 5 SF-36v2 domains and in the Mental Component Summary score. Significant advantages were seen in Social Functioning, Mental Health, Physical Functioning, Role Physical, and Bodily Pain, as well as the Mental Component Summary.

In the zuranolone group, mean day-45 scores for Physical Functioning, Bodily Pain, and General Health, and for the Physical Component Summary, reached US population normative levels. The Role Physical domain score was within 1 minimal important difference of population normative levels.

This was the phase 3 ROBIN trial, a randomized, double-blind, placebo-controlled study in adult women with postpartum depression. Women were 18 to 45 years old, were no more than 6 months postpartum, had onset of a DSM-5-defined major depressive episode in the third trimester or within 4 weeks postpartum, and had a baseline HDRS-17 total score of at least 26.

A total of 153 women were randomized 1:1 to oral zuranolone 30 mg or placebo once daily for 14 days as outpatients, with follow-up through day 45. The efficacy analyses included 150 evaluable participants: 76 in the zuranolone group and 74 in the placebo group.

Yes. Psychotropic medications intended to treat depressive symptoms were permitted if the patient had been on a stable dose for at least 30 days before day 1 and intended to remain on the same dose through the day 15 assessments.

At baseline, 21.1% of women in the zuranolone group and 17.6% in the placebo group were receiving stable antidepressant therapy. A small proportion initiated antidepressant therapy during follow-up: 7.9% in the zuranolone group and 5.4% in the placebo group.

On indirect benefit-risk measures reported in this trial, zuranolone had NNT estimates of 5 for both HDRS-17 response and remission at day 15. The 95% confidence intervals were 5 [3 to 13] for response and 5 [3 to 17] for remission.

NNT was also 5 for sustained response (95% CI, 3 to 27) and sustained remission (95% CI, 3 to 10). Number needed to harm estimates were at least 10 for treatment-emergent adverse events and for discontinuation due to an adverse event, but the article notes that the NNH estimates were nonsignificant, so likelihood-to-be-helped-or-harmed values were not calculated.

The authors identified several important limitations. These analyses focused on non-primary endpoints and were not controlled for multiplicity, so the findings should be interpreted as exploratory.

• Generalizability may be limited because the trial used strict inclusion and exclusion criteria.
• The short study duration limited the ability to assess delayed adverse events.
• The relatively small sample size limited sensitivity for uncommon adverse events and subgroup effects.
• The number needed to harm analyses were nonsignificant and may not fully reflect tolerability in routine clinical practice.

Anxiety and insomnia are clinically important in postpartum depression because both are linked to worse outcomes. The article states that anxiety symptoms in women with postpartum depression have been associated with more severe depression, longer time to treatment response, and increased risk of self-harm ideation.

Sleep disturbance and poor sleep quality are also common in the peripartum period and have been associated with frequent self-harm thoughts, poor mental health status, and postpartum anxiety symptoms. The authors therefore argue that addressing anxiety and insomnia alongside depressive symptoms is important for improving functioning and psychological health.