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Zuranolone shows rapid-acting efficacy in postpartum depression

Presented by
Dr Kristina Deligiannidis, Zucker Hillside Hospital, NY, USA
ECNP 2022
Phase 3, SKYLARK
A 2-week treatment with zuranolone 50 mg daily significantly decreased symptoms of postpartum depression, results from the phase 3 SKYLARK study showed.

Postpartum depression (PPD) affects approximately 10–15% of women globally, with adverse effects on both maternal and infant health [1,2]. Amongst others, altered levels of allopregnanolone and disrupted γ-aminobutyric acid (GABA) signalling are thought to be driving contributors to the aetiology of PPD. Zuranolone is an oral, neuroactive steroid modulating synaptic and extrasynaptic GABAA receptors.

Previously, results of the ROBIN study (NCT02978326) showed the efficacy and safety of zuranolone (30 mg daily) in the treatment of PPD at day 15 [3]. SKYLARK (NCT04442503) is a phase 3, double-blind, randomised, placebo-controlled study aiming to replicate the findings of the ROBIN study, using 50 mg zuranolone daily. Dr Kristina Deligiannidis (Zucker Hillside Hospital, NY, USA) presented the results [4].

SKYLARK enrolled 195 women aged 18–45 years with severe PPD (Hamilton Rating Scale for Depression total score [HAMD-17] ≥26) that lasted from the third trimester until <4 weeks postpartum. Women were 1:1 randomised to receive 50 mg zuranolone daily or placebo and were followed up through day 45. The primary endpoint was a change from baseline in HAMD-17 at day 15.

SKYLARK met its primary endpoint, as the change from baseline in HAMD-17 at day 15 was -15.6 versus -11.6 for patients treated with zuranolone and placebo, respectively (P=0.0007). A statistically significant difference in favour of zuranolone was observed from day 3 to day 45 (the end of the study). HAMD-response, defined as a ≥50% decrease from baseline HAMD-17, was significantly higher in the zuranolone arm compared with the placebo arm all along from day 3 to day 45. In addition, zuranolone treatment also favoured HAMD-17 remission (defined as HAMD-17 ≤7).

Zuranolone was generally well tolerated and demonstrated a safety profile consistent with that already observed in the zuranolone clinical programme. Based on these results, Dr Deligiannidis concluded that “this data supports the potential role of zuranolone as a novel, oral, and rapid-acting, 14-day treatment for PPD.”

  1. Wang Z, et al. Transl Psychiatry. 2021;11:543.
  2. Shapiro AF, et al. Early Child Dev Care. 2020;190:1919–1930.
  3. Deligiannidis KM, et al. JAMA Psychiatry. 2021;78:951–959.
  4. Deligiannidis KM, et al. Efficacy and safety of zuranolone 50 mg in postpartum depression: SKYLARK study, a double-blind, placebo-controlled randomised, phase 3 study. Abstract S07.01, ECNP Congress 2022, 15–18 October, Vienna, Austria.


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