Zuranolone shows rapid-acting efficacy in postpartum depression

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 GABA_A 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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Posted on 28 November, 2022