Improvement in HAMD-17 Subscale Scores With 14-Day Treatment Course of Zuranolone in Postpartum Depression: Results From the SKYLARK Study [ID: 1372313

Abstract

INTRODUCTION: Postpartum depression (PPD) is a serious perinatal complication. SKYLARK (phase 3, randomized, double-blind, placebo-controlled trial [NCT04442503]) evaluated zuranolone, an investigational, neuroactive steroid positive allosteric modulator of both synaptic and extrasynaptic GABA(A) receptors, in adult patients with PPD. The primary endpoint, change from baseline (CFB) in HAMD-17 total score at day 15, was met. Zuranolone was generally well tolerated. The HAMD-17 can be divided into subscales that group specific items from the HAMD-17 scale that measure different aspects of depression presentation. Here, we present HAMD-17 subscale data from SKYLARK. METHODS: Patients aged 18–45 years with severe PPD (HAMD 17 total score ≥26) were randomized 1:1 to oral, once-daily zuranolone 50 mg or placebo for 14 days. The secondary endpoint was day 15 CFB in HAMD-17 subscale (Core Depression, Anxiety, Bech-6, Maier) scores. Subscales were analyzed separately by a mixed-effects model for repeated measures. Institutional review board approval was obtained. RESULTS: One hundred ninety-five patients (zuranolone, 98; placebo, 97) were randomized, received study drug, and had valid baseline and one or more post-baseline efficacy assessments. At day 15, patients receiving a 14-day treatment course of zuranolone showed nominally significant improvements across all HAMD-17 subscales versus placebo (least squares mean [SE] CFB treatment difference: Core Depression, −5.9 [2.4], P=.0151; Anxiety, −5.7 [2.3], P=.0123; Bech-6, −8.6 [3.0], P=.0040; Maier, −7.6 [2.6], P=.0041). Improvement in all subscales was observed starting at day 3. CONCLUSION: In SKYLARK, zuranolone was associated with rapid improvement in depressive and anxiety symptoms in patients with PPD across multiple domains, supporting its development as a potential oral, rapid-acting treatment option for PPD.