Post-Hoc Analysis of Zuranolone Efficacy and Safety by Baseline MADRS Depressive Symptom Severity in SKYLARK and ROBIN
K. M. Deligiannidis, J. A. Ramos-Quiroga, B. Nair, A. Artemyeva, K. LaGuerre, H. Finnigan, F. Forrestal, J. Jung, V. Nguyen, M. AdamsIntroduction
Postpartum depression (PPD) is a common perinatal condition with significant consequences for the patient, child, and family. The efficacy and safety of zuranolone, an oral, once-daily, 14-day treatment for PPD in adults, was assessed in the pivotal SKYLARK and ROBIN studies. The Hamilton Depression Rating Scale 17 (HAMD-17) and Montgomery-Asberg Depression Rating Scale (MADRS) were the primary and a secondary endpoint, respectively. Both studies enrolled participants with a HAMD-17 score ≥ 26 (indicative of severe depressive symptoms). However, the efficacy and safety of zuranolone in patients with moderate PPD remains uncertain.
Objectives
This post-hoc analysis of SKYLARK and ROBIN aimed to characterize the efficacy and safety of zuranolone in patients with PPD with moderate or severe depressive symptoms defined by baseline MADRS score.
Methods
Two severity subgroups were defined based on baseline MADRS total score: moderate (20-34) and severe (≥ 35) depressive symptoms. Changes from baseline (CFB) in HAMD-17 and in MADRS total scores were analyzed in each subgroup using a mixed-effects model for repeated measures. Treatment-emergent adverse events were evaluated by subgroup.
Results
Both SKYLARK and ROBIN showed similar demographic and baseline characteristics in the moderate and severe subgroups, with a balanced distribution of moderate and severe MADRS scores. In each study, the least squares mean (LSM) treatment differences in CFB in HAMD-17 and MADRS total scores for each subgroup favored zuranolone at Day 15, with effects sustained to Day 45 (Tables 1 and 2). No clinically meaningful differences in safety were observed across the subgroups in either study.
LSM Treatment Differences in CFB versus placebo in HAMD-17 and MADRS Total Scores at Days 15 and 45 Tables 1 and 2. Long description.