(408) Effect of Zuranolone on Insomnia Symptoms in Patients With Postpartum Depression in the SKYLARK Study

Objective: Symptoms of insomnia are frequently present at diagnosis of women with postpartum depression (PPD). These symptoms often complicate management. Addressing insomnia may improve the function and mental health of women with PPD. Gamma-amino-butyric acid (GABA) plays a well-established role in sleep regulation. Zuranolone (ZRN) is an investigational neuroactive steroid and positive allosteric modulator of synaptic and extrasynaptic GABA_A receptors in clinical development as a once-daily (qd), oral 14-day treatment for PPD and major depressive disorder (MDD). Results from the SKYLARK Study (NCT04442503) on the effect of ZRN on insomnia symptoms in women with PPD are reported.

Study Design: SKYLARK was a randomized, double-blind, placebo (PBO)-controlled Phase 3 trial evaluating the efficacy and safety of ZRN 50mg (ZRN50) in women with severe PPD. Women aged 18–45 years with PPD and a baseline 17-item Hamilton Rating Scale for Depression (HAMD-17) total score ≥26 were randomized 1:1 to receive ZRN50 or PBO qd for 14 days. Symptoms of insomnia were assessed by HAMD-17 early, middle, and late insomnia item scores at baseline and on Days 3, 8, 15, 21, 28, and 45.

Results: Of 200 randomized patients, 195 received study drug and had ≥1 valid, post-baseline efficacy assessment (ZRN50, N=98; PBO, N=97). Demographic/baseline characteristics were generally balanced between ZRN and PBO. SKYLARK met its primary endpoint of change from baseline (CFB) in HAMD-17 total score at Day 15 (least squares mean [LSM] (SE) −15.6 (0.8) vs −11.6 (0.8); p=0.0007). In a prespecified analysis, improvement in symptoms of insomnia was achieved by women receiving ZRN vs PBO at Day 15 as assessed by HAMD-17 early, middle, and late insomnia item scores (Figure). Consistent with previous studies, ZRN was generally well-tolerated (Table).

Conclusion: Results reported here suggest that women with PPD receiving ZRN may experience improvements in symptoms of insomnia in addition to improvements in their depressive symptoms; ZRN was generally well-tolerated.