Reduction in Insomnia Symptoms in Patients With Postpartum Depression (PPD) Treated With the Neuroactive Steroid Brexanolone Injection

Background: PPD is one of the most common medical complications during and after pregnancy, with insomnia as a common symptom. Brexanolone injection (BRX) is a neuroactive steroid GABAA receptor positive allosteric modulator, approved by the FDA for the treatment of PPD in adults. Post-hoc analyses of an integrated dataset from three BRX PPD pivotal trials assessed for an effect on insomnia symptoms using the 17-item Hamilton Rating Score for Depression (HAMD-17) insomnia subscale (HAMD-17-Ins).

Methods: Women (N=247) ages 18-45, ≤6 months postpartum, with PPD and qualifying HAMD-17 (Studies A,B≥26; C=20-25) received 60-hour infusions of placebo or BRX titrated to 60 µg/kg/h (BRX60) or 90 µg/kg/h (BRX90), with follow-up through Day 30. Post-hoc analyses examined HAMD-17-Ins (sum of individual items for early, middle, and late insomnia, with totals ≥4 considered “high” insomnia). Adverse events (AEs) were assessed.

Results: BRX integrated data demonstrated statistically significantly greater least squares mean (LSM) HAMD-17 total score change from baseline (CFB±SE; BRX90: -16.95±0.74; BRX60: -19.05±1.18; both p < 0.0001) versus placebo:  12.83±0.71 at Hour 60 (primary endpoint). In post-hoc analyses, baseline mean HAMD-17-Ins scores were BRX90: 4.39±1.50, BRX60: 5.14±1.25, and Placebo: 4.58±1.47. Significant differences versus placebo in LSM HAMD-17-Ins CFB favoring BRX were observed at Hour 24 (BRX90: -0.95±0.24, p=0.0001; BRX60: -1.15±0.34, p=0.0008), Hour 60 (BRX90: -0.97±0.26, p=0.0003; BRX60: -1.02±0.37, p=0.0060), and Day 30 (BRX90: -0.65±0.29, p=0.0245; BRX60: -1.00±0.40, p=0.0130). AEs in ≥5% BRX, ≥2x placebo included sedation and/or somnolence, dry mouth, loss of consciousness, and flushing/hot flush.

Conclusions: BRX demonstrated improvements in depressive and insomnia-related symptoms.