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

Background: Anxiety is a prominent symptom and comorbidity of PPD. Post-hoc analyses of an integrated dataset from three BRX PPD trials evaluated effects of BRX on anxiety symptoms using the 17-item Hamilton Rating Score for Depression (HAMD-17) anxiety/somatization subscale (HAMD-17-A/S). 

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 60µg/kg/h (BRX60:Study B) or 90µg/kg/h (BRX90:Studies A-C) with follow-up through Day 30. Regardless of final maximum dosage, all BRX patients received the same dose titration for the first 24h (BRX-pooled). Post-hoc analyses examined HAMD-17-A/S scores (≥7 considered anxious depression). Adverse events (AEs) were assessed.
 
Results: BRX integrated analysis demonstrated statistically significantly greater reduction in 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-A/S scores were 8.2±2.06 in BRX-pooled and 8.0±2.06 in placebo groups. In BRX-pooled group, significant differences versus placebo in HAMD-17-A/S were observed at Hour 4 (-0.70±0.30, p=0.0188), and all measured timepoints to Hour 24 (-1.21±0.33, p=0.0003). Significant differences from placebo in HAMD-17-A/S occurred at Hour 24 for BRX90 (-1.04±0.35, p=0.0030), and BRX60 (-1.63±0.49, p=0.0011), and at all measured timepoints to Day 30 (BRX90: -0.79±0.40, p=0.0490; BRX60: -1.59±0.56, p=0.0051). AEs in ≥5% BRX and ≥2x placebo included sedation and/or somnolence, dry mouth, loss of consciousness, and flushing/hot flush.

Conclusions: BRX demonstrated statistically significant reductions in depressive and anxiety-related symptoms in PPD compared with placebo.