Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• Postpartum depression (PPD) is a significant mood disorder in women, potentially linked to hormonal shifts.
• Allopregnanolone, a positive allosteric modulator of GABA_A receptors, is being investigated for PPD treatment.

Purpose of the Study:

• To evaluate the efficacy and safety of brexanolone, an intravenous allopregnanolone formulation, for treating severe postpartum depression.

Main Methods:

• A double-blind, randomized, placebo-controlled phase 2 trial enrolled women with severe PPD.
• Participants received a continuous 60-hour intravenous infusion of brexanolone or placebo.
• The primary endpoint was the change in the Hamilton Rating Scale for Depression (HAM-D) score at 60 hours.

Main Results:

• Brexanolone demonstrated a statistically significant reduction in HAM-D scores compared to placebo at 60 hours (p=0.0075).
• The mean reduction in HAM-D score was 21.0 points for brexanolone versus 8.8 points for placebo.
• No serious adverse events or treatment discontinuations due to adverse events were reported; dizziness and somnolence were the most common side effects.

Conclusions:

• Brexanolone infusion led to significant and clinically meaningful symptom reduction in women with severe postpartum depression.
• These findings support targeting GABA_A receptors for PPD therapy development.
• A pivotal clinical program for brexanolone in PPD is currently underway.