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The findings “demonstrate a substantial treatment effect of brexanolone” in a group of patients “for which there are no currently approved pharmacological therapies,” Steven Kanes, M.D., of Sage Therapeutics and colleagues wrote. Sage Therapeutics funded this research, and assisted in the study design, data collection, data analysis, data interpretation and writing of the report.
For the double-blind, randomized, controlled trial, the researchers assigned 21 women with severe postpartum depression (Hamilton Depression Rating Scale [HAM-D] score of at least 26) to a 60-hour, continuous intravenous dose of brexanolone or placebo. To make the sample as representative as possible, the researchers recruited patients from urban, suburban, and rural settings in the United States to receive treatment at four research sites.
By 60 hours, seven (70%) women had achieved remission (HAM-D total score of ≤7) compared to one (9%) in the placebo group. Furthermore, mean HAM-D scores for the women who received brexanolone remained significantly lower for a follow-up period of 30 days compared with the placebo group.
Brexanolone is an allosteric modulator of both synaptic and extra-synaptic GABA-A receptors. The results support the rationale for targeting GABA-A receptors in the development of therapies for the estimated 10% to 20% of birth mothers who suffer from postpartum depression, wrote the researchers.
“Our findings provide the first placebo-controlled clinical support for the role of extrasynaptic GABA-A receptors in the modulation of mood and affective states in any clinical population,” wrote the authors. A treatment with rapid onset of action is considered important in severe postpartum depression because of the adverse impact of the depression on the mother, infant, and family.
Brexanolone, a formulation of the neuroactive steroid allopregnanolone, was found to be generally well tolerated among the study participants. There were no deaths, serious adverse events, or discontinuations. The most commonly reported adverse events in the brexanolone group were dizziness (two brexanolone-treated subjects; three placebo-treated subjects) and somnolence (two brexanolone-treated subjects; no placebo-treated subjects).
The author of an accompanying commentary published in The Lancet commented on the study’s “potentially important implication for our understanding of the pathophysiology of postpartum mood disorders,” but he also raised questions such as “Is this a treatment for postpartum episodes specifically or could it be used generally in depression?”
Brexanolone is currently being evaluated in a phase 3 clinical program under way at various other sites across the country.
For related information, see the Psychiatric News article “Synthetic Oxytocin May Increase Risk of Postpartum Depression, Anxiety” and the Psychiatric Services article “Collaborative Care for Perinatal Depression Among Socioeconomically Disadvantaged Women: Adverse Neonatal Birth Events and Treatment Response.”
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