NEW YORK (Reuters Health) – A 60-hour infusion of brexanolone significantly improves symptoms in women with postpartum depression, according to results from two phase 3 trials.
The results “confirm and extend the previous work showing that brexanolone has a rapid onset of action that is unlike anything else currently available,” said Dr. Samantha Meltzer-Brody from the University of North Carolina at Chapel Hill School of Medicine.
“Further, the robust treatment response to a single 60-hour infusion was maintained through the 30 days of follow-up in this clinical trial,” she told Reuters Health by email.
Brexanolone is a proprietary, intravenous formulation of allopregnanolone, an endogenous progesterone metabolite that appears to modulate gamma-aminobutyric acid (GABA) receptors. Brexanolone showed rapid and durable antidepressant effects during an earlier phase 2 clinical trial.
Dr. Meltzer-Brody and colleagues investigated the efficacy and safety of brexanolone injection in 246 women with moderate to severe postpartum depression in two randomized, placebo-controlled phase 3 trials at 30 U.S. centers.
In study 1, Hamilton Rating Scale for Depression (HAM-D) total scores decreased to a significantly greater extent at the end of the 60-hour infusion in the group receiving brexanolone 60 mcg/kg per hour (mean reduction, 19.5 points) and in the group on brexanolone 90 mcg/kg per hour (17.7 points) than in the placebo group (14.0 points).
Similarly, in study 2, HAM-D scores improved significantly more in the higher-dose group (mean, 14.6 points) than in the placebo group (12.1 points), the team reports in The Lancet, online August 31.
Depression scores had not returned to baseline by day 30 in any of the brexanolone groups and remained significantly lower in both treatment groups than in the placebo group of study 1 at day 30.
Remission (HAM-D total score 7 or less) and response (reduction in HAM-D total score of at least 50%) rates were higher in the brexanolone groups than in the placebo groups.
Brexanolone injection was generally well tolerated in both studies, with dizziness and somnolence occurring more frequently in women receiving brexanolone injection than placebo.
“If approved, brexanolone would be a powerful new tool that would act quickly (within a few days or less) to treat women suffering with postpartum depression (PPD),” Dr. Meltzer-Brody said. “PPD can often be debilitating to women and their families, and a rapidly acting treatment would be a most welcome addition to current options. It is important for symptoms of PPD to be quickly treated, as this can prevent long-term adverse consequences including impairing mother-child bonding and attachment.”
Dr. Michael E. Silverman from Icahn School of Medicine at Mount Sinai, in New York CIty, who has researched various aspects of postpartum depression, told Reuters Health by email, “Probably the most important finding is the reported 60-hr effect of brexanolone infusion treatment. This is a potentially important finding given the time course of currently available psychopharmacologic treatments for depression.”
“The fact that brexanolone must be infused over an extended period of time and cannot be taken orally complicates matters as a first-line treatment option,” he said.
He pointed out a number of issues complicating the interpretation of this report: why did the lower dosage of brexanolone appear to have a larger effect? Why did study 2 not show a significant 30-day effect of brexanolone? The placebo effect in both studies was considerable. These issues, he said, require further study.
“Brexanolone as a treatment for PPD is a potentially exciting avenue; indeed, as clinicians we could use more options in our treatment toolbox,” Dr. Silverman said. “I’m hopeful additional work, including replications of the above study to clarify the reported findings, will continue to be conducted.”
Sage Therapeutics, Inc. funded the studies and employed several of the authors. Dr. Meltzer-Brody reports financial ties to the company.