Brexanolone Appears Promising for Treating Postpartum Depression
Abstract
The study’s results support the rationale for targeting GABA-A receptors in the development of therapies to treat the disorder.
A new intravenous medication—brexanolone—showed promising results in a small, but diverse sample of women with severe postpartum depression, according to a study published online June 12 in The Lancet.
Samantha Meltzer-Brody, M.D., says she is encouraged by the results of early clinical trials of brexanolone—an allosteric modulator of both synaptic and extra-synaptic GABA-A receptors—now entering a phase 3 clinical trial.
“Postpartum depression (PPD) is one of the most common complications of childbirth, but currently there are no treatment options specifically indicated to treat women with PPD,” said Samantha Meltzer-Brody, M.D., the trial’s principal investigator. Meltzer-Brody is an associate professor of psychiatry and director of the Perinatal Psychiatry Program at the University of North Carolina School of Medicine.
Because of the serious adverse impact that depression can have on the mother, infant, and family, a medication that acts quickly is important. Psychotherapy and antidepressants can often take weeks to be effective.
For the double-blind, randomized, controlled trial, 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 percent) women had achieved remission (HAM-D total score of ≤7) compared with one (9 percent) 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. Two patients in the brexanolone group who had reported active suicidal ideation with a specific plan at baseline did not report the same feelings or behavior at the post-treatment assessment.
Brexanolone was found to be generally well tolerated among the study participants. There were no deaths, other 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).
Brexanolone—a formulation of the neuroactive steroid allopregnanolone—is an allosteric modulator of both synaptic and extra-synaptic GABA-A receptors. The results of the study support the rationale for targeting GABA-A receptors in the development of therapies for the estimated 10 percent to 20 percent of birth mothers who suffer from postpartum depression, Meltzer-Brody and colleagues wrote.
“Of the pharmacologic treatment options that are available, none targets the underlying mechanism or biology,” noted Meltzer-Brody.
While these results are encouraging, an ongoing phase 3 clinical program will further evaluate the safety and efficacy of brexanolone. “If successfully developed and approved, this medication would be an enormous step forward for the field,” she said.
Peripartum fluctuations in reproductive hormones have a pivotal pathophysiological role in postpartum depression, according to several studies cited by the researchers. Symptoms can begin as early as the beginning of the third trimester or in the acute postpartum period and may persist well beyond the perinatal period if untreated. The prevalence of severe postpartum depression ranges from 5 percent to 10 percent of all cases of postpartum depression, and is a leading cause of maternal mortality.
“Feelings of guilt, shame, or fear can make it difficult for women to speak up about their symptoms, so it is essential for clinicians to be proactive and encourage open and honest conversations about this condition,” Meltzer-Brody said. Partners, family, and friends should recognize signs and symptoms that their loved one might be experiencing and seek help from their health care provider, she added.
An accompanying commentary published in The Lancet reflected on the study’s “potentially important implication for our understanding of the pathophysiology of postpartum mood disorders,” but also raised questions such as whether the medication is a treatment for postpartum episodes specifically or could be used generally in depression.
Sage Therapeutics funded this research and assisted in the study design, data collection, data analysis, data interpretation, and writing of the report. ■
